De-escalated Teclistamab Dosing in Relapsed/Refractory Multiple Myeloma: Czech Myeloma Group Real- World Evidence Analysis

De-escalated Teclistamab Dosing in Relapsed/Refractory Multiple Myeloma: Czech Myeloma Group Real- World Evidence Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article De-escalated Teclistamab Dosing in Relapsed/Refractory Multiple Myeloma: Czech Myeloma Group Real- World Evidence Analysis Martin Stork, Jakub Radocha, Jana Mihalyova, Ivan Spicka, Tomas Pika, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6764594/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Aug, 2025 Read the published version in Annals of Hematology → Version 1 posted 10 You are reading this latest preprint version Abstract Teclistamab, a BCMA×CD3 bispecific antibody, demonstrates high efficacy in relapsed/refractory multiple myeloma (RRMM). However, optimal dosing strategies outside clinical trials remain undefined. Thus, we performed a retrospective, multicentre analysis of 73 RRMM patients treated with teclistamab monotherapy at Czech Myeloma Group centres between 2023 and 2025. The study compared efficacy and safety between patients receiving standard weekly dosing and those with reduced-frequency dosing. The whole cohort had a median age of 67 years; 68.5% were penta-refractory. Dosing was de-escalated in 24.7% of patients, typically within one month of treatment initiation. Median progression-free survival (PFS) was 9.41 months and was comparable between weekly and non-weekly groups (9.1 vs. 11.3 months; p = 0.141), despite a significantly lower relative dose intensity in the latter (60.5% vs. 87.0%; p < 0.001). Infection rates and severe adverse events were similar between groups. A lower incidence of neutropenia was observed with less frequent dosing, but this did not translate into reduced infection burden. In conclusion, in real-world practice, early de-escalation of teclistamab dosing appears to maintain clinical efficacy. These findings support ongoing efforts to individualize treatment schedules with the aim of balancing effectiveness, tolerability, and patient-specific factors in BCMA-targeted therapy. multiple myeloma teclistamab immunotherapy real-world-evidence Figures Figure 1 Introduction Teclistamab is a bispecific antibody that targets multiple myeloma (MM) by binding to B-cell maturation antigen (BCMA) on MM cells and CD3 on T cells, triggering a T-cell-mediated anti-tumor response. In the MajesTEC-1 trial, it showed high efficacy in heavily pretreated patients with relapsed/refractory MM (RRMM) [ 1 ], supported by emerging real-world evidence [ 2 – 4 ]. However, teclistamab carries a high risk of infections due to B-cell depletion and immune dysregulation. Recurrent infections affect ~ 60–75% of patients, mostly related to teclistamab-induced hypogammaglobulinemia [ 5 ]. In the MajesTEC-1 trial, patients received an initial step-up dosing of teclistamab followed by a fixed weekly maintenance dose. For those who achieved a complete response after six months of treatment, the dosing frequency could be reduced to biweekly administration [ 1 ]. In real-world clinical practice, however, dosing schedules are often adapted for various reasons, potentially deviating from the standardized protocols used in controlled clinical trials. Patients and methods We conducted a retrospective analysis of teclistamab monotherapy in heavily pretreated RRMM patients across all major Czech haematology centres between 2023 and 2025. The primary objective of this study was to compare the efficacy and safety of standard dosing versus reduced-frequency dosing. All data were collected and analysed from the Czech Registry of Monoclonal Gammopathies (RMG) of Czech Myeloma Group (CMG). All participants provided written informed consents approved by institutional Ethics boards in accordance with the latest Helsinki declaration. Data collection cut-off date was 10th January 2025. The study population consisted of 73 RRMM patients with a median age of 67.0 years (range, 41–83). The median number of prior lines of therapy was 5 (range, 3–13), with 68.5% (50/73) of patients being penta-refractory. Totally 24.7% (18/73) of patients had extramedullary plasmacytomas (EMD, not associated to bone lesions). Of the 59 patients with available cytogenetics, 45.8% (27/59) had two or more high-risk cytogenetic aberrations (HR-CA, defined as t(4;14), t(14;16), del(17p), del(1p32) and gain/amp(1q21)). The median follow-up was 4 months (range, 1–17). Teclistamab was administered subcutaneously in all patients according to a step-up dosing protocol (0.06 mg/kg on Day 1 and 0.3 mg/kg on Day 4, followed by the first full dose of 1.5 mg/kg on Day 7). Subsequently, in the Weekly group, teclistamab is given at a maintenance dose of 1.5 mg/kg once weekly until disease progression or unacceptable toxicity occurs. In patients who achieved a complete response (CR) or better for at least six months, the dosing frequency of teclistamab was reduced to every other week. Patients who had earlier dosing frequency de-escalation for various reasons were categorized as the Non-weekly group. Response was assessed according to International Myeloma Working Group criteria. Relative dose intensity (RDI) was counted as the ratio of real cumulative dose (RCD) to maximal ideal dose (MID). Event-free survival (progression free survival - PFS, and overall survival - OS) was defined as the time from treatment initiation to the event or patient’s last follow-up. If the event didn’t occur, the censoring was done at the time of a last follow-up. It was assessed using the Kaplan-Meier methodology and all point estimates include 95% confidence intervals (95% CI). The statistical significance of differences in survival between subgroups was assessed using the log-rank test. The statistical significance of differences in categorical or continuous variables between the subgroups was tested by Fisher Exact test or Mann-Whitney U test. All statistical tests were performed at a significance level of α = 0.05 (all tests two-sided). Results Response and survival in all patients The overall response rate (ORR) in evaluable patients was 58.8% (40 out of 68), with 52.9% (36 out of 68) achieving a very good partial response (VGPR) or better. The median PFS was 9.41 months (95% CI: 7.11–not applicable), and the median OS was 15.38 months (95% CI: 10.95–not applicable). Supplementary figure 1 Progression free survival (PFS) – all patients. Supplementary figure 2 Overall survival (OS) – all patients. Prognostic subgroups Achievement of a deeper response was strongly associated with improved survival outcomes. Patients who achieved a VGPR or better had significantly longer median PFS compared to those with a partial response (PR) or less: 15.38 months (95% CI: 11.18–not estimable) vs. 1.38 months (95% CI: 1.28–3.48), respectively (p < 0.001). This benefit was also reflected in estimated 12-month overall survival (OS) rates, which were 75.0% (95% CI: 57.2–98.4) for patients with VGPR or better, compared to 27.8% (95% CI: 12.5–61.8) for those with PR or worse (p < 0.001). Supplementary figure 3 Progression free survival (PFS) – best response. Supplementary figure 3 Overall survival (OS)– best response. Additionally, patients with extramedullary disease (EMD) had shortest median PFS compared to those with para-skeletal plasmacytomas (growing outside of bone lesions) or those with the absence of plasmacytomas: 3.87 months (95% CI: 1.38–not estimable) vs. 10.1 months (95% CI: 6.4– not estimable) vs. not estimable; p=0.059. Moreover, patients harbouring ≥2 high-risk HR-CA had shorter median PFS when compared to those with 1 or no HR-CA: 1.84 months (95% CI: 1.38–not estimable) vs. 9.4 months (95% CI: 7.97–not estimable); p=0.022, respectively. A full overview of survival outcomes in whole cohort and subgroups is provided in Supplementary Figures 1–8. Supplementary Figure 5 Progression free survival (PFS) – Extraosseous plasmacytomas in multiple myeloma (EMM) – Extramedullary (EMD) plasmacytomas vs. Para-skeletal (PS) plasmacytoma vs. No plasmacytomas Supplementary Figure 6 Overall survival (OS) – Extraosseous plasmacytomas in multiple myeloma (EMM) – Extramedullary (EMD) plasmacytomas vs. Para-skeletal (PS) plasmacytoma vs. No plasmacytomas Supplementary Figure 7 Progression free survival (PFS) – Two or more high-risk cytogenetic aberration* (“double hit multiple myeloma”) Supplementary Figure 8 Overall survival (OS) – Two or more high-risk cytogenetic aberration* (“double hit multiple myeloma”) Dosing frequency and relative dose intensity Dosing frequency was modified in 24.7% (18/73) of patients, with 72.2% (13/18) receiving teclistamab every two weeks and 27.8% (5/18) every four weeks. The median time to de-escalation was 1 month (range, 0–3). The most common reason for de-escalation was achievement of a favourable response (55.6%, 10/18), followed by adverse events (33.3%, 6/18) and patient frailty (11.1%, 2/18). The median relative dose intensity (RDI), calculated as the ratio of actual cumulative dose (RCD) to the maximum ideal dose (MID), was 80.1% (range, 25.3%–100.0%) across the entire cohort. Patients in the non-weekly dosing group had a significantly lower median RDI of 60.5% (range, 37.2%–93.8%) compared to 87.0% (range, 25.3%–100.0%) in the weekly group (p < 0.001). Baseline characteristics were generally balanced between groups. The median age was slightly higher in the non-weekly group (69 years [range, 49–83]) than in the weekly group (66 years [range, 41–85]; p = 0.065). Median ECOG performance status was 1 in both groups (range, 0–3; p = 0.37). Additional comparisons of baseline characteristics and supportive treatment are provided in Table 1. T able 1 . Demographic characteristics and treatment in non-weekly and weekly dosing groups Non weekly dosing Weekly dosing p value* Number of pts (N) 24.7 % (18/73) 75.3 % (55/73) - Median age (y) 69.0 (49.0-83.0) 66.0 (41.0-85.0) 0.065 ECOG performance status (median) 1 (0-3) 1 (0-3) 0.370 No. of previous treatment lines (median) 4 (3-9) 5 (3-13) 0.459 Penta-refractory patients 55.6 % (10/18) 88.9 % (40/55) 0.242 Previous anti-BCMA therapy 5.6 % (1/18 14.5 % (8/55) 0.436 Extramedullary plasmacytomas 11.1 % (2/18) 29.1 % (16/55) 0.207 2 or more HR-CA + 28.6 % (4/14) 48.9 % (22/45) 0.227 Without IVIG* administration 27.8 % (5/18) 23.6% (13/55) 0.758 Median monthly IVIG* dose (grams/patient) 19.1 (4.0-22.7) 22.4 (4.0-100.0) 0.056 HR-CA – high-risk cytogenetic aberrations + ;* intravenous immunoglobulins * Fisher Exact test, Mann-Whitney U test + t(4;14), t(14;16), del(17p), del(1p32) and gain/amp(1q21) Survival outcomes by dosing frequency Progression-free survival (PFS) was comparable between patients receiving weekly and non-weekly teclistamab dosing. The median PFS was 9.1 months (95% CI: 2.7–not estimable) in the weekly group and 11.3 months (95% CI: 6.4–not estimable) in the non-weekly group (p = 0.141). Overall survival (OS) data were still immature at the time of analysis. However, estimated 12-month OS rates suggested a clinically meaningful trend in favour of weekly dosing: 62.3% (95% CI: 47.6–81.5) in the weekly group versus 36.6% (95% CI: 14.0–95.9) in the non-weekly group. This difference did not reach statistical significance (p = 0.667). The survival according to dosing frequency is shown in Figure 1 a,b. Adverse events by dosing frequency Cytokine release syndrome (CRS) occurred in 49.3% (36/73) of patients, predominantly grade 1 (39.7%, 29/73), with an additional 9.6% (7/73) experiencing grade 2 events. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in two patients (2.7%), both cases being grade 1. Tocilizumab was administered to 9.6% (7/73) of patients to manage CRS and/or ICANS. Infection rates were comparable between dosing groups when analysed after de-escalation. Infections occurred in 80.0% (44/55) of patients in the weekly group and 66.7% (12/18) in the non-weekly group (p = 0.335). Severe infections (grade 3–4) were reported in 29.1% (16/55) of weekly-dosed patients and 50.0% (9/18) of non-weekly patients (p = 0.152). Among patients in the non-weekly group, infection incidence remained similar before and after dose de-escalation. A total of 55.6% (10/18) experienced infections prior to de-escalation, and 66.7% (12/18) thereafter (p = 0.733). Severe infections occurred in 22.2% (4/18) before de-escalation and in 50.0% (9/18) afterward (p = 0.164), indicating a numerical increase that did not reach statistical significance. When assessing cumulative infection episodes irrespective of timing, the median number of all infection events was 2 (range, 0–12) in the weekly group and 1 (range, 0–11) in the non-weekly group (p = 0.730). However, the median number of grade 3–4 infection episodes was significantly higher in the non-weekly group (median 1; range, 0–3) compared to the weekly group (median 0; range, 0–4; p = 0.033). Neutropenia occurred more frequently in patients receiving weekly dosing: 61.8% (34/55) versus 22.2% (4/18) in the non-weekly group (p = 0.006). The incidence of severe neutropenia (grade 3–4) was similar between groups (23.6% vs. 16.7%; p = 0.745). In the non-weekly group, severe neutropenia occurred in 5.5% (1/18) of patients prior to de-escalation and in 16.7% (3/18) after de-escalation (p = 0.603). Rates of anemia and thrombocytopenia were comparable between the two groups. Detailed toxicity data are provided in Table 2. Table 2. - Toxicity according to dosing scheme Adverse event Gr. Non-weekly dosing Weekly dosing p value* CRS Gr.1-2 44.4% (8/18) 49.1 % (27/55) 0.790 ICANS Gr.1 11.1% (2/18) 0.0 % 1.000 Infection + Total 66.7% (12/18) 80.0% (44/55) 0.335 Gr.3-4 50.0% (9/18) 29.1% (16/55) 0.152 Anemia + Total 38.9% (7/18) 63.6% (35/55) 0.099 Gr.3-4 5.6% (1/18) 7.3% (4/55) 1.000 Thrombopenia + Total 22.2% (4/18) 41.8% (23/55) 0.167 Gr.3-4 16.7% (3/18) 10.9% (6/55) 0.680 Neutropenia + Total 22.2% (4/18) 61.8% (34/55) 0.006 Gr.3-4 16.7% (3/18) 23.6% (13/55) 0.745 CRS – Cytokine Release Syndrome; ICANS – Immune effector Cell Associated Neurotoxicity Syndrome; * Fisher exact test; + - counted in the non-weekly group after the de-escalation; Bold values are statistically significant Discussion This multicentre real-world study demonstrates that teclistamab dosing in routine clinical practice often diverges from the fixed weekly maintenance schedule employed in the MajesTEC-1 trial. Despite less frequent dosing, PFS remained comparable to weekly dosing, indicating sustained efficiency in responding patients. Clinical data on dosing de-escalation of anti-BCMA bispecific antibodies remain limited. In a real-world study, 32% (25/77) of patients transitioned to every-other-week dosing of teclistamab after three months due to toxicity or achieving partial response. At six months, the progression-free survival rate was 94% among these patients, compared to 52% in the overall cohort, likely reflecting positive selection of responders [6]. For elranatamab, the MagnetisMM-3 trial showed that responders could reduce dosing from weekly to every-other-week after six months, then to every-four-week after another six months without losing efficacy [7]. Our data uniquely show the median time to dosing frequency de-escalation was just one month—much shorter than previous studies. Despite maintained efficacy in non-weekly dosing, no reduction of infection events was observed. This may be due to the prolonged impact of teclistamab on immunoglobulin production, extending beyond the 2- or 4-week off-therapy periods. Variability in intravenous immunoglobulin administration and supportive care across real-world settings also likely contributes to generally inconsistent toxicity outcomes [5; 8; 9]. Moreover, response to treatment was the primary reason for dose de-escalation, but frailty and recurring infections also contributed, potentially biasing adverse event reports in the non-weekly group. Also, these patients were generally older. While bispecific antibodies' efficacy is unaffected by age [1; 6; 11], elderly patients are more susceptible to infections and hematologic toxicity. Both groups were balanced regarding EMD and high-risk cytogenetics, which negatively influenced prognosis both in our study and in so far published works [1; 3]. We noted a reduced incidence of neutropenia with the non-weekly dosing schedule. Since BCMA is not typically expressed on myeloid cells or neutrophils, this might result from less immune cell-mediated myelosuppression due to lower teclistamab plasma levels [10]. The impact of teclistamab dosing frequency on myeloid cells remains unclear and warrants further study. The OS data, though still immature, seems to favor weekly dosing. Factors such as patient age or alternative treatments like GPRC5D or FCRH5 bispecific antibodies for teclistamab-refractory patients may influence results [11; 12]. More research is needed on how reduced anti-BCMA bispecific antibody dosing affects subsequent therapy efficacy, particularly regarding T-cell exhaustion [13; 14]. The retrospective nature of our study and the variability in clinical decision-making processes are limitations that should be acknowledged. However, our findings offer valuable insights into the real-world application of teclistamab and may guide future research efforts aimed at optimizing dosing protocols to balance efficacy, safety, and treatment costs. Taken together, in a real-world setting, early de-escalation of teclistamab dosing did not compromise efficacy especially in responding patients. However, reduced dosing was not associated with a lower rate of infectious complications. These findings suggest that flexible, response-adapted dosing strategies may be appropriate in select patients, particularly those with frailty or tolerability concerns. Further prospective studies are needed to validate these observations and to better define the impact of dosing modifications on long-term outcomes, immune recovery, and subsequent therapy sequencing. Declarations Conflicts of Interest: MS : Jonhson & Jonhnson: Consultancy, Other: Travel support, Honoraria for lectures JR : BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Johnson & Johnson: Consultancy, Honoraria; GSK: Consultancy; Pfizer: Consultancy, Honoraria. TJ : Janssen: Consultancy, Other: Honoraria for lectures, Research Funding; Sanofi: Other: Honoraria for lectures, Research Funding; Pfizer: Consultancy,Other: Honoraria for lectures; BristolMyers Squibb:Other:Honoraria for lectures; GlaxoSmithKline: Consultancy, Other: Honoraria for lectures; Amgen: Research Funding. IS: BMS: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support; GSK: Consultancy, Membership on an entity’s Board of Directors or advisory committees. JM : Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; GSK: Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. RH : Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Acknowledgments The authors would like to thank all the patients and their caregivers who participated in this study, and data managers from participating centers. This work was supported by Ministry of Health, Czech Republic - conceptual development of research organization (FNBr, 65269705). This work was supported by OPJAK SALVAGE project (No. CZ.02.01.01/00/22_008/0004644) and by the European Union project LERCO (No. CZ.10.03.01/00/22_003/0000003). Author contribution statement: MS designed the study and wrote the manuscript. MS, JR, JM, IS, TP, AJ, IB, KM, JS, FS, JM, PK, DN, MH, TD, VM, TJ, LP and RH treated the patients and provided clinical data. ZK and NS provided preclinical data. All authors interpreted and discussed the results. All authors approved the final version of the manuscript prior to submission. Funding Supported by Ministry of Health, Czech Republic - conceptual development of research organization (FNBr, 65269705). This work was supported by OPJAK SALVAGE project (No. CZ.02.01.01/00/22_008/0004644) and by the European Union project LERCO (No. CZ.10.03.01/00/22_003/0000003). Data Availability Statement: The datasets analyzed during the current study are available from the corresponding author on reasonable request. References Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, et al. (2022) Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 387(6):495-505. doi: 10.1056/NEJMoa2203478. Mohan M, Monge J, Shah N, Luan D, Forsberg M, Bhatlapenumarthi V, et al. (2024) Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study. Blood Cancer J. 14(1):35. doi: 10.1038/s41408-024-01003-z. Riedhammer C, Bassermann F, Besemer B, Bewarder M, Brunner F, Carpinteiro A, et al. (2024) Real-world analysis of teclistamab in 123 RRMM patients from Germany. Leukemia. 38(2):365-371. doi: 10.1038/s41375-024-02154-5. Tan CRC, Asoori S, Huang CY, Brunaldi L, Popat R, Kastritis E, et al. (2025) Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study. Blood Cancer J. 15(1):53. Nooka AK, Rodriguez C, Mateos MV, Manier S, Chastain K, Banerjee A, et al. (2024) Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study. Cancer. 130(6):886-900. doi: 10.1002/cncr.35107 Tan CRC, Derkach A, Maclachlan K, Hultcrant M, Hassoun V, Mailankody S, et al. (2024) Real-world schedule de-escalation of teclistamab in patients with relapsed/refractory multiple myeloma. Journal of Clinical Oncology. 42;7536-7536. 10.1200/JCO.2024.42.16_suppl.7536. Prince HM, Bahlis NJ, Rodríguez-Otero P, Karlin L, Akard Luke, Varshavsky-Yanovsky A, et al. (2024) MagnetisMM-3: Long-Term Update of Efficacy and Safety of Less Frequent Dosing of Elranatamab in Patients with Relapsed or Refractory Multiple Myeloma. Blood. 144 (Supplement 1): 4738. https://doi.org/10.1182/blood-2024-208192 Cortes-Selva D, Perova T, Skerget S, Vishwamitra D, Stein S, Boominathan R, et al. (2024) Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in the MajesTEC-1 study. Blood. 144(6):615-628. doi: 10.1182/blood.2023022823. Lancman G, Parsa K, Kotlarz K, Avery L, Lurie A, Lieberman-Cribbin A, et al. (2023) IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies. Blood Cancer Discov. 4(6):440-451. doi: 10.1158/2643-3230.BCD-23-0049. Leclercq G, Servera LA, Danilin S, Challier J, Steinhoff N, Bossen C, et al. (2022) Dissecting the mechanism of cytokine release induced by T-cell engagers highlights the contribution of neutrophils. Oncoimmunology. 11(1):2039432. doi: 10.1080/2162402X.2022.2039432. Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodríguez-Otero P, et al. (2022) Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 387(24):2232-2244. doi: 10.1056/NEJMoa2204591. Richter J, Thomas SK, Krishnan AY, Laubach JP, Cohen AD, Trudel S, et al. (2024) Cevostamab in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies. Blood ; 144 (Supplement 1): 1021. doi: https://doi.org/10.1182/blood-2024-199542 Merz M, Dima D, Hashmi H, Ahmed N, Stölzel F, Holderried TAW, et al. (2024) Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy. Blood Cancer J. 14(1):214. doi: 10.1038/s41408-024-01197-2. van de Donk NWCJ, Chari A, Mateos MV. (2024) Mechanisms of resistance against T-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies. Lancet Haematol. 11(9):e693-e707. doi: 10.1016/S2352-3026(24)00186-8. Additional Declarations Competing interest reported. MS: Jonhson & Jonhnson: Consultancy, Other: Travel support, Honoraria for lectures JR: BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Johnson & Johnson: Consultancy, Honoraria; GSK: Consultancy; Pfizer: Consultancy, Honoraria. TJ: Janssen: Consultancy, Other: Honoraria for lectures, Research Funding; Sanofi: Other: Honoraria for lectures, Research Funding; Pfizer: Consultancy,Other: Honoraria for lectures; BristolMyers Squibb:Other:Honoraria for lectures; GlaxoSmithKline: Consultancy, Other: Honoraria for lectures; Amgen: Research Funding. IS: BMS: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support; GSK: Consultancy, Membership on an entity’s Board of Directors or advisory committees. JM: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; GSK: Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. RH: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Supplementary Files SupplementstoAOHe.docx Cite Share Download PDF Status: Published Journal Publication published 18 Aug, 2025 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 05 Jul, 2025 Reviews received at journal 01 Jul, 2025 Reviews received at journal 29 Jun, 2025 Reviewers agreed at journal 19 Jun, 2025 Reviewers agreed at journal 19 Jun, 2025 Reviewers agreed at journal 11 Jun, 2025 Reviewers invited by journal 10 Jun, 2025 Editor assigned by journal 04 Jun, 2025 Submission checks completed at journal 04 Jun, 2025 First submitted to journal 28 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6764594","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469738619,"identity":"7772137e-456d-4d61-b0d2-9beda1458e8b","order_by":0,"name":"Martin Stork","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYJACxgYY9cGGIYGwejaYFjbGBsYZaaRpYWBg5iFGi/z85mMfZzBskzef39z22CbhTp757OYDDD/+4NZicIwteeYGhtuGc44xthvnJDwrlrlzLIGxhwePFjYeY8YHDLcZZ7Axtknn/jicOEMix4CZQQKPw9ogWuzBWiwSYFoM8HjmGFAL0GGJYC0McC0J+PySlsw4w+B28gy2xDbJnoTDxRISaQkHew7gcVjz4cOMPRW3bWcwH38m8SPhcJ6ERPLBB/hCDGoXGh+PHaNgFIyCUTAKiAEAeABNEYI9DZUAAAAASUVORK5CYII=","orcid":"","institution":"University Hospital Brno and Faculty of Medicine, Masaryk University","correspondingAuthor":true,"prefix":"","firstName":"Martin","middleName":"","lastName":"Stork","suffix":""},{"id":469738620,"identity":"36bf2909-263c-4505-b4bb-74e6ac99eff3","order_by":1,"name":"Jakub Radocha","email":"","orcid":"","institution":"University Hospital Hradec Králové","correspondingAuthor":false,"prefix":"","firstName":"Jakub","middleName":"","lastName":"Radocha","suffix":""},{"id":469738621,"identity":"448348c3-d74f-4c82-993d-a407478c08cb","order_by":2,"name":"Jana Mihalyova","email":"","orcid":"","institution":"University Hospital Ostrava","correspondingAuthor":false,"prefix":"","firstName":"Jana","middleName":"","lastName":"Mihalyova","suffix":""},{"id":469738622,"identity":"1a07769d-e9bc-4952-a6ac-e0383282a2f0","order_by":3,"name":"Ivan Spicka","email":"","orcid":"","institution":"Hospital Charles University","correspondingAuthor":false,"prefix":"","firstName":"Ivan","middleName":"","lastName":"Spicka","suffix":""},{"id":469738623,"identity":"928bb9bd-4021-4331-bb7a-b521baa903e7","order_by":4,"name":"Tomas Pika","email":"","orcid":"","institution":"University Hospital Olomouc, Palacky University Olomouc","correspondingAuthor":false,"prefix":"","firstName":"Tomas","middleName":"","lastName":"Pika","suffix":""},{"id":469738624,"identity":"d81ba791-9fb8-41ae-9c33-e5a1abac0acf","order_by":5,"name":"Alexandra Jungova","email":"","orcid":"","institution":"Charles University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Jungova","suffix":""},{"id":469738625,"identity":"f7864c23-c78c-4d72-b207-bfc884e57093","order_by":6,"name":"Ivanna Boichuk","email":"","orcid":"","institution":"University Hospital Brno and Faculty of Medicine, Masaryk University","correspondingAuthor":false,"prefix":"","firstName":"Ivanna","middleName":"","lastName":"Boichuk","suffix":""},{"id":469738626,"identity":"51905d83-0215-4743-8fa6-34df5415f0bb","order_by":7,"name":"Klara Mensikova","email":"","orcid":"","institution":"University Hospital Brno and Faculty of Medicine, Masaryk University","correspondingAuthor":false,"prefix":"","firstName":"Klara","middleName":"","lastName":"Mensikova","suffix":""},{"id":469738627,"identity":"0bdea9d4-74fe-4fbe-b9d0-1a2a7913dc6a","order_by":8,"name":"Jan Straub","email":"","orcid":"","institution":"Hospital Charles University","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Straub","suffix":""},{"id":469738628,"identity":"9462845e-89b3-4ea9-8d79-1f53579ca6a3","order_by":9,"name":"Frantisek Sedlak","email":"","orcid":"","institution":"Hospital Charles University","correspondingAuthor":false,"prefix":"","firstName":"Frantisek","middleName":"","lastName":"Sedlak","suffix":""},{"id":469738629,"identity":"bc7f5b30-267c-440e-a71b-7fd4dbf8fe7b","order_by":10,"name":"Jiri Minarik","email":"","orcid":"","institution":"University Hospital Olomouc, Palacky University Olomouc","correspondingAuthor":false,"prefix":"","firstName":"Jiri","middleName":"","lastName":"Minarik","suffix":""},{"id":469738630,"identity":"307b3992-b5c6-4d4a-a288-7021fbf3f593","order_by":11,"name":"Petra Krhovska","email":"","orcid":"","institution":"University Hospital Olomouc, Palacky University Olomouc","correspondingAuthor":false,"prefix":"","firstName":"Petra","middleName":"","lastName":"Krhovska","suffix":""},{"id":469738631,"identity":"bca3427f-3b8f-4b6b-870d-70ab7dfad2d2","order_by":12,"name":"Denisa Novakova","email":"","orcid":"","institution":"University Hospital Hradec Králové","correspondingAuthor":false,"prefix":"","firstName":"Denisa","middleName":"","lastName":"Novakova","suffix":""},{"id":469738632,"identity":"7efda951-6a0a-4972-a3f7-f3e4a70f7d6b","order_by":13,"name":"Michaela Hornakova","email":"","orcid":"","institution":"University Hospital Ostrava","correspondingAuthor":false,"prefix":"","firstName":"Michaela","middleName":"","lastName":"Hornakova","suffix":""},{"id":469738633,"identity":"9f96754a-90b8-435c-8eea-5d7fbaceec01","order_by":14,"name":"Zdenka Knechtova","email":"","orcid":"","institution":"University Hospital Brno and Faculty of Medicine, Masaryk University","correspondingAuthor":false,"prefix":"","firstName":"Zdenka","middleName":"","lastName":"Knechtova","suffix":""},{"id":469738634,"identity":"8e59d331-c0dd-45ef-a73e-5443e2dca2f2","order_by":15,"name":"Nela Sendlerova","email":"","orcid":"","institution":"University Hospital Brno and Faculty of Medicine, Masaryk University","correspondingAuthor":false,"prefix":"","firstName":"Nela","middleName":"","lastName":"Sendlerova","suffix":""},{"id":469738635,"identity":"a5334139-0977-4d14-8bc2-7b7bb3a25837","order_by":16,"name":"Tereza Dekojova","email":"","orcid":"","institution":"Charles University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tereza","middleName":"","lastName":"Dekojova","suffix":""},{"id":469738636,"identity":"8b8f54aa-5452-422a-ad74-9f40f0d86348","order_by":17,"name":"Vladimir Maisnar","email":"","orcid":"","institution":"University Hospital Hradec Králové","correspondingAuthor":false,"prefix":"","firstName":"Vladimir","middleName":"","lastName":"Maisnar","suffix":""},{"id":469738637,"identity":"4118da1a-bc3f-4b01-a60f-415bf7143ce5","order_by":18,"name":"Tomas Jelinek","email":"","orcid":"","institution":"University Hospital Ostrava","correspondingAuthor":false,"prefix":"","firstName":"Tomas","middleName":"","lastName":"Jelinek","suffix":""},{"id":469738638,"identity":"408aca20-b4c7-44c0-acd3-be4654f78f90","order_by":19,"name":"Roman Hajek","email":"","orcid":"","institution":"University Hospital Ostrava","correspondingAuthor":false,"prefix":"","firstName":"Roman","middleName":"","lastName":"Hajek","suffix":""},{"id":469738639,"identity":"de00d345-d659-4fe1-b312-7f7564ac8be2","order_by":20,"name":"Ludek Pour","email":"","orcid":"","institution":"University Hospital Brno and Faculty of Medicine, Masaryk University","correspondingAuthor":false,"prefix":"","firstName":"Ludek","middleName":"","lastName":"Pour","suffix":""}],"badges":[],"createdAt":"2025-05-28 06:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6764594/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6764594/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-025-06529-1","type":"published","date":"2025-08-18T16:29:07+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84545334,"identity":"832b993a-c962-42d0-b987-5e7006a6d3af","added_by":"auto","created_at":"2025-06-13 09:13:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":211633,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003e- PFS – Non-weekly vs. Weekly dosing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb \u003c/strong\u003eOS\u003cstrong\u003e \u003c/strong\u003e– Non-weekly vs. Weekly dosing.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6764594/v1/a6bca4249e22ea67ee41b7dd.png"},{"id":89847772,"identity":"b4a10300-148a-4e8f-86ac-47e77f7440e8","added_by":"auto","created_at":"2025-08-25 16:44:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":900345,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6764594/v1/1314c52b-9ca7-4ee9-ad29-78e61c82d504.pdf"},{"id":84545335,"identity":"556ffc54-52ff-4ce2-baa7-63b129a1a644","added_by":"auto","created_at":"2025-06-13 09:13:20","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":122509,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementstoAOHe.docx","url":"https://assets-eu.researchsquare.com/files/rs-6764594/v1/eea622969d5a995ec2fa052b.docx"}],"financialInterests":"Competing interest reported. MS: Jonhson \u0026 Jonhnson: Consultancy, Other: Travel support, Honoraria for lectures JR: BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Johnson \u0026 Johnson: Consultancy, Honoraria; GSK: Consultancy; Pfizer: Consultancy,\nHonoraria. TJ: Janssen: Consultancy, Other: Honoraria for lectures, Research Funding; Sanofi: Other: Honoraria for lectures, Research Funding; Pfizer: Consultancy,Other: Honoraria for lectures; BristolMyers Squibb:Other:Honoraria for lectures; GlaxoSmithKline: Consultancy, Other: Honoraria for lectures; Amgen: Research Funding. IS: BMS: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees,\nOther: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel\nSupport; GSK: Consultancy, Membership on an entity’s Board of Directors or advisory committees. JM: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; GSK: Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory\ncommittees. RH: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding.","formattedTitle":"De-escalated Teclistamab Dosing in Relapsed/Refractory Multiple Myeloma: Czech Myeloma Group Real- World Evidence Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTeclistamab is a bispecific antibody that targets multiple myeloma (MM) by binding to B-cell maturation antigen (BCMA) on MM cells and CD3 on T cells, triggering a T-cell-mediated anti-tumor response. In the MajesTEC-1 trial, it showed high efficacy in heavily pretreated patients with relapsed/refractory MM (RRMM) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], supported by emerging real-world evidence [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, teclistamab carries a high risk of infections due to B-cell depletion and immune dysregulation. Recurrent infections affect\u0026thinsp;~\u0026thinsp;60\u0026ndash;75% of patients, mostly related to teclistamab-induced hypogammaglobulinemia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the MajesTEC-1 trial, patients received an initial step-up dosing of teclistamab followed by a fixed weekly maintenance dose. For those who achieved a complete response after six months of treatment, the dosing frequency could be reduced to biweekly administration [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In real-world clinical practice, however, dosing schedules are often adapted for various reasons, potentially deviating from the standardized protocols used in controlled clinical trials.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eWe conducted a retrospective analysis of teclistamab monotherapy in heavily pretreated RRMM patients across all major Czech haematology centres between 2023 and 2025. The primary objective of this study was to compare the efficacy and safety of standard dosing versus reduced-frequency dosing. All data were collected and analysed from the Czech Registry of Monoclonal Gammopathies (RMG) of Czech Myeloma Group (CMG). All participants provided written informed consents approved by institutional Ethics boards in accordance with the latest Helsinki declaration. Data collection cut-off date was 10th January 2025.\u003c/p\u003e \u003cp\u003eThe study population consisted of 73 RRMM patients with a median age of 67.0 years (range, 41\u0026ndash;83). The median number of prior lines of therapy was 5 (range, 3\u0026ndash;13), with 68.5% (50/73) of patients being penta-refractory. Totally 24.7% (18/73) of patients had extramedullary plasmacytomas (EMD, not associated to bone lesions). Of the 59 patients with available cytogenetics, 45.8% (27/59) had two or more high-risk cytogenetic aberrations (HR-CA, defined as t(4;14), t(14;16), del(17p), del(1p32) and gain/amp(1q21)). The median follow-up was 4 months (range, 1\u0026ndash;17).\u003c/p\u003e \u003cp\u003eTeclistamab was administered subcutaneously in all patients according to a step-up dosing protocol (0.06 mg/kg on Day 1 and 0.3 mg/kg on Day 4, followed by the first full dose of 1.5 mg/kg on Day 7). Subsequently, in the Weekly group, teclistamab is given at a maintenance dose of 1.5 mg/kg once weekly until disease progression or unacceptable toxicity occurs. In patients who achieved a complete response (CR) or better for at least six months, the dosing frequency of teclistamab was reduced to every other week. Patients who had earlier dosing frequency de-escalation for various reasons were categorized as the Non-weekly group.\u003c/p\u003e \u003cp\u003eResponse was assessed according to International Myeloma Working Group criteria. Relative dose intensity (RDI) was counted as the ratio of real cumulative dose (RCD) to maximal ideal dose (MID). Event-free survival (progression free survival - PFS, and overall survival - OS) was defined as the time from treatment initiation to the event or patient\u0026rsquo;s last follow-up. If the event didn\u0026rsquo;t occur, the censoring was done at the time of a last follow-up. It was assessed using the Kaplan-Meier methodology and all point estimates include 95% confidence intervals (95% CI). The statistical significance of differences in survival between subgroups was assessed using the log-rank test. The statistical significance of differences in categorical or continuous variables between the subgroups was tested by Fisher Exact test or Mann-Whitney U test. All statistical tests were performed at a significance level of α\u0026thinsp;=\u0026thinsp;0.05 (all tests two-sided).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eResponse and survival in all patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall response rate (ORR) in evaluable patients was 58.8% (40 out of 68), with 52.9% (36 out of 68) achieving a very good partial response (VGPR) or better. The median PFS was 9.41 months (95% CI: 7.11\u0026ndash;not applicable), and the median OS was 15.38 months (95% CI: 10.95\u0026ndash;not applicable). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary figure\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e Progression free survival (PFS) \u0026ndash; all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary figure 2\u003c/strong\u003e Overall survival (OS) \u0026ndash; all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrognostic subgroups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAchievement of a deeper response was strongly associated with improved survival outcomes. Patients who achieved a VGPR or better had significantly longer median PFS compared to those with a partial response (PR) or less: 15.38 months (95% CI: 11.18\u0026ndash;not estimable) vs. 1.38 months (95% CI: 1.28\u0026ndash;3.48), respectively (p \u0026lt; 0.001). This benefit was also reflected in estimated 12-month overall survival (OS) rates, which were 75.0% (95% CI: 57.2\u0026ndash;98.4) for patients with VGPR or better, compared to 27.8% (95% CI: 12.5\u0026ndash;61.8) for those with PR or worse (p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary figure 3\u003c/strong\u003e Progression free survival (PFS) \u0026ndash; best response.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary figure 3\u003c/strong\u003e Overall survival (OS)\u0026ndash; best response.\u003c/p\u003e\n\u003cp\u003eAdditionally, patients with extramedullary disease (EMD) had shortest median PFS compared to those with para-skeletal plasmacytomas (growing outside of bone lesions) or those with the absence of plasmacytomas: 3.87 months (95% CI: 1.38\u0026ndash;not estimable) vs. 10.1 months (95% CI: 6.4\u0026ndash; not estimable) vs. not estimable; p=0.059. Moreover, patients harbouring \u0026ge;2 high-risk HR-CA had shorter median PFS when compared to those with 1 or no HR-CA: 1.84 months (95% CI: 1.38\u0026ndash;not estimable) vs. 9.4 months (95% CI: 7.97\u0026ndash;not estimable); p=0.022, respectively. A full overview of survival outcomes in whole cohort and subgroups is provided in Supplementary Figures 1\u0026ndash;8.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure 5\u003c/strong\u003e Progression free survival (PFS) \u0026ndash; Extraosseous plasmacytomas in multiple myeloma (EMM) \u0026ndash; Extramedullary (EMD) plasmacytomas vs. Para-skeletal (PS) plasmacytoma vs. No plasmacytomas\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure 6\u0026nbsp;\u003c/strong\u003eOverall survival (OS) \u0026ndash; Extraosseous plasmacytomas in multiple myeloma (EMM) \u0026ndash; Extramedullary (EMD) plasmacytomas vs. Para-skeletal (PS) plasmacytoma vs. No plasmacytomas\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure 7\u003c/strong\u003e Progression free survival (PFS) \u0026ndash; Two or more high-risk cytogenetic aberration* (\u0026ldquo;double hit multiple myeloma\u0026rdquo;)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure 8\u003c/strong\u003e Overall survival (OS) \u0026ndash; Two or more high-risk cytogenetic aberration* (\u0026ldquo;double hit multiple myeloma\u0026rdquo;)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDosing frequency and relative dose intensity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDosing frequency was modified in 24.7% (18/73) of patients, with 72.2% (13/18) receiving teclistamab every two weeks and 27.8% (5/18) every four weeks. The median time to de-escalation was 1 month (range, 0\u0026ndash;3). The most common reason for de-escalation was achievement of a favourable response (55.6%, 10/18), followed by adverse events (33.3%, 6/18) and patient frailty (11.1%, 2/18).\u003c/p\u003e\n\u003cp\u003eThe median relative dose intensity (RDI), calculated as the ratio of actual cumulative dose (RCD) to the maximum ideal dose (MID), was 80.1% (range, 25.3%\u0026ndash;100.0%) across the entire cohort. Patients in the non-weekly dosing group had a significantly lower median RDI of 60.5% (range, 37.2%\u0026ndash;93.8%) compared to 87.0% (range, 25.3%\u0026ndash;100.0%) in the weekly group (p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eBaseline characteristics were generally balanced between groups. The median age was slightly higher in the non-weekly group (69 years [range, 49\u0026ndash;83]) than in the weekly group (66 years [range, 41\u0026ndash;85]; p = 0.065). Median ECOG performance status was 1 in both groups (range, 0\u0026ndash;3; p = 0.37). Additional comparisons of baseline characteristics and supportive treatment are provided in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003e\u003cstrong\u003eable 1\u003c/strong\u003e. Demographic characteristics and treatment in non-weekly and weekly dosing groups\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon weekly dosing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeekly dosing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eNumber of pts (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e24.7 % (18/73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e75.3 % (55/73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eMedian age (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e69.0 (49.0-83.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e66.0 (41.0-85.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eECOG performance status (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e1 (0-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eNo. of previous treatment lines (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e4 (3-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e5 (3-13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003ePenta-refractory patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e55.6 % (10/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e88.9 % (40/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003ePrevious anti-BCMA therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e5.6 % (1/18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e14.5 % (8/55)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.436\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eExtramedullary plasmacytomas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e11.1 % (2/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e29.1 % (16/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e2 or more HR-CA\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e28.6 % (4/14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e48.9 % (22/45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eWithout IVIG* administration\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e27.8 % (5/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e23.6% (13/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eMedian monthly IVIG* dose (grams/patient)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e19.1 (4.0-22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e22.4 (4.0-100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eHR-CA \u0026ndash; high-risk cytogenetic aberrations\u003csup\u003e+\u0026nbsp;\u003c/sup\u003e;* intravenous immunoglobulins\u003c/p\u003e\n\u003cp\u003e* Fisher Exact test, Mann-Whitney U test\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e+\u003c/sup\u003e t(4;14), t(14;16), del(17p), del(1p32) and gain/amp(1q21)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival outcomes by dosing frequency\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProgression-free survival (PFS) was comparable between patients receiving weekly and non-weekly teclistamab dosing. The median PFS was 9.1 months (95% CI: 2.7\u0026ndash;not estimable) in the weekly group and 11.3 months (95% CI: 6.4\u0026ndash;not estimable) in the non-weekly group (p = 0.141).\u003c/p\u003e\n\u003cp\u003eOverall survival (OS) data were still immature at the time of analysis. However, estimated 12-month OS rates suggested a clinically meaningful trend in favour of weekly dosing: 62.3% (95% CI: 47.6\u0026ndash;81.5) in the weekly group versus 36.6% (95% CI: 14.0\u0026ndash;95.9) in the non-weekly group. This difference did not reach statistical significance (p = 0.667). The survival according to dosing frequency is shown in Figure 1 a,b.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse events by dosing frequency\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCytokine release syndrome (CRS) occurred in 49.3% (36/73) of patients, predominantly grade 1 (39.7%, 29/73), with an additional 9.6% (7/73) experiencing grade 2 events. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in two patients (2.7%), both cases being grade 1. Tocilizumab was administered to 9.6% (7/73) of patients to manage CRS and/or ICANS.\u003c/p\u003e\n\u003cp\u003eInfection rates were comparable between dosing groups when analysed after de-escalation. Infections occurred in 80.0% (44/55) of patients in the weekly group and 66.7% (12/18) in the non-weekly group (p = 0.335). Severe infections (grade 3\u0026ndash;4) were reported in 29.1% (16/55) of weekly-dosed patients and 50.0% (9/18) of non-weekly patients (p = 0.152).\u003c/p\u003e\n\u003cp\u003eAmong patients in the non-weekly group, infection incidence remained similar before and after dose de-escalation. A total of 55.6% (10/18) experienced infections prior to de-escalation, and 66.7% (12/18) thereafter (p = 0.733). Severe infections occurred in 22.2% (4/18) before de-escalation and in 50.0% (9/18) afterward (p = 0.164), indicating a numerical increase that did not reach statistical significance.\u003c/p\u003e\n\u003cp\u003eWhen assessing cumulative infection episodes irrespective of timing, the median number of all infection events was 2 (range, 0\u0026ndash;12) in the weekly group and 1 (range, 0\u0026ndash;11) in the non-weekly group (p = 0.730). However, the median number of grade 3\u0026ndash;4 infection episodes was significantly higher in the non-weekly group (median 1; range, 0\u0026ndash;3) compared to the weekly group (median 0; range, 0\u0026ndash;4; p = 0.033).\u003c/p\u003e\n\u003cp\u003eNeutropenia occurred more frequently in patients receiving weekly dosing: 61.8% (34/55) versus 22.2% (4/18) in the non-weekly group (p = 0.006). The incidence of severe neutropenia (grade 3\u0026ndash;4) was similar between groups (23.6% vs. 16.7%; p = 0.745). In the non-weekly group, severe neutropenia occurred in 5.5% (1/18) of patients prior to de-escalation and in 16.7% (3/18) after de-escalation (p = 0.603). Rates of anemia and thrombocytopenia were comparable between the two groups. Detailed toxicity data are provided in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. - Toxicity according to dosing scheme\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"472\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eAdverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eNon-weekly dosing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eWeekly dosing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003ep value*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eCRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.1-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e44.4% (8/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e49.1 % (27/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.790\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eICANS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e11.1% (2/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.0 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eInfection\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e66.7% (12/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e80.0% (44/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.335\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e50.0% (9/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e29.1% (16/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eAnemia\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e38.9% (7/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e63.6% (35/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e5.6% (1/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e7.3% (4/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eThrombopenia\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e22.2% (4/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e41.8% (23/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e16.7% (3/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e10.9% (6/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.680\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eNeutropenia\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e22.2% (4/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e61.8% (34/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eGr.3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e16.7% (3/18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e23.6% (13/55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCRS \u0026ndash; Cytokine Release Syndrome; ICANS \u0026ndash; Immune effector Cell Associated Neurotoxicity Syndrome; * Fisher exact test; \u003csup\u003e+\u003c/sup\u003e - counted in the non-weekly group after the de-escalation;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBold values\u003c/strong\u003e are statistically significant\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis multicentre real-world study demonstrates that teclistamab dosing in routine clinical practice often diverges from the fixed weekly maintenance schedule employed in the MajesTEC-1 trial. Despite less frequent dosing, PFS remained comparable to weekly dosing, indicating sustained efficiency in responding patients.\u003c/p\u003e\n\u003cp\u003eClinical data on dosing de-escalation of anti-BCMA bispecific antibodies remain limited. In a real-world study, 32% (25/77) of patients transitioned to every-other-week dosing of teclistamab after three months due to toxicity or achieving partial response. At six months, the progression-free survival rate was 94% among these patients, compared to 52% in the overall cohort, likely reflecting positive selection of responders [6]. For elranatamab, the MagnetisMM-3 trial showed that responders could reduce dosing from weekly to every-other-week after six months, then to every-four-week after another six months without losing efficacy [7]. Our data uniquely show the median time to dosing frequency de-escalation was just one month\u0026mdash;much shorter than previous studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite maintained efficacy in non-weekly dosing, no reduction of infection events was observed. This may be due to the prolonged impact of teclistamab on immunoglobulin production, extending beyond the 2- or 4-week off-therapy periods. Variability in intravenous immunoglobulin administration and supportive care across real-world settings also likely contributes to generally inconsistent toxicity outcomes [5; 8; 9]. \u0026nbsp;Moreover, response to treatment was the primary reason for dose de-escalation, but frailty and recurring infections also contributed, potentially biasing adverse event reports in the non-weekly group. Also, these patients were generally older. While bispecific antibodies\u0026apos; efficacy is unaffected by age [1; 6; 11], elderly patients are more susceptible to infections and hematologic toxicity. Both groups were balanced regarding EMD and high-risk cytogenetics, which negatively influenced prognosis both in our study and in so far published works [1; 3].\u003c/p\u003e\n\u003cp\u003eWe noted a reduced incidence of neutropenia with the non-weekly dosing schedule. Since BCMA is not typically expressed on myeloid cells or neutrophils, this might result from less immune cell-mediated myelosuppression due to lower teclistamab plasma levels [10]. The impact of teclistamab dosing frequency on myeloid cells remains unclear and warrants further study.\u003c/p\u003e\n\u003cp\u003eThe OS data, though still immature, seems to favor weekly dosing. Factors such as patient age or alternative treatments like GPRC5D or FCRH5 bispecific antibodies for teclistamab-refractory patients may influence results [11; 12]. More research is needed on how reduced anti-BCMA bispecific antibody dosing affects subsequent therapy efficacy, particularly regarding T-cell exhaustion [13; 14].\u003c/p\u003e\n\u003cp\u003eThe retrospective nature of our study and the variability in clinical decision-making processes are limitations that should be acknowledged. However, our findings offer valuable insights into the real-world application of teclistamab and may guide future research efforts aimed at optimizing dosing protocols to balance efficacy, safety, and treatment costs.\u003c/p\u003e\n\u003cp\u003eTaken together, in a real-world setting, early de-escalation of teclistamab dosing did not compromise efficacy especially in responding patients. However, reduced dosing was not associated with a lower rate of infectious complications. These findings suggest that flexible, response-adapted dosing strategies may be appropriate in select patients, particularly those with frailty or tolerability concerns. Further prospective studies are needed to validate these observations and to better define the impact of dosing modifications on long-term outcomes, immune recovery, and subsequent therapy sequencing.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e \u003cstrong\u003eMS\u003c/strong\u003e: Jonhson \u0026amp; Jonhnson: Consultancy, Other: Travel support, Honoraria for lectures \u003cstrong\u003eJR\u003c/strong\u003e: BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Johnson \u0026amp; Johnson: Consultancy, Honoraria; GSK: Consultancy; Pfizer: Consultancy,\u003c/p\u003e\n\u003cp\u003eHonoraria. \u003cstrong\u003eTJ\u003c/strong\u003e: Janssen: Consultancy, Other: Honoraria for lectures, Research Funding; Sanofi: Other: Honoraria for lectures, Research Funding; Pfizer: Consultancy,Other: Honoraria for lectures; BristolMyers Squibb:Other:Honoraria for lectures; GlaxoSmithKline: Consultancy, Other: Honoraria for lectures; Amgen: Research Funding. \u003cstrong\u003eIS:\u0026nbsp;\u003c/strong\u003eBMS: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees,\u003c/p\u003e\n\u003cp\u003eOther: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees, Other: Travel\u003c/p\u003e\n\u003cp\u003eSupport; GSK: Consultancy, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees. \u003cstrong\u003eJM\u003c/strong\u003e: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees; GSK: Membership on an entity\u0026rsquo;s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity\u0026rsquo;s Board of Directors or advisory\u003c/p\u003e\n\u003cp\u003ecommittees. \u003cstrong\u003eRH\u003c/strong\u003e: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the patients and their caregivers who participated in this study, and data managers from participating centers. This work was supported by Ministry of Health, Czech Republic - conceptual development of research organization (FNBr, 65269705). This work was supported by OPJAK SALVAGE project (No. CZ.02.01.01/00/22_008/0004644) and by the European Union project LERCO (No. CZ.10.03.01/00/22_003/0000003).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution statement:\u003c/strong\u003e MS designed the study and wrote the manuscript. MS, JR, JM, IS, TP, AJ, IB, KM, JS, FS, JM, PK, DN, MH, TD, VM, TJ, LP and RH treated the patients and provided clinical data. ZK and NS provided preclinical data. All authors interpreted and discussed the results. All authors approved the final version of the manuscript prior to submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupported by Ministry of Health, Czech Republic - conceptual development of research organization (FNBr, 65269705). This work was supported by OPJAK SALVAGE project (No. CZ.02.01.01/00/22_008/0004644) and by the European Union project LERCO (No. CZ.10.03.01/00/22_003/0000003).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eMoreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, et al. (2022) Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 387(6):495-505. doi: 10.1056/NEJMoa2203478.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMohan M, Monge J, Shah N, Luan D, Forsberg M, Bhatlapenumarthi V, et al. (2024) Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study. Blood Cancer J. 14(1):35. doi: 10.1038/s41408-024-01003-z.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRiedhammer C, Bassermann F, Besemer B, Bewarder M, Brunner F, Carpinteiro A, et al. (2024) Real-world analysis of teclistamab in 123 RRMM patients from Germany. Leukemia. 38(2):365-371. doi: 10.1038/s41375-024-02154-5.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTan CRC, Asoori S, Huang CY, Brunaldi L, Popat R, Kastritis E, et al. (2025) Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study. Blood Cancer J. 15(1):53.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eNooka AK, Rodriguez C, Mateos MV, Manier S, Chastain K, Banerjee A, et al. (2024) Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study. Cancer. 130(6):886-900. doi: 10.1002/cncr.35107\u003c/li\u003e\n \u003cli\u003eTan CRC, Derkach A, Maclachlan K, Hultcrant M, Hassoun V, Mailankody S, et al. (2024) Real-world schedule de-escalation of teclistamab in patients with relapsed/refractory multiple myeloma. Journal of Clinical Oncology. 42;7536-7536. 10.1200/JCO.2024.42.16_suppl.7536.\u003c/li\u003e\n \u003cli\u003ePrince HM, Bahlis NJ, Rodr\u0026iacute;guez-Otero P, Karlin L, Akard Luke, Varshavsky-Yanovsky A, et al. (2024) MagnetisMM-3: Long-Term Update of Efficacy and Safety of Less Frequent Dosing of Elranatamab in Patients with Relapsed or Refractory Multiple Myeloma. Blood. 144 (Supplement 1): 4738. https://doi.org/10.1182/blood-2024-208192\u003c/li\u003e\n \u003cli\u003eCortes-Selva D, Perova T, Skerget S, Vishwamitra D, Stein S, Boominathan R, et al. (2024) Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in the MajesTEC-1 study. Blood. 144(6):615-628. doi: 10.1182/blood.2023022823.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLancman G, Parsa K, Kotlarz K, Avery L, Lurie A, Lieberman-Cribbin A, et al. (2023) IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies. Blood Cancer Discov. 4(6):440-451. doi: 10.1158/2643-3230.BCD-23-0049.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLeclercq G, Servera LA, Danilin S, Challier J, Steinhoff N, Bossen C, et al. (2022) Dissecting the mechanism of cytokine release induced by T-cell engagers highlights the contribution of neutrophils. Oncoimmunology. 11(1):2039432. doi: 10.1080/2162402X.2022.2039432.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eChari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodr\u0026iacute;guez-Otero P, et al. (2022) Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 387(24):2232-2244. doi: 10.1056/NEJMoa2204591.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRichter J,\u0026nbsp;Thomas SK,\u0026nbsp;Krishnan AY,\u0026nbsp;Laubach JP,\u0026nbsp;Cohen AD,\u0026nbsp;Trudel S, et al. (2024) Cevostamab in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies. \u003cem\u003eBlood\u003c/em\u003e; 144 (Supplement 1): 1021. doi: https://doi.org/10.1182/blood-2024-199542\u003c/li\u003e\n \u003cli\u003eMerz M, Dima D, Hashmi H, Ahmed N, St\u0026ouml;lzel F, Holderried TAW, et al. (2024) Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy. Blood Cancer J. 14(1):214. doi: 10.1038/s41408-024-01197-2.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003evan de Donk NWCJ, Chari A, Mateos MV. (2024) Mechanisms of resistance against T-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies. Lancet Haematol. 11(9):e693-e707. doi: 10.1016/S2352-3026(24)00186-8.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"multiple myeloma, teclistamab, immunotherapy, real-world-evidence","lastPublishedDoi":"10.21203/rs.3.rs-6764594/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6764594/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTeclistamab, a BCMA\u0026times;CD3 bispecific antibody, demonstrates high efficacy in relapsed/refractory multiple myeloma (RRMM). However, optimal dosing strategies outside clinical trials remain undefined. Thus, we performed a retrospective, multicentre analysis of 73 RRMM patients treated with teclistamab monotherapy at Czech Myeloma Group centres between 2023 and 2025. The study compared efficacy and safety between patients receiving standard weekly dosing and those with reduced-frequency dosing. The whole cohort had a median age of 67 years; 68.5% were penta-refractory. Dosing was de-escalated in 24.7% of patients, typically within one month of treatment initiation. Median progression-free survival (PFS) was 9.41 months and was comparable between weekly and non-weekly groups (9.1 vs. 11.3 months; p\u0026thinsp;=\u0026thinsp;0.141), despite a significantly lower relative dose intensity in the latter (60.5% vs. 87.0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Infection rates and severe adverse events were similar between groups. A lower incidence of neutropenia was observed with less frequent dosing, but this did not translate into reduced infection burden. In conclusion, in real-world practice, early de-escalation of teclistamab dosing appears to maintain clinical efficacy. These findings support ongoing efforts to individualize treatment schedules with the aim of balancing effectiveness, tolerability, and patient-specific factors in BCMA-targeted therapy.\u003c/p\u003e","manuscriptTitle":"De-escalated Teclistamab Dosing in Relapsed/Refractory Multiple Myeloma: Czech Myeloma Group Real- World Evidence Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-13 09:13:15","doi":"10.21203/rs.3.rs-6764594/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-05T19:39:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-01T21:31:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-29T16:31:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"241801127190623976095874971901911583818","date":"2025-06-19T17:29:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289502612531341662441134314212461061237","date":"2025-06-19T12:14:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"130693701752614233455597695373089795629","date":"2025-06-11T10:11:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-10T08:58:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-04T08:42:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-04T08:37:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-05-28T05:53:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4b178cdd-b0ec-4df8-b157-7d6a2e703f7f","owner":[],"postedDate":"June 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T16:39:36+00:00","versionOfRecord":{"articleIdentity":"rs-6764594","link":"https://doi.org/10.1007/s00277-025-06529-1","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2025-08-18 16:29:07","publishedOnDateReadable":"August 18th, 2025"},"versionCreatedAt":"2025-06-13 09:13:15","video":"","vorDoi":"10.1007/s00277-025-06529-1","vorDoiUrl":"https://doi.org/10.1007/s00277-025-06529-1","workflowStages":[]},"version":"v1","identity":"rs-6764594","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6764594","identity":"rs-6764594","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}