Long enduring response on Teclistamab in a patient with myeloma relapse after allogeneic hematopoietic stem cell transplantation – a case report | 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 Case Report Long enduring response on Teclistamab in a patient with myeloma relapse after allogeneic hematopoietic stem cell transplantation – a case report P Ebner, J Fauser, G Hetzenauer, S Köck, W Willenbacher, LM Rossetti, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8435478/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Apr, 2026 Read the published version in Annals of Hematology → Version 1 posted 10 You are reading this latest preprint version Abstract Cellular based therapies, such as bispecific T-cell engagers (TCE), have changed the landscape of myeloma treatment, still less is known about the use of these therapies in patients with prior allogeneic hematopoietic stem cell transplantation (alloHSCT). In this case report, we present a patient with multi-refractory multiple myeloma (MM), who relapsed after alloHSCT and was ultimately successfully treated with teclistamab, a BCMA-directed TCE, and we discuss underlying immunological mechanisms, that might have contributed to a long enduring treatment response. Figures Figure 1 Figure 2 Introduction In relapsed/refractory (r/r) MM, treatment with TCE has become an established therapeutic option. Teclistamab was the first BCMA-directed TCE approved for r/r myeloma 1 based on the data generated in the Majes-TEC-1 study, showing a remarkable overall response rate of 63% in myeloma patients with 3 or more prior treatment lines. Currently, two additional BCMA-directed TCE and one GPRC5D-directed TCE as well as BCMA-directed CAR-T-cells are approved, changing the treatment landscape of MM. Still, alloHSCT represents a viable treatment option for a few multirefractory, but young and fit patients, leading to long-term disease control in about 25%. 2 However, many patients experience disease relapse after alloHSCT and conceptually, the subsequent use of TCE is a promising treatment option, even though the induction of graft-versus-host-disease is a potential risk. To the best of our knowledge only one case report of teclistamab after alloHSCT has been published so far, with a short follow-up and limited extramedullary involvement. 3 In this article, we present the case of a heavily pretreated patient with multi-refractory MM, who relapsed after allo-HSCT and anti-SLAMF-7-CART-cell-therapy, and was successfully treated with teclistamab. Case report A male patient was diagnosed with IgG kappa multiple myeloma at the age of 43 in May 2019. He initially presented with a pathological fracture of the right clavicula and histology showed plasma cell infiltration of. In addition to multiple bone lesions, extramedullary disease was present in the left ethmoidal cells. Despite extensive bone and extramedullary manifestations, paraprotein serum levels were only slightly elevated (low secretory MM) and a random bone marrow biopsy did not show clonal plasma cell infiltration. Cytogenetics showed a hyperploid karyotype, which classified MM as standard risk. Initial risk stratification revealed a R-ISS and ISS stage I. No other relevant comorbidities were present. First line treatment with 5 cycles of bortezomib, lenalidomide and dexamethason (VRd) was initiated and autologous stem cell transplantation (ASCT) was performed in November 2019 after followed by 2 VRd consolidation cycles and subsequent lenalidomide maintenance. Best response was a serologic very good partial response and a partial metabolic remission, and a partial metabolic remission was achieved as determined by PET-CT. In July 2020 the patient presented with an early and rapid disease progression and due to the dynamic, two cycles of D-PACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide) were performed, but no significant response was obtained. We next exposed our patient to daratumumab together with carfilzomib, pomalidomide and dexamethasone, according Jasiliec et. al. 4 Some limited clinical benefit could be obtained, whereas PET-CT showed only stable disease. At this point, as TCE or other BCMA-directed therapies were not yet available, we decided to proceed to alloHSCT. A fully matched sibling donor was available and alloHSCT was performed in February 2021 after conditioning with fludarabine, busulfan and melphalan (FBM) without ATG but with cyclosporin a and mycofenolate mofetil as primary immunesuppression. No major complications occurred and the patient did not show any signs of acute graft versus host disease, even after tapering immunosuppression. Unfortunately, after an initial partial metabolic response, the benefit did not last and disease relapse was observed already one year after alloHSCT. Meanwhile, clinical studies with myeloma CAR-T-cells were recruiting and we were able to enroll the still very fit patient into the CARAMBA trials (SLAMF7-directed CAR-T-cells) in collaboration with the University Hospital of Würzburg, Germany. Treatment with carfilzomib, pomalidomide and dexamethason was used to bridge the patient to CAR-T-cell infusion, which he received in April 2022. No CRS or ICANS occurred, but again there was no significant response and disease progression was observed already two months after CAR-T-cell-therapy. Next, we tried an individual therapy approach with the BCMA-directed antibody drug conjugate belantamab mafodotin in combination with pomalidomide and dexamethasone in June 2022, but again after 2 cycles no relevant clinical response could be observed. In August 2022 donor lymphocyte infusion (DLI) was performed, but did not show any effect at all. As the patient was – despite the heavy pre-treatment (overall treatment history shown in Fig. 1 ) – still in good condition, we were able to enroll him into a named patient program with the TCE teclistamab and initiated treatment in September 2022, even though at this time no data supporting the use of teclistamab after alloHSCT were available. Step-up dosing proceeded without any relevant complications and teclistamab was finally administered once weekly in a dosage of 1,5 mg per kg bodyweight. Soon after, serological and metabolic response was observed, with PET CT showing a stable metabolic complete remission (mCR) (Fig. 2 ). Notably, there were no signs of GvHD and a full donor chimerism was documented. The most relevant adverse event were recurrent infections, which were however were clearly reduced in frequency and severity by continuous substitution of immunoglobulins. Due to the excellent and long-lasting disease control, we decided to extend the treatment intervals to biweekly from March 2024 and lately even to 4-weekly intervals. The most recent checkup in December 2025 again revealed an excellent condition of the patient (ECOG 0) with full integration in his work-life as a consequence of the continuous mCR and an absence of relevant signs of GvHD. Discussion This case report impressively demonstrates the potency of teclistamab in r/r myeloma after alloHSCT. The immunologic mechanisms explaining the excellent myeloma control without induction of GvHD are complex and very limited clinical data is available regarding the use of TCE after alloHSCT. We found one similar case of myeloma treatment published, which provides a very limited follow-up time of 34 weeks. 3 AlloHSCT is a potential curative treatment option for myeloma patients, but malignant plasma cells often evade the graft-versus myeloma effects. Boosting immunological disease surveillance after alloHSCT is difficult and often linked to the induction of GvHD. 5 In our patient, treatment response was established by the donor immune system and teclistamab could play a pivotal role in regaining the graft versus myeloma effect, hence providing a long-lasting disease control. In the Majes-TEC1-study, median progression free survival (mPFS) was 11 months an in patients who obtained a complete remission, mPFS was still not reached (at least 27 months) in the latest update. 6 Our patient is now on teclistamab for 3 years with a CR lasting much longer than the data of the Majes-TEC1-study supply. We thus hypothesize, that the enduring treatment effect is mainly driven by the donor immune system and could not be obtained without prior AlloHSCT, but we found no data to further support our presumption. However, it was previously hypothesized that CD8 + effector T cells, which expand after BCMA bispecific antibodies, may possess tumor-reactive properties and interact with MHC molecules on tumor cells. 7 In the post-alloHSCT setting, the frequency of potentially tumor-reactive T cells could increase, allowing redirection therapies to exert pronounced activity. Regarding the use of other TCE after HSCT, very limited data is available for blinatumomab, an Anti-CD19-directed TCE used in B-lineage acute lymphoblastic leukemia (B-ALL). In the approval study, patients with prior alloHSCT were included, but the number was small and no further subgroup analysis was made. 8 As for the safety of blinatumomab after HSCT, it seems that no greater immunological complications (CRS, ICANS or GvHD) are to be expected (e.g. 9 ). Gaballa et al. conducted a single-center, single-arm Phase 2 study on blinatumomab maintenance after HSCT in B-ALL patients. 10 Their findings suppose that the composition of the patient's T-cell subsets is indicative for treatment response. Unfortunately, we were not able to investigate T-cell clonality and selectivity in our patient due to lack of samples. Another recent case report is available for the use of Epcoritamab, another Anti-CD20-directed TCE, after alloHSCT in a case of DLBCL. 11 Intriguingly, Epcoritamab only achieved limited efficacy in this patient, resulting in SD before alloHSCT. However, re-exposure with Epcoritamab following early progression 2 months after alloHSCT resulted in an ongoing CR of at least 6 months without any GvHD flare. In conclusion, we postulate that in our reported case, alloHSCT induced a permissive environment for teclistamab-induced long-lasting graft-versus-myeloma response without induction of relevant GvHD. Even though alloHSCT is not a frequent therapy concept in MM, the subsequent use of TCE is a viable treatment option in case of relapse. The still very limited data at hand indicate that the use of TCE after alloHSCT could overcome the challenges of T-cell exhaustion in this subset of patients, which so often limits treatment efficacy in heavily pretreated multiple myeloma. 12 Still, further research on this specific constellation would be of interest to provide more data on efficacy, safety and underlying immunological mechanisms of such complex treating algorithms. Declarations Author contribution declaration Writing and editing: P Ebner Writing and reviewing: L Rasche, N Steiner, D Wolf Reviewing: TA Buchwald, J Fauser, E Gunsilius, G Hetzenauer, S Köck, D Nachbaur, LM Rossetti, W Willenbacher Providing PET-CT scan pictures: LM Rossetti All authors have read and agreed to the published version of the manuscript. Funding declaration No fundings were received. Consent to Publish declaration Written informed consent for publication was obtained from the patient. Ethics declaration Not applicable. References Moreau P, Garfall AL, Van de Donk NWCJ, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med 2022;387:495–505 Richardson T, Kobbe G, Fenk R, et al. Allogeneic Hematopoietic Stem Cell Transplantation in Refractory Multiple Myeloma—A Retrospective Multicenter Analysis. Eur J Haematol. 2024;114(3):423–428 Zaja F, Lucchini M, Poiani M, et. al. Teclistamab salvage therapy for multiple myeloma relapse after allogeneic hemopoietic stem cell transplant: A case report. Am J Hematol 2024; 99(1):E29-E31A Derman BA, Zonder J, Donna Reece et al. Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. Blood Adv 2023; 7(19):5703–5712 Schmid C, Labopin M, Schaap N, et al. Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia. Bone Marrow Transplant. 2022;57(2):215–223 Garfall AL, Nooka AK, Van de Donk NWCJ, et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol 2024; 42(16_suppl):7540 Friedrich MJ, Neri P, Kehl N, et al. The Pre-Existing T cell Landscape Determines the Response to Bispecific T cell Engagers in Multiple Myeloma Patients. Cancer Cell 2023;41(4):711–725.e6 Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med 2017;376:836–847 Ji J, Liu Z, Chen X, et al. Mini-Dosed Blinatumomab Maintenance Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute B-Cell Lymphoblastic Leukemia. Blood 2024;144(Suppl 1):1049 Gaballa MR, Banerjee P, Milton DR, et al. Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia. Blood 2022;139(12):1908–1919 Ikoma Y, Kaneda Y, Shimazu R, et al. Donor-Derived T-Cell Redirection With Epcoritamab Achieving Complete Response After Early Post-Allo-HSCT Relapse of DLBCL. EJHaem 2025;6(6):e70186 Verkleij CPM, O’Neill CA, Broekmans MEC, et al. T-Cell Characteristics Impact Response and Resistance to T-Cell-Redirecting Bispecific Antibodies in Multiple Myeloma. Clin Cancer Res. 2024;30(14):3006–3022 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 07 Apr, 2026 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 10 Feb, 2026 Reviews received at journal 10 Feb, 2026 Reviews received at journal 09 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers invited by journal 02 Feb, 2026 Editor assigned by journal 26 Jan, 2026 Submission checks completed at journal 26 Jan, 2026 First submitted to journal 23 Dec, 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-8435478","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":584346107,"identity":"8b46d556-643e-4494-a296-2d216f1c63ab","order_by":0,"name":"P Ebner","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"P","middleName":"","lastName":"Ebner","suffix":""},{"id":584346109,"identity":"89638ac1-8189-47c0-80b1-0044c2e3ad3c","order_by":1,"name":"J Fauser","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"J","middleName":"","lastName":"Fauser","suffix":""},{"id":584346111,"identity":"27a58d67-a20a-4ed0-bc67-cb76aa8aa64b","order_by":2,"name":"G Hetzenauer","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"G","middleName":"","lastName":"Hetzenauer","suffix":""},{"id":584346112,"identity":"3684291b-71fd-4dc5-9ce9-d90afad017b9","order_by":3,"name":"S Köck","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"S","middleName":"","lastName":"Köck","suffix":""},{"id":584346113,"identity":"160ee23f-7e38-413d-a647-fe473399bdc6","order_by":4,"name":"W Willenbacher","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"W","middleName":"","lastName":"Willenbacher","suffix":""},{"id":584346115,"identity":"b19feb6a-03b8-4586-803a-ee4d020f7a41","order_by":5,"name":"LM Rossetti","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"LM","middleName":"","lastName":"Rossetti","suffix":""},{"id":584346116,"identity":"6bdda047-67a9-46d7-8052-7ca4f28864e3","order_by":6,"name":"TA Buchwald","email":"","orcid":"","institution":"University Hospital of Würzburg","correspondingAuthor":false,"prefix":"","firstName":"TA","middleName":"","lastName":"Buchwald","suffix":""},{"id":584346120,"identity":"88487837-c7d1-4d62-ad71-5a2501bb2a5c","order_by":7,"name":"L Rasche","email":"","orcid":"","institution":"University Hospital of Würzburg","correspondingAuthor":false,"prefix":"","firstName":"L","middleName":"","lastName":"Rasche","suffix":""},{"id":584346121,"identity":"559bc501-41a1-4fb7-8f44-59afa68071c6","order_by":8,"name":"E Gunsilius","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"E","middleName":"","lastName":"Gunsilius","suffix":""},{"id":584346122,"identity":"d4193b55-788f-4908-82a0-4023c1f3847c","order_by":9,"name":"D Nachbaur","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"D","middleName":"","lastName":"Nachbaur","suffix":""},{"id":584346124,"identity":"9a5f173e-8970-4abf-975c-33d6c2cf62c6","order_by":10,"name":"D Wolf","email":"","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":false,"prefix":"","firstName":"D","middleName":"","lastName":"Wolf","suffix":""},{"id":584346125,"identity":"0727fc76-6cf3-4747-bc09-79deacad2379","order_by":11,"name":"N Steiner","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIiWNgGAWjYLCDA0AsxwZi8RClng2ixRhJCzNhLSCQ2EBIizl779MNP3fcYZCf33zwcEHFvfQ+Bu7EB28Y7OQZ2M8fwKbFsue42c3eM88YDI6xJRyecaY4t42Bd7PhHIZkwwaeZKy2GNxIY7vB23aYwYCNx+Awb1tCbpv8223SPAzMCQwMuLXc/AvUIt/G/+Ew77+EdDYG3u2/eRjqExj4H+PUchtkC8MxHobDvA0JCUAt25iB7AQGCRy2nDnGdlu27TCPwbE0g8M8xxIMQX6RnGNw3LBN4rEBVi3H29huvm07LCfffPjxZ56aBHn5Bt6NH95UVMvz8yc+wGoNFKBHtwE8okbBKBgFo2AUkAEAW61YsCg8XE0AAAAASUVORK5CYII=","orcid":"","institution":"Medical University of Innsbruck","correspondingAuthor":true,"prefix":"","firstName":"N","middleName":"","lastName":"Steiner","suffix":""}],"badges":[],"createdAt":"2025-12-23 15:39:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8435478/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8435478/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-026-06990-6","type":"published","date":"2026-04-07T15:58:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":101792532,"identity":"7c587a65-3314-4e36-a675-04338eec0e55","added_by":"auto","created_at":"2026-02-03 16:12:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16933,"visible":true,"origin":"","legend":"\u003cp\u003eOverall treatment history\u003c/p\u003e\n\u003cp\u003eV = bortezomib, R = lenalidomide, d = dexamethasone, MT = maintenance therapy, D = daratumumab, K = carfilzomib, P = pomalidomide, Belmaf = belantamab mafodotin, DLI = donor lymphocyte infusion\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8435478/v1/b48ba9f0b0643d8ad111d1d7.png"},{"id":101792544,"identity":"554b7c99-26d2-4644-ab33-a43b006fbdf5","added_by":"auto","created_at":"2026-02-03 16:12:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":108509,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT. \u003cem\u003eLeft\u003c/em\u003e: 09/2022 before teclistamab was started.\u003cem\u003eRight\u003c/em\u003e: most recent follow-up 09/2025, mCR.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8435478/v1/74e4dad508c1a06861018035.png"},{"id":106808995,"identity":"0b9bcb4c-ca00-4406-a311-573ef0297b23","added_by":"auto","created_at":"2026-04-13 16:05:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":452916,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8435478/v1/d450b400-2bdd-4656-9416-caa5bf66f21d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long enduring response on Teclistamab in a patient with myeloma relapse after allogeneic hematopoietic stem cell transplantation – a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn relapsed/refractory (r/r) MM, treatment with TCE has become an established therapeutic option. Teclistamab was the first BCMA-directed TCE approved for r/r myeloma\u003csup\u003e1\u003c/sup\u003e based on the data generated in the Majes-TEC-1 study, showing a remarkable overall response rate of 63% in myeloma patients with 3 or more prior treatment lines. Currently, two additional BCMA-directed TCE and one GPRC5D-directed TCE as well as BCMA-directed CAR-T-cells are approved, changing the treatment landscape of MM. Still, alloHSCT represents a viable treatment option for a few multirefractory, but young and fit patients, leading to long-term disease control in about 25%.\u003csup\u003e2\u003c/sup\u003e However, many patients experience disease relapse after alloHSCT and conceptually, the subsequent use of TCE is a promising treatment option, even though the induction of graft-versus-host-disease is a potential risk. To the best of our knowledge only one case report of teclistamab after alloHSCT has been published so far, with a short follow-up and limited extramedullary involvement.\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this article, we present the case of a heavily pretreated patient with multi-refractory MM, who relapsed after allo-HSCT and anti-SLAMF-7-CART-cell-therapy, and was successfully treated with teclistamab.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA male patient was diagnosed with IgG kappa multiple myeloma at the age of 43 in May 2019. He initially presented with a pathological fracture of the right clavicula and histology showed plasma cell infiltration of. In addition to multiple bone lesions, extramedullary disease was present in the left ethmoidal cells. Despite extensive bone and extramedullary manifestations, paraprotein serum levels were only slightly elevated (low secretory MM) and a random bone marrow biopsy did not show clonal plasma cell infiltration. Cytogenetics showed a hyperploid karyotype, which classified MM as standard risk. Initial risk stratification revealed a R-ISS and ISS stage I. No other relevant comorbidities were present.\u003c/p\u003e \u003cp\u003eFirst line treatment with 5 cycles of bortezomib, lenalidomide and dexamethason (VRd) was initiated and autologous stem cell transplantation (ASCT) was performed in November 2019 after followed by 2 VRd consolidation cycles and subsequent lenalidomide maintenance. Best response was a serologic very good partial response and a partial metabolic remission, and a partial metabolic remission was achieved as determined by PET-CT.\u003c/p\u003e \u003cp\u003eIn July 2020 the patient presented with an early and rapid disease progression and due to the dynamic, two cycles of D-PACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide) were performed, but no significant response was obtained. We next exposed our patient to daratumumab together with carfilzomib, pomalidomide and dexamethasone, according Jasiliec \u003cem\u003eet. al.\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e Some limited clinical benefit could be obtained, whereas PET-CT showed only stable disease. At this point, as TCE or other BCMA-directed therapies were not yet available, we decided to proceed to alloHSCT. A fully matched sibling donor was available and alloHSCT was performed in February 2021 after conditioning with fludarabine, busulfan and melphalan (FBM) without ATG but with cyclosporin a and mycofenolate mofetil as primary immunesuppression. No major complications occurred and the patient did not show any signs of acute graft versus host disease, even after tapering immunosuppression.\u003c/p\u003e \u003cp\u003eUnfortunately, after an initial partial metabolic response, the benefit did not last and disease relapse was observed already one year after alloHSCT. Meanwhile, clinical studies with myeloma CAR-T-cells were recruiting and we were able to enroll the still very fit patient into the CARAMBA trials (SLAMF7-directed CAR-T-cells) in collaboration with the University Hospital of W\u0026uuml;rzburg, Germany. Treatment with carfilzomib, pomalidomide and dexamethason was used to bridge the patient to CAR-T-cell infusion, which he received in April 2022. No CRS or ICANS occurred, but again there was no significant response and disease progression was observed already two months after CAR-T-cell-therapy. Next, we tried an individual therapy approach with the BCMA-directed antibody drug conjugate belantamab mafodotin in combination with pomalidomide and dexamethasone in June 2022, but again after 2 cycles no relevant clinical response could be observed. In August 2022 donor lymphocyte infusion (DLI) was performed, but did not show any effect at all. As the patient was \u0026ndash; despite the heavy pre-treatment (overall treatment history shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) \u0026ndash; still in good condition, we were able to enroll him into a named patient program with the TCE teclistamab and initiated treatment in September 2022, even though at this time no data supporting the use of teclistamab after alloHSCT were available. Step-up dosing proceeded without any relevant complications and teclistamab was finally administered once weekly in a dosage of 1,5 mg per kg bodyweight. Soon after, serological and metabolic response was observed, with PET CT showing a stable metabolic complete remission (mCR) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Notably, there were no signs of GvHD and a full donor chimerism was documented. The most relevant adverse event were recurrent infections, which were however were clearly reduced in frequency and severity by continuous substitution of immunoglobulins. Due to the excellent and long-lasting disease control, we decided to extend the treatment intervals to biweekly from March 2024 and lately even to 4-weekly intervals.\u003c/p\u003e \u003cp\u003eThe most recent checkup in December 2025 again revealed an excellent condition of the patient (ECOG 0) with full integration in his work-life as a consequence of the continuous mCR and an absence of relevant signs of GvHD.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eThis case report impressively demonstrates the potency of teclistamab in r/r myeloma after alloHSCT. The immunologic mechanisms explaining the excellent myeloma control without induction of GvHD are complex and very limited clinical data is available regarding the use of TCE after alloHSCT. We found one similar case of myeloma treatment published, which provides a very limited follow-up time of 34 weeks.\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlloHSCT is a potential curative treatment option for myeloma patients, but malignant plasma cells often evade the graft-versus myeloma effects. Boosting immunological disease surveillance after alloHSCT is difficult and often linked to the induction of GvHD.\u003csup\u003e5\u003c/sup\u003e In our patient, treatment response was established by the donor immune system and teclistamab could play a pivotal role in regaining the graft versus myeloma effect, hence providing a long-lasting disease control. In the Majes-TEC1-study, median progression free survival (mPFS) was 11 months an in patients who obtained a complete remission, mPFS was still not reached (at least 27 months) in the latest update.\u003csup\u003e6\u003c/sup\u003e Our patient is now on teclistamab for 3 years with a CR lasting much longer than the data of the Majes-TEC1-study supply. We thus hypothesize, that the enduring treatment effect is mainly driven by the donor immune system and could not be obtained without prior AlloHSCT, but we found no data to further support our presumption. However, it was previously hypothesized that CD8\u0026thinsp;+\u0026thinsp;effector T cells, which expand after BCMA bispecific antibodies, may possess tumor-reactive properties and interact with MHC molecules on tumor cells.\u003csup\u003e7\u003c/sup\u003e In the post-alloHSCT setting, the frequency of potentially tumor-reactive T cells could increase, allowing redirection therapies to exert pronounced activity.\u003c/p\u003e \u003cp\u003eRegarding the use of other TCE after HSCT, very limited data is available for blinatumomab, an Anti-CD19-directed TCE used in B-lineage acute lymphoblastic leukemia (B-ALL). In the approval study, patients with prior alloHSCT were included, but the number was small and no further subgroup analysis was made.\u003csup\u003e8\u003c/sup\u003e As for the safety of blinatumomab after HSCT, it seems that no greater immunological complications (CRS, ICANS or GvHD) are to be expected (e.g.\u003csup\u003e9\u003c/sup\u003e). Gaballa et al. conducted a single-center, single-arm Phase 2 study on blinatumomab maintenance after HSCT in B-ALL patients.\u003csup\u003e10\u003c/sup\u003e Their findings suppose that the composition of the patient's T-cell subsets is indicative for treatment response. Unfortunately, we were not able to investigate T-cell clonality and selectivity in our patient due to lack of samples.\u003c/p\u003e \u003cp\u003eAnother recent case report is available for the use of Epcoritamab, another Anti-CD20-directed TCE, after alloHSCT in a case of DLBCL.\u003csup\u003e11\u003c/sup\u003e Intriguingly, Epcoritamab only achieved limited efficacy in this patient, resulting in SD before alloHSCT. However, re-exposure with Epcoritamab following early progression 2 months after alloHSCT resulted in an ongoing CR of at least 6 months without any GvHD flare.\u003c/p\u003e \u003cp\u003eIn conclusion, we postulate that in our reported case, alloHSCT induced a permissive environment for teclistamab-induced long-lasting graft-versus-myeloma response without induction of relevant GvHD. Even though alloHSCT is not a frequent therapy concept in MM, the subsequent use of TCE is a viable treatment option in case of relapse. The still very limited data at hand indicate that the use of TCE after alloHSCT could overcome the challenges of T-cell exhaustion in this subset of patients, which so often limits treatment efficacy in heavily pretreated multiple myeloma.\u003csup\u003e12\u003c/sup\u003e Still, further research on this specific constellation would be of interest to provide more data on efficacy, safety and underlying immunological mechanisms of such complex treating algorithms.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eAuthor contribution declaration\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWriting and editing: P Ebner\u003c/p\u003e\n\u003cp\u003eWriting and reviewing: L Rasche, N Steiner, D Wolf\u003c/p\u003e\n\u003cp\u003eReviewing: TA Buchwald, J Fauser, E Gunsilius, G Hetzenauer, S Köck, D Nachbaur, LM Rossetti,\u003c/p\u003e\n\u003cp\u003eW Willenbacher\u003c/p\u003e\n\u003cp\u003eProviding PET-CT scan pictures: LM Rossetti\u003c/p\u003e\n\u003cp\u003eAll authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding declaration\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNo fundings were received.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent to Publish declaration\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEthics declaration\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Moreau P, Garfall AL, Van de Donk NWCJ, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. \u003cem\u003eN Engl J Med\u003c/em\u003e 2022;387:495\u0026ndash;505\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Richardson T, Kobbe G, Fenk R, et al. Allogeneic Hematopoietic Stem Cell Transplantation in Refractory Multiple Myeloma\u0026mdash;A Retrospective Multicenter Analysis. \u003cem\u003eEur J Haematol.\u003c/em\u003e 2024;114(3):423\u0026ndash;428\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Zaja F, Lucchini M, Poiani M, et. al. Teclistamab salvage therapy for multiple myeloma relapse after allogeneic hemopoietic stem cell transplant: A case report. Am J Hematol 2024; 99(1):E29-E31A\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Derman BA, Zonder J, Donna Reece et al. Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. \u003cem\u003eBlood Adv\u003c/em\u003e 2023; 7(19):5703\u0026ndash;5712\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Schmid C, Labopin M, Schaap N, et al. Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia. \u003cem\u003eBone Marrow Transplant.\u003c/em\u003e 2022;57(2):215\u0026ndash;223\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Garfall AL, Nooka AK, Van de Donk NWCJ, et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol 2024; 42(16_suppl):7540\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Friedrich MJ, Neri P, Kehl N, et al. The Pre-Existing T cell Landscape Determines the Response to Bispecific T cell Engagers in Multiple Myeloma Patients. Cancer Cell 2023;41(4):711\u0026ndash;725.e6\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Kantarjian H, Stein A, G\u0026ouml;kbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. \u003cem\u003eN Engl J Med\u003c/em\u003e 2017;376:836\u0026ndash;847\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Ji J, Liu Z, Chen X, et al. Mini-Dosed Blinatumomab Maintenance Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute B-Cell Lymphoblastic Leukemia. Blood 2024;144(Suppl 1):1049\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Gaballa MR, Banerjee P, Milton DR, et al. Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia. \u003cem\u003eBlood\u003c/em\u003e 2022;139(12):1908\u0026ndash;1919\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Ikoma Y, Kaneda Y, Shimazu R, et al. Donor-Derived T-Cell Redirection With Epcoritamab Achieving Complete Response After Early Post-Allo-HSCT Relapse of DLBCL. \u003cem\u003eEJHaem\u003c/em\u003e 2025;6(6):e70186\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Verkleij CPM, O\u0026rsquo;Neill CA, Broekmans MEC, et al. T-Cell Characteristics Impact Response and Resistance to T-Cell-Redirecting Bispecific Antibodies in Multiple Myeloma. \u003cem\u003eClin Cancer Res.\u003c/em\u003e 2024;30(14):3006\u0026ndash;3022\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"","lastPublishedDoi":"10.21203/rs.3.rs-8435478/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8435478/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCellular based therapies, such as bispecific T-cell engagers (TCE), have changed the landscape of myeloma treatment, still less is known about the use of these therapies in patients with prior allogeneic hematopoietic stem cell transplantation (alloHSCT). In this case report, we present a patient with multi-refractory multiple myeloma (MM), who relapsed after alloHSCT and was ultimately successfully treated with teclistamab, a BCMA-directed TCE, and we discuss underlying immunological mechanisms, that might have contributed to a long enduring treatment response.\u003c/p\u003e","manuscriptTitle":"Long enduring response on Teclistamab in a patient with myeloma relapse after allogeneic hematopoietic stem cell transplantation – a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-03 16:11:50","doi":"10.21203/rs.3.rs-8435478/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-10T13:48:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-10T13:01:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T21:01:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23749350911421690190934836915199781924","date":"2026-02-04T10:46:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"241801127190623976095874971901911583818","date":"2026-02-04T09:41:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"339797804491191632530633561242926654653","date":"2026-02-04T09:26:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-02T08:25:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-26T09:29:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-26T09:26:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-12-23T15:23:39+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":"e3ffa144-70e4-441f-8397-bb0845c06ae1","owner":[],"postedDate":"February 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-13T16:01:57+00:00","versionOfRecord":{"articleIdentity":"rs-8435478","link":"https://doi.org/10.1007/s00277-026-06990-6","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2026-04-07 15:58:47","publishedOnDateReadable":"April 7th, 2026"},"versionCreatedAt":"2026-02-03 16:11:50","video":"","vorDoi":"10.1007/s00277-026-06990-6","vorDoiUrl":"https://doi.org/10.1007/s00277-026-06990-6","workflowStages":[]},"version":"v1","identity":"rs-8435478","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8435478","identity":"rs-8435478","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.