Cytokine Release Syndrome–Compatible Fever After Initiation of Local Radiotherapy During Late-Phase Epcoritamab Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Case Report

Cytokine Release Syndrome–Compatible Fever After Initiation of Local Radiotherapy During Late-Phase Epcoritamab Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: 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 Cytokine Release Syndrome–Compatible Fever After Initiation of Local Radiotherapy During Late-Phase Epcoritamab Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Case Report Naoaki Nishimura, Hajime Nakashima, Yuto Ogasa, Kenji Yoshikuni, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9059446/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Mar, 2026 Read the published version in Journal of Pharmaceutical Health Care and Sciences → Version 1 posted You are reading this latest preprint version Abstract Background Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has demonstrated promising activity in relapsed or refractory diffuse large B‑cell lymphoma. Cytokine release syndrome is a key adverse event associated with T‑cell–engaging therapies; however, it typically occurs early after treatment initiation and is generally manageable with step‑up dosing and premedication. Evidence regarding the safety of delivering radiotherapy during late-phase epcoritamab therapy remains limited. Case presentation A 58-year-old man with diffuse large B-cell lymphoma received epcoritamab. On cycle 8 day 8, local radiotherapy (40 Gy in 20 fractions) was initiated for a residual abdominal lymph node lesion. Approximately 12 hours after irradiation on radiotherapy day 2, he developed fever (38°C) and fatigue without hypotension or hypoxia and with preserved neutrophil counts, consistent with a cytokine release syndrome–compatible febrile episode (grade 1 by the American Society for Transplantation and Cellular Therapy criteria). Blood cultures were obtained and empiric cefepime with acetaminophen was initiated, resulting in transient defervescence; however, fever recurred on radiotherapy day 3. Blood cultures, (1,3)-β-D-glucan, and galactomannan assays were negative. Given the reproducible temporal association with radiotherapy, a cytokine release syndrome–compatible event was considered, and tocilizumab (8 mg/kg) was administered in line with standard cytokine release syndrome management guidance, with defervescence within 1 hour. He remained afebrile thereafter and completed radiotherapy without recurrence. Conclusions Cytokine release syndrome–compatible fever is uncommon after multiple cycles of epcoritamab. This case suggests a temporal association between radiotherapy and a cytokine release syndrome–compatible febrile episode during late-phase therapy and supports the possibility that radiotherapy acted as an inflammatory trigger. When radiotherapy is delivered during bispecific antibody therapy, fever should prompt concurrent evaluation for infection while keeping cytokine release syndrome in the differential diagnosis, and standard cytokine release syndrome management should be applied promptly when clinically indicated. bispecific antibody epcoritamab radiotherapy cytokine release syndrome tocilizumab diffuse large B-cell lymphoma Figures Figure 1 Background Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma, and outcomes remain poor in relapsed or refractory (R/R) disease. Patients with limited responsiveness to salvage cytotoxic chemotherapy require additional therapeutic options. The treatment landscape for DLBCL has recently been reshaped by bispecific antibodies. Epcoritamab is a subcutaneous CD3×CD20 bispecific antibody (BsAb) that mediates T-cell–dependent cytotoxicity against malignant B cells and provides an off-the-shelf option for patients who are ineligible for, or refractory to, chimeric antigen receptor (CAR) T-cell therapy [ 1 , 2 ]. Cytokine release syndrome (CRS) is a characteristic acute toxicity associated with on-target immune activation during T-cell–engaging immunotherapies. CRS reflects systemic inflammation driven by immune-cell activation and cytokine release, including interleukin-6 (IL-6), and is clinically defined by fever with or without hypotension, hypoxemia, and organ dysfunction [ 3 – 5 ]. CRS severity should be graded according to the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria [ 5 ]. To mitigate CRS risk, epcoritamab is administered using step-up dosing with standard premedication. In the pivotal large B-cell lymphoma (LBCL) cohort, CRS occurred predominantly after the first full dose on cycle 1 day 15 and was mostly low grade; grade 3 CRS occurred in a small proportion of patients, and CRS typically resolved within a short timeframe with standard management, including tocilizumab when indicated [ 3 , 6 ]. In extended follow-up of EPCORE NHL-1, most CRS events were confined to early cycles, with the latest reported CRS onset at cycle 4 day 1 and no new CRS events observed thereafter [ 2 ]. Accordingly, febrile episodes with CRS-like features occurring in later cycles warrant careful assessment for concurrent triggers (e.g., infection) while maintaining CRS in the differential diagnosis [ 2 , 5 ]. Here, we report a case in which fever temporally associated with radiotherapy (RT) recurred during late-phase epcoritamab therapy, prompting parallel evaluation for infection while maintaining a CRS-compatible event in the differential diagnosis. Case presentation A 58-year-old man was diagnosed with DLBCL, not otherwise specified (DLBCL, NOS), stage IV in August of year X − 2. He received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for six cycles; however, left axillary lymphadenopathy developed in January of year X − 1, and biopsy confirmed refractory DLBCL. He subsequently received two cycles of rituximab plus etoposide, methylprednisolone, cytarabine, and cisplatin (R-ESHAP) and polatuzumab vedotin plus rituximab, followed by CAR T-cell therapy with lisocabtagene maraleucel in June of year X − 1. No CRS occurred after CAR T-cell therapy. Positron emission tomography–computed tomography in October of year X − 1 showed complete remission; however, relapse was documented on computed tomography in March of year X, and epcoritamab therapy was initiated in March of year X. Epcoritamab was administered subcutaneously using a step-up dosing regimen: 0.16 mg on cycle 1 day 1 (C1D1), 0.8 mg on C1D8, and 48 mg on C1D15 and C1D22. Thereafter, 48 mg was administered weekly in cycles 2–3, every 2 weeks in cycles 4–9, and every 4 weeks from cycle 10 onward [ 6 ]. This step-up approach is intended to mitigate CRS risk [ 7 , 8 ]. Concomitant prophylaxis included fluconazole, trimethoprim–sulfamethoxazole, and valacyclovir. The clinical course is summarized in Fig. 1 , and selected laboratory data are shown in Table 1 . On epcoritamab cycle 8 day 8 (C8D8), local RT (40 Gy in 20 fractions) was initiated for a residual abdominal nodal lesion. RT was started one week after the most recent epcoritamab dose in cycle 8 (C8D1), during the every-2-week dosing phase (cycles 4–9). Approximately 12 hours after the second fraction (RT day 2), he developed fever (38.0°C) and fatigue without hypotension, hypoxemia, or other localizing symptoms. Vital signs remained stable (no shock-level hypotension; SpO₂ ≥98% on room air; respiratory rate approximately 16/min). He had no respiratory symptoms, urinalysis was negative, and he had no indwelling central venous catheter, making line-related infection unlikely. Blood cultures were obtained, and empiric cefepime with acetaminophen was initiated, resulting in transient defervescence; however, fever recurred approximately 12 hours after the third fraction (RT day 3). He remained hemodynamically stable without oxygen requirement, and neutrophil counts were preserved. Blood cultures were negative, and serum (1,3)-β-D-glucan and galactomannan assays were negative, making invasive fungal infection unlikely. Given the reproducible timing after RT fractions and the clinical course, a CRS-compatible event (ASTCT grade 1) was considered; however, alternative causes of fever could not be completely excluded. Because the fever recurred in close temporal association with RT and there was concern that further progression might compromise the safe continuation of RT, tocilizumab (8 mg/kg) was administered on RT day 3 at the grade 1 stage based on ASTCT grading and clinical risk assessment, resulting in prompt resolution of fever within 1 hour. He remained afebrile thereafter, and RT was continued to completion (40 Gy in 20 fractions) without recurrent fever. Discussion and Conclusions Clinical studies of epcoritamab monotherapy indicate that CRS is predominantly an early-event toxicity, clustering after the first full dose on cycle 1 day 15 and remaining largely low grade in LBCL. Extended follow-up suggests that de novo CRS is uncommon beyond the early cycles, with the latest reported onset at cycle 4 day 1 [ 2 , 6 ]. One proposed explanation for the lower CRS frequency during later cycles is a priming effect with step-up and repeated dosing, which can attenuate cytokine release compared with initial exposure [ 4 , 9 ]. Against this established temporal pattern, the reproducible fever that occurred approximately 12 hours after RT fractions during cycle 8 suggests an immune-mediated process consistent with a CRS-compatible event. At the time of fever, vital signs were stable (no shock-level hypotension; SpO₂ ≥98% on room air; respiratory rate approximately 16/min), and there were no respiratory symptoms or indwelling central venous catheter; urinalysis was negative, making line-related infection less likely. An infectious workup was performed in parallel (including blood cultures), and no hemodynamic instability or hypoxemia was observed. Rapid defervescence within 1 hour of tocilizumab is consistent with a cytokine-mediated mechanism, although viral testing and cytokine measurements were not performed and infection or other non-CRS causes of fever cannot be completely excluded. Published reports of CRS or CRS-like inflammatory events temporally associated with RT remain very limited, particularly during CD3×CD20 bispecific antibody therapy. Most reported cases have arisen in other immunotherapy settings; Barker et al. described CRS after RT in a patient receiving anti–programmed cell death protein 1 immunotherapy, together with a review of previously reported cases [ 10 ]. Against this background, the present case is clinically informative because it occurred during late-phase epcoritamab therapy, recurred after consecutive RT fractions, and improved rapidly after IL-6 blockade, thereby illustrating a CRS-compatible febrile episode arising outside the usual early-cycle window of epcoritamab therapy. Mechanistically, RT may have acted as an inflammatory trigger. Local tissue injury and immunogenic cell death can release inflammatory mediators and augment immune activation in some settings [ 11 ]. CRS-like inflammatory events temporally associated with RT have been described in other immunotherapy settings, with systemic symptoms recurring after irradiation and accompanied by transient increases in pro-inflammatory cytokines, including TNF-α and IL-6 [ 10 ]. Although the therapeutic context differs, these observations support the possibility that RT may transiently amplify cytokine-driven systemic symptoms in selected settings [ 10 ]. In our patient, the irradiated abdominal lymph node may have contained residual target B cells. RT-induced tumor or tissue injury may have transiently augmented local inflammatory signaling during ongoing epcoritamab exposure, thereby contributing to a transient systemic febrile episode consistent with a CRS-compatible event. This interpretation is hypothesis-generating rather than confirmatory. Clinically, in patients receiving BsAb therapy, fever developing during RT should prompt concurrent evaluation for infection while keeping CRS in the differential diagnosis [ 3 – 5 ]. Management should be guided by ASTCT criteria, with timely initiation of standard therapy, including IL-6 blockade when clinically warranted based on the overall risk assessment (e.g., recurrent fever with a reproducible temporal pattern and concern for deterioration that could compromise RT completion) [ 3 – 5 ]. A key limitation is that cytokine measurements were not obtained at symptom onset; therefore, causality cannot be established and the association remains clinical and temporal. However, in real-world practice, management decisions must often be made before cytokine data are available; thus, prompt parallel infectious workup and early CRS-directed management based on clinical grading remain essential when patients develop fever during BsAb therapy. In conclusion, while CRS with epcoritamab is typically confined to early treatment, this case suggests that RT delivered during late-phase therapy may be associated with a CRS-compatible febrile episode. When RT is administered during BsAb therapy, clinicians should remain alert to CRS even in later cycles and manage suspected events promptly using established grading and management principles, including tocilizumab when clinically indicated. Abbreviations ASTCT American Society for Transplantation and Cellular Therapy BsAb bispecific antibody CAR chimeric antigen receptor CRS cytokine release syndrome DLBCL diffuse large B-cell lymphoma IL-6 interleukin-6 LBCL large B-cell lymphoma R/R relapsed/refractory RT radiotherapy TNF-α tumor necrosis factor-α Declarations Ethics approval and consent to participate: The Institutional Review Board at the Japan Community Health Care Organization (JCHO) Kyushu Hospital determined that this single-patient case report does not constitute human subjects research and waived the requirement for review. Consent for publication: Written informed consent for publication of this case report was obtained from the patient. Funding: No specific funding was received for this work. Author Contribution Conceptualization: NN, HN. Investigation: NN, YO, KK. Data curation: NN. Writing—original draft: NN. Writing—review and editing: HN, YO, KK, KY, RO. Supervision: RO. All authors read and approved the final manuscript. Acknowledgements: Not applicable Data Availability All data generated or analyzed during this study are included in this published article. References Minson AG, Dickinson MJ. New bispecific antibodies in diffuse large B-cell lymphoma. Haematologica. 2025;110(7):1483–99. 10.3324/haematol.2024.285343 . Thieblemont C, Karimi YH, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial. Leukemia. 2024;38:2653–62. 10.1038/s41375-024-02410-8 . Jamois C, Turner DC, Gibiansky L, Li F, Menuet J, Pereira LR, et al. Tocilizumab dosing for management of T cell-engaging bispecific antibody-related CRS in patients with R/R B-cell NHL. Clin Pharmacol Ther. 2025;118:917–27. 10.1002/cpt.3751 . Radtke KK, Bender BC, Li Z, Turner DC, Roy S, Belousov A, et al. Clinical pharmacology of cytokine release syndrome with T-cell-engaging bispecific antibodies: current insights and drug development strategies. Clin Cancer Res. 2025;31:245–57. 10.1158/1078-0432.CCR-24-2247 . Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transpl. 2019;25:625–38. 10.1016/j.bbmt.2018.12.758 . Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41:2238–47. 10.1200/JCO.22.01725 . Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021;398:1157–69. 10.1016/S0140-6736(21)00889-8 . Li T, Gibiansky L, Parikh A, Putnins M, Chiu CW, Sacchi M, et al. Optimal dosing regimen for epcoritamab, a subcutaneous bispecific antibody, in relapsed or refractory large B-cell lymphoma. Clin Pharmacol Ther. 2025;117:1437–50. 10.1002/cpt.3588 . Chen X, Kamperschroer C, Wong G, Xuan D. A modeling framework to characterize cytokine release upon T-cell-engaging bispecific antibody treatment: methodology and opportunities. Clin Transl Sci. 2019;12:600–8. 10.1111/cts.12662 . Barker CA, Kim SK, Budhu S, Matsoukas K, Daniyan AF, D’Angelo SP. Cytokine release syndrome after radiation therapy: case report and review of the literature. J Immunother Cancer. 2018;6:1. 10.1186/s40425-017-0311-9 . Zhu M, Yang M, Zhang J, Yin Y, Fan X, Zhang Y, et al. Immunogenic cell death induction by ionizing radiation. Front Immunol. 2021;12:705361. 10.3389/fimmu.2021.705361 . Tables Table 1 Parameter Value Unit Complete blood count WBC 6900 /μL Neutrophils 65.3 % Lymphocytes 18.7 % Monocytes 9.3 % Eosinophils 5.8 % Basophils 0.9 % Hb 13.9 g/dL PLT 326×10 3 /μL Biochemistry Total bilirubin 0.3 mg/dL AST 17 U/L ALT 6 U/L ALP 128 U/L GGT 46 U/L LDH 241 U/L BUN 18 mg/dL Serum creatinine 1.10 mg/dL Creatinine clearance 49.4 mL/min Calcium 9.1 mg/dL CRP 2.86 mg/dL Immunoglobulin IgG 495 mg/dL Tumor markers soluble interleukin-2 receptor 1780 U/mL Fungal markers Galactomannan (GM) index 0.1 — (1,3)-β-D-glucan (BDG) 3 pg/mL Table 1 footnotes (timing): Results were obtained at admission unless otherwise noted. The following were measured during hospitalization: galactomannan (GM) index and (1,3)-β-D-glucan (BDG). Creatinine clearance was estimated using the Cockcroft–Gault equation. Abbreviations used in Table 1: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BDG, (1,3)-β-D-glucan; BUN, blood urea nitrogen; CRP, C-reactive protein; GGT, gamma-glutamyl transferase; GM, galactomannan; Hb, hemoglobin; IgG, immunoglobulin G; LDH, lactate dehydrogenase; PLT, platelet count; WBC, white blood cell. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Mar, 2026 Read the published version in Journal of Pharmaceutical Health Care and Sciences → Version 1 posted 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-9059446","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":604147006,"identity":"0b3b29bb-88e1-4804-a186-57d5c6ce89a1","order_by":0,"name":"Naoaki Nishimura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYJCCA4wNEhCGhIGNHJjxgEgtjAcsKtKMwSIJhKxhbABTzAcqzhxOBLPxaTFn4D148OcOi2iD24cfHLjZlpY+P+zwQ6AtdnK6Ddi1WDbwJRzmPSORu+FcmsHBmW02uRtvpxkAtSQbmx3ArsXgAI/BYcY2oJYzDAaHJdvScjfOTgBpOZC4DY+Wgz/BWtg/HP7bdjjdcHb6B4JaDvCCtQAZEmcOJ8hL5xCw5TDQYSAtM8/wFByQqEgz3CCdU3AgwQCPX473GH/82VaX23eGffMHYFTKy89O3/zhQ4WdHC4tDMyYTgWTOJRjBfINpKgeBaNgFIyCkQAAucVr/kYh+CUAAAAASUVORK5CYII=","orcid":"","institution":"Japan Community Health Care Organization (JCHO) Kyushu Hospital","correspondingAuthor":true,"prefix":"","firstName":"Naoaki","middleName":"","lastName":"Nishimura","suffix":""},{"id":604147007,"identity":"6a07aa4a-18ab-46cf-9093-37c99863dee6","order_by":1,"name":"Hajime Nakashima","email":"","orcid":"","institution":"Japan Community Health Care Organization (JCHO) Kyushu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hajime","middleName":"","lastName":"Nakashima","suffix":""},{"id":604147008,"identity":"54a63ad7-9349-4744-9970-ebe6f5736cc9","order_by":2,"name":"Yuto Ogasa","email":"","orcid":"","institution":"Japan Community Health Care Organization (JCHO) Kyushu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuto","middleName":"","lastName":"Ogasa","suffix":""},{"id":604147009,"identity":"beab30f5-c2a0-49b8-91ed-9b03ff9cd35d","order_by":3,"name":"Kenji Yoshikuni","email":"","orcid":"","institution":"Japan Community Health Care Organization (JCHO) Kyushu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kenji","middleName":"","lastName":"Yoshikuni","suffix":""},{"id":604147010,"identity":"9567695c-4bf7-430e-90be-310e21df0ae0","order_by":4,"name":"Kentaro Kohno","email":"","orcid":"","institution":"Japan Community Health Care Organization (JCHO) Kyushu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Kohno","suffix":""},{"id":604147011,"identity":"dc3eb05c-a9eb-4cfa-a5c2-7ff3b346751d","order_by":5,"name":"Ryosuke Ogawa","email":"","orcid":"","institution":"Japan Community Health Care Organization (JCHO) Kyushu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ryosuke","middleName":"","lastName":"Ogawa","suffix":""}],"badges":[],"createdAt":"2026-03-07 15:23:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9059446/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9059446/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40780-026-00568-0","type":"published","date":"2026-03-27T16:08:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":104583536,"identity":"63ae71ed-b0fa-4af6-9480-7eda57711d24","added_by":"auto","created_at":"2026-03-13 15:21:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":88745,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical course during late-phase epcoritamab therapy and radiotherapy.\u003cbr\u003e\n \u003c/strong\u003eTimeline of epcoritamab treatment, local radiotherapy (RT; 40 Gy in 20 fractions) for a residual abdominal nodal lesion, fever episodes, infectious workup, and clinical interventions. RT was initiated on epcoritamab cycle 8 day 8 (C8D8). The x-axis indicates hospital days (hospital day 0 corresponds to the day of admission). RT day numbering is based on the day of RT initiation (RT day 1 = first fraction). Within this timeline, the first and second post-initiation fever episodes occurred on RT day 2 and RT day 3, respectively (corresponding to the second and third RT fractions). Blood cultures were obtained, and empiric cefepime plus acetaminophen was initiated after the first fever episode, resulting in transient defervescence. After fever recurrence on RT day 3, tocilizumab (8 mg/kg) was administered for a CRS-compatible event, in accordance with standard CRS management, with defervescence within 1 hour and no recurrent fever thereafter. Body temperature (BT) (daily maximum) and systolic blood pressure (sBP) (daily minimum) are plotted using values recorded in the electronic medical record and are shown to visualize the overall clinical course rather than exact event-time measurements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: \u003c/strong\u003eRT, radiotherapy; BT, body temperature; sBP, systolic blood pressure; CRS, cytokine release syndrome.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9059446/v1/85ee81d752a5345f35539f76.png"},{"id":105755995,"identity":"80559bf3-ef1a-4899-9ba5-190fc599f4be","added_by":"auto","created_at":"2026-03-30 16:34:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":604784,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9059446/v1/cba4e0d5-fe94-442c-9a7f-7ab9b5dd920c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cytokine Release Syndrome–Compatible Fever After Initiation of Local Radiotherapy During Late-Phase Epcoritamab Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eDiffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma, and outcomes remain poor in relapsed or refractory (R/R) disease. Patients with limited responsiveness to salvage cytotoxic chemotherapy require additional therapeutic options. The treatment landscape for DLBCL has recently been reshaped by bispecific antibodies.\u003c/p\u003e \u003cp\u003eEpcoritamab is a subcutaneous CD3\u0026times;CD20 bispecific antibody (BsAb) that mediates T-cell\u0026ndash;dependent cytotoxicity against malignant B cells and provides an off-the-shelf option for patients who are ineligible for, or refractory to, chimeric antigen receptor (CAR) T-cell therapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Cytokine release syndrome (CRS) is a characteristic acute toxicity associated with on-target immune activation during T-cell\u0026ndash;engaging immunotherapies. CRS reflects systemic inflammation driven by immune-cell activation and cytokine release, including interleukin-6 (IL-6), and is clinically defined by fever with or without hypotension, hypoxemia, and organ dysfunction [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. CRS severity should be graded according to the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. To mitigate CRS risk, epcoritamab is administered using step-up dosing with standard premedication. In the pivotal large B-cell lymphoma (LBCL) cohort, CRS occurred predominantly after the first full dose on cycle 1 day 15 and was mostly low grade; grade 3 CRS occurred in a small proportion of patients, and CRS typically resolved within a short timeframe with standard management, including tocilizumab when indicated [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In extended follow-up of EPCORE NHL-1, most CRS events were confined to early cycles, with the latest reported CRS onset at cycle 4 day 1 and no new CRS events observed thereafter [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Accordingly, febrile episodes with CRS-like features occurring in later cycles warrant careful assessment for concurrent triggers (e.g., infection) while maintaining CRS in the differential diagnosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we report a case in which fever temporally associated with radiotherapy (RT) recurred during late-phase epcoritamab therapy, prompting parallel evaluation for infection while maintaining a CRS-compatible event in the differential diagnosis.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 58-year-old man was diagnosed with DLBCL, not otherwise specified (DLBCL, NOS), stage IV in August of year X − 2. He received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for six cycles; however, left axillary lymphadenopathy developed in January of year X − 1, and biopsy confirmed refractory DLBCL. He subsequently received two cycles of rituximab plus etoposide, methylprednisolone, cytarabine, and cisplatin (R-ESHAP) and polatuzumab vedotin plus rituximab, followed by CAR T-cell therapy with lisocabtagene maraleucel in June of year X − 1. No CRS occurred after CAR T-cell therapy. Positron emission tomography–computed tomography in October of year X − 1 showed complete remission; however, relapse was documented on computed tomography in March of year X, and epcoritamab therapy was initiated in March of year X.\u003c/p\u003e \u003cp\u003eEpcoritamab was administered subcutaneously using a step-up dosing regimen: 0.16 mg on cycle 1 day 1 (C1D1), 0.8 mg on C1D8, and 48 mg on C1D15 and C1D22. Thereafter, 48 mg was administered weekly in cycles 2–3, every 2 weeks in cycles 4–9, and every 4 weeks from cycle 10 onward [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. This step-up approach is intended to mitigate CRS risk [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Concomitant prophylaxis included fluconazole, trimethoprim–sulfamethoxazole, and valacyclovir. The clinical course is summarized in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, and selected laboratory data are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eOn epcoritamab cycle 8 day 8 (C8D8), local RT (40 Gy in 20 fractions) was initiated for a residual abdominal nodal lesion. RT was started one week after the most recent epcoritamab dose in cycle 8 (C8D1), during the every-2-week dosing phase (cycles 4–9). Approximately 12 hours after the second fraction (RT day 2), he developed fever (38.0°C) and fatigue without hypotension, hypoxemia, or other localizing symptoms. Vital signs remained stable (no shock-level hypotension; SpO₂ ≥98% on room air; respiratory rate approximately 16/min). He had no respiratory symptoms, urinalysis was negative, and he had no indwelling central venous catheter, making line-related infection unlikely. Blood cultures were obtained, and empiric cefepime with acetaminophen was initiated, resulting in transient defervescence; however, fever recurred approximately 12 hours after the third fraction (RT day 3). He remained hemodynamically stable without oxygen requirement, and neutrophil counts were preserved. Blood cultures were negative, and serum (1,3)-β-D-glucan and galactomannan assays were negative, making invasive fungal infection unlikely. Given the reproducible timing after RT fractions and the clinical course, a CRS-compatible event (ASTCT grade 1) was considered; however, alternative causes of fever could not be completely excluded. Because the fever recurred in close temporal association with RT and there was concern that further progression might compromise the safe continuation of RT, tocilizumab (8 mg/kg) was administered on RT day 3 at the grade 1 stage based on ASTCT grading and clinical risk assessment, resulting in prompt resolution of fever within 1 hour. He remained afebrile thereafter, and RT was continued to completion (40 Gy in 20 fractions) without recurrent fever.\u003c/p\u003e "},{"header":"Discussion and Conclusions","content":"\u003cp\u003eClinical studies of epcoritamab monotherapy indicate that CRS is predominantly an early-event toxicity, clustering after the first full dose on cycle 1 day 15 and remaining largely low grade in LBCL. Extended follow-up suggests that de novo CRS is uncommon beyond the early cycles, with the latest reported onset at cycle 4 day 1 [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. One proposed explanation for the lower CRS frequency during later cycles is a priming effect with step-up and repeated dosing, which can attenuate cytokine release compared with initial exposure [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAgainst this established temporal pattern, the reproducible fever that occurred approximately 12 hours after RT fractions during cycle 8 suggests an immune-mediated process consistent with a CRS-compatible event. At the time of fever, vital signs were stable (no shock-level hypotension; SpO₂ ≥98% on room air; respiratory rate approximately 16/min), and there were no respiratory symptoms or indwelling central venous catheter; urinalysis was negative, making line-related infection less likely. An infectious workup was performed in parallel (including blood cultures), and no hemodynamic instability or hypoxemia was observed. Rapid defervescence within 1 hour of tocilizumab is consistent with a cytokine-mediated mechanism, although viral testing and cytokine measurements were not performed and infection or other non-CRS causes of fever cannot be completely excluded.\u003c/p\u003e\u003cp\u003ePublished reports of CRS or CRS-like inflammatory events temporally associated with RT remain very limited, particularly during CD3×CD20 bispecific antibody therapy. Most reported cases have arisen in other immunotherapy settings; Barker et al. described CRS after RT in a patient receiving anti–programmed cell death protein 1 immunotherapy, together with a review of previously reported cases [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Against this background, the present case is clinically informative because it occurred during late-phase epcoritamab therapy, recurred after consecutive RT fractions, and improved rapidly after IL-6 blockade, thereby illustrating a CRS-compatible febrile episode arising outside the usual early-cycle window of epcoritamab therapy.\u003c/p\u003e\u003cp\u003eMechanistically, RT may have acted as an inflammatory trigger. Local tissue injury and immunogenic cell death can release inflammatory mediators and augment immune activation in some settings [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. CRS-like inflammatory events temporally associated with RT have been described in other immunotherapy settings, with systemic symptoms recurring after irradiation and accompanied by transient increases in pro-inflammatory cytokines, including TNF-α and IL-6 [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Although the therapeutic context differs, these observations support the possibility that RT may transiently amplify cytokine-driven systemic symptoms in selected settings [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our patient, the irradiated abdominal lymph node may have contained residual target B cells. RT-induced tumor or tissue injury may have transiently augmented local inflammatory signaling during ongoing epcoritamab exposure, thereby contributing to a transient systemic febrile episode consistent with a CRS-compatible event. This interpretation is hypothesis-generating rather than confirmatory.\u003c/p\u003e\u003cp\u003eClinically, in patients receiving BsAb therapy, fever developing during RT should prompt concurrent evaluation for infection while keeping CRS in the differential diagnosis [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]. Management should be guided by ASTCT criteria, with timely initiation of standard therapy, including IL-6 blockade when clinically warranted based on the overall risk assessment (e.g., recurrent fever with a reproducible temporal pattern and concern for deterioration that could compromise RT completion) [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]. A key limitation is that cytokine measurements were not obtained at symptom onset; therefore, causality cannot be established and the association remains clinical and temporal. However, in real-world practice, management decisions must often be made before cytokine data are available; thus, prompt parallel infectious workup and early CRS-directed management based on clinical grading remain essential when patients develop fever during BsAb therapy.\u003c/p\u003e\u003cp\u003eIn conclusion, while CRS with epcoritamab is typically confined to early treatment, this case suggests that RT delivered during late-phase therapy may be associated with a CRS-compatible febrile episode. When RT is administered during BsAb therapy, clinicians should remain alert to CRS even in later cycles and manage suspected events promptly using established grading and management principles, including tocilizumab when clinically indicated.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eASTCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican Society for Transplantation and Cellular Therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBsAb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebispecific antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echimeric antigen receptor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecytokine release syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDLBCL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ediffuse large B-cell lymphoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-6\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterleukin-6\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLBCL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elarge B-cell lymphoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eR/R\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erelapsed/refractory\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eradiotherapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTNF-α\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etumor necrosis factor-α\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003eThe Institutional Review Board at the Japan Community Health Care Organization (JCHO) Kyushu Hospital determined that this single-patient case report does not constitute human subjects research and waived the requirement for review.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eWritten informed consent for publication of this case report was obtained from the patient.\u003c/p\u003e \u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo specific funding was received for this work.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: NN, HN. Investigation: NN, YO, KK. Data curation: NN. Writing\u0026mdash;original draft: NN. Writing\u0026mdash;review and editing: HN, YO, KK, KY, RO. Supervision: RO. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMinson AG, Dickinson MJ. New bispecific antibodies in diffuse large B-cell lymphoma. Haematologica. 2025;110(7):1483\u0026ndash;99. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3324/haematol.2024.285343\u003c/span\u003e\u003cspan address=\"10.3324/haematol.2024.285343\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThieblemont C, Karimi YH, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial. Leukemia. 2024;38:2653\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41375-024-02410-8\u003c/span\u003e\u003cspan address=\"10.1038/s41375-024-02410-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJamois C, Turner DC, Gibiansky L, Li F, Menuet J, Pereira LR, et al. Tocilizumab dosing for management of T cell-engaging bispecific antibody-related CRS in patients with R/R B-cell NHL. Clin Pharmacol Ther. 2025;118:917\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cpt.3751\u003c/span\u003e\u003cspan address=\"10.1002/cpt.3751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadtke KK, Bender BC, Li Z, Turner DC, Roy S, Belousov A, et al. Clinical pharmacology of cytokine release syndrome with T-cell-engaging bispecific antibodies: current insights and drug development strategies. Clin Cancer Res. 2025;31:245\u0026ndash;57. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1158/1078-0432.CCR-24-2247\u003c/span\u003e\u003cspan address=\"10.1158/1078-0432.CCR-24-2247\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transpl. 2019;25:625\u0026ndash;38. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bbmt.2018.12.758\u003c/span\u003e\u003cspan address=\"10.1016/j.bbmt.2018.12.758\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41:2238\u0026ndash;47. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.22.01725\u003c/span\u003e\u003cspan address=\"10.1200/JCO.22.01725\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021;398:1157\u0026ndash;69. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(21)00889-8\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(21)00889-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi T, Gibiansky L, Parikh A, Putnins M, Chiu CW, Sacchi M, et al. Optimal dosing regimen for epcoritamab, a subcutaneous bispecific antibody, in relapsed or refractory large B-cell lymphoma. Clin Pharmacol Ther. 2025;117:1437\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cpt.3588\u003c/span\u003e\u003cspan address=\"10.1002/cpt.3588\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen X, Kamperschroer C, Wong G, Xuan D. A modeling framework to characterize cytokine release upon T-cell-engaging bispecific antibody treatment: methodology and opportunities. Clin Transl Sci. 2019;12:600\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/cts.12662\u003c/span\u003e\u003cspan address=\"10.1111/cts.12662\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarker CA, Kim SK, Budhu S, Matsoukas K, Daniyan AF, D\u0026rsquo;Angelo SP. Cytokine release syndrome after radiation therapy: case report and review of the literature. J Immunother Cancer. 2018;6:1. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s40425-017-0311-9\u003c/span\u003e\u003cspan address=\"10.1186/s40425-017-0311-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu M, Yang M, Zhang J, Yin Y, Fan X, Zhang Y, et al. Immunogenic cell death induction by ionizing radiation. Front Immunol. 2021;12:705361. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2021.705361\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2021.705361\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1\u003c/p\u003e\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eUnit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eComplete blood count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e6900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e/\u0026mu;L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eNeutrophils\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e65.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLymphocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e18.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMonocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eEosinophils\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBasophils\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e326\u0026times;10\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e/\u0026mu;L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBiochemistry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTotal bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eALP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eGGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLDH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBUN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSerum creatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCreatinine clearance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e49.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emL/min\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCalcium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eImmunoglobulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTumor markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003esoluble interleukin-2 receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e1780\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eU/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eFungal markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eGalactomannan (GM) index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e(1,3)-\u0026beta;-D-glucan (BDG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003epg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 footnotes (timing):\u003c/strong\u003e Results were obtained at admission unless otherwise noted. The following were measured during hospitalization: galactomannan (GM) index and (1,3)-\u0026beta;-D-glucan (BDG). Creatinine clearance was estimated using the Cockcroft\u0026ndash;Gault equation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations used in Table 1:\u0026nbsp;\u003c/strong\u003eALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BDG, (1,3)-\u0026beta;-D-glucan; BUN, blood urea nitrogen; CRP, C-reactive protein; GGT, gamma-glutamyl transferase; GM, galactomannan; Hb, hemoglobin; IgG, immunoglobulin G; LDH, lactate dehydrogenase; PLT, platelet count; WBC, white blood cell.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"bispecific antibody, epcoritamab, radiotherapy, cytokine release syndrome, tocilizumab, diffuse large B-cell lymphoma","lastPublishedDoi":"10.21203/rs.3.rs-9059446/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9059446/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEpcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has demonstrated promising activity in relapsed or refractory diffuse large B‑cell lymphoma. Cytokine release syndrome is a key adverse event associated with T‑cell–engaging therapies; however, it typically occurs early after treatment initiation and is generally manageable with step‑up dosing and premedication. Evidence regarding the safety of delivering radiotherapy during late-phase epcoritamab therapy remains limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 58-year-old man with diffuse large B-cell lymphoma received epcoritamab. On cycle 8 day 8, local radiotherapy (40 Gy in 20 fractions) was initiated for a residual abdominal lymph node lesion. Approximately 12 hours after irradiation on radiotherapy day 2, he developed fever (38°C) and fatigue without hypotension or hypoxia and with preserved neutrophil counts, consistent with a cytokine release syndrome–compatible febrile episode (grade 1 by the American Society for Transplantation and Cellular Therapy criteria). Blood cultures were obtained and empiric cefepime with acetaminophen was initiated, resulting in transient defervescence; however, fever recurred on radiotherapy day 3. Blood cultures, (1,3)-β-D-glucan, and galactomannan assays were negative. Given the reproducible temporal association with radiotherapy, a cytokine release syndrome–compatible event was considered, and tocilizumab (8 mg/kg) was administered in line with standard cytokine release syndrome management guidance, with defervescence within 1 hour. He remained afebrile thereafter and completed radiotherapy without recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCytokine release syndrome–compatible fever is uncommon after multiple cycles of epcoritamab. This case suggests a temporal association between radiotherapy and a cytokine release syndrome–compatible febrile episode during late-phase therapy and supports the possibility that radiotherapy acted as an inflammatory trigger. When radiotherapy is delivered during bispecific antibody therapy, fever should prompt concurrent evaluation for infection while keeping cytokine release syndrome in the differential diagnosis, and standard cytokine release syndrome management should be applied promptly when clinically indicated.\u003c/p\u003e","manuscriptTitle":"Cytokine Release Syndrome–Compatible Fever After Initiation of Local Radiotherapy During Late-Phase Epcoritamab Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 15:21:35","doi":"10.21203/rs.3.rs-9059446/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"60f9efef-5d6a-4f8e-9fd7-ca89a2beaf6c","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T16:28:48+00:00","versionOfRecord":{"articleIdentity":"rs-9059446","link":"https://doi.org/10.1186/s40780-026-00568-0","journal":{"identity":"journal-of-pharmaceutical-health-care-and-sciences","isVorOnly":false,"title":"Journal of Pharmaceutical Health Care and Sciences"},"publishedOn":"2026-03-27 16:08:42","publishedOnDateReadable":"March 27th, 2026"},"versionCreatedAt":"2026-03-13 15:21:35","video":"","vorDoi":"10.1186/s40780-026-00568-0","vorDoiUrl":"https://doi.org/10.1186/s40780-026-00568-0","workflowStages":[]},"version":"v1","identity":"rs-9059446","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9059446","identity":"rs-9059446","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}