{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:38:23Z","timestamp":1792118303390,"version":"4.4.0"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec id=\"ab-coi260029-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>T-cell\u2013engaging bispecific antibodies (BsAbs) are increasingly used in B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). As these agents transition into earlier courses of therapy and broader clinical use, understanding their safety profile is critical. While second primary malignant neoplasms (SPMs) represent a key long-term safety signal, small sample sizes, single-arm trials, short follow-up, and heterogeneous reporting have limited reliable estimation of their frequency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate the frequency of reported SPMs after BsAb therapy and evaluate whether study-level characteristics and reporting definitions influence observed estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>PubMed and Embase were searched from inception through October 1, 2025, following a prespecified protocol registered in PROSPERO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Clinical trials and real-world studies of BsAbs in adults with NHL or MM reporting SPM outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Data were extracted following PRISMA guidelines. Pooled SPM frequencies were calculated using random-effects meta-analysis of single proportions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Reported SPM occurrence during available follow-up was categorized as (1) total SPMs reported, (2) SPMs leading to treatment discontinuation, and (3) SPMs leading to death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 494 records, 20 studies (26 cohorts; 2551 patients) met inclusion criteria. Among 8 studies (10 cohorts; 1003 patients) reporting total SPMs, random-effects meta-analysis yielded a pooled estimated proportion of 3.5% (95% CI, 1.8-6.9) at a median (range) follow-up of 17.4 (5.7-25.6) months. Disease-specific estimates were 3.8% (95% CI, 2.3-6.3) for NHL and 3.4% (95% CI, 0-76.7) for MM. A total of 6 studies (8 cohorts; 748 patients) reporting SPMs leading to treatment discontinuation showed a pooled estimate of 2.2% (95% CI, 1.5-3.1). A total of 19 studies (24 cohorts; 2330 patients) reporting SPMs leading to death yielded a pooled estimate of 1.4% (95% CI, 1.1-1.9). In exploratory meta-regression analyses of prespecified study-level covariates (follow-up duration, disease category, prior therapy courses, and age), no variables were associated with total SPM estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260029-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this systematic review and meta-analysis, despite relatively short follow-up, SPMs were a measurable and clinically relevant complication of BsAb therapy. Heterogeneous and inconsistent reporting currently complicates their comprehensive assessment, highlighting the need for standardized long-term safety surveillance in clinical trials examining BsAbs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.1859","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:00:20Z","timestamp":1781794820000},"page":"828","source":"Crossref","is-referenced-by-count":2,"title":["Second Primary Malignant Neoplasms After T-Cell\u2013Engaging Bispecific Antibody Therapy"],"prefix":"10.1001","volume":"12","author":[{"given":"Jaromir","family":"Tomasik","sequence":"first","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland"},{"name":"Doctoral School, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Tix","sequence":"additional","affiliation":[{"name":"Department of Medicine III - Hematology\/Oncology, LMU University Hospital Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Alhomoud","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Yamshon","sequence":"additional","affiliation":[{"name":"Perlmutter Cancer Center, NYU Langone Health, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward R. S.","family":"Cliff","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Iacoboni","sequence":"additional","affiliation":[{"name":"Vall d\u2019Hebron University Hospital, Barcelona, Spain"},{"name":"Vall d\u2019Hebron Institute of Oncology (VHIO), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Cordas dos Santos","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Merz","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Subklewe","sequence":"additional","affiliation":[{"name":"Department of Medicine III - Hematology\/Oncology, LMU University Hospital Munich, Munich, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and LMU University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Gafter-Gvili","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel"},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad Z.","family":"Usmani","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Salles","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York"},{"name":"Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel-Angel","family":"Perales","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz W.","family":"Basak","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Rejeski","sequence":"additional","affiliation":[{"name":"Department of Medicine III - Hematology\/Oncology, LMU University Hospital Munich, Munich, Germany"},{"name":"Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"},{"name":"German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and LMU University Hospital, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni","family":"Shouval","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York"},{"name":"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"19","key":"coi260029r1","doi-asserted-by":"publisher","first-page":"5713","DOI":"10.1182\/bloodadvances.2022009066","article-title":"The race is on: bispecifics vs CAR T cells in B-cell lymphoma.","volume":"7","author":"Gurumurthi","year":"2023","journal-title":"Blood Adv"},{"issue":"1","key":"coi260029r2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41408-024-00997-w","article-title":"Bispecific antibodies and CAR-T cells: dueling immunotherapies for large B-cell lymphomas.","volume":"14","author":"Trabolsi","year":"2024","journal-title":"Blood Cancer J"},{"issue":"4","key":"coi260029r3","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-011200","article-title":"Characteristics of second primary malignancies following bispecific antibodies therapy.","volume":"13","author":"Liang","year":"2025","journal-title":"J Immunother Cancer"},{"issue":"10396","key":"coi260029r4","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0140-6736(23)00521-4","article-title":"T-cell-engaging bispecific antibodies in cancer.","volume":"402","author":"van de Donk","year":"2023","journal-title":"Lancet"},{"issue":"7","key":"coi260029r5","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s41571-024-00905-y","article-title":"Bispecific and multispecific antibodies in oncology: opportunities and challenges.","volume":"21","author":"Goebeler","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"coi260029r6","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1038\/s41591-024-02964-1","article-title":"Bispecific T cell engager therapy for refractory rheumatoid arthritis.","volume":"30","author":"Bucci","year":"2024","journal-title":"Nat Med"},{"key":"coi260029r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114071","article-title":"Application of blinatumomab, a bispecific anti-CD3\/CD19 T-cell engager, in treating severe systemic sclerosis: a case study.","volume":"204","author":"Subklewe","year":"2024","journal-title":"Eur J Cancer"},{"issue":"20","key":"coi260029r8","doi-asserted-by":"publisher","first-page":"4690","DOI":"10.1158\/1078-0432.CCR-24-1798","article-title":"Second primary malignancies after CAR T-cell therapy: a systematic review and meta-analysis of 5,517 lymphoma and myeloma patients.","volume":"30","author":"Tix","year":"2024","journal-title":"Clin Cancer Res"},{"issue":"6","key":"coi260029r9","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1001\/jamaoncol.2024.0662","article-title":"T-cell malignant neoplasms after chimeric antigen receptor T-cell therapy.","volume":"10","author":"Storgard","year":"2024","journal-title":"JAMA Oncol"},{"issue":"3","key":"coi260029r10","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1002\/jrsm.1543","article-title":"Reevaluation of statistically significant meta-analyses in advanced cancer patients using the Hartung-Knapp method and prediction intervals\u2014a methodological study.","volume":"13","author":"Siemens","year":"2022","journal-title":"Res Synth Methods"},{"issue":"22","key":"coi260029r11","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1200\/JCO.24.01008","article-title":"Linvoseltamab for treatment of relapsed\/refractory multiple myeloma.","volume":"42","author":"Bumma","year":"2024","journal-title":"J Clin Oncol"},{"issue":"24","key":"coi260029r12","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.1182\/blood.2025029360","article-title":"Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study.","volume":"146","author":"Chari","year":"2025","journal-title":"Blood"},{"issue":"4","key":"coi260029r13","doi-asserted-by":"publisher","first-page":"e269","DOI":"10.1016\/S2352-3026(24)00385-5","article-title":"Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study.","volume":"12","author":"Chari","year":"2025","journal-title":"Lancet Haematol"},{"issue":"2","key":"coi260029r14","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1056\/NEJMoa2406536","article-title":"Talquetamab plus teclistamab in relapsed or refractory multiple myeloma.","volume":"392","author":"Cohen","year":"2025","journal-title":"N Engl J Med"},{"issue":"1","key":"coi260029r15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41408-025-01314-9","article-title":"Outcomes of teclistamab in patients with relapsed\/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium.","volume":"15","author":"Dima","year":"2025","journal-title":"Blood Cancer J"},{"issue":"4","key":"coi260029r16","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.70114","article-title":"A German multicenter real-world analysis of talquetamab in 138 patients with relapsed\/refractory multiple myeloma.","volume":"9","author":"Frenking","year":"2025","journal-title":"Hemasphere"},{"issue":"3","key":"coi260029r17","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s12185-025-03991-5","article-title":"Phase 1 study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in Japanese patients with relapsed\/refractory MM.","volume":"122","author":"Iida","year":"2025","journal-title":"Int J Hematol"},{"issue":"2","key":"coi260029r18","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1007\/s12185-024-03884-z","article-title":"A phase 1\/2 study of teclistamab, a humanized BCMA?\u00d7?CD3 bispecific Ab in Japanese patients with relapsed\/refractory MM.","volume":"121","author":"Ishida","year":"2025","journal-title":"Int J Hematol"},{"issue":"17","key":"coi260029r19","doi-asserted-by":"publisher","first-page":"4926","DOI":"10.1182\/bloodadvances.2022009260","article-title":"Mosunetuzumab monotherapy is active and tolerable in patients with relapsed\/refractory diffuse large B-cell lymphoma.","volume":"7","author":"Bartlett","year":"2023","journal-title":"Blood Adv"},{"issue":"15","key":"coi260029r20","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1182\/blood.2024026830","article-title":"Epcoritamab plus GemOx in transplant-ineligible relapsed\/refractory DLBCL: results from the EPCORE NHL-2 trial.","volume":"145","author":"Brody","year":"2025","journal-title":"Blood"},{"issue":"18","key":"coi260029r21","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1182\/blood.2025029117","article-title":"Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab.","volume":"146","author":"Brooks","year":"2025","journal-title":"Blood"},{"issue":"1","key":"coi260029r22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41591-023-02726-5","article-title":"Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b\/2 trial.","volume":"30","author":"Budde","year":"2024","journal-title":"Nat Med"},{"issue":"7","key":"coi260029r23","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/s43018-025-00941-2","article-title":"Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study.","volume":"6","author":"Cartron","year":"2025","journal-title":"Nat Cancer"},{"issue":"22","key":"coi260029r24","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.1182\/blood.2025029909","article-title":"Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma.","volume":"146","author":"Falchi","year":"2025","journal-title":"Blood"},{"issue":"2","key":"coi260029r25","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s10147-024-02662-5","article-title":"Efficacy and safety of mosunetuzumab monotherapy for Japanese patients with relapsed\/refractory follicular lymphoma: FLMOON-1.","volume":"30","author":"Goto","year":"2025","journal-title":"Int J Clin Oncol"},{"issue":"10","key":"coi260029r26","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1080\/10428194.2025.2525983","article-title":"Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial.","volume":"66","author":"Izutsu","year":"2025","journal-title":"Leuk Lymphoma"},{"issue":"11","key":"coi260029r27","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.annonc.2024.08.2239","article-title":"Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma.","volume":"35","author":"Kim","year":"2024","journal-title":"Ann Oncol"},{"issue":"8","key":"coi260029r28","doi-asserted-by":"publisher","first-page":"e593","DOI":"10.1016\/S2352-3026(24)00166-2","article-title":"Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study.","volume":"11","author":"Linton","year":"2024","journal-title":"Lancet Haematol"},{"issue":"23","key":"coi260029r29","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1200\/JCO-25-00481","article-title":"Glofitamab combined with Pola-R-CHP or R-CHOP as first therapy in younger patients with high-risk large B-cell lymphoma: results from the COALITION study.","volume":"43","author":"Minson","year":"2025","journal-title":"J Clin Oncol"},{"issue":"3","key":"coi260029r30","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1200\/JCO.23.02470","article-title":"Glofitamab in relapsed\/refractory mantle cell lymphoma: results from a phase I\/II study.","volume":"43","author":"Phillips","year":"2025","journal-title":"J Clin Oncol"},{"issue":"4","key":"coi260029r32","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.ccell.2023.02.008","article-title":"The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.","volume":"41","author":"Friedrich","year":"2023","journal-title":"Cancer Cell"},{"issue":"10","key":"coi260029r33","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1182\/blood.2022015956","article-title":"T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals.","volume":"140","author":"Philipp","year":"2022","journal-title":"Blood"},{"issue":"10","key":"coi260029r34","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1200\/JCO-25-01844","article-title":"Gene therapy-related malignancy and the risk of cancer exceptionalism.","volume":"44","author":"Benedetti","year":"2026","journal-title":"J Clin Oncol"},{"key":"coi260029r31","unstructured":"US Food and Drug Administration. Long term follow-up after administration of human gene therapy products. Accessed March 16, 2026. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/long-term-follow-after-administration-human-gene-therapy-products"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2850671\/jamaoncology_tomasik_2026_oi_260029_1787161680.51382.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:02:18Z","timestamp":1787238138000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2850671"}},"subtitle":["A Systematic Review and Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2026.1859","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}