{"entity":{"id":"paper-magnetismm-3-elranatamab-natmed-2023","kind":"paper","name":"MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response","aka":[],"tldr":"Elranatamab produced responses in 61% of heavily pretreated myeloma patients and showed that dosing can be thinned to every two weeks once patients respond.","summary":"MagnetisMM-3 was a phase 2 single-arm study of elranatamab, a subcutaneous BCMA x CD3 bispecific, in 123 patients with triple-class-exposed relapsed or refractory multiple myeloma who had not received prior BCMA-directed therapy (cohort A). After two step-up doses and weekly dosing, patients who had responded for at least six months moved to every-two-week dosing. The overall response rate was 61% with complete response or better in 35%; most responses were ongoing at a year. CRS occurred in about 58% of patients, all grade 1-2 with the priming regimen, and neurotoxicity in a small minority. Infections were the main serious toxicity. The FDA granted accelerated approval in 2023.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=MagnetisMM-3%20elranatamab%20Lesokhin%20Nature%20Medicine%202023"},{"label":"ClinicalTrials.gov NCT04649359","url":"https://clinicaltrials.gov/study/NCT04649359"}],"tags":[],"related":["paper-majestec-1-teclistamab-nejm-2022","bispecific-infection-prophylaxis"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["bcma","cd3","gprc5d"],"drugs":["elranatamab","teclistamab","talquetamab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":["crs","orr"],"trials":["magnetismm-3","linker-mm1"],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02528-9","pmid":"37582952","authors":"Lesokhin AM, Tomasson MH, Arnulf B, et al.","paperType":"translational","findings":["123 BCMA-naive, triple-class-exposed patients (cohort A); median 5 prior lines.","Overall response 61%; complete response or better 35%.","Responses were durable, with most responders still in response at 12 months.","CRS in about 58%, all grade 1-2 after two step-up doses; ICANS uncommon.","Responders switched to every-two-week dosing after 6 months without loss of response in most cases."],"whatItMeans":"Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.","caveats":["Single-arm; no comparator or randomised evidence at approval.","Excluded patients with prior BCMA therapy in the registrational cohort; cohort B (BCMA-exposed) had lower responses.","Infection risk and hypogammaglobulinaemia similar to teclistamab.","Durability beyond two years still being reported."],"changedPractice":true,"participants":123},"route":"/key-papers/paper-magnetismm-3-elranatamab-natmed-2023/","neighbours":{"paper":[{"id":"paper-majestec-1-teclistamab-nejm-2022","kind":"paper","name":"MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma","route":"/key-papers/paper-majestec-1-teclistamab-nejm-2022/"}],"pairing":[{"id":"bispecific-infection-prophylaxis","kind":"pairing","name":"Caution: T-cell redirectors and infections","route":"/pairings/bispecific-infection-prophylaxis/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"bcma","kind":"target","name":"BCMA","route":"/targets/bcma/"},{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"},{"id":"gprc5d","kind":"target","name":"GPRC5D","route":"/targets/gprc5d/"}],"drug":[{"id":"elranatamab","kind":"drug","name":"Elranatamab","route":"/drugs/elranatamab/"},{"id":"talquetamab","kind":"drug","name":"Talquetamab","route":"/drugs/talquetamab/"},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"trial":[{"id":"linker-mm1","kind":"trial","name":"LINKER-MM1","route":"/trials/linker-mm1/"},{"id":"magnetismm-3","kind":"trial","name":"MagnetisMM-3","route":"/trials/magnetismm-3/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}