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Clinical Trial
. 2023 Sep;29(9):2259-2267.
doi: 10.1038/s41591-023-02528-9. Epub 2023 Aug 15.

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results

Alexander M Lesokhin  1 , Michael H Tomasson  2 , Bertrand Arnulf  3 , Nizar J Bahlis  4 , H Miles Prince  5 , Ruben Niesvizky  6 , Paula Rodrίguez-Otero  7 , Joaquin Martinez-Lopez  8 , Guenther Koehne  9 , Cyrille Touzeau  10 , Yogesh Jethava  11 , Hang Quach  12 , Julien Depaus  13 , Hisayuki Yokoyama  14 , Afshin Eli Gabayan  15 , Don A Stevens  16 , Ajay K Nooka  17 , Salomon Manier  18 , Noopur Raje  19 , Shinsuke Iida  20 , Marc-Steffen Raab  21 , Emma Searle  22 , Eric Leip  23 , Sharon T Sullivan  23 , Umberto Conte  24 , Mohamed Elmeliegy  25 , Akos Czibere  24 , Andrea Viqueira  26 , Mohamad Mohty  27
Affiliations
Clinical Trial

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results

Alexander M Lesokhin et al. Nat Med. 2023 Sep.

Abstract

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled patients without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met with an ORR of 61.0% (75/123); 35.0% ≥complete response. Fifty responders switched to biweekly dosing, and 40 (80.0%) improved or maintained their response for ≥6 months. With a median follow-up of 14.7 months, median duration of response, progression-free survival and overall survival (secondary endpoints) have not been reached. Fifteen-month rates were 71.5%, 50.9% and 56.7%, respectively. Common adverse events (any grade; grade 3-4) included infections (69.9%, 39.8%), cytokine release syndrome (57.7%, 0%), anemia (48.8%, 37.4%), and neutropenia (48.8%, 48.8%). With biweekly dosing, grade 3-4 adverse events decreased from 58.6% to 46.6%. Elranatamab induced deep and durable responses with a manageable safety profile. Switching to biweekly dosing may improve long-term safety without compromising efficacy. ClinicalTrials.gov identifier: NCT04649359 .

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Conflict of interest statement

A.M.L. reports consulting or advisory roles for Pfizer, Trillium Therapeutics and Arcellx; personal fees from ITeos Therapeutics, Janssen, Legend Biotech, Pfizer, Sanofi and Trillium Therapeutics; institutional research support from Bristol-Myers Squibb, Genentech, Janssen Oncology, Pfizer, Sanofi, Trillium Therapeutics and patents, royalties and/or other intellectual property interests with Serametrix. M.H.T. reports consulting or advisory roles for Janssen. G.K., Y.J., A.E.G. and D.A.S. have no competing interests to report. B.A. reports consulting or advisory roles for Amgen, Celgene, Janssen-Cilag and Sanofi; personal fees from Celgene, Janssen-Cilag, Sanofi and Takeda; research support from Janssen-Cilag and travel and accommodations expenses paid for by Amgen, Celgene, Janssen-Cilag and Takeda. N.J.B. reports consulting or advisory roles for Amgen, Celgene, Janssen, Karyopharm Therapeutics, Pfizer, Sanofi and Takeda; personal fees from AbbVie, Amgen, Celgene, Genentech/Roche, GSK, Janssen, Karyopharm Therapeutics, Sanofi and Takeda and patents, royalties, and/or other intellectual property interests with Celgene and Janssen. H.M.P. reports consulting or advisory roles for Bristo-Myers Squibb, GSK, Janssen, Takeda and Sanofi and research support from AbbVie and Bristol-Myers Squibb. R.N. reports consulting or advisory roles for Bristol-Myers Squibb, GSK, Janssen, Karyopharm Therapeutics and Takeda and research support from Bristol-Myers Squibb, GSK, Janssen, Karyopharm Therapeutics and Takeda. P.R.O. reports consulting or advisory roles for AbbVie, Bristol-Myers Squibb, GSK, Janssen, Pfizer and Sanofi; personal fees from AbbVie, Celgene, GSK, H3 Biomedicine, Janssen, Pfizer and Sanofi; travel and accommodations expenses paid for by Pfizer and speaker’s bureau roles with Bristol-Myers Squibb, GSK, Janssen and Sanofi. J.M.L. reports consulting or advisory roles for Bristol-Myers Squibb, Janssen Oncology and Novartis; institutional research support from Astellas Pharma and Bristol-Myers Squibb and speaker’s bureau roles with Bristol-Myers Squibb, Janssen-Cilag and Roche. C.T. reports consulting or advisory roles for AbbVie, Amgen, Celgene, GSK, Janssen, Novartis and Takeda; personal fees from AbbVie, Amgen, Celgene, GSK, Janssen, Novartis, Sanofi and Takeda; research support from AbbVie, GSK and Sanofi and travel and accommodations expenses paid for by Pfizer and Janssen. H.Q. reports consulting or advisory roles for Amgen, Antengene, Bristol-Myers Squibb/Celgene, Celgene, CSL Behring, GSK, Janssen-Cilag, Karyopharm Therapeutics, Pfizer, Roche and Sanofi and research support from Amgen, Bristol-Myers Squibb/Celgene, Celgene, GSK, Karyopharm Therapeutics and Sanofi. J.D. reports a consulting or advisory role for Novartis and travel and accommodations expenses paid for by AstraZeneca Spain. H.Y. reports research support from Astellas Pharma. A.K.N. reports consulting or advisory roles for Adaptive Biotechnologies, Amgen, BeyondSpring Pharmaceuticals, Bristol-Myers Squibb, Cellectar, Genzyme, GSK, Janssen Oncology, Karyopharm Therapeutics, Oncopeptides, ONK Therapeutics, Pfizer, Secura Bio and Takeda; personal fees from Adaptive Biotechnologies, Amgen, BeyondSpring Pharmaceuticals, Bristol-Myers Squibb/Celgene, Cellectar, Genzyme, GSK, Janssen Oncology, Karyopharm Therapeutics, Oncopeptides, ONK Therapeutics, Pfizer, Secura Bio and Takeda; institutional research support from Amgen, Arch Oncology, Bristol-Myers Squibb/Celgene, Cellectar, GSK, Janssen Oncology, Pfizer and Takeda and travel and accommodations expenses paid for by GSK. S.M. reports consulting or advisory roles for AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb/Celgene, GSK, Janssen, Regeneron, Roche, Sanofi and Takeda. N.R. reports consulting or advisory roles for Amgen, Bristol-Myers Squibb, Celgene, GSK, Janssen, Merck and Takeda; personal fees from Medscape and Research To Practice and research support from 2Seventy Bio. S.I. reports consulting or advisory roles for Janssen, Sanofi, Takeda, Pfizer, Novartis, Bristol-Myers Squibb and AbbVie; personal fees from Bristol-Myers Squibb, Celgene, Janssen, Ono Pharmaceutical, Pfizer, Sanofi, and Takeda and research support from AbbVie, Amgen, Bristol-Myers Squibb, Caelum Biosciences, Celgene, Daiichi Sankyo Pharmaceutical, Janssen, Ono Pharmaceutical, Otsuka, Sanofi, Shionogi and Takeda. M.S.R. reports consulting or advisory roles for Amgen, Bristol-Myers Squibb, GSK, Janssen, Oncopeptides, Pfizer and Sanofi; personal fees from AbbVie, Bristol-Myers Squibb, GSK and Takeda and research support from Bristol-Myers Squibb, Janssen, Novartis and Sanofi. E.S. reports consulting or advisory roles for Shattuck Labs and Sanofi; personal fees from AbbVie, Janssen and travel and accommodations expenses paid for by Janssen. E.L., S.T.S., U.C., M.E., A.C. and A.V. report employment and stock ownership at Pfizer. M.M. reports consulting or advisory roles for Adaptive Biotechnologies, GSK, Jazz Pharmaceuticals, MaaT Pharma, Novartis, Sanofi and Xenikos; personal fees from Amgen, Astellas, Bristol-Myers Squibb, Celgene, Pfizer, Stemline-Menarini and Takeda and speaker’s bureau roles with Janssen, Jazz Pharmaceuticals and Sanofi.

Figures

Fig. 1
Fig. 1
CONSORT diagram of MagnetisMM-3.
Fig. 2
Fig. 2. Response to elranatamab in patients with relapsed or refractory multiple myeloma.
a, Stacked bar graph illustrating the rate of sCR, CR, VGPR and PR in 123 patients who were treated with elranatamab. Responses were assessed by BICR. b, Forest plot illustrating the ORR by BICR in subgroups. Blue squares denote ORR, and whiskers indicate 95% CIs. c, Swimmer plot showing responses over time in 75 patients who had a response following elranatamab treatment. Responses were assessed by BICR, whereas treatment decisions, including switch to Q2W dosing, were made by the investigator. EOT, end of treatment; MR, minimal response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
Fig. 3
Fig. 3. Kaplan–Meier analysis of DOR, PFS and OS.
a, DOR in 75 patients who had an objective response (OR; red line) and in 43 patients who had CR or better (≥CR) (blue line). b, PFS in the overall population (red line) and in 43 patients who had ≥CR (blue line). c, OS in the overall population (red line) and in 43 patients who had ≥CR (blue line). Tick marks indicate censored data. NE, not estimable.
Fig. 4
Fig. 4. CRS profile of patients who received the 12/32-mg two-step-up priming regimen.
CRS experienced by each of the 119 patients who received the 12/32-mg two step-up priming regimen is shown by grade after each dose received. Grade 0 denotes no CRS.
Extended Data Fig. 1
Extended Data Fig. 1. Objective response rate and duration of response (DOR) by blinded independent central review (BICR) in select poor prognosis subgroups.
a, Stacked bar graphs illustrating the rate of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) in patients with or without extramedullary disease (EMD) at baseline, with R-ISS disease stage I-II or III, and with or without penta-refractory disease. Responses were assessed by BICR. b, Kaplan-Meier analysis of the DOR in patients with or without EMD. c, Kaplan-Meier analysis of the DOR in patients with R-ISS disease stage I-II or III. d, Kaplan-Meier analysis of the DOR in patients with or without penta-refractory disease. NE, not estimable; penta-ref, penta-refractory; R-ISS, Revised International Staging System.
Extended Data Fig. 2
Extended Data Fig. 2. Treatment-emergent adverse events (TEAEs) up to 3 months before and after switching to once every 2 weeks (Q2W) dosing.
TEAEs occurring in ≥20% of patients at the level of SOC and in ≥10% of patients at the level of PT in up to 3 months before or after switching to Q2W dosing are reported in the 58 patients who switched to Q2W dosing. Asterisks (*) indicate a difference ≥10% in TEAE incidence after switching to Q2W dosing. COVID, coronavirus disease; PT, preferred terms; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SOC, system organ class.
See this image and copyright information in PMC

References

    1. Mateos MV, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia. 2022;36:1371–1376. doi: 10.1038/s41375-022-01531-2. - DOI - PMC - PubMed
    1. Rodriguez-Otero P, San-Miguel JF. Cellular therapy for multiple myeloma: what’s now and what’s next. Hematol. Am. Soc. Hematol. Educ. Program. 2022;2022:180–189. doi: 10.1182/hematology.2022000396. - DOI - PMC - PubMed
    1. Shah N, Chari A, Scott E, Mezzi K, Usmani SZ. B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. Leukemia. 2020;34:985–1005. doi: 10.1038/s41375-020-0734-z. - DOI - PMC - PubMed
    1. Moreau P, et al. Teclistamab in relapsed or refractory multiple myeloma. N. Engl. J. Med. 2022;387:495–505. doi: 10.1056/NEJMoa2203478. - DOI - PMC - PubMed
    1. Munshi NC, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 2021;384:705–716. doi: 10.1056/NEJMoa2024850. - DOI - PubMed

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