Efficacy and safety of elranatamab in patients with high-risk relapsed/refractory multiple myeloma (RRMM): A subgroup analysis from MagnetisMM-3.

person Sarah Marie Larson UCLA Medical Center, Santa Monica, CA info_outline Sarah Marie Larson, Nizar J. Bahlis, Christopher Maisel, Lionel Karlin, Asya Varshavsky Yanovsky, Eric Leip, Sharon T. Sullivan, Andrea Viqueira, Cyrille Touzeau

Authors person Sarah Marie Larson UCLA Medical Center, Santa Monica, CA info_outline Sarah Marie Larson, Nizar J. Bahlis, Christopher Maisel, Lionel Karlin, Asya Varshavsky Yanovsky, Eric Leip, Sharon T. Sullivan, Andrea Viqueira, Cyrille Touzeau Organizations UCLA Medical Center, Santa Monica, CA, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, Baylor University Medical Center, Dallas, TX, Service d’Hématologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France, Fox Chase Cancer Center, Philadelphia, PA, Pfizer Inc., Cambridge, MA, Pfizer Inc., New York, NY, Pfizer SLU, Madrid, Spain, CHU de Nantes, Nantes, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Pfizer Background: Data from the ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in patients (pts) with RRMM and no prior BCMA-directed therapy (Cohort A). Results in high-risk subgroups are reported. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups analyzed were R-ISS stage (I/II/III ) , cytogenetic abnormalities (standard/high risk [high-risk defined by the presence of t(4;14), t(14;16) or del(17p)]), extramedullary disease (EMD) at baseline (Y/N), bone marrow plasma cell involvement (BMPC) at baseline (<50%/≥50%), and penta-refractory disease (Y/N). Results include data up through ~12 months after last pt initial dose. Results: Median treatment durations and the proportions of pts receiving treatment at the data cut-off are reported in the Table. The most frequent cause of discontinuation was progressive disease which was higher for all high-risk subgroups than the corresponding lower risk subgroups. A clinical benefit, assessed by the objective response rate (ORR), was observed across subgroups (Table). A multivariable logistic regression analysis for ORR including baseline age, ECOG, sex, region, cytogenetic risk, presence of EMD, BMPC involvement, prior stem cell transplant, R-ISS stage, number of prior lines, type of myeloma, and penta-refractory disease showed presence of EMD at baseline and non-IgG myeloma (vs IgG) as predictive of lower ORR. Light chain-only myeloma (vs IgG) was predictive of higher ORR. Median duration of response (DOR) was not reached in subgroups by 12 months, DOR rate at 12 months is reported in the Table. Any grade TEAEs were reported in 100% of pts in the study. The incidence of grade 3/4 TEAEs was overall similar across subgroups (Table). Conclusions: Elranatamab is efficacious and has a manageable safety profile in pts with high-risk RRMM and no prior BCMA-directed therapy. Clinical trial information: NCT04649359. R-ISS stage I (n=28) R-ISS stage II (n=68) R-ISS stage III (n=19) Standard cytogenetic risk (n=83) High cytogenetic risk (n=31) EMD - N (n=84) EMD - Y (n=39) <50% BMPC (n=89) ≥50% BMPC (n=26) Penta-refractory disease – N (n=71) Penta-refractory disease - Y (n=52) Median treatment duration (mo) 10.7 5.7 1.4 7.9 2.6 8.4 2.2 8.2 3.0 10.0 2.3 Receiving treatment at data cut-off (%) 42.9 38.2 5.3 41.0 19.4 38.1 25.6 38.2 26.9 42.3 23.1 ORR (%, 95% CI) 75.0 (55.1, 89.3) 63.2 (50.7, 74.6) 26.3 (9.1, 51.2) 63.9 (52.6, 74.1) 54.8 (36.0, 72.7) 71.4 (60.5, 80.8) 38.5 (23.4, 55.4) 67.4 (56.7, 77.0) 46.2 (26.6, 66.6) 71.8 (59.9, 81.9) 46.2 (32.2, 60.5) DOR rate at 12 mo (%, 95% CI) 76.2 (45.4, 91.0) 78.8 (61.8, 88.8) 53.3 (6.8, 86.3) 79.4 (63.4, 89.0) 57.0 (27.4, 78.3) 73.8 (58.3, 84.3) 73.4 (37.4, 90.8) 72.0 (56.6, 82.7) 81.5 (43.5, 95.1) 74.7 (58.6, 85.3) 71.9 (41.2, 88.4) Grade 3/4 TEAEs (%) 75.0 73.5 63.2 73.5 64.5 77.4 56.4 73.0 69.2 73.2 67.3

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