Efficacy and Safety of Elranatamab in Patients with Relapsed/Refractory Multiple Myeloma Naïve to B-Cell Maturation Antigen (BCMA)-Directed Therapies: Results from Cohort a of the Magnetismm-3 Study

Introduction: Elranatamab is a humanized bispecific antibody that targets both B-cell maturation antigen (BCMA)-expressing multiple myeloma (MM) cells and CD3-expressing T cells. MagnetisMM-3 (NCT04649359) is an open-label, multicenter, non-randomized, phase 2 study to evaluate the safety and efficacy of elranatamab monotherapy in patients (pts) with relapsed/refractory MM (RRMM). Results in pts with RRMM and no prior BCMA-targeted treatment (Cohort A) are presented.

Methods: MagnetisMM-3 enrolled pts refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Pts received subcutaneous elranatamab 76 mg QW on a 28-day cycle with a 2-step-up priming dose regimen (12 mg and 32 mg) administered during the first week. Primary endpoint was objective response rate (ORR) by blinded independent central review (BICR) per IMWG criteria. Objective response was defined as confirmed stringent complete response, complete response, very good partial response, or partial response. Treatment-emergent adverse events (TEAEs) were graded by CTCAE v5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) by ASTCT criteria. Data cut-off: June 17, 2022 (~6 months after last pt's initial dose).

Results: A total of 123 pts were enrolled and treated with elranatamab in Cohort A. Median age was 68.0 years (range, 36−89), 55.3% were male, 58.5% were White, 13.0% were Asian and 7.3% were Black/African American. At baseline, pts had an ECOG performance status of 0 (36.6%), 1 (57.7%) or 2 (5.7%); 25.2% of pts had high risk cytogenetics, 15.4% had R-ISS III, and 31.7% had extramedullary disease. Pts had received a median of 5.0 (range, 2−22) prior lines of therapy; 96.7% and 42.3% of pts were triple-class- and penta-drug refractory, respectively.

After a median follow-up of 6.8 months (range, 0.2−16.2), the median duration of elranatamab treatment was 5.3 months (range, 0.03−16.1); 51.2% of pts were still receiving elranatamab at the data cut-off. Most common primary reasons for permanent treatment discontinuation were progressive disease (32.5%) and adverse events (7.3%). The ORR by BICR was 61.0% (95% CI, 51.8−69.6); a clinical benefit was observed across subgroups (Figure). Among responders, median time to objective response was 1.2 months (range, 0.9−6.9). The median duration of objective response has not been reached, and the probability of maintaining the response at 6 months was 90.4% (95% CI, 79.8−95.6).

Any grade and grade 3/4 TEAEs were reported in 100% and 74.8% of pts, respectively. The most commonly occurring TEAEs are shown in Table 1. Infections were reported in 61.8% (grade 3/4, 31.7%) of pts; most frequently (≥10% of pts) reported were upper respiratory tract infections (14.6% [no grade 3/4]) and pneumonia (10.6% [grade 3/4, 5.7%]). Peripheral neuropathy was reported in 17.1% (grade 3/4, 0.8%) of pts; most common events (≥2% of pts) were peripheral sensory neuropathy (4.9% [no grade 3/4]), paresthesia (4.1% [no grade 3/4]) and gait disturbance (2.4% [no grade 3/4]). Among pts with peripheral neuropathy events (n=21), 47.6% had a medical history of neuropathy. There were 13.8% of pts with TEAEs leading to death, none were assessed as related to elranatamab. Among pts who received the 2-step-up priming regimen (n=119), CRS and ICANS, respectively, were reported in 56.3% and 3.4%; of those pts, 44.8% (n=30/67) and 50.0% (n=2/4) received tocilizumab and/or steroids. All CRS and ICANS were grade 1 or 2. CRS events were confined to the first 2 priming doses (90.6%) and the first 3 doses (98.8%). No pts permanently discontinued treatment due to CRS or ICANS.

Data will be updated at the time of presentation to include ~3 additional months of follow-up.

Conclusions: Results suggest that subcutaneous 76 mg QW elranatamab is efficacious and has a manageable safety profile in pts with triple-class- and penta-drug refractory MM and no prior BCMA-targeted treatment. These results support continued development of elranatamab for pts with MM.

Bahlis:Sanofi: Consultancy, Honoraria; GSK: Consultancy, Other; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Forus: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Genentech: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Honoraria. Tomasson:Pfizer Inc: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria; GSK: Honoraria; Adaptive Biotechnologies: Honoraria; Oncopeptides: Honoraria; Pfizer,: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria. Niesvizky:Takeda: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Nooka:Bristol-Myers Squibb, Janssen, Takeda, Amgen, Adaptive, GlaxoSmithKline, Sanofi, Oncopeptides, Karyophram, SecureBio, and BeyondSprings: Consultancy, Honoraria. Maisel:ADC: Speakers Bureau; Blueprint Medicine: Speakers Bureau; BMS: Speakers Bureau; GSK: Speakers Bureau; Janssen: Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau. Martinez-Lopez:Altum Sequencing Co.: Current equity holder in private company. Arnulf:Pfizer: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodriguez Otero:Janssen, BMS, Sanofi, Pfizer, GSK.: Consultancy; Amgen, Sanofi, GSK, Janssen, BMS-Celgene, Regeneron: Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Speakers Bureau; BMS-Celgene: Speakers Bureau; Amgen: Speakers Bureau; GSK: Consultancy, Speakers Bureau; Pfizer: Consultancy; Sanofi: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; BMS: Consultancy; Hematology Clínica Universidad de Navarra: Current Employment. Raje:Medscape: Honoraria; Amgen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Research to Practice: Honoraria; Two Seventy Bio: Research Funding; Massachusetts General Hospita: Current Employment; Celgene: Honoraria; Janssen: Consultancy, Honoraria. Iida:Janssen Pharmaceutical: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; AbbVie: Research Funding; Amgen BioPharma: Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Otsuka: Research Funding; Caelum: Research Funding. Raab:Amgen: Membership on an entity's Board of Directors or advisory committees; Heidelberg Pharma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Leip:Pfizer: Current Employment, Current equity holder in publicly-traded company. Sullivan:Pfizer Inc: Current Employment, Current equity holder in publicly-traded company. Conte:Pfizer Inc: Current Employment, Current equity holder in publicly-traded company. Viqueira:Pfizer Inc: Current Employment, Current equity holder in publicly-traded company. Lesokhin:Memorial Sloan Kettering Cancer Center: Current Employment; BMS: Honoraria; Sanofi: Research Funding; Trillium Therapeutics: Consultancy, Research Funding; Amgen: Honoraria; Janssen, Pfizer, Iteos, Sanofi, Genmab: Honoraria; Serametrix, inc: Patents & Royalties; Janssen, Pfizer, BMS, Genentech/Roche: Research Funding; Pfizer, Genmab, Sanofi, Iteos, BMS, Janssen: Consultancy.