Introduction

Linvoseltamab is an investigational, BCMA×CD3 bispecific antibody designed for the treatment of RRMM. High objective response rates (ORR) to linvoseltamab 200 mg in the LINKER-MM1 trial (NCT03761108) were demonstrated across high-risk subgroups, including patients aged ≥75 years, patients with high-risk cytogenetics, and patients with penta-class refractory status. The aim of this study was to compare ORR, overall and in key subgroups, between patients in Phase 2 of the LINKER-MM1 trial and patients in an international RW SOC external control arm (ECA).

Methods

The ECA was derived from a chart review of 16 academic sites across 10 countries that are part of the International Myeloma Foundation (IMF)-International Myeloma Working Group (IMWG) and 2 US electronic health record databases (COTA and Guardian Research Network [GRN]). Included patients initiated ≥1 anti-MM treatment after meeting key eligibility criteria of LINKER-MM1. Weighted random sampling and inverse probability of treatment weighting (IPTW) were used to select 1 line of therapy (LOT) per patient and balance the overall ECA and trial populations on prespecified prognostic factors (Kumar S, et al. IMS 2023). For ORR assessment, LINKER-MM1 and IMF-IMWG used independent central review committees per IMWG criteria, COTA used algorithmic assessment based on IMWG criteria, and GRN used physician-assessed responses. Prior to conducting comparative analyses, an independent committee of epidemiology and oncology experts reviewed the comparability of the cohorts and endpoint assessments, and approved study continuation.

ORR among patients in LINKER-MM1 and patients in the ECA was compared overall and across prespecified subgroups (≥10 patients per subgroup), including age, race, cytogenetic risk score, international Staging System (ISS), presence of extramedullary plasmacytoma (EMP), refractory class, bone marrow plasma cell (BMPC) proportion, and number of prior LOTs.

Results

Median duration of follow-up was 14.3 months (data cut-off: January 6, 2024) for patients receiving linvoseltamab (n=105) and 13.6 months for the ECA (n=307; n=194, n=72, and n=41 from IMF-IMWG, COTA, and GRN, respectively). Following IPTW, 13 prognostic factors with <30% missingness were balanced between cohorts, with an effective sample size in the ECA of 197. After adjustment, ORR was significantly higher in patients who received linvoseltamab compared with patients in the ECA (69.5% vs 45.7%, odds ratio [OR] 2.5 [95% confidence interval (CI) 1.6-4.1]) and in key subgroups with age 65-74 years (76.9% vs 48.3%, OR 3.6 [1.6-8.6]), age ≥75 years (72.4% vs 48.5%, OR 2.8 [1.1-7.4]), Black or African American race (82.4% vs 25.0%, OR 14.0 [3.0-85.4]), White race (68.9% vs 49.7%, OR 2.2 [1.3-4.0]), standard cytogenetic risk (72.3% vs 51.3%, OR 2.5 [1.3-4.8]), ISS stage III (58.8% vs 19.7%, OR 5.8 [1.5-25.2]), absence of EMP (71.6% vs 49.3%, OR 2.6 [1.5-4.6]), triple-class refractory status (68.2% vs 45.7%, OR 2.6 [1.5-4.4]), quadruple-class refractory status (66.7% vs 45.9%, OR 2.4 [1.3-4.3]), 4-5 prior LOTs (65.1% vs 40.4%, OR 2.8 [1.3-6.0]), and >5 prior LOTs (75.7% vs 36.1%, OR 5.5 [2.4-13.6]).

Numerically higher (not statistically significant) or similar ORR was observed for patients receiving linvoseltamab compared with patients in the ECA with age <65 years (59.5% vs 46.8%, OR 1.7 [0.79-3.6]), high-risk cytogenetics (65.0% vs 63.1%, OR 1.1 [0.41-2.9]), ISS stage I (73.3% vs 64.6%, OR 1.5 [0.62-3.7]), ISS stage II (67.6% vs 53.5%, OR 1.8 [0.72-4.7]), presence of EMP (58.8% vs 56.9%, OR 1.1 [0.32-3.8]), penta-class refractory status (64.3% vs 48.5%, OR 1.9 [0.78-4.8]), BMPC <50% (77.0% vs 67.2%, OR 1.6 [0.61-4.3]), BMPC ≥50% (41.7% vs 36.0%, OR 1.3 [0.36-4.7]), and ≤3 prior LOTs (68.0% vs 66.4%, OR 1.1 [0.43-2.9]). Separate findings will be presented for IMF-IMWG and COTA/GRN data at the congress.

Conclusions

Linvoseltamab induced better ORR vs RW SOC treatments overall, and better or similar ORR in the key subgroups assessed, highlighting its therapeutic value across a range of patients with RRMM with heterogeneous risk profiles and levels of disease burden.

Disclosures

Kumar:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Roche: Research Funding; Oncopeptides: Other: Independent review committee participation; Sanofi: Research Funding. Jagannath:Janssen: Consultancy; BMS: Consultancy; Caribou: Consultancy; Legend Biotech: Consultancy; Regeneron: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Posieda Therapeutics: Consultancy; Grail: Consultancy; IMS: Membership on an entity's Board of Directors or advisory committees; SOHO: Membership on an entity's Board of Directors or advisory committees. Weisel:AbbVie: Other: Research grant to institution; Amgen: Consultancy, Honoraria, Other: Research grant to institution; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Research grant to institution; GlaxoSmithKline: Consultancy, Honoraria, Other: Research grant to institution; Janssen: Consultancy, Honoraria, Other: Research grant to institution; Sanofi: Consultancy, Honoraria, Other: Research grant to institution; Adaptive Biotechnologies: Consultancy, Honoraria; AstraZeneca: Honoraria; BeiGene: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Novartis: Honoraria; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche Pharma: Consultancy, Honoraria; Stemline: Honoraria; Takeda: Consultancy, Honoraria; Regeneron: Consultancy. Rosiñol Dachs:Janssen Pharmaceutica: Honoraria, Other: Honoraria for lectures and meeting travel support; Amgen: Honoraria, Other: Educational lectures; Sanofi: Honoraria, Other: Honoraria for lectures; GSK: Honoraria, Other: Honoraria for lectures; Janssen, BMS, Takeda, Menarini, Pfizer: Honoraria. Dimopoulos:SWIXX: Honoraria; ASTRA ZENECA: Honoraria; BEIGENE: Honoraria; JANSSEN: Honoraria; BMS: Honoraria; GSK: Honoraria; TAKEDA: Honoraria; MENARINI: Honoraria; REGENERON: Honoraria; SANOFI: Honoraria; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees. Siegel:Pfizer: Honoraria; Sebia: Honoraria; Envision Pharma: Honoraria; Envision Pharma: Honoraria; Sanofi: Honoraria; K36 Therapeutics: Honoraria; Prothena: Honoraria; Merck: Honoraria; BMS: Honoraria; COTA: Current holder of stock options in a privately-held company; Roche: Honoraria. Monge:Pfizer: Consultancy; Johnson & Johnson: Consultancy; Janssen: Consultancy. Leleu:Kite, A Gilead Company: Consultancy, Honoraria. de la Rubia:Sanofi: Speakers Bureau; Takeda: Research Funding; Bristol-Myers Squibb: Honoraria; Menarini: Honoraria; Pfizer: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Oncopharm: Honoraria; GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau. Mateos:GSK: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy; AbbVie: Consultancy, Honoraria; Kite: Consultancy. Ocio:GSK: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy; Menarini: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria, Research Funding; Regeneron: Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Honoraria; AbbVie: Consultancy, Honoraria. Bladé:Celgene/Bristol Myers Squibb: Other: Honoraria for lectures; Sanofi: Other: Honoraria for lectures; Amgen: Other: Honoraria for lectures; Janssen: Other: Honoraria for lectures. Beksac:Menarini: Consultancy, Other: advisory; Janssen: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; GSK: Research Funding; Amgen: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Speakers Bureau. Spin:EVERSANA: Current Employment. Bonar:EVERSANA: Current Employment. Shokoohi:EVERSANA: Current Employment. Siddiqui:EVERSANA: Current Employment. Wang:EVERSANA: Current Employment; CSL Behring: Research Funding. Hou:EVERSANA: Current Employment. Green:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Humblet:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Breskin:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Harnett:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company; Pfizer Inc.: Current holder of stock options in a privately-held company. Ge:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Sobel:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Jalbert:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Kroog:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Rodriguez Lorenc:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Ma:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Hampp:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company.

Off Label Disclosure:

Linvoseltamab, an investigational BCMAxCD3 bispecific antibody, for the treatment of patients with relapsed or refractory multiple myeloma

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2024
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