Introduction

Multiple myeloma (MM) is considered incurable. Despite improved outcomes with novel agents, including BCMA-targeted chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), and bispecific antibodies, patients with relapsed/refractory MM (RRMM) often have poor prognoses. LINKER-MM1 (NCT03761108) is a global, single-arm, Phase 1/2 study of linvoseltamab, a BCMA×CD3 bispecific antibody, in patients with RRMM who were either triple-class exposed (TCE; previously treated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody) during ≥3 prior lines of therapy (LOTs), or triple-class refractory to these therapies. Here, we present comparisons of clinical outcomes from LINKER-MM1 with those of a current, international, real-world (RW) external control arm (ECA; NCT05673967).

Methods

The ECA was derived from 16 academic sites of the International Myeloma Foundation International Myeloma Working Group (IMWG) (N=203; 309 eligible LOTs) and compared with linvoseltamab (N=105; Phase 2 200 mg cohort). Patients in the ECA initiated ≥1 anti-MM therapy after meeting key LINKER-MM1 eligibility criteria. Weighted random sampling and inverse probability of treatment weighting were used to select 1 LOT per patient and balance the ECA and trial populations on prespecified prognostic factors (Kumar S, et al. IMS 2023). The primary endpoint was objective response rate (ORR; IMWG criteria) determined by an independent central review committee (ICRC) based on myeloma laboratories. An independent data review committee reviewed comparability of cohorts and endpoint assessments prior to conducting comparative analyses.

Results

Median follow-up was 14.3 months for the linvoseltamab cohort (data cutoff: Jan 6, 2024) and 13.4 months for the ECA. After weighting, 15 prognostic factors were balanced between cohorts. Patients in the ECA received 68 distinct regimens, most commonly CAR T-cell therapies (11.3%) and ADCs (10.3%). After balancing the cohorts, patients in the ECA evaluable for response had ICRC-assessed ORR of 46.3% (40.8% by treating physician assessment), among whom 24.0% had very good partial response or better (≥VGPR). When including patients who died without evaluable response, ECA ICRC-assessed ORR was 44.2%. Linvoseltamab induced significantly higher ICRC-assessed ORR (69.5% vs 46.3%, odds ratio [OR] 2.65 [95% confidence interval (CI) 1.66-3.69]) and rate of ≥VGPR (62.9% vs 24.0%, OR 5.37 [95% CI 3.61-8.49]) compared with ECA regimens.

Conclusion

Despite current use of novel therapies, there is no well-established RW standard of care (SOC) for patients with TCE RRMM treated at IMWG sites. To our knowledge, this is the first RW ECA study in MM with a high percentage of anti-BCMA therapies and response ascertainment for all patients by ICRC. Linvoseltamab induced significantly higher response rates, including rate of ≥VGPR, compared with current RW SOC therapies, highlighting its potential as a highly effective treatment in patients with TCE RRMM.

Disclosures

Kumar:Merck: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Other: Independent review committee participation; Roche: Research Funding; MedImmune/AstraZeneca: 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; Novartis: Research Funding; Takeda: 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; Adaptive: 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; 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:Oncopeptides: Consultancy, Honoraria; Novartis: Honoraria; Menarini: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; AstraZeneca: Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Other: Research grant to institution; Janssen: Consultancy, Honoraria, Other: Research grant to institution; GlaxoSmithKline: Consultancy, Honoraria, Other: Research grant to institution; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Research grant to institution; Amgen: Consultancy, Honoraria, Other: Research grant to institution; AbbVie: Other: Research grant to institution; Pfizer: Consultancy, Honoraria; Roche Pharma: Consultancy, Honoraria; Stemline: Honoraria; Takeda: Consultancy, Honoraria; Regeneron: Consultancy. Rosiñol Dachs:GSK: Honoraria, Other: Honoraria for lectures; BMS, Takeda, Pfizer, Menarini: Honoraria; Janssen Pharmaceutica: Honoraria, Other: Honoraria for lectures and meeting travel support; Amgen: Honoraria, Other: Educational lectures; Sanofi: Honoraria, Other: Honoraria for lectures. Dimopoulos:Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Swixx: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Abbvie, Takeda, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. Siegel:Envision Pharma: Honoraria; Prothena: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Merck: Honoraria; K36 Therapeutics: Honoraria; BMS: Honoraria; COTA: Current holder of stock options in a privately-held company; Roche: Honoraria; Envision Pharma: Honoraria; Sebia: Honoraria. Monge:Pfizer: Consultancy; Johnson & Johnson: Consultancy; Janssen: Consultancy. de la Rubia:Janssen: Honoraria, Speakers Bureau; Menarini: Honoraria; Pfizer: Speakers Bureau; Bristol-Myers Squibb: Honoraria; Sanofi: Speakers Bureau; Takeda: Research Funding; GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau; Oncopharm: Honoraria. Mateos:BMS/Celgene, Janssen-Cilag, Sanofi, Abbvie, Stemline, Oncopeptides, GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Takeda, Regeneron: Honoraria. Ocio:Janssen: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; AstraZeneca: Consultancy; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Honoraria; Menarini: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Regeneron: Honoraria. Bladé:Amgen: Other: Honoraria for lectures; Celgene/Bristol Myers Squibb: Other: Honoraria for lectures; Sanofi: Other: Honoraria for lectures; Janssen: Other: Honoraria for lectures. Green: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. Hampp: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.

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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