Background
Phase 1/2, open-label, single-arm trial (LINKER-MM1). N=117 treated at the 200 mg dose (primary cohort) with relapsed or refractory multiple myeloma after ≥3 prior lines including a PI, IMiD, and anti-CD38 antibody (triple-class exposed); ≥2 prior lines required at entry. Linvoseltamab (REGN5458) is an off-the-shelf BCMAxCD3 bispecific antibody (Regeneron).
Interventions and follow up
Regimen: Linvoseltamab IV step-up then 200 mg every 2 weeks; de-escalation to q4wk in responders after week 24 (BCMA × CD3 bispecific)
Population: Triple-class–exposed R/R MM
Primary endpoint: Overall response rate (ORR)
mFollow up: 14.3 months
Population: Triple-class–exposed R/R MM
Primary endpoint: Overall response rate (ORR)
mFollow up: 14.3 months
Results
ORR (200 mg): 70.9% (95% CI 61.6–79.0%)
≥VGPR rate: 63.2%
≥CR rate: 49.6%
mDOR: 29.4 months
mPFS: NR at primary analysis
≥VGPR rate: 63.2%
≥CR rate: 49.6%
mDOR: 29.4 months
mPFS: NR at primary analysis
Adverse events
CRS/neurotoxicity: CRS any grade 67.5%, grade ≥3 1.7%; ICANS any grade 6.0%, grade ≥3 2.6%
Infections: Any grade 64.1%, grade ≥3 29.1%
Hematologic: Neutropenia grade ≥3 49.6%; planned Q4W de-escalation improved tolerability in sustained responders
Infections: Any grade 64.1%, grade ≥3 29.1%
Hematologic: Neutropenia grade ≥3 49.6%; planned Q4W de-escalation improved tolerability in sustained responders
Conclusions
Linvoseltamab 200 mg achieved a 70.9% ORR with an exceptional 49.6% ≥CR rate and a median DOR of 29.4 months in RRMM — among the highest ≥CR rates reported for a BCMAxCD3 bispecific antibody — with a favorable profile including planned de-escalation to monthly dosing.
Key Limitations
Single-arm design without a randomized comparator. Cross-trial comparisons of ≥CR with other bispecifics are confounded by differing populations and response criteria. Grade ≥3 infections (29.1%) reflect class-typical hypogammaglobulinemia requiring IVIG and prophylaxis. mPFS not reached, so long-term durability is not yet established beyond the response endpoints.
Clinical Context
Linvoseltamab (Lynozyfic) received FDA accelerated approval in July 2025 for RRMM after ≥4 prior lines, and EMA conditional approval in 2025. It joins teclistamab and elranatamab as a BCMAxCD3 bispecific, distinguished by a response-adapted dosing-frequency reduction. Infection prophylaxis and IVIG are standard supportive care.
References