Linvoseltamab Shows Prolonged Efficacy and Safety in High-Risk Relapsed or Refractory MM

The BCMAxCD3 bispecific antibody linvoseltamab induced deep, durable responses in patients with relapsed or refractory multiple myeloma (RRMM), including those in high-risk subgroups, according to updated data from the LINKER-MM1 study recently published in Blood.

In this phase 2 expansion cohort, 117 patients with triple-class–exposed or refractory MM received IV linvoseltamab 200 mg weekly through weeks 14 to 16, then transitioned to receipt once every 2 weeks. After week 24, patients in the 200 mg expansion cohort who achieved a very good partial response or better transitioned to receipt once every 4 weeks. Objective response rate (ORR) was the study’s primary end point, with secondary end points including duration of response (DOR), progression-free survival (PFS), overall survival (OS), and minimal residual disease (MRD).

The overall ORR was 70.9%, with 49.6% achieving a complete response or better. The Kaplan-Meier estimated median DOR was 29.4 months (95% CI, 19.2-not evaluable [NE]). Median PFS was not reached (95% CI, 17.3 months-NE) with a 70% probability of PFS at 12 months, and median OS was 31.4 months (95% CI, 21.6-NE). Among patients who switched to dosing every 4 weeks, median DOR was not reached (95% CI, 19.2 months-NE), suggesting lasting benefits with less frequent administration.

Subgroup analyses focused on high-risk features, including baseline bone marrow plasma cell (BMPC) percentage, disease refractoriness, and soluble B-cell maturation antigen (sBCMA) concentration.

For patients with baseline BMPC less than 50% (n=65), ORR was 78.5%, and median DOR, PFS, and OS were not reached (DOR: 95% CI, 29.4 months-NE; PFS: 95% CI, NE-NE; OS: 31.4 months; 95% CI, 21.6-NE). Those with BMPC of at least 50% (n=28) had an ORR of 50%, with a median DOR of 19.2 months (95% CI, 11.6-NE) and a median PFS of 17.3 months (95% CI, 2.5-NE); OS was not reached (95% CI, 10.2 months-NE), demonstrating the impact of tumor burden.

Patients with triple-class refractory MM (n=19) achieved a 73.7% ORR; median DOR and PFS were not reached (DOR: 95% CI, 11.6 months-NE; PFS: 95% CI,7.6 months-NE), and median OS was 21.6 months (95% CI, 12.2-NE). Patients with penta-class refractory MM (n=33) had a 66.7% ORR, median DOR of 29.4 months (95% CI, 11.2-NE) and a median OS of 31.4 months (95% CI, 10.2-NE); median PFS was not reached (95% CI, 5.4 months-NE).

Patients with sBCMA levels below 400 ng/mL (n=59) had an ORR of 83.1%, with median DOR, PFS, and OS all not reached (DOR: 95% CI, 19.2 months-NE; PFS: 95% CI, 19.8 months-NE; OS: 95% CI, 21.6 months-NE). Individuals with an sBCMA level of at least 400 ng/mL (n=52) had a 55.8% ORR, median DOR of 29.4 months (95% CI, 16.6-NE), median PFS of 17.3 months (95% CI, 3.0-NE), and median OS of 31.4 months (95% CI, 11.7-NE).

Safety was consistent with prior findings within this population, with a median follow-up of 14.3 months and no new signals emerging. The most common treatment-emergent adverse event was cytokine release syndrome at 46.2% (any grade), followed by neutropenia (42.7%), anemia (38.5%), diarrhea (37.6%), cough (36.8%), and fatigue (33.3%).

This updated data suggest that linvoseltamab has potential as a versatile, tolerable option for patients with RRMM, particularly patients with complex, high-risk disease who are frequently underrepresented in clinical trials. “Linvoseltamab 200 mg induced prolonged response and survival in patients with RRMM, including those with difficult to treat refractory disease and high tumor burden (high sBCMA concentration or BMPC percentage), while maintaining a generally manageable safety profile,” the authors concluded.