Linvoseltamab/Carfilzomib Shows Promising Efficacy in Heavily Pretreated RRMM

Early findings from the phase 1b LINKER-MM2 trial (NCT05137054) show that combining linvoseltamab (REGN5458), a BCMA×CD3 bispecific antibody, with carfilzomib (Kyprolis) delivers high response rates in patients with relapsed/refractory multiple myeloma (RRMM), including those heavily pretreated with triple-class exposure.

In this dose-escalation cohort, 18 patients with RRMM who had progressed after ≥2–3 prior lines of therapy received the combination. Most had prior exposure to anti-CD38 antibodies, immunomodulatory drugs, and proteasome inhibitors (PIs), with about 50% refractory to at least 1 PI. Despite this challenging population, the combination yielded robust outcomes: the overall response rate reached 91% at the 100 mg dose level (DL1) and 100% at 150 mg (DL1b), with ≥VGPR achieved in most responders. Notably, complete response (CR) or better was observed in 76% of patients, a marked improvement compared with historical linvoseltamab monotherapy data.

With a median follow-up of about 15 months, early durability signals are encouraging. The one-year duration of response was 87%, and progression-free survival at 1 year reached 83%.

“At a medium for about 15 months, the overall response rate was about 90% and a complete response or better was 76%, so pretty robust. Complete response or better in this cohort of responses are overall durable, with the 1-year duration of response being 87% and 1-year PFS being about 83%,” Chakraborty says.

Safety findings were consistent with known profiles of each agent. The most common treatment-emergent adverse events included neutropenia, thrombocytopenia, and cytokine release syndrome, which was mostly low grade. Only one case of grade 1 ICANS was reported, and one dose-limiting toxicity occurred at DL1.

While longer follow-up and a larger patient cohort are needed to confirm durability and potential synergy, early data suggest that this combination may offer deeper and more durable responses than either agent alone in this difficult-to-treat population. Enrollment continues at the 200 mg linvoseltamab dose.

Here, Rajshekhar Chakraborty, MD, Department of Medicine, Columbia University Irving Medical Center, New York, NY, discusses the efficacy findings.