Linvoseltamab Plus Carfilzomib Shows Manageable Safety in RRMM

Rajshekhar Chakraborty, MD, Department of Medicine, Columbia University Irving Medical Center, New York, NY, discusses the safety and tolerability of linvoseltamab (REGN5458), a BCMA×CD3 bispecific antibody, with carfilzomib (Kyprolis) when used for the treatment of patients with relapsed/refractory multiple myeloma (RRMM).

Linvoseltamab has previously demonstrated strong single-agent efficacy in patients with triple-class exposed (TCE) multiple myeloma. Combining it with carfilzomib, a second-generation proteasome inhibitor, is hypothesized to enhance antitumor activity through both cytoreduction and immunostimulatory mechanisms, including immunogenic cell death and antigen spreading.

In LINKER-MM2 (NCT05137054), patients with ≥3 prior lines of therapy (or ≥2 if TCE or double-class refractory) received linvoseltamab step-up dosing during cycle 0, followed by full-dose linvoseltamab plus carfilzomib starting in cycle 1. The study assessed 2 dose levels of linvoseltamab 100 mg and 150 mg, with carfilzomib administered on a 20/56 mg/m² schedule.

Chakraborty notes that safety was a key end point in this early-phase study. Encouragingly, only 1 dose-limiting toxicity occurred (grade 4 thrombocytopenia in the context of tumor lysis syndrome, which resolved with continued treatment).

Common treatment-emergent adverse events included cytokine release syndrome in 61% of patients (all were grade 1 or 2), neutropenia (78% overall; 56% grade ≥3), and thrombocytopenia (61%; 39% grade ≥3). Infections occurred in 89% of patients, with 44% being grade ≥3, which Chakraborty notes is comparable with the monotherapy experience. Only 1 case of immune effector cell–associated neurotoxicity syndrome was observed, and it was grade 1 and fully resolved.

Early results from LINKER-MM2 show that linvoseltamab plus carfilzomib led to a safety profile consistent with the known effects of each agent. These findings support ongoing development and dose expansion, including evaluation of a 200 mg linvoseltamab dose in combination with carfilzomib.

REFERENCE:

Manier S, Ocio EM, Martinez-Chamorro C, et al. Linvoseltamab (LINVO) + carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the LINKER-MM2 trial. J Clin Oncol. 2025;43(supl_16):7513. doi:10.1200/JCO.2025.43.16_suppl.7513