As reported in the Journal of Clinical Oncology by Bumma et al, the phase II portion of a first-in-human phase I/II trial (LINKER-MM1) showed strong activity with the B-cell maturation antigen (BCMA) x CD3 bispecific antibody linvoseltamab in patients with relapsed or refractory multiple myeloma.

Study Details

In the international open-label trial, 211 patients with disease progression on/after at least three lines of therapy—including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody—or who were triple-class refractory were enrolled between January 2019 and October 2022. Patients received the candidate linvoseltamab phase II doses of 200 mg (n = 117) or 50 mg (n = 104) once weekly through week 14 followed by once every 2 weeks. Patients receiving 200 mg who achieved very good partial response or better by week 24 received 200 mg once every 4 weeks. The primary outcome measure of the trial was partial response or better in the 200-mg group. Among patients in the 200-mg group, 39% had high-risk cytogenetics, and 28% had pentarefractory disease.

Responses

Among patients receiving 200 mg of linvoseltamab, median follow-up was 14.3 months (range = 0.2–38.4 months). Partial response or better was achieved in 70.9% of patients, with 49.6% achieving complete response or better. Estimated median duration of response was 29.4 months (95% confidence interval [CI] = 19.2 months to not evaluable), with a probability of maintaining response of 81% at 12 months.

Among patients receiving 50 mg of linvoseltamab, median follow-up was 7.4 months (range = 0.4–42.0 months). Partial response or better was achieved in 48.1% of patients, with 21.2% achieving complete response or better.

Adverse Events

Among patients in the 200-mg group, grade 3 or 4 adverse events occurred in 73.5%, most commonly neutropenia (in 41.9%) and anemia (in 30.8%). Cytokine-release syndrome of any grade occurred in 46.2% of patients (grade 3–4 in 1 patient, 0.9%). Immune effector cell–associated neurotoxicity syndrome occurred in 7.7% of patients (grade 3 in 2.6%). Adverse events led to discontinuation of linvoseltamab in 18.8% of patients. Grade 3 or 4 infections occurred in 36% of patients, with the frequency and severity of all infections declining over time. Adverse events led to death within 30 days of the last treatment dose in six patients (5.1%), with five dying from infection.

The investigators concluded, “Linvoseltamab [at] 200 mg induced deep and durable responses, with a median duration of response of 29.4 months, in patients with relapsed/refractory multiple myeloma with an acceptable safety profile.”

Madhav V. Dhodapkar, MD, of the Emory University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Regeneron Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.