In the phase I/II MajesTEC-1 trial presented at the 2022 ASCO Annual Meeting (Abstract 8007) and simultaneously published in The New England Journal of Medicine, Philippe Moreau, MD, and colleagues found that the bispecific antibody teclistamab produced responses in nearly two-thirds of patients with relapsed or refractory multiple myeloma who had triple-class exposure to an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody.

Teclistamab is a T cell–redirecting antibody targeting both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells.

Philippe Moreau, MD

Study Details

A total of 165 patients from sites in nine countries enrolled in the study between March 2020 and August 2021. Patients received weekly subcutaneous teclistamab at the recommended phase II dose of 1.5 mg/kg after step-up doses of 0.06 mg and 0.3 mg/kg. Patients had received a median of five prior lines of therapy, and 77.8% had triple-class refractory disease. The primary endpoint was overall response (partial response or better).

Responses

Median follow-up was 14.1 months (range = 0.3–24.4 months). Responses occurred in 104 (63.0%, 95% confidence interval [CI] = 55.2%–70.4%) of 165 patients, with a very good partial response or better in 97 (58.8%) and a complete response or better in 65 (39.4%). Measurable residual disease (MRD)-negative status (10^–5) was achieved in 44 patients (26.7%), with an MRD negativity rate of 46% among patients with a complete response or better. The median duration of response was 18.4 months (95% CI = 14.9 months–not estimable); data were not mature at time of analysis after censoring of data for 71 patients.

Median progression-free survival was 11.3 months (95% CI = 8.8–17.1 months). Median overall survival was 18.3 months (95% CI = 15.1 months–not estimable); data were not mature after censoring of data for 97 patients.

Adverse Events

Common adverse events included infections (any-grade in 76.4%, grade 3–4 in 44.8%), cytokine-release syndrome (any-grade in 72.1%, grade 3 in 0.6%, no grade 4), neutropenia (any-grade in 70.9%, grade 3–4 in 64.2%), anemia (any-grade in 52.1%, grade 3–4 in 37.0%), and thrombocytopenia (any-grade in 40.0%, grade 3–4 in 21.2%). Neurologic adverse events of any grade occurred in 14.5% of patients, including immune effector cell–associated neurotoxicity syndrome in five patients (3.0%; all grade 1–2).

A total of 19 patients died from adverse events, including 12 due to COVID-19 infection. Death considered related to treatment occurred in five patients, with causes including COVID-19 infection in two, progressive multifocal leukoencephalopathy in one, hepatic failure in one, and streptococcal pneumonia in one.

The investigators concluded, “Teclistamab resulted in a high rate of deep and durable response in patients with triple class–exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2.”

Dr. Moreau, of University Hospital Hôtel-Dieu, Nantes, and Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, are the corresponding authors for The New England Journal of Medicine article.

Disclosure: The study was funded by Janssen Research and Development. For full disclosures of the study authors, visit nejm.org.