Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies

• Published in: Blood 2024-12, Vol.144 (23), p.2375-2388
• Main Authors: Touzeau, Cyrille, Krishnan, Amrita Y., Moreau, Philippe, Perrot, Aurore, Usmani, Saad Z., Manier, Salomon, Cavo, Michele, Martinez Chamorro, Carmen, Nooka, Ajay K., Martin, Thomas G., Karlin, Lionel, Leleu, Xavier, Bahlis, Nizar J., Besemer, Britta, Pei, Lixia, Stein, Sarah, Wang Lin, Shun Xin, Trancucci, Danielle, Verona, Raluca I., Girgis, Suzette, Miao, Xin, Uhlar, Clarissa M., Chastain, Katherine, Garfall, Alfred L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Bispecific - administration & dosage; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - therapeutic use; B-Cell Maturation Antigen - antagonists & inhibitors; B-Cell Maturation Antigen - immunology; Female; Humans; Immunotherapy, Adoptive - adverse effects; Male; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - therapy; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023023616

•Teclistamab provides clinically meaningful responses in patients with R/RMM with prior anti-BCMA treatment.•The two treatment-emergent grade ≥3 toxicities most frequently reported in patients with prior exposure to anti-BCMA therapy were cytopenias and infections [Display omitted] Teclistamab is a B-cell maturation antigen (BCMA)–directed bispecific antibody approved for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma (R/RMM). In the phase 1/2 MajesTEC-1 study, a cohort of patients who had prior BCMA-targeted therapy (antibody-drug conjugate [ADC] or chimeric antigen receptor T-cell [CAR-T] therapy) was enrolled to explore teclistamab in patients previously exposed to anti-BCMA treatment. At a median follow-up of 28.0 months (range, 0.7-31.1), 40 patients with prior BCMA-targeted therapy had received subcutaneous 1.5 mg/kg weekly teclistamab. The median prior lines of treatment was 6 (range, 3-14). Prior anti-BCMA therapy included ADC (n = 29), CAR-T (n = 15), or both (n = 4). The overall response rate was 52.5%; 47.5% of patients achieved very good partial response or better, and 30.0% achieved complete response or better. The median duration of response was 14.8 months, the median progression-free survival was 4.5 months, and the median overall survival was 15.5 months. The most common treatment-emergent adverse events (TEAEs) were neutropenia, infections, cytokine release syndrome, and anemia; cytopenias and infections were the most common grade ≥3 TEAEs. Infections occurred in 28 patients (70.0%; maximum grade 3/4, n = 13 [32.5%]; grade 5, n = 4 [10%]). Before starting teclistamab, baseline BCMA expression and immune characteristics were unaffected by prior anti-BCMA treatment. The MajesTEC-1 trial cohort C results demonstrate favorable efficacy and safety of teclistamab in patients with heavily pretreated R/RMM and prior anti-BCMA treatment. This trial was registered at www.ClinicalTrials.gov as #NCT03145181 and #NCT04557098. Two articles in this issue highlight the impact of B-cell maturation antigen (BCMA)–targeted therapies on relapsed/refractory multiple myeloma (R/RMM). Touzeau and colleagues report a phase 1/2 trial of teclistamab, a BCMA-directed bispecific antibody for patients with R/RMM with prior exposure to other BCMA-targeted therapy and a median of 6 prior lines of treatment. Overall response rate was over 50% with a median progression-free survival (PFS) of 4.5 months, with tolerable side effect