Teclistamab, Daratumumab, and Pomalidomide in Patients with Relapsed/Refractory Multiple Myeloma: Results from the Majestec-2 Cohort a and Trimm-2 Studies

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.495-495
• Main Authors: D'Souza, Anita, Costa, Luciano J., San-Miguel, Jesús F., Berdeja, Jesus G, Morillo Giles, Daniel, Touzeau, Cyrille, McKay, John T, Dholaria, Bhagirathbhai, Martin, Thomas G, Perrot, Aurore, Oriol, Albert, Sureda Balari, Anna, Prior, Thomas, Ghosh, Debopriya, Kang, Lijuan, Larsen, Julie S, Ludlage, Hein, Vandenberk, Lien, Chen, Lingling, Koster, Bas D, Sun, Weili, Kobos, Rachel, Searle, Emma, Matous, Jeffrey V, Chari, Ajai, Kampfenkel, Tobias
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-200181

Introduction: Teclistamab (tec) is the first approved B-cell maturation antigen × CD3 bispecific antibody (BsAb) for the treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM), with weight-based dosing and the longest study follow-up of any BsAb in MM. Both daratumumab (D) and pomalidomide (P) have immunomodulatory effects that may augment the function of tec, potentially enhancing its antimyeloma activity. We present safety and efficacy data for patients with MM who received tec in combination with D and P (tec-DP) in 2 phase 1b studies, MajesTEC-2 (NCT04722146) and TRIMM-2 (NCT04108195). Methods: Eligible patients in this cohort of MajesTEC-2 had 1-3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and lenalidomide, and in TRIMM-2 had ≥3 prior LOT, including a PI and an immunomodulatory drug (IMiD) or were double refractory to a PI and an IMiD. Patients received weekly doses of tec (0.72, 0.75, or 1.5 mg/kg with step-up dosing [SUD]) and approved schedules of D (1800 mg) and P (2 or 4 mg). P was introduced after SUD was completed. Responses and adverse events (AEs) were investigator assessed per International Myeloma Working Group criteria and Common Terminology Criteria for Adverse Events v5.0, respectively. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per American Society of Transplantation and Cellular Therapy guidelines. Results: Twenty-seven patients received tec-DP (TRIMM-2, n=10, enrolled Apr 8-Aug 23, 2021; MajesTEC-2, n=17, enrolled Nov 17, 2020-Mar 29, 2021). At the data cut-offs (Apr 9, 2024 [TRIMM-2]; Apr 15, 2024 [MajesTEC-2]), median follow-up was 25.8 months (mo; range, 0.5-39.6) and median treatment duration of tec-DP was 12.0 mo (range, 0.5-33.9). Median age was 62 years (range, 35-79); 59.3% were male. Median prior LOT was 2 (range, 1-16), with 33% having had >3 prior LOT; 40.7% were D exposed. AEs of any grade in ≥50% of patients were neutropenia (77.8%), cough (59.3%), and CRS (55.6%). Grade 3/4 AEs in ≥15% of patients were neutropenia (77.8%), lymphopenia (22.2%), anemia (18.5%), COVID-19 pneumonia (18.5%), and pneumonia (18.5%). All CRS events were grade 1/2 and resolved. There was 1 case of ICANS (grade 1) that resolved. Infections occurred in 25 (92.6%; grade 3/4, 63.0%) patients, most commonly upper respiratory infection (44.4%; all grade 1/2), pneumonia (29.6%; grade 3/4, 18.5%), sinusitis (29.6%; grade 3/4, 3.7%), and COV