In patients with transplant-eligible newly diagnosed multiple myeloma (NDMM), the addition of teclistamab — a first-in-class B-cell maturation antigen x CD3 bispecific antibody — to the regimens of daratumumab plus lenalidomide, and dexamethasone (DRd) or daratumumab with bortezomib plus lenalidomide and dexamethasone (DVRd) as induction therapy showed manageable safety profiles and high clinical efficacy, as assessed by rates of measurable residual disease (MRD)-negativity rates. This is according to the interim analysis of the phase II MajesTEC-5 study presented at the 66th American Society of Hematology Annual Meeting and Exposition.
“Despite the recently newly defined standard of care in induction therapy for patients with transplant-eligible NDMM (i.e. DVRd as per PERSEUS trial), the combination of teclistamab with both DVRd as well as with DRd has achieved MRD negativity in all patients tested, before high-dose therapy and autologous hematopoietic cell transplant, indicating superior efficacy compared to the current standard of care,” said study presenter Marc Raab, MD, of Heidelberg Myeloma Center in Germany.
The multicohort study included 49 patients (median age = 58 years, 16.3% aged ≥65 years, 63.3% male, 100% white, 95.9% Eastern Cooperative Oncology Group performance status score of 0-1) with transplant-eligible NDMM. Patients received subcutaneous teclistamab in six cycles combined with DRd (arm A = 10, first dose December 2022; arm A1 = 20, first dose October 2023) or DVRd (arm B = 19, first dose October 2023). Primary endpoints included adverse event (AE) and serious AE rates. Secondary endpoints included response rates and MRD-negativity rates (10–5).
The researchers planned for the first post-treatment MRD assessment to follow the completion of the third cycle of induction therapy. All 49 patients have completed the three cycles. Of these patients, 46 had samples available for MRD testing, and all 46 achieved MRD negativity after three cycles of induction therapy, Dr. Raab said. Across the arms, stem cell mobilization after three cycles was feasible, yielding a median number of CD34-positive cells of 8.4 x 106/kg. As of data cutoff in September 2024, all patients in arm A had completed six cycles of induction therapy, and 14 patients in Arm A1 and 10 patients in Arm B are completing the last two cycles. In the patients who completed six cycles of induction therapy, all maintained MRD negativity.
Grade 3 or 4 treatment-emergent AEs (TEAEs) occurring in 10% or more of patients included neutropenia (57.1%), lymphopenia (42.9%), and leukopenia (18.4%). Infections were common, with grade 3 or 4 infections occurring in 34.7% of patients, primarily COVID-19 and upper respiratory tract infections. One patient experienced grade 3 pancreatitis. While 65.3% of patients experienced cytokine release syndrome (CRS) events, all were grade 1 or 2. No patient experienced immune effector cell-associated neurotoxicity syndrome. No TEAEs led to treatment discontinuation or death.
“This interim analysis of the study shows that adding a bispecific antibody to the standard-of-care combination regimen DVRd or DRd is feasible and safe and achieves unprecedented high MRD-negativity rates as early as after three cycles of the six cycles of induction therapy,” Dr. Raab said.
“This is a phase II study with relatively small patient numbers. The highly promising results need to be confirmed in larger randomized trials,” Dr. Raab concluded.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Raab MS, Weinhold N, Kortüm KM, et al. Phase 2 study of teclistamab-based induction regimens in patients with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): results from the GMMG-HD10/DSMM-XX (MajesTEC-5) trial. Abstract 493. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 8, 2024; San Diego, California.
