Janssen's teclistamab is showing promise as a frontline combination therapy for patients with newly diagnosed multiple myeloma (NDMM). Data from the MajesTEC-5 and MajesTEC-4 studies, presented at the 2024 American Society of Hematology (ASH) Annual Meeting, suggest that teclistamab-based regimens could offer high efficacy and a tolerable safety profile in induction and maintenance settings.
In the MajesTEC-5 study, 49 transplant-eligible NDMM patients were treated with teclistamab in combination with daratumumab subcutaneous (SC) formulation, lenalidomide and dexamethasone (Tec-DRd) or daratumumab SC, bortezomib, lenalidomide and dexamethasone (Tec-DVRd) as induction therapy. All patients evaluated for minimal residual disease (MRD) negativity after cycle 3 of induction therapy achieved MRD negativity (10-5) and maintained it through cycle 6.
Manageable Safety Profile
The safety profiles observed in the studies were manageable and consistent with individual safety profiles. In MajesTEC-5, no treatment-emergent adverse events (TEAEs) led to study treatment discontinuation or death. Cytokine release syndrome (CRS; Grade 1 or 2) occurred in 65 percent of patients. No patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Grade 3/4 TEAEs included lymphopenia (43 percent), neutropenia (57 percent) and infections (35 percent).
Teclistamab as Maintenance Therapy
Results from the safety run-in of the Phase 3 MajesTEC-4 study highlighted the potential of teclistamab to be administered as a maintenance therapy following autologous stem cell transplant (ASCT). MajesTEC-4 is the first study to present data on a B-cell maturation antigen (BCMA) bispecific as monotherapy or combination therapy after ASCT. Low rates of non-haematologic Grade 3/4 TEAEs and discontinuation of treatment due to all TEAEs (5.3 percent) were observed. CRS events were all Grade 1/2, mostly occurring during step-up dosing, and ICANS was not observed. Neutropenia and infections were the most common Grade 3/4 TEAEs. Grade 3/4 neutropenia at 6 months showed a decreased trend in cohorts 2 and 3 with less frequent teclistamab dosing (cohort 1: 94 percent, cohort 2: 63 percent, cohort 3: 47 percent). A similar trend was observed for all-grade infections (cohort 1: 94 percent; cohort 2: 78 percent; cohort 3: 77 percent). All evaluable patients in cohort 1 who underwent MRD assessment after 12 months of therapy were MRD negative, and 100 percent of evaluable patients assessed in cohorts 2 and 3 were also MRD negative at cycle 6.
Expert Commentary
"These data from the MajesTEC-5 study build on the growing body of evidence of teclistamab combinations that support the potential combinability of teclistamab with other effective therapies, demonstrating high rates of MRD-negative responses for evaluable patients with newly diagnosed multiple myeloma," said Rachel Kobos, M.D., Vice President, Oncology Research & Development, Johnson & Johnson Innovative Medicine.
Marc S. Raab, M.D., Heidelberg University Hospital, Germany, noted, "There remains opportunity to achieve even deeper and more sustained outcomes for a broader patient population in the frontline setting. These data reinforce the potential of teclistamab when used in earlier lines and show that teclistamab can be leveraged to optimise existing standard regimens in combination."
Ongoing Research
Further analysis of combination therapies will be evaluated in the Phase 3 MajesTEC-7 study, which is currently enrolling.
