TECVAYLI® shows promise as initial combination therapy for new multiple myeloma patients

Johnson & Johnson has unveiled promising new frontline data from the MajesTEC-5 and MajesTEC-4 studies featuring TECVAYLI® (teclistamab-cqyv) in patients with newly diagnosed multiple myeloma (NDMM). These findings, presented at the 2024 American Society of Hematology (ASH) Annual Meeting, highlight TECVAYLI®'s potential as an induction and maintenance therapy with notable efficacy and a manageable safety profile.

The MajesTEC-5 study involved 49 transplant-eligible NDMM patients treated with TECVAYLI® combined with either DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), lenalidomide, and dexamethasone (Tec-DRd), or DARZALEX FASPRO®, bortezomib, lenalidomide, and dexamethasone (Tec-DVRd). All patients assessed for minimal residual disease (MRD) negativity after the third cycle of induction therapy achieved MRD negativity and maintained this status through the sixth cycle. Dr. Rachel Kobos, Vice President of Oncology Research & Development at Johnson & Johnson, emphasized these findings support TECVAYLI®’s potential when combined with other therapies for newly diagnosed multiple myeloma patients.

The safety profile observed in the MajesTEC-5 study was consistent with expectations. No treatment-emergent adverse events (TEAEs) led to discontinuation or death. Cytokine release syndrome (CRS) occurred in 65 percent of patients but was limited to Grades 1 and 2. Importantly, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. The most common Grade 3/4 TEAEs included lymphopenia (43 percent), neutropenia (57 percent), and infections (35 percent).

Dr. Marc S. Raab from Heidelberg University Hospital underscored the need for deeper and more sustained outcomes in frontline settings, noting these results reinforce TECVAYLI®'s potential to enhance existing regimens.

The Phase 3 MajesTEC-4 study, which examined TECVAYLI® as a maintenance therapy following autologous stem cell transplant (ASCT), also showed encouraging results. This study is notable for being the first to present data on a B-cell maturation antigen (BCMA) bispecific as monotherapy or in combination therapy post-ASCT. Low rates of non-hematologic Grade 3/4 TEAEs and treatment discontinuation due to TEAEs were observed. CRS events were all limited to Grades 1 and 2 and primarily occurred during step-up dosing. No ICANS cases were reported. The most frequent Grade 3/4 TEAEs were neutropenia and infections, with neutropenia showing a decreasing trend with less frequent TECVAYLI® dosing across cohorts. All evaluable patients in cohort 1 achieved MRD negativity after 12 months of therapy, and 100 percent of evaluable patients in cohorts 2 and 3 were MRD negative at cycle 6.

Further evaluation of combination therapies will continue in the Phase 3 MajesTEC-7 study, which is currently enrolling participants.

MajesTEC-5 is an ongoing Phase 2 study that evaluates the safety and efficacy of teclistamab and talquetamab combination regimens in transplant-eligible multiple myeloma patients. The MajesTEC-4 study is a multicenter, randomized, open-label Phase 3 study comparing teclistamab in combination with lenalidomide or alone versus lenalidomide alone in newly diagnosed multiple myeloma patients post-ASCT. The MajesTEC-7 study is a Phase 3 randomized study comparing teclistamab in combination with daratumumab SC and lenalidomide versus talquetamab in combination with daratumumab SC and lenalidomide in newly diagnosed multiple myeloma patients not intended for ASCT.

TECVAYLI® is a bispecific T-cell engager antibody therapy approved by the U.S. FDA for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy. The European Commission also granted it conditional marketing authorization for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior therapies. In 2023, the EC approved a reduced dosing frequency of 1.5 mg/kg every two weeks for patients who have achieved a complete response for a minimum of six months.

DARZALEX FASPRO® is a CD38-directed antibody approved for multiple myeloma treatment in various combinations and settings, including for patients who are transplant eligible or ineligible. It has been used in over 585,000 patients worldwide.

Multiple myeloma remains an incurable blood cancer affecting plasma cells in the bone marrow. It is the third most common blood cancer globally, with estimated diagnoses exceeding 35,000 in the U.S. in 2024. The five-year survival rate for multiple myeloma patients is approximately 59.8 percent.