TECVAYLI and DARZALEX FASPRO Combination Achieves 100% MRD Negativity in Newly Diagnosed Multiple Myeloma Patients
核心洞察
Johnson & Johnson's Phase 2 MajesTEC-5 study demonstrates that 100% of evaluable patients achieved minimal residual disease negativity following TECVAYLI and DARZALEX FASPRO-based induction therapy.
The investigational immune-based regimen achieved 100% overall response rates and 85.7% complete response rates in 49 transplant-eligible patients with newly diagnosed multiple myeloma (搜索).
Safety analysis showed manageable tolerability with no treatment discontinuations, no Grade 5 adverse events, and no cases of immune effector cell-associated neurotoxicity syndrome.
Johnson & Johnson announced promising results from the Phase 2 MajesTEC-5 study, demonstrating that an investigational immune-based induction regimen combining TECVAYLI (teclistamab-cqyv) and DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) achieved remarkable clinical efficacy in transplant-eligible patients with newly diagnosed multiple myeloma (搜索).
Unprecedented Response Rates
The study treated 49 patients across three treatment cohorts using a steroid-sparing approach, including regimens of TECVAYLI with DARZALEX FASPRO and lenalidomide, with and without bortezomib. The results demonstrated exceptional efficacy, with 100% of patients achieving overall response (≥partial response) following induction therapy.
Most significantly, all 46 MRD-evaluable patients with available samples after Cycle 3 and/or Cycle 6 achieved minimal residual disease (MRD) negativity by next-generation flow at 10⁻⁵ sensitivity threshold. By next-generation sequencing, all patients were MRD-negative at 10⁻⁶ after Cycle 6. Additionally, 85.7% (42/49) of patients achieved a complete response or better (≥CR) and were MRD-negative at Cycle 6 (≤10⁻⁵).
"Multiple myeloma (搜索) weakens the immune system over time, making it difficult to eliminate cancerous plasma cells," said Marc S. Raab, M.D., Heidelberg University Hospital, Germany. "It's critical to treat patients with the most effective regimens in the newly diagnosed setting. TECVAYLI and DARZALEX FASPRO work synergistically to significantly reduce cancer cells – resulting in deep responses with potential for long term benefit."
Successful Stem Cell Mobilization
The study also demonstrated successful preparation for transplantation, with 96% of patients successfully completing stem cell mobilization with a median total stem cell yield of 8.1×10⁶/kg.
Manageable Safety Profile
Safety analysis reinforced the tolerability of the combination approach. The most common treatment-emergent adverse events (TEAEs) were hematologic, and Grade 3/4 infections occurred in 36.7% of patients. Serious TEAEs occurred in 53% (n=26) of patients. Importantly, no TEAEs led to full study treatment discontinuation and no Grade 5 adverse events were observed.
Notably, no patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome (CRS) was observed in 65% of patients (n=32) and were all Grade 1/2, indicating manageable severity.
Clinical Significance
"Exploring TECVAYLI, with its established use in later lines of treatment, and DARZALEX FASPRO, a foundational therapy across all lines, together helps us understand how this doublet immunotherapy can support patients across different stages of disease," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma (搜索), Johnson & Johnson Innovative Medicine.
The results are particularly significant given that multiple myeloma (搜索) is the third most common blood cancer worldwide and remains an incurable disease. In 2024, it was estimated that more than 35,000 people would be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease. People living with multiple myeloma have a 5-year survival rate of 59.8 percent.
Study Design and Collaboration
MajesTEC-5 (NCT05695508) is an ongoing Phase 2 study evaluating the safety and efficacy of combination regimens including teclistamab and daratumumab in participants with newly diagnosed transplant eligible multiple myeloma (搜索). The clinical trial is sponsored by the German-Speaking Myeloma Multicenter Group (搜索) (GMMG) and Deutsche Studiengruppe Multiples Myelom (搜索) (DSMM), and conducted in collaboration with Johnson & Johnson.
Therapeutic Background
TECVAYLI is a first-in-class, bispecific T-cell engager antibody therapy that activates the immune system by binding to the CD3 (搜索) receptor on T-cells and to the B-cell maturation antigen (搜索) (BCMA (搜索)) on multiple myeloma (搜索) cells. Since FDA approval in October 2022, more than 15,900 patients have been treated worldwide with TECVAYLI.
DARZALEX FASPRO received U.S. FDA approval in May 2020 and is approved for ten indications in multiple myeloma (搜索), three of which are for frontline treatment in newly diagnosed patients. It is the only subcutaneous CD38 (搜索)-directed antibody approved to treat patients with multiple myeloma, and DARZALEX-based regimens have been used in the treatment of more than 618,000 patients worldwide.