Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).
MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.
MajesTEC‑9 Phase 3 Results
MajesTEC-9 (NCT05572515) is a phase 3 randomized clinical trial comparing teclistamab monotherapy, a bispecific T-cell engager (BiTe) antibody, versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in patients with relapsed or refractory MM who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.
A total of 593 patients were randomized and had a median follow-up of 17.3 months. Teclistamab was observed to significantly improve both progression free survival and overall survival versus PVd/Kd. Of 174 patients treated with PVd/Kd who received subsequent treatment, 68.4% received BsAb or CAR-T. Progression free survival favored teclistamab across all prespecified subgroups, including anti-CD38-refractory patients and len-refractory patients. Complete response or better rate was significantly higher with teclistamab versus PVd/Kd.
At data cutoff, 65.3% of patients remained on teclistamab versus 24.0% on PVd/Kd. Treatment emergent adverse events were similar for teclistamab and PVd/Kd. Grade 3/4 adverse events (84.9% vs 76.3%) and grade 5 adverse events (6.5% vs 3.5%) were higher with teclistamab vs PVd/Kd, noting the median treatment duration was 13.1 months with teclistamab 7.0 months with PVd/Kd. Treatment discontinuation lower with teclistamab versuss PVd/Kd. CRS occurred in 66.0% of pts with teclistamab (Gr and ICANS in 4.1%.
This data was presented at ASCO 2026. For more information, click here.
CARTITUDE-4 Cytogenetic Subgroup Analysis
CARTITUDE-4 (NCT04181827) is a phase 3 randomized clinical trial comparing Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T Cell (CAR-T) therapy directed against BCMA, versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory MM.
Previous analyses of cilta-cel showed significant overall (OS) and progression-free survival (PFS) benefits of cilta-cel in patients with lenalidomide-refractory MM after 1 to 3 lines of therapy. The data presented at ASCO 2026 looked at the safety and efficacy in patients who received cilta-cel as study treatment with high- and standard-risk cytogenetics who responded to bridging therapy.
Of 176 total patients who received cilta-cel as study treatment, with a median follow-up, of 33.6 months, 64 patients had high-risk cytogenetics and achieved partial response or better to bridging therapy. In these patients, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 65.1% and 87.2%, respectively. In 40 patients with standard-risk cytogenetics and partial response or better to bridging therapy, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 85.0% and 92.5%, respectively.
Safety analysis included 64 patients with high-risk and 40 with standard-risk cytogenetics. In the high-risk subgroup, cytokine release syndrome was reported in 73.4% of patients, serious nonhematological adverse events in 64.1%, grade 3/4 infections in 43.8%, and immune effector cell-associated neurotoxicity syndrome in 7.8%. Corresponding rates in the standard-risk subgroup were 70.0%, 57.5%, 30.0%, and 0. Nonrelapse mortality occurred in 9 patients and there were 4 infection-related deaths in the high-risk population. No cases of immune effector cell (IEC)-parkinsonism were reported in either subgroup.
For more information, click here.
To learn more about MM and other rare cancers, visit https://checkrare.com/diseases/cancers/
