Binod Dhakal, MD, Associate Professor of Medicine at Medical College of Wisconsin, discusses results from the CARTITUDE-4 clinical trial in patients with multiple myeloma (MM).
MM is a form of cancer that occurs due to abnormal and uncontrolled growth of plasma cells in the bone marrow. When present, the most common symptom is anemia, which can be associated with fatigue and shortness of breath. Other features of the condition may include multiple infections, abnormal bleeding, bone pain, weak and/or easily broken bones, and numbness and/or weakness of the arms and legs. The exact underlying cause of MM is currently unknown.
The CARTITUDE-4 (NCT04181827) study was a phase 3 randomized trial comparing cilta-cel versus pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in patients with relapsed/lenalidomide-refractory MM. Cilta-cel is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen on the surface of cancer cells in B cell malignancies.
Recently, data was presented at the 2025 American Society of Hematology (ASH) Annual Meeting on the correlation between response to bridging therapy before cilta-cel with efficacy and safety outcomes post infusion. Patients in the cilta-cel arm underwent apheresis, received at least 1 cycle of bridging therapy with either PVd or DPd, lymphodepletion (cyclophosphamide and fludarabine), and then a single cilta-cel infusion five to seven days after the start of lymphodepletion.
Among the 196 patients who received cilta-cel in CARTITUDE-4, 87.8% received DPd and 12.2% received PVd during the bridging period. Following bridging therapy and prior to lymphodepletion, 42 patients had very good partial response or better, 70 had partial response, 61 had minimal response, 20 had progressive disease, and 3 were not evaluable.
Progression free survival rates 30 months from cilta-cel infusion were 75.9%, 72.9%, 56.5%, and 30%, respectively. 30 month overall survival rates were 85.1%, 91.4%, 74.8%, and 40%, respectively. No movement or neurocognitive treatment-emergent adverse events were reported in patients with very good partial response or better or in patients with partial response. There was one case of MNT in patients with progressive disease and one in a patient with a best response of stable disease. Cranial nerve palsy was reported in 11.9%, 7.1%, 8.2%, and 5.0% of patients, respectively. Fatal infections occurred in 2.4%, 4.3%, 13.1%, and 15.0% of patients, respectively.
Rates of prolonged thrombocytopenia were lowest among patients who achieved very good partial response or better (9.5%), followed by patients with partial response (11.4%) or minimal response/stable disease (11.5%) after bridging therapy, and markedly higher in those with progressive disease (50%). Prolonged neutropenia was lowest in patients who achieved very good partial response or better before cilta-cel (2.4%) versus 9.8–15.7% in patients with partial response or lower. Non-relapse mortality was 7.1%, 8.6%, 18.0%, and 30.0% in patients, respectively.
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To learn more about MM and other rare cancers, visit https://checkrare.com/diseases/cancers/
