Initial results of CARTITUDE-4, an international phase III clinical trial for multiple myeloma, showed that a notable percentage of patients had significantly improved survival and no progression of their disease when treated with a chimeric antigen receptor T-cell therapy (CAR T) called ciltacabtagene autoleucel or cilta-cel. 

With CAR T-cell therapy, T cells are extracted from a patient’s immune system, re-engineered in a lab, and infused back into the bloodstream to identify and attack unique cancer cells. 

Trial participants were multiple myeloma patients who previously had one to three types of therapy and whose cancer did not respond to a drug called lenalidomide. 

Binod Dhakal, MD

Binod Dhakal, MD, medical oncologist, Medical College of Wisconsin faculty member and one of the lead investigators for the global trial, compared results of patients receiving standard-of-care treatment to those treated with cilta-cel, which binds to two B-cell maturation antigens (BCMA). These antigens are heavily present on the surface of myeloma cells. BCMAs help regulate the growth and survival of B cells. The study tested the premise that slowing down these antigens could slow myeloma’s progression and could work better than standard-of-care treatments. 

Another CAR T-cell therapy called idecabtagene vicleucel or ide-cel has also been used to treat myeloma, but cilta-cel may prove more effective. 

“Ide-cel binds to only one BCMA site, while cilta-cel binds to two sites,” Dr. Dhakal said. “This could make the difference for patients who require a second form of therapy.” 

Trial Results

Trial results showed that the median one-year progression-free survival rate was 76% for participants given cilta-cel, compared with 49% for participants who had standard-of-care treatment. 

“Since lenalidomide is often used as a first treatment for myeloma, it is becoming more common to see lack of response to this drug early in a patient’s disease course,” Dr. Dhakal said. “That rules out using lenalidomide for subsequent treatments. CARTITUDE-4 is the first study of its kind to effectively assess CAR T-cell therapy as a second line of treatment in patients whose disease is progressing.” 

Dr. Dhakal presented the trial’s findings at the 2023 American Society for Clinical Oncology annual meeting and was co-first author of an article published in The New England Journal of Medicine. He is the local primary investigator for two additional trials testing cilta-cel for multiple myeloma — CARTITUDE-5 and CARTITUDE-6.   
 

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