CAR-T Therapy Slows Multiple Myeloma in Patients Who Have Stopped Responding to Other Treatments

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MCW cancer researcher Binod Dhakal, MD, associate professor, Hematology and Medical Oncology, presented the first results from the Phase 3 CARTITUDE-4 study at the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting, the world’s largest cancer conference. He compared results of providing standard of care treatment in 419 patients with multiple myeloma (MM) who had 1-3 prior lines of therapy and were lenalidomide refractory, with results of cilta-cel–a CAR-T therapy, like ide-cel, that binds to B-cell maturation antigen (BCMA) on the surface of myeloma cells.

Results of this global study, published in the New England Journal of Medicine in June, showed that cilta-cel reduced the risk of MM progression or death by approximately 74%. “The marked difference between ide-cel and cilta-cel is cilta-cel’s ability to bind to two BCMA sites, as opposed to just one. This could make the difference for patients who require a second form of therapy,” said Dhakal, co-first author of the study.

CARTITUDE-4 is one of only two phase 3 clinical trials of CAR-T therapy for MM in early lines of therapy and is the only study so far to evaluate CAR-T therapy in patients after one prior line of therapy. Prognosis for patients with lenalidomide-refractory disease is generally worse than those with lenalidomide-sensitive disease or those who have never previously received lenalidomide (a prescription medicine extensively used as a frontline therapy in adults with MM), with median progression free survival as poor as 12 months.

However, the promising findings presented at ASCO show that in a heavily pretreated, relapsed/refractory population, median progression-free survival with cilta-cel is almost 3 years. The results make cilta-cel the first CAR-T therapy to achieve a significant response for specific subgroups of patients, including those with high-risk disease after the first relapse.

“Since lenalidomide is extensively used as a frontline therapy in myeloma patients, lenalidomide refractoriness early in patient disease course is becoming increasingly common. This rules out the use of lenalidomide-based regimens in subsequent lines. This study is the first of its kind to effectively assess the use of CAR-T therapy as a second line of treatment in patients with progressive disease,” said Dr. Dhakal.