Updated CARTITUDE-2 Data Support Earlier Cilta-Cel Use in Multiple Myeloma

Adam D. Cohen, MD, director of Myeloma Immunotherapy and professor of medicine at the Hospital of the University of Pennsylvania, reviewed updated findings from cohort A of the phase 2 CARTITUDE-2 trial (NCT04133636), which were presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹ The cohort evaluated ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with lenalidomide (Revlimid)-refractory multiple myeloma after 1 to 3 prior lines of therapy, a population similar to that of the phase 3 CARTITUDE-4 trial (NCT04181827), which supported approval of cilta-cel in earlier lines.²

With all patients now beyond 5 years of follow-up, 10 of 20 were alive and progression free after a single infusion without any further therapy. Cohen cautioned that the cohort is small and that long-term follow-up from CARTITUDE-4 is needed to confirm the finding. Matthew J. Frigault, MD, clinical director of the Cellular Immunotherapy Program at Mass General Brigham Cancer Institute, noted that about one-third of heavily pretreated patients in the phase 1b/2 CARTITUDE-1 trial (NCT03548207) were progression free at 5 years, suggesting that the long-term benefit may be greater when CAR T-cell therapy is given earlier.³

The experts then turned to late toxicities, including parkinsonism and enterocolitis. Cohen explained that these events may be less frequent in less heavily pretreated patients, and that effective bridging therapy to reduce disease burden before infusion has been associated with a lower risk of parkinsonism. When bridging has not adequately controlled the disease, his team may hold the CAR T-cell infusion and give additional therapy first.