Dr. Dhakal on the Onset of CAR T-Cell Therapy–Induced CRS in Multiple Myeloma

Binod Dhakal, MD, associate professor of medicine, Division of Hematology, Medical College of Wisconsin, discusses the differences in onset of cytokine release syndrome (CRS) with CAR T-cell therapies in multiple myeloma.

CRS and neurotoxicity remain the main adverse effects of concern with CAR T-cell therapy across the hematologic cancer space, says Dhakal. In relapsed/refractory multiple myeloma, 3 CAR T-cell products are moving through the pipeline toward FDA approval: idecabtagene vicleucel (ide-cel; bb2121), orvacabtagene autoleucel (orva-cel; JCARH125), and ciltacabtagene autoleucel (cilta-cel; JNJ-68284528).

Although cross-trial comparisons are discouraged, the median onset of CRS appears to differ between the approved products. CRS onset typically occurs 1 to 2 days after infusion with ide-cel and orva-cel, respectively. However, the median onset of CRS was 7 days with cilta-cel. Currently, the field is unclear about why the onset of CRS is delayed with cilta-cel, but experts hypothesize that it could be due to the dose of the infused T cells. Ide-cel and orva-cel are dosed much higher compared with cilta-cel, suggesting that CAR T-cell expansion occurs later with cilta-cel, concludes Dhakal.