Cytokine release syndrome (CRS) after treatment with ciltacabtagene autoleucel (cilta-cel) was found to be manageable and low grade in most patients with relapsed or refractory multiple myeloma (RRMM), according to results from the phase 1b/2 CARTITUDE study.
A known side effect of chimeric antigen receptor (CAR) T-cell therapy, CRS can be mild to life-threatening and requires careful management. Cilta-cel is a CAR-T therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, and has been investigated as a potential therapy in patients with RRMM.
The phase 1b/2 CARTITUDE-1 study (NCT03548207) included adult patients with RRMM and measureable disease who received at least 3 prior treatment regimens or were double refractory to treatment with a proteasome inhibitor and immunomodulatory drug, as well as those who received an anti-CD38 antibody.
In the current analysis, the researchers assessed CRS and cytokine profiles to assess the incidence and severity of CRS in patients with RRMM. Serum samples for cytokine profiling were collected prior to the patients receiving lymphodepletion and cilta-cel infusion. Further, serum samples were collected 2 hours post-infusion on day 1, at regular timepoints until day 100, and as needed, if CRS was suspected or reported.
A total of 97 patients received cilta-cel in CARTITUDE-1; CRS was reported in 92 (94.8%) patients of whom 48 (49.5%) had grade 1 CRS, 38 (39.2%) had grade 2, 4 (4.1%) had grade 3, and 1 had grade 5 (1.0%). The median time to onset of CRS from the time of cilta-cel infusion was 7.0 days (range, 1-12 days) and median duration of CRS was 4.0 days (range, 1-27), with 1 patient experiencing CRS after 97 days.
Supportive measures for managing CRS were administered to 87 (89.7%) patients, which most commonly involved treatment with tocilizumab (69.1%), acetaminophen (68.0%), corticosteroids (20.6%), and anakinra (18.6%). The CRS resolved in 91 of the 92 patients (98.9%). However, the patient with grade 5 CRS/hemophagocytic lymphohistiocytosis died on day 99 of the study after sequelae of grade 4 CRS.
Overall, the researchers determined that CRS after treatment with cilta-cel was low grade and manageable in most patients with RRMM. The low rate of grade 3 or higher CRS, median duration of 4 days, and onset of 7 days suggested that outpatient administration of cilta-cel may be feasible.
The outpatient administration is being investigated in the phase 2 CARTITUDE-2 study (NCT04133636).
Lin Y, Martin T, Cohen AD, et al. Cytokine release syndrome in patients with relapsed/refractory multiple myeloma treated with ciltacabtagene autoleucel in the phase 1b/2 CARTITUDE-1 study. Transplant Cell Ther. 2021;3S(suppl):S43-S44. doi:10.1016/S2666-6367(21)00071-3