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Medically reviewed by Dr. Shani S. Saks, D.O. on August 2, 2023

In a phase 3 trial, ciltacabtagene autoleucel caused a significantly lower risk of disease progression or death than standard care in lenalidomide-refractory multiple myeloma patients.

The frequency of lenalidomide resistance early in multiple myeloma (MM) treatment is increasing, leading to a need for new effective therapies for lenalidomide-refractory disease. Research on ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy, demonstrated effectiveness in heavily pretreated patients with relapsed or refractory MM. A phase III study in The New England Journal of Medicine investigated cilta-cel in earlier treatment lines in lenalidomide-refractory MM patients.

Study Population

Of 419 patients, 208 were randomized to the cilta-cel group and 211 to the standard care group. A total of 176 patients in the cilta-cel group and 208 patients in the standard care groups received the assigned therapy, with 131 of those in the standard care group discontinuing standard-care treatment, primarily due to disease progression. Baseline patient characteristics were comparable between the groups.   

Significantly Lower Disease Progression Risk With Cilta-Cel

Cilta-cel resulted in a significantly lower risk of disease progression or death compared to standard care (P<0.001). At a median follow-up of 15.9 months, the median duration of progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group. In the intention-to-treat population at 12 months, progression-free survival was 75.9% in the cilta-cel group and 48.6% in the standard care group. Similar effects were seen in all patient subgroups. More patients in the cilta-cel group had a complete response or better than in the standard-care group (P<0.001). The overall response (partial response or better) was 84.6% and 67.3%, respectively (P<0.001). Among those who had a response, 84.7% in the cilta-cel and 63% in the standard-care group continued to have a response for at least 12 months.

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Minimal Residual Disease Negativity Rates

Minimal residual disease negativity at any time during the trial occurred in 60.6% and 15.6% of patients in the cilta-cel and standard-care groups, respectively. In those with evaluable samples, minimal residual disease negativity occurred in 87.5% and 32.7%, respectively.     

Adverse Event Severity and Occurrence Rates

Grade 3 or 4 adverse events occurred in 96.6% of the cilta-cel group and 94.2% of the standard-care group patients. The most common grade 3 or 4 adverse events were hematologic. Serious adverse events occurred in 44.2% of patients in the cilta-cel group and 38.9% in the standard-care group.

Mortality Incidents Across Study Groups

Death from any cause was reported in 39 patients in the cilta-cel group and 46 patients in the standard-care group, of whom 15 and 11 in each group were deemed unrelated to trial treatment.

Adverse Events in Cilta-Cel Recipients

Among the 176 patients who received cilta-cel, 134 developed cytokine release syndrome (grade 3 in two, grade 1 or 2 in the rest); 8 had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2); 1 had movement and neurocognitive symptoms (grade 1); 16 had cranial nerve palsy (grade 3 in two, grade 1 or 2 in the rest); and 5 had CAR-T-related peripheral neuropathy.


Miguel, J. F. S., Dhakal, B., Yong, K., Spencer, A., Anguille, S., Mateos, M., De Larrea, C. F., Martinez-Lopez, J., Moreau, P., Touzeau, C., Leleu, X., Avivi, I., Cavo, M., Ishida, T., Kim, S. J., Roeloffzen, W., Van De Donk, N. W., Dytfeld, D., Sidana, S., . . . Einsele, H. (2023). Cilta-Cel or standard care in Lenalidomide-Refractory multiple myeloma. The New England Journal of Medicine, 389(4), 335–347. https://doi.org/10.1056/nejmoa2303379