Cilta-Cel Shows Long-Term Efficacy in Patients With Relapsed/Refractory Multiple Myeloma


A single infusion of ciltacabtagene autoleucel produced a lower risk of death and disease progression, as well as deep and durable responses, in heavily pretreated patients with relapsed/refractory multiple myeloma.

A single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti) resulted in a lower risk of death or disease progression in patients with lenalidomide-refractory multiple myeloma compared to standard, highly effective treatments, according to a new study published in The New England Journal of Medicine.

Microscopic image of bone marrow. Plasma cell dyscrasia or Multiple myeloma. A type of bone marrow cancer of malignant plasma cells. Credit: MdBabul -

Credit: MdBabul -

“These results indicate that cilta-cel is an effective treatment for patients with lenalidomide- refractory disease as early as the first relapse,” the researchers said.

The open-label study randomized 419 participants who had received 1 to 3 previous treatments, with 208 administered ciltacabtagene autoleucel and 211 administered the physician’s choice of effective standard care. The trial’s primary outcome was progression-free survival (PFS).

The results showed that at a median follow-up of 15.9 months (range, 0.1 to 27.3), median PFS was not reached in the cohort administered ciltacabtagene autoleucel compared with 11.8 months in the standard-care cohort (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). PFS was 75.9% (95% CI, 69.4 to 81.1) after 12 months in the study drug cohort compared to 48.6% (95% CI, 41.5 to 55.3) in the standard care cohort.

Further, the patients administered ciltacabtagene autoleucel exhibited deep and durable response rates to the treatment, as well as high response rates compared to the standard care group.

In analyzing overall response rates (ORR) to the study drug, 84.6% of patients in the ciltacabtagene autoleucel group responded to treatment compared to 67.3% of those given standard care. The rate of complete response was 73.1% in the ciltacabtagene autoleucel cohort compared to 21.8% with standard care. Additionally, the absence of minimum residual disease was 60.6% in the ciltacabtagene autoleucel group in contrast with 15.6% of standard care patients.

These effects were similar across all patient subgroups, including among those with high-risk disease factors such as soft-tissue plasmacytomas, triple-class refractory disease, and patients with high-risk cytogenetic features.

According to the researchers, most patients experienced grade 3 or 4 adverse effects (AEs) during the treatment. Of the 176 patients in the as-treated population who were given ciltacabtagene autoleucel, 76.1% had cytokine release syndrome, 4.5% developed immune effector cell-associated neurotoxicity syndrome, 9.1% had cranial nerve palsy, and 2.8% had chimeric antigen receptor T-related peripheral neuropathy.

However, these AEs were more manageable and appeared at a lower rate than in prior studies, which the researchers suggest is related to the administration of ciltacabtagene autoleucel early on in disease progression resulting in a smaller AE profile.

Many patients with multiple myeloma will relapse after their first treatment, with worsening outcomes as lines of therapy continue. Use of lenalidomide has become widespread in early-line treatment of both newly diagnosed and relapsed patients, as well as those with refractory multiple myeloma. This common usage has resulted in lenalidomide resistance and high treatment attrition in a growing number of patients, necessitating the need for a new drug that could be highly effective against multiple myeloma, according to the investigators.

In early clinical trials in those with relapsed or refractory multiple myeloma—a phase with patients who had at least 3 lines of treatment and another in smaller groups who were in earlier disease stages—ciltacabtagene autoleucel was shown to be effective and resulted in strong responses. The goal of the researchers was to determine whether the robust efficacy from prior trials would carry over to patients with lenalidomide-refractory multiple myeloma.

“In this trial, we found a favorable risk–benefit profile for a single infusion of cilta-cel as compared with standard care,” the researchers wrote.

They noted that the translation of these clinical results into real-world solutions will be influenced by a myriad of factors, including patient heterogeneity, the selection and fitness of patients, preferences of the physician and patient, and where the treatment takes place.

Furthermore, the absence of 2 highly effective triplet regimens being approved for use at the time of the study could be a potential limitation of the trial design; yet, as the researchers note, the population of those trials differed from the population used for this current study, and that “lenalidomide resistance was not a criterion for inclusion.”

Despite these possible limitations, the researchers are keen to point out the possibilities in effectively treating multiple myeloma with ciltacabtagene autoleucel in the future.

“The strong progression-free survival benefit and rapid and deep response with cilta-cel highlight the potential for cilta-cel to become a therapeutic option for patients with myeloma after the first relapse,” the study authors concluded.


San-Miguel, J. et al. (2023) CILTA-CEL or standard care in lenalidomide-refractory multiple myeloma. The New England Journal of Medicine. Available at Accessed June 13, 2023.

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