Idecabtagene vicleucel (ide-cel) improves outcomes in patients with triple-class-exposed multiple myeloma (MM), when compared with standard care, according to research published in The New England Journal of Medicine.
Id-cel, a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy, improved response rates and prolonged progression-free survival (PFS) when compared with 1 of 5 standard treatment regimens.
These findings come from the phase 3 KarMMa-3 trial (ClinicalTrials.gov Identifier: NCT03651128), which enrolled 386 patients with relapsed/refractory MM. They were randomly assigned to receive ide-cel (n=254) or standard care (n=132).
In the overall cohort, patients had received a median of 3 prior treatment regimens (range, 2-4). Most patients had disease that was refractory to immunomodulatory agents (90%), proteasome inhibitors (74%), and daratumumab (95%). The proportion of patients with triple-class-refractory disease was 66% in the ide-cel arm and 67% in the standard care arm.
Patients in the ide-cel arm underwent lymphodepletion with fludarabine and cyclophosphamide before receiving a single infusion of ide-cel (target dose range, 150×106 to 450×106 CAR-T cells). The standard care options included daratumumab plus pomalidomide and dexamethasone, daratumumab plus bortezomib and dexamethasone, ixazomib plus lenalidomide and dexamethasone, carfilzomib and dexamethasone, or elotuzumab plus pomalidomide and dexamethasone. Patients in the standard care arm received treatment until disease progression, unacceptable toxicity, or trial withdrawal.
The overall response rate was 71% in the ide-cel arm and 42% in the standard care arm (odds ratio, 3.47; 95% CI, 2.24-5.39; P <.001). The complete response rate was 39% and 5%, respectively.
At a median follow-up of 18.6 months, the median PFS was 13.3 months in the ide-cel arm and 4.4 months in the standard care arm (hazard ratio, 0.49; 95% CI, 0.38-0.65; P <.001). The 12-month PFS rate was 55% and 30%, respectively.
The PFS benefit with ide-cel was seen regardless of age, race, number of previous treatment regimens, or the presence or absence of high-risk cytogenetic abnormalities, extramedullary disease, high tumor burden, or triple-class-refractory status.
The rate of grade 3-4 adverse events was 93% in the ide-cel arm and 75% in the standard care arm. The most common hematologic adverse events were neutropenia (78% in the ide-cel arm and 44% in the standard arm), anemia (66% and 36%, respectively), and thrombocytopenia (54% and 29%, respectively).
Fatal treatment-related adverse events occurred in 3% of patients in the ide-cel arm and 1% of patients in the standard care arm.
Cytokine release syndrome (CRS) of any grade occurred in 88% of patients who received ide-cel, and grade 3 or higher CRS occurred in 5%. Neurotoxicity of any grade occurred in 15% of patients in the ide-cel group, and grade 3 or higher neurotoxicity occurred in 3%.
“These findings provide potential support for the use of ide-cel in patients with triple-class-exposed, relapsed and refractory multiple myeloma, a population with poor survival outcomes,” the researchers concluded.
Disclosures: This research was supported by 2seventy bio and Celgene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed or refractory multiple myeloma. N Engl J Med. Published online February 10, 2023. doi:10.1056/NEJMoa2213614
This article originally appeared on Cancer Therapy Advisor