Idecabtagene vicleucel (ide-cel) reduced the risk of disease progression or death by 51% in patients with triple-class–exposed relapsed or refractory multiple myeloma (R/R MM).
Phase 3 data from the KarMMa-3 study show chimeric antigen receptor (CAR) T-cell therapy significantly prolongs progression-free survival (PFS) compared with standard treatment in harder-to-treat patients with relapsed or refractory (R/R) multiple myeloma.
Findings were published in a recent issue of The New England Journal of Medicine.
Compared with a standard treatment regimen, idecabtagene vicleucel (ide-cel) reduced the risk of disease progression or death by 51% in patients with triple-class–exposed R/R disease.
Ide-cel was approved in 2021 for adults with R/R multiple myeloma after 4 or more prior lines of therapy. Data from this recent study showed that the CAR T-cell therapy improved outcomes in these harder-to-treat patients who had previously received 2 to 4 regimens. Improved outcomes were seen regardless of the number of previous regimens, which may have important implications for the patient population with historically poor survival outcomes.
“The treatment landscape for relapsed and refractory multiple myeloma has evolved with the use of immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies in doublet, triplet, or quadruplet combinations in the context of first-line therapy and treatment for relapsed disease,” wrote the researchers. “Although these combinations have helped control disease, relapse is common. Consequently, patients have triple-class exposure earlier in their treatment course and have limited treatment options,” underscoring the lack of standard of care for these patients.
The international study included nearly 400 patients randomized 2:1 to receive ide-cel or a standard regimen, which could have included daratumumab, pomalidomide, and dexamethasone; carfilzomib and dexamethasone; elotuzumab, pomalidomide, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; or daratumumab, bortezomib, and dexamethasone.
At a median of 18.6 months, median PFS was 13.3 months for patients receiving ide-cel compared with 4.4 months for patients receiving a standard regimen. The researchers noted that the median PFS among patients receiving a standard regimen was consistent with real-world data in later lines of treatment.
At 12 months, PFS was 55% for ide-cel and 30% for standard regimens. Improvements associated with the CAR T-cell treatment were seen in prespecified subgroups, which included age, race, and a number of others. Data on overall survival were immature at the time of publication.
Response rates were also higher for the CAR T-cell treatment, with a 71% response rate among the 254 patients receiving ide-cel vs 42% among the 132 patients receiving a standard regimen.
“The efficacy of ide-cel therapy was striking, considering that 65% of patients had triple-class–refractory disease in a short time from diagnosis (4 years), with disease relapse at a median of approximately 7 months during the last previous regimen,” commented the researchers.
Safety findings of the CAR T-cell treatment were consistent with previous data. Cytokine release syndrome was reported in 88% of patients receiving ide-cel, 5% of which experienced a grade 3 or higher adverse event. Neurotoxicity occurred in 15%, with 3% being grade 3 or higher. Overall, grade 3 or 4 adverse events occurred in 93% of patients receiving ide-cel and in 75% of patients receiving a standard regimen.
Rodriguez-Otero P, Ailwadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. Published online February 10, 2023. doi:10.1056/NEJMoa2213614