Idecabtagene vicleucel led to “deeper and more durable responses” than standard regimens in patients with triple class–exposed relapsed/refractory multiple myeloma, according to results from the phase III KarMMa-3 trial.
Paula Rodríguez-Otero, MD, PhD, of the Clínica Universidad de Navarra in Pamplona, Spain, and colleagues conducted the research and presented results from KarMMa-3 during the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR T-cell Meeting.
They conducted the research because survival outcomes are poor in patients with triple class–exposed relapsed/refractory multiple myeloma, and treatment options are limited as patients become triple class–exposed in earlier lines of therapy.
“In the absence of an established standard of care for [triple class–exposed relapsed/refractory multiple myeloma], therapies with new mechanisms of action are needed,” Dr. Rodríguez-Otero and colleagues wrote, noting that idecabtagene vicleucel, a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy has “demonstrated deep, durable responses” in this population.
KarMMa-3 Design and Methods
The international, open-label phase III KarMMa-3 trial enrolled 386 patients with relapsed or refractory multiple myeloma who received two to four prior regimens, including an immunomodulatory agent, proteasome inhibitor, and daratumumab, and were refractory to the last regimen.
Dr. Rodríguez-Otero and colleagues randomized patients 2:1 to receive idecabtagene vicleucel (n=254) or a standard regimen selected by the investigator based on prior regimens (n=132). Of the 254 patients randomized to the idecabtagene vicleucel group, 225 underwent treatment, while 126 of the 132 patients randomized to the standard regimen underwent treatment. Baseline characteristics such as median age, median time since diagnosis, median number of prior therapies, high-risk cytogenetics, triple-class refractoriness, and daratumumab refractoriness “were generally balanced between arms,” the study’s investigators said.
Patients underwent lymphodepletion with fludarabine and cyclophosphamide and optional bridging therapy before receiving an idecabtagene vicleucel infusion. The target dose was 150 to 450 × 106 CAR+ T cells (median dose, 445 × 106 CAR+ T cells). Patients who received standard regimens continued therapy until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was progression-free survival (PFS) as assessed by an independent response committee. The median follow-up from randomization to data cutoff was 18.6 months.
KarMMa-3 Efficacy and Safety Results
Patients who received idecabtagene vicleucel had a median PFS of 13.3 months, a significant improvement over the median PFS of 4.4 months in patients who received standard regimens (P<.0001). The overall response rate (ORR) was 71% in patients receiving idecabtagene vicleucel, while it was 42% in patients receiving standard regimens (P<0.0001). Patients receiving idecabtagene vicleucel also had “deeper, more durable responses” than those receiving standard regimens, according to the study’s authors.
“[The] PFS and ORR benefit of [idecabtagene vicleucel] was consistent across subgroups including patients with high-risk features,” Dr. Rodríguez-Otero and colleagues wrote, noting that overall survival “was immature at data cutoff.”
Grade 3 to grade 4 adverse events occurred in 93% of patients who received idecabtagene vicleucel and in 75% of those who received a standard regimen. Grade 5 adverse events occurred in 14% of patients who received idecabtagene vicleucel and in 6% of those who received a standard regimen, while grade 5 treatment-related adverse events occurred in 3% and 1%, respectively. Grade 3 to grade 4 infections occurred in 24% of patients receiving idecabtagene vicleucel and in 18% of those receiving a standard regimen.
Nearly all patients (88%) receiving idecabtagene vicleucel experienced cytokine release syndrome of any grade. A grade 3 or grade 4 cytokine release event occurred in 4%, and a grade 5 event occurred in 1%. Investigator-identified neurotoxicity occurred in 15% of patients, with 3% experiencing a grade 3 or grade 4 neurotoxicity event.
“[Idecabtagene vicleucel] treatment resulted in a significant improvement in PFS and ORR, with deeper and more durable responses than standard regimens. [Idecabtagene vicleucel’s] benefit was consistent across difficult-to-treat subgroups,” Dr. Rodríguez-Otero and colleagues concluded. “The toxicity profile of [idecabtagene vicleucel] was consistent with previous studies. These results support use of [idecabtagene vicleucel] in [triple class–exposed relapsed/refractory multiple myeloma], a population with poor survival outcomes.”
Pictured at top is Paula Rodriguez-Otero, MD, PhD, of the Clínica Universidad de Navarra in Pamplona, Spain.
This research was supported by 2seventy bio (formerly bluebird bio) and Celgene, a Bristol Myers Squibb company.
Rodriguez Otero P, Ailawadhi S, Arnulf B, et al. Idecabtagene vicleucel (ide-cel; bb2121) versus standard regimens in triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): phase 3 randomized controlled trial (RCT) KarMMa-3. Presented at the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR-T cell Meeting; February 9-11, 2023; Rotterdam, Netherlands.