The BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (previously known as bb2121) induced responses in nearly three-quarters of patients with relapsed/refractory multiple myeloma, according to results from the phase II KarMMa trial, which were presented by Jesus San-Miguel, MD, PhD, as part of EHA25 Virtual, the 25th European Hematology Association Annual Congress.
KarMMa enrolled 140 patients with triple-class–exposed myeloma, whose disease had progressed after receiving immunomodulatory agents, proteasome inhibitors, and CD38 monoclonal antibodies and was refractory to the last regimen.
Participants underwent lymphodepletion with cyclophosphamide 300 mg/m2 plus fludarabine 30 mg/m2, then received an infusion of idecabtagene vicleucel at a target dose of 150-450×106 cells/kg.
A total of 128 patients received idecabtagene vicleucel, and the manufacturing success rate was 99%. Patients’ median age was 61 years and the median number of prior regimens was 6. Most enrolled patients (84%) had disease that was triple-refractory and 26% had disease that was penta-refractory.
Over a median follow-up of 13 months, the overall response rate (ORR) was 73% and patients had a median progression-free survival of 8.8 months. Across all subgroups (including older patients and those with high-risk disease), the ORR was more than 50%, Dr. San-Miguel noted, and one-third achieved complete response (CR).
The authors added that responses occurred rapidly, at a median of 1 month following infusion, and response rates were higher in those who received a higher dose of idecabtagene vicleucel (TABLE). Efficacy was highest at the target dose of 450×106 cells/kg, Dr. San-Miguel reported, with an ORR of 82%. Some responses to idecabtagene vicleucel were deep, with 26% of patients becoming negative for measurable residual disease. The median duration of response was 10.7 months among all responders, and 19 months among those who achieved a CR or stringent CR.
The safety profile observed in this trial was similar to previous reports of idecabtagene vicleucel, the investigators wrote. The most common any-grade toxicities were cytopenias (97%) and cytokine release syndrome (CRS; 84%). CRS events were mainly grade 1 or 2 in severity, with 5 patients experiencing a grade 3 event, 1 grade 4, and 1 grade 5. CRS frequency increased with dose, the investigators noted, and events were managed with tocilizumab or corticosteroids.
Twenty-three patients (18%) developed neurotoxicity, and again, this was mostly low-grade, except for 4 who experienced grade 3 neurotoxicity.
Grade ≥3 hematologic adverse events (AEs) were common (89%), but incidence of cytopenias was not dose related.
Five patients died within 8 weeks of idecabtagene vicleucel infusion; 2 deaths occurred following myeloma progression and 3 were related to AEs (CRS, aspergillus pneumonia, and hemorrhage).
Together, these results support an encouraging benefit-risk profile for idecabtagene vicleucel across the target dose ranges, and the CAR T-cell therapy provides “an attractive option for treatment of triple-class exposed relapsed/refractory myeloma,” Dr. San-Miguel concluded.
Study authors report relationships with Celgene, which sponsored this trial.