|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Hematology Advisor’s conference coverage.|
Anti-BCMA chimeric antigen receptor (CAR) T-cell (CAR-T) therapy idecabtagene vicleucel (ide-cel; bb2121) demonstrated promising efficacy among patients with relapsed/refractory multiple myeloma (RRMM), according to results from a phase 2 trial presented at the ASCO20 Virtual Scientific Program.
“Outcomes of patients with triple-exposed RRMM is poor, with infrequent deep and durable responses and a median survival of 3 to 4 months,” said Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute in New York City, who was lead author and presenter of the study.
This pivotal phase 2 KarMMa trial treated 128 patients with MM — who had received 3 or more prior regimens, including an immunomodulatory drug, proteosome inhibitor, and an anti-CD38 antibody and who were refractory to their last regimen — with ide-cel at 150 to 450 × 106 CAR T cells. All patients underwent lymphodepletion with cyclophosphamide and fludarabine. Ide-cel manufacturing had a 99% success rate, and median peak CAR-positive T-cell expansion was at 11 days.
The primary endpoint was objective response rate (ORR) and secondary endpoints included complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS).
At baseline, the median patient age was 61. Patients had received a median of 6 prior lines of therapy, and 84% of patients were triple-refractory and 26% were penta-refractory. A high tumor burden was present in 51% of patients, 35% had high-risk cytogenetics, and 39% had extramedullary disease.
The majority of patients (88%) had received bridging therapy, “suggesting an aggressive nature of the disease for the patients who were entered in the study,” Dr Munshi noted.
The ORR was 73% overall, including 50% in the 150 × 106 group, 69% in the 300 × 106 group, and 82% in the 450 × 106 group, during a median follow-up of 13.3 months. The CR/stringent CR was 33% overall, and 25%, 29%, and 39% among the 150, 300, and 450 × 106 dosage groups, respectively. Very good partial response (VGPR) occurred in 20% of patients, including 25%, 14%, and 26% in the different dose groups, respectively.
The median time to first response was 1 month and the median DOR was 10.7 months.
Overall, 39% of patients with at least a VGPR were negative for minimal residual disease, as well as 26% of patients who achieved at least a CR.
Overall, the median PFS was 8.8 months, which included 2.8 months in the 150 × 106 group, 5.8 months in the 300 × 106 group, and 12.1 months in the 450 × 106 group. The median OS was 19.4 months.
The most common any-grade toxicities were cytopenias (97%) and cytokine release syndrome (CRS; 84%). Most patients developed grade 1 to 2 CRS, but 5 patients developed grade 3, 1 patient grade 4, and 1 patient grade 5. Neurotoxicity occurred in 18% of patients; no patients developed grade 4 or 5 neurotoxicity.
The median time to CAR T-cell expansion was 11 days, and expansion was greater among patients who responded to the treatment. CAR T cells were detected in 59% of patients at 6 months and 36% of patients at 12 months.
There were 5 deaths within 8 weeks following ide-cel infusion: 2 deaths were following progression of disease, while the other 3 deaths were from CRS, aspergillus pneumonia, and gastrointestinal hemorrhage. Another death due to adverse events, which happened within 6 months of infusion in the absence of myeloma disease progression, was said to be due to cytomegalovirus pneumonia.
Dr Munshi concluded that “ide-cel provides an attractive option for treatment of triple class-exposed MM.”
Disclosure: This study was supported by bluebird bio and Bristol-Myers Squibb. For a full list of disclosures, please refer to the abstract.
Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 8503.
This article originally appeared on Cancer Therapy Advisor