|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy 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.
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.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
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.