|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Hematology Advisor‘s conference coverage.|
Idecabtagene vicleucel (ide-cel) has a favorable clinical benefit-risk profile across a range of target doses among heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), according to research presented at the 2021 American Society of Clinical Oncology Annual Meeting.
Investigators reported updated results from the KarMMa trial (ClinicalTrials.gov Identifier: NCT03361748) with ide-cel, a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy. Eligible participants had 3 or more prior regimens (including an immunomodulatory agent, proteasome inhibitor, and CD38 mAb) and were refractory to their last regimen according to International Myeloma Working Group criteria.
Patients received 150 × 106 CAR+ T cells (n=4), 300 × 106 CAR+ T cells (n=70), or 450 × 106 CAR+ T cells (n=54) after 3 days of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2). Overall response rate (ORR) was the primary endpoint, and complete response (CR) rate was the key secondary endpoint. Other secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
A total of 140 patients were enrolled, of whom 128 received ide-cel. Participants’ median age was 61 years and they had a median of 6 previous regimens (range, 3-16); 84% were triple-class refractory, and 26% were penta-class refractory (lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab). In addition, 88% of patients had prior bridging therapy.
The median follow-up was 15.4 months at the data cutoff on April 7, 2020. The ORR was 73%, and the median PFS was 8.8 months, with both values increasing at a higher dose.
At the highest target dose of 450 × 106 CAR+ T cells, patients’ ORR was 81%, the CR rate was 39%, and the median PFS increased to 12.2 months with a longer follow-up. At a dose of 300 × 106 CAR+ T cells, the ORR was 69% and the CR was 29%. At a dose of 150 × 106 CAR+ T cells, the ORR was 50% and the CR was 25%.
Responses also were found in subsets of patients who were difficult to treat, such as those who had extramedullary disease (ORR, 70%), high tumor burden (71%), and R-ISS stage III disease (48%). OS continued to mature, and the median was not achieved, noted the study authors. The 15-month event-free rate for OS was 71%.
The most common toxicities of any grade were cytopenias (97%) and cytokine release syndrome (CRS, 84%). CRS was primarily grade 1/2; 5 patients (4%) had grade 3, 1 had grade 4 (at 300 × 106), and 1 had grade 5 (at 300 × 106). Neurotoxicity was reported in 23 participants (18%); 4 patients (3%) had grade 3 and no patients had worse than grade 4. Tocilizumab was used in 67 patients with CRS and in 3 patients with neurotoxicity.
“Updated results from the KarMMa trial continue to demonstrate deep, durable responses with ide-cel in heavily pretreated patients with RRMM,” the researchers concluded.
Disclosure: This clinical trial was supported by Celgene, a Bristol-Myers Squibb Company, and bluebird bio. Please see the original reference for a full list of authors’ disclosures.
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Anderson LD Jr, Munshi NC, Shah N, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: updated KarMMa results. J Clin Oncol. 2021;39:(suppl 15; abstr 8016). doi:10.1200/JCO.2021.39.15_suppl.8016