The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of MPR‘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.


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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.

Read more of MPR’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.

Reference

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

This article originally appeared on Hematology Advisor