Studies Offer Promising Data on CAR T-Cell Therapy in B-ALL, Multiple Myeloma

Abstracted presented recently at the American Society of Clinical Oncology annual meeting offered promising data for 2 chimeric antigen receptor (CAR) T-cell therapies, one in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and one in R/R multiple myeloma.

Approved in 2020 for patients with R/R mantle cell lymphoma, brexucabtagene autoleucel, sold as Tecartus, is also now being studied in patients with R/R B-ALL, with the recent conference data suggesting the treatment offers a clinical benefit in these patients.1

After a median follow-up of 16.4 months, median overall survival (OS) was not reached among the patients who responded to Tecartus. These patients had a mean relapse-free survival of 14.2 months.

Across the 55 patients receiving Tecartus, 71% achieved a complete response (CR) or CR with incomplete hematologic recovery (CRi), 97% of which were negative for minimal residual disease.

The patients included in the study were heavily pretreated, with 45% having previously received blinatumomab, 22% having previously received inotuzumab ozogamicin, and 42% having previously received allogeneic stem cell transplant.

Ninety-five percent of patients experienced grade ≥3 adverse events. The most common adverse events included anemia (49%) and neutropenia (49%). Grade ≥3 cytokine release syndrome and neurologic events—commonly reported among patients treated with CAR T-cell therapies—were reported in 24% and 25% of patients, respectively, with a median time to onset of 5 days and 9 days, respectively. According to the researchers, they were generally reversible.

Novel therapy in multiple myeloma. During the conference, researchers also offered data from 2 different time points of an ongoing phase 1 study of CART-ddBCMA in R/R multiple myeloma. CART-ddBCMA is an autologous CAR-T cell therapy that uses a novel BCMA-targeting binding domain and is designed to reduce the risk of immunogenicity and have high stability.

As of January 29, 2021, there were 9 evaluable patients, all of which responded to CART-ddBCMA. Four patients achieved a stringent CR (sCR), one achieved a very good partial response (VGPR), and 4 achieved a PR. One of the patients who achieved a PR had disease relapse and was retreated, while the rest of the patients had ongoing responses.

Similar findings were seen as of April 2021,3 with all 12 evaluable patients achieving a response, including 5 sCR, 1 CR, 3 VGPR, and 3 PR. Eleven of these responses are ongoing and data from the study suggests that responses deepen over time. According to the researchers, despite previously progressing on BCMA-targeted therapy, a patient still achieved a VGPR.

All 12 of these patients have received at least 3 prior lines of therapy, and 10 were penta-refractory.

References

1. Shah B, Ghobadi A, Oluwole O, et al. Phase 2 results of the ZUMA-3 study evaluating KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). J Clin Oncol. 2021; 39(Suppl 15): abstr 7002. doi: 10.1200/JCO.2021.39.15_suppl.7002

2. Frigault M. Phase 1 Study of CART-ddBCMA, a CAR-T therapy utilizing a novel synthetic binding domain, for the treatment of subjects with relapsed and refractory multiple myeloma. J Clin Oncol. 2021; 39(Suppl 15): abstr 8015. doi: 10.1200/JCO.2021.39.15_suppl.8015

3. Arcellx Announces Presentation of Positive Clinical Results from Ongoing Phase 1 Study of CART-ddBCMA at the 2021 ASCO Annual Meeting. News release. June 4, 2021. Accessed July 2, 2021. https://arcellx.com/arcellx-announces-presentation-of-positive-clinical-results-from-ongoing-phase-1-study-of-cart-ddbcma-at-the-2021-asco-annual-meeting/