Obe-cel improves EFS in advanced B-cell acute lymphoblastic leukemia
Key takeaways:
- 40% of responders remained in remission without subsequent stem cell transplantation or other therapy.
- Ongoing CAR T-cell persistence appeared associated with longer EFS.
Obecabtagene autoleucel conferred durable benefit to certain patients with relapsed or refractory B-cell acute lymphoblastic leukemia, according to results of the phase 1B/phase 2 FLEIX study presented at ASCO Annual Meeting.
More than 60% of patients remained alive at 1 year.
“Persistence of CAR T cells and B-cell aplasia both were associated with improved event-free survival,” Elias Jabbour, MD, professor of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release. “These outcomes demonstrate a potential of a long-term plateau in the survival curve, which supports this therapy being considered as a standard-of-care for adults with relapsed or refractory [B-cell ALL], who currently have limited treatment options.”
Background, methodology
Obecabtagene autoleucel (Autolus Therapeutics) — often called obe-cel — is a novel anti-CD19 autologous chimeric antigen receptor T-cell therapy designed to mitigate immunotoxicity and improve expansion or persistence.
The FELIX study assessed efficacy of obe-cel among 127 adults (median age, 47 years; range, 20-81; 51.9% male) with relapsed or refractory B-cell ALL.
Study participants had received a median two (range, 1-6) prior lines of therapy.
Patients received bridging therapy as appropriate underwent preconditioning lymphodepletion, followed by split-dose infusions of obe-cel on days 1 and day 10 as determined by pre-lymphodepletion leukemic burden. The target total dose was 410 x 106 CAR T cells.
At ASCO, researchers presented data on OS and EFS among all treated patients, as well as data about the impact of CAR T-cell persistency and consolidative stem cell transplantation for patients in remission.
Median follow-up was 21.5 months (range, 8.6-41.4).
Results, next steps
At data cut-off, 99 (78%) of infused patients achieved complete remission or complete remission with incomplete count recovery.
Forty responders (40%) remained in ongoing remission without subsequent stem cell therapy or other therapy.
Eighteen responders (18%) proceeded to consolidative stem cell transplantation while in remission. Ten of those 18 exhibited ongoing CAR T persistence prior to stem cell transplant.
Five responders (5%) started new anti-cancer therapy, and 36 (36%) developed disease relapse or died.
Researchers reported a 12-month EFS rate of 49.5% (95% CI, 39.6-58.6) and a 12-month OS rate of 61.1% (95% CI, 52-69).
Loss of CAR T-cell persistence correlated with poorer EFS compared with ongoing CAR T-cell persistence (HR = 2.7; 95% CI, 1.4-5.3). B-cell recovery correlated with poorer EFS compared with ongoing B-cell aplasia (HR = 1.7; 9% CI, 0.7-3.8).
Stem cell transplant consolidation during remission after obe-cel infusion did not correlate with improved OS or EFS.
References:
- Jabbour E, et al. Abstract 6504. Presented at: ASCO Annual Meeting 2014; May 30-June 4; Chicago.
- MD Anderson Cancer Center. ASCO: Novel CAR T therapy and shorter targeted therapy durations show promise for patients with leukemia (press release). Available at: https://www.mdanderson.org/newsroom/asco--novel-car-t-therapy-shorter-targeted-therapy-durations-show-promise-patients-leukemia.h00-159697545.html. Published May 31, 2024. Accessed July 17, 2024.
Collapse
Jabbour E, et al. Abstract 6504. Presented at: ASCO Annual Meeting; May 31-June 4, 2024; Chicago.