Obe-Cel Achieves High Response Rates, Durable Outcomes in r/r B-Cell Acute Lymphoblastic Leukemia

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Obecabtagene autoleucel (obe-cel; Autolus Therapeutics)—a CD19 chimeric antigen receptor (CAR) T-cell therapy—produced high response rates and durable outcomes with limited toxicity in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to data from the Phase Ib-II FELIX trial (NCT04404660) published by The New England Journal of Medicine.^1-3 Based on results from the trial, the FDA approved obe-cel under the brand name Aucatzyl for this indication in November 2024.⁴

“With its low rates of serious side effects coupled with compelling long-term survival data and durable responses, obe-cel offers real hope for adult lymphoblastic leukemia patients,” FELIX trial lead investigator Claire Roddie, MD, PhD, FRCPath, associate professor of Haematology at the University College London Cancer Institute, said in a press release. “Obe-cel’s durable responses were particularly observed in patients with low-intermediate bone marrow burden, including patients who did not receive consolidative allo-stem cell transplant and there could be an opportunity to use obe-cel as earlier-line consolidation.”³

The study authors noted that CAR T-cell therapies have previously been found to produce sustained responses in relapsed or refractory B-cell cancers, such as B-cell acute ALL. Obe-cel differs from CAR T-cell therapies tisa-cel and brexu-cel in that those treatments both use the same high-affinity single-chain variable fragment (scFv) to identify CD19, whereas obe-cel uses a different scFv with intermediate affinity because of a rapid binding off-rate, according to the investigators. They hypothesize that this may lower the toxic effects of CAR T-cell treatment and improve engraftment and persistence.¹

“Obe-cel was subsequently tested in the phase 1 ALLCAR19 study involving adults 18 years of age or older with relapsed or refractory B-cell ALL,” the study authors wrote. “Given the increased susceptibility of adults with B-cell ALL to immune-related toxic effects, a bone marrow burden–guided split-dose regimen was used. Obe-cel showed high efficacy, with an incidence of measurable residual disease (MRD)–negative remission of 85% and a low incidence of grade 3 or higher cytokine release syndrome (0%) and immune effector cell–associated neurotoxicity syndrome (ICANS; 15%); a total of 36% of the patients were in ongoing remission at a median follow-up of 43 months.”¹

The open-label, multi-center, single arm FELIX trial evaluated obe-cel in patients aged 18 years and above with relapsed or refractory B-cell ALL. The trial’s main cohort, cohort 2A, enrolled patients with morphologic disease, whereas patients enrolled in cohort 2B had measurable residual disease. The primary endpoint was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A, with secondary endpoints that included event-free survival (EFS), overall survival (OS), and safety.

Among 153 patients enrolled in the trial, 83.0% were administered at least one infusion of obe-cel and were deemed evaluable. At a median follow-up of 20.3 months, among 94 patients in cohort 2A, overall remission was observed in 77% (95% confidence interval [CI], 67 to 85), complete remission was observed in 55% (95% CI, 45 to 66), and complete remission with incomplete hematologic recovery was observed in 21% (95% CI, 14 to 31).

At a median follow-up of 21.5 months, among 127 patients administered at least one obe-cel infusion, median EFS was 11.9 months (95% CI, 8.0 to 22.1) and the estimated six- and 12-month EFS rates were 65.4% and 49.5%, respectively; median OS was 15.6 months (95% CI, 12.9 to not evaluable), with estimated six- and 12-month OS rates of 80.3% and 61.1%, respectively. In terms of safety, grade 3 or higher cytokine release syndrome was observed in 2.4% of patients, and grade 3 or higher immune effector cell–associated neurotoxicity syndrome was observed in 7.1% of patients.

“In the FELIX study, obe-cel resulted in a high incidence of response among adults with relapsed or refractory B-cell ALL, with toxic effects mostly limited to patients with a high bone marrow burden,” the study authors concluded. “Furthermore, obe-cel was associated with durable responses, particularly in patients with a low-to-intermediate bone marrow burden, including patients who did not receive consolidative allogeneic stem-cell transplantation.”¹

References

1. Roddie C., et al. Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia. N Engl J Med 2024; DOI: 10.1056/NEJMoa2406526.

2. A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL). ClinicalTrials.gov. September 3, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT04404660

3. Autolus Therapeutics Announces Publication of Data from the FELIX study of obe-cel in r/r Adult B-ALL Patients in The New England Journal of Medicine. News release. Autolus Therapeutics. Published December 2, 2024. Accessed December 3, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-publication-data-felix-study-obe

4. Autolus Therapeutics Announces FDA Approval of AUCATZYL® (obecabtagene autoleucel – obe-cel) for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Autolus. November 8, 2024. Accessed December 3, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-fda-approval-aucatzylr