High response rates with novel CAR T-cell therapy for adults with advanced B-cell ALL

The US Food and Drug Administration recently approved obecabtagene autoleucel (obe-cel) for the treatment of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).¹

Approval was based on the FELIX trial, a phase 1b/2, multicenter study including 153 adults with relapsed or refractory B-cell acute ALL that examined the safety and efficacy of the novel chimeric antigen receptor (CAR) T-cell therapy in this setting. The study results were presented at the 66th American Society of Hematology (ASH) Meeting and Exposition and published in The New England Journal of Medicine.^{2, 3} The study builds on prior phase 1 data showing high efficacy and low numbers of immune-related toxic effects with obe-cel in both children/young adults and adults.

Of the 153 patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. These patients were divided into two cohorts: cohort 2A (94 patients), which presented with morphologic disease, and cohort 2B, which presented with measurable residual disease. The main outcome of the study was overall remission in cohort 2A.

Patients in cohort 2A achieved a high overall response rate of 76.6%, with a complete remission achieved by 55.3% of the patients. Patients also achieved high rates of durability, with a 12-month event-free survival rate of 49.5% in all patients at the end of the trial.

“This data is practice changing,” says the lead author of the study, Claire Roddie, MD, PhD, an associate professor of hematology and oncology at the University College London.

An important finding of the study was the low incidence of immune-related toxicity. Grade 3 or higher cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome were observed in only 2.4% and 7.1% of infused patients, respectively. Toxicities were seen primarily in patients with a high bone marrow burden (>75% blasts).

“One thing that makes this CAR T product different is the safety profile, which means that even older patients and those with multiple comorbidities can receive treatment with obe-cel, even those with higher burden disease before treatment,” says Dr Roddie.

Further results suggest that patients with a low-to-intermediate bone marrow burden may be optimal candidates for CAR T-cell efficacy and toxicity. When the researchers looked at the entire study population, better event-free survival was seen in patients with a low (<5% blasts) or intermediate bone marrow burden (5%–75% blasts) before lymphodepletion. These patients also had better event-free survival than those with a high bone marrow burden (>75% blasts).

Elias Jabbour, MD, a professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center and senior author of the study, who presented the results at the ASH meeting, said in a press release that, until now, these patients had limited treatment options. “Patients with B-cell ALL need effective standalone treatment options, and obe-cel demonstrated strong long-term efficacy and response rates in patients treated on the FELIX study,” he said. “We observed minimal immunotoxicity and a strong persistence of CAR T cells, which support obe-cel being the standard of care for this population.”