Sufferers with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) who had been handled with the novel anti-CD19 chimeric antigen receptor (CAR) T cell remedy, obecabtagene autoleucel (obe-cel), skilled excessive response charges and most didn’t want a subsequent stem cell transplant (SCT), based on outcomes from the Section Ib/II FELIX trial co-led by researchers at The College of Texas MD Anderson Most cancers Middle.
The findings, printed as we speak within the New England Journal of Drugs, confirmed a 76.6% response charge and 55.3% full remission charge in 127 evaluable sufferers. The median event-free survival (EFS) was 11.9 months, and the EFS charges at six and 12 months had been 65.4% and 49.5%, respectively. The median general survival (OS) for infused sufferers was 15.6 months. At six and 12 months, the estimated OS charges had been 80.3% and 61.1%, respectively.
Based mostly on these knowledge, the Meals and Drug Administration authorised obe-cel for the therapy of relapsed or refractory B-cell ALL in grownup sufferers in Nov. 2024. Further findings from the examine will likely be offered Dec. 9 on the 2024 American Society of Hematology (ASH) Annual Assembly by Elias Jabbour, M.D., professor of Leukemia and the examine’s U.S. lead investigator.
“Sufferers with B-cell ALL want efficient standalone therapy choices, and obe-cel demonstrated robust long-term efficacy and response charges in sufferers handled on the FELIX examine,” Jabbour mentioned. “Till now, these sufferers had restricted therapy choices. We noticed minimal immunotoxicity and a powerful persistence of CAR T cells, which help obe-cel being the usual of look after this inhabitants.”
The worldwide, multi-center FELIX trial handled 127 adults with relapsed or refractory B-cell ALL. Previous to receiving obe-cel, trial members had lymphodepletion – an essential step to eradicate current T cells and create a clean slate for CAR T cell remedy – adopted by obe-cel infusion in cut up doses on days one and 10. The median age of trial members was 47 years and 52% had been male. Sufferers had been 74% white, 12.6% Asian, 1.6% Black and 11.8% unknown.
Toxicities had been principally restricted to sufferers with excessive bone marrow burden. Sufferers skilled a low grade of cytokine launch syndrome (CRS) and neurotoxicity, that are related to CAR T cell therapies. Three sufferers skilled CRS signs of grade 3 or larger, and 9 sufferers skilled immune effector cell-associated neurotoxicity syndrome of grade 3 or larger. Noticed negative effects had been in step with earlier research, and no new adversarial results had been recognized.
Among the many 99 sufferers who responded to obe-cel, solely 18 went on to obtain a SCT whereas in remission at a median of 101 days after their infusion. Researchers noticed no distinction in EFS and OS between sufferers who obtained a SCT and people who didn’t, suggesting a sturdy response from obe-cel remedy.
The trial additionally demonstrated important clearance of minimal residual illness (MRD) following obe-cel therapy. In sufferers with blood cancers, MRD refers to a small variety of most cancers cells remaining after therapy which have the potential to trigger relapse.
On the examine, 68 high-risk sufferers – outlined as these with bone marrow blasts larger than 5% previous to lymphodepletion – achieved a whole remission. On this group, 62 sufferers had MRD knowledge obtainable, and 58 sufferers had been MRD-negative after obe-cel infusion.
Within the upcoming ASH presentation, Jabbour will spotlight the correlation between depth of MRD-negative remission and medical outcomes in sufferers handled with obe-cel. Previous to lymphodepletion, researchers evaluated affected person bone marrow samples by subsequent technology sequencing (NGS). The findings point out decrease ranges of MRD had been related to a stronger response, together with larger EFS and OS charges, Jabbour defined.
