FDA Approves Obe-cel for ALL

The US Food and Drug Administration (FDA) has approved obecabtagene autoleucel, or obe-cel (AUTO1, Autolus Therapeutics) for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).
Approval of the CD19 chimeric antigen receptor T-cell therapy (CAR T) — which, according to Autolus, was specifically “designed to have a ‘fast-off’ kinetic” to minimize excessive activation of the programmed T cells and thereby increase T-cell persistence and reduce T-cell exhaustion — was based on efficacy and safety findings from the open-label, single-arm FELIX study. 
Initial study findings were presented at the 2023 American Society of Clinical Oncology (ASCO) meeting, and updated findings from a pooled analysis of FELIX phase 1b/2 data were presented at the 2023 American Society of Hematology conference.
The pooled analysis showed a complete response (CR) or CR with incomplete hematologic recovery (CR/CRi) rate of 77% and a CR rate of 57% at a median follow up of 11 months in 124 patients treated between September 2020 and December 2022.
Among evaluable patients, 96% achieved minimal residual disease (MRD)-negative status. Median duration of response was not reached.
Safety findings showed a low 2.4% and 7.1% rate of grade 3 or higher cytokine release syndrome (CRS) and/or grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. 
FELIX study participants were 18 years of age or older with relapsed/refractory B-cell ALL and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients underwent lymphodepletion with fludarabine as 4 x 30 mg/m2 and cyclophosphamide at 2 x 500 mg/m2. Obe-cel was administered at a target dose of 410 x 106 CAR T cells as a split dose on days 1 and 10 based on pre-lymphodepletion bone marrow blast burden.
CAR T expansion was similar across the study cohorts, and CAR T persistence was ongoing in most responders at follow up. 
A particular benefit was observed in patients’ low leukemia burden, defined as morphological remission per investigator assessment (less than 5% bone marrow blasts without extramedullary disease) as measured at screening or at the start of lymphodepletion, prior to obe-cel infusion.
For example, of 10 evaluable patients with MRD at screening, nine achieved CR or Cri, and all 10 achieved MRD-negative status after infusion. Median duration of response was not reached; no grade 3 or higher CRS occurred; and one patient had grade 3 or higher ICANS. And i n a subset of 27 evaluable patients in morphological remission at the time of lymphodepletion, 24 (89%) achieved CR/CRi, and 100% of MRD evaluable responders achieved MRD negative CR/CRi after infusion. In this subset, median duration of response was not reached, and no patients experienced grade 3 or higher CRS or ICANS. 
Autolus Technologies announced in January 2024 that the FDA had accepted its Biologics License Application for obe-cel and noted the treatment had also been granted Orphan Drug Designation by the FDA. 
In June 2024, an additional update presented at the annual ASCO meeting showed that 12-month event-free survival was 50% and 43% with or without censoring for consolidative stem cell transplant or new therapies, respectively, and overall survival was 61% and 59%, respectively. 
Ongoing CAR T cell persistency and B-cell aplasia were associated with improved event-free survival without further consolidation after obe-cel infusion, the investigators reported, noting that consolidative stem cell transplant for those in MRD-negative remission did not improve event-free survival or overall survival at 12 months. 
In a commentary for Medscape Medical News, Jorge Cortes, MD, director of the Georgia Cancer Center in Augusta, Georgia, said the findings presented at ASCO suggest that obe-cel is “very promising and may [represent] a different strategy that decreases the toxicity for CAR T cells.” 
The study was funded by Merck. Smith reports receiving grant funding from Merck. Jones reports no relevant financial relationships. 
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] on Twitter: @SW_MedReporter. 
 
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