Obe-cel Shows Complete Remissions up to 3 Years in R/R B-ALL
A pooled analysis of the ALLCAR19 and FELIX trials including patients with R/R B-ALL, B-CLL, and B-NHL were presented at ASH 2023.
Obecabtagene autoleucel (obe-cel) CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated over 3 years of safety and efficacy in patients with relapsed/refractory B-cell acute lymphocytic leukemia (R/R B-ALL).
Updated data from a pooled analysis of the phase 1 ALLCAR19 trial (NCT02935257) and the phase 1b/2 FELIX trial (NCT04404660) were presented by Claire Roddie, MD, PhD, FRCPath, MBChB, MRCP, associate professor, haemato-oncology, University College London, at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.
“Obe-cel is an autologous CAR T-cell product designed to reduce toxicity and improve persistence through a fast off-rate CD19 binding domain.Additionally, obe-cel has been tested in patients with R/R B-cell chronic lymphocytic leukemia (B-CLL) and R/R B-cell non-Hodgkin lymphoma (B-NHL),” Roddie and colleagues wrote in the abstract.
ALLCAR19 is a multicenter, open-label phase 1 trial in patients aged at least 16 years, originally limited to R/R B-ALL but then amended to include patients with R/R B-CLL and NHL in an extension study. FELIX is a global, single-arm Phase Ib/II study enrolling adult patients with R/R B-ALL. Obe-cel was administered as a split dose in patients with B-ALL (target dose of 410 × 106 CAR T cells) andCLL (target dose 230 × 106 CAR T cells), and as a single infusion in patients with B-NHL (target dose 200 × 106 CAR T cells). Patient populations were similar between studies and patients with B-ALL are continuing to be followed for disease progression and survival.
The new data in B-ALL are from 20 patients in ALLCAR19 (data cutoff June 2023) and 16 in FELIX (data cutoff March 2023). The median age was 41.5 years (range, 18-74) and the median lines of prior therapy was 3 (range, 2-6). Twenty-nine patients (81%) achieved complete remission (CR) with incomplete hematologic recovery per investigator assessment. Event-free survival rate was 64% at 6 months and 49% at 12 months. Patients had a median of 43 months (range, 19-62) of follow up and 13 of 36 responders (36%) remain in remission (8 from ALLCAR19 and 5 from FELIX) with minimal residual disease negativity. Two of these ongoing responders had consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT)and 10 who did not still had detectable CAR T cells at the last follow up.The estimated 2-, 3- and 4-year overall survival rates were 44%, 39% and 39%, respectively.
Looking at patients with R/R B-CLL and B-NHL, 26 treated patients (5 with B-CLL and 21 with B-NHL) had a median age of 61 years (range, 39-79) and a median 3 prior lines of treatment (range, 2-8). Overall response rate was 92% (n = 24) at a median follow up of 24 months and 58% (n = 14) were alive without disease progression at the last follow up.
In terms of safety, 10 of the ongoing B-ALL responders that did not receive allo-HSCT had ongoing B-cell aplasia. Of the 14 ongoing responders with B-CLL/NHl, 12 have ongoing B-cell aplasia. These cases did not correlate with an increased risk of late serious infection and no other long-term toxicties related to obe-cel were reported.
“The combined analysis of data from the ALLCAR19 and FELIX Phase Ib studies shows long-term efficacy and safety of obe-cel in pts with R/R B-ALL, with approximately one-third of pts still in remission without consolidative allo-HSCT after a median follow up of >3 years. Durable responses of >2 years were also seen in pts with R/R B-CLL and R/R B-NHL.B-cell aplasia was commonly found in long-term follow up of obe-cel recipients, but without a corresponding rise in serious late infections. Obe-cel can effect durable long-term remissions in B-cell malignancies,” Roddie and colleagues concluded.
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