Obecabtagene autoleucel (obe-cel, AUTO1) in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL): Overall survival (OS), event-free survival (EFS) and the potential impact of chimeric antigen receptor (CAR)-T cell persistency and consolidative stem cell transplantation (SCT) in the open-label, single-arm FELIX phase Ib/II study.
Elias Jabbour, Eleni Tholouli, Karamjeet Sandhu, Paul Shaughnessy, Pere Barba, Manuel Guerreiro, Deborah Yallop, Aaron C. Logan, Mehrdad Abedi, Pierre Lao‐Sirieix, Yiyun Zhang, Wolfram Brugger, Martin Pulé, Bijal Shah, Michael Bishop, Jae H. Park, Daniel J. DeAngelo, Karl S. Peggs, Claire Roddie
Abstract
6504 Background: Obe-cel is an autologous CAR-T cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve expansion/persistence. Pooled results from the pivotal FELIX phase Ib/II study (NCT04404660) of obe-cel in adults with R/R B-ALL were recently presented (Roddie C et al. Blood 2023;142[Suppl 1]:222). Here, OS and EFS in all patients (pts) treated with obe-cel are reported, alongside the impact of CAR-T cell persistency and consolidative SCT for pts in remission. Methods: Pts aged ≥18 yrs with R/R B-ALL were enrolled. CAR-T products were generated via an automated process (Roddie C et al. Blood 2023;142[Suppl 1]:222). Pts received bridging therapy as appropriate and underwent lymphodepletion (fludarabine, 4×30mg/m 2 ; cyclophosphamide, 2×500mg/m 2 ), followed by obe-cel split dose infusions on Days 1 and 10 based on pre-lymphodepletion leukemic burden at a target dose of 410×10 6 CAR-T cells. Results: A total of 127/153 (83%) enrolled pts were infused. At screening, pts’ median age was 47 yrs; 42%/31%/44% had received prior blinatumomab/inotuzumab ozogamicin/allogeneic SCT; median bone marrow blast burden was 36% (range: 0−100). At data cut-off (13 September 2023), median follow-up was 16.6 mos (range 3.7−36.6 mos). The overall complete remission or complete remission with incomplete count recovery rate among infused pts was 78%. Among responding pts, 17/99 (17%) proceeded to consolidative SCT while in remission; all 17 (100%) were in measurable residual disease (MRD)-negative remission (≤10 –4 leukemic blasts) and 10/17 (59%) showed CAR-T cell persistency prior to SCT. Loss of CAR-T cell persistency was associated with a hazard risk of relapse or death 2.9 times compared with pts who had ongoing CAR-T cell persistency. Pts who experienced B-cell recovery had a hazard risk of relapse or death 1.7 times compared with pts without B-cell recovery. At 12 mos, the EFS rate was 50% and 43% with or without censoring for consolidative SCT or new therapies, respectively; the OS rate was 61% and 59% with or without censoring for SCT, respectively. Conclusions: Ongoing CAR-T cell persistency and B-cell aplasia were associated with improved EFS without further consolidation post-obe-cel. At the current follow-up, consolidative SCT for pts in MRD-negative remission post-obe-cel did not improve EFS or OS. Clinical trial information: NCT04404660 .