Risk Factors Associated with Sub-Optimal Outcomes and Hematotoxicity Following Obecabtagene Autoleucel (obe-cel) for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL)
Year: 2025
Type: article
Abstract: Introduction Obe-cel, an anti-CD19 autologous CAR T with a fast off-rate binding domain to improve persistence/reduce toxicity, is being investigated for treatment of adult R/R B-ALL. The pathophysiology of prolonged hematotoxicity , a common side effect of CAR T therapy, is poorly understood. Objectives Here, we report outcomes for patients (pts) with R/R B-ALL, risk-stratified using the CAR-HEMATOTOX (HT) model. Methods FELIX (NCT04404660) is a Phase Ib/II study evaluating the efficacy and safety of obe-cel in adults with R/R B-ALL. Pts received bridging therapy as appropriate and underwent lymphodepletion (LD), followed by tumor burden-guided CAR T-cell infusions on Days 1 and 10 to a target dose of 410 × 10 6 cells. HT scores calculated using the HT model (Rejeski K, et al. Blood 2023;142[10]:865–77), determined low-risk (0–1) and high-risk (≥2) of hematotoxicity ; parameters comprise pre-LD platelet count, absolute neutrophil count, hemoglobin, and inflammatory markers. Associations between hematotoxicity risk, immunotoxicity risk, and outcomes were assessed (data cut-off: 7 Feb 2024). Results In FELIX, most obe-cel infused pts were high-risk (102/127 [80.3%]), while 25/127 (19.7%) pts were low-risk/unknown. Table 1 shows baseline characteristics. Median bone marrow blasts at LD were increased in high-risk (45.5%) vs low-risk pts (7.0%), representing greater disease burden . Overall remission rate was numerically lower for high-risk pts (73.5%) vs low-risk pts (96.0%). High-risk pts had worse survival outcomes (Table 2), with 12-month event-free survival (95% confidence interval [CI]) and overall survival (95% CI) rates of 45.4% vs 65.5% and 57.6% vs 75.0% for high- and low-risk pts, respectively. While in remission, 17.3% of high-risk pts and 20.8% of low-risk pts proceeded to allogeneic stem cell transplantation . Incidence of any-grade (Gr) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were increased in high- vs low-risk pts (71.6% vs 56.0% and 25.5% vs 12.0%); however, Gr ≥3 CRS and ICANS were comparable. High-risk pts had slightly prolonged CRS vs low-risk pts (6.0 vs 4.0 days), while ICANS duration was comparable (Table 2). In responders, incidence of Gr ≥3 infections within 3 months post-infusion were higher in high- vs low-risk pts (26.7% vs 12.5%), reflecting underlying baseline and disease characteristics. Time to recovery of neutrophil (1 × 10 9 ) and platelet (100 × 10 9 ) counts was longer in high- vs low-risk pts (Table 2). Conclusion Risk-stratification for hematotoxicity , using pre-LD clinical parameters together with disease burden , has potential use for identifying pts more likely to benefit from obe-cel treatment and experience reduced toxicity. Pts with high-risk HT scores had consistently worse outcomes than pts with low-risk HT scores. © American Society of Hematology (2024). Reused with permission.
Institutions: City Of Hope National Medical Center, Memorial Sloan Kettering Cancer Center, Methodist Healthcare, University of California, San Francisco, University of California, Davis, Moffitt Cancer Center, University of Chicago, Dana-Farber Cancer Institute, The University of Texas MD Anderson Cancer Center, University College London
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4407977526