Tumor burden-guided dosing contributes to mitigation of immunotoxicities following treatment with obecabtagene autoleucel in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
Jabbour, Elias Sandhu, Karamjeet S Shaughnessy, Paul Logan, Aaron C Abedi, Mehrdad Shah, Bijal D Bishop, Michael R Park, Jae H DeAngelo, Daniel J Tholouli, Eleni
Jabbour, Elias
Sandhu, Karamjeet S
Shaughnessy, Paul
Logan, Aaron C
Abedi, Mehrdad
Shah, Bijal D
Bishop, Michael R
Park, Jae H
DeAngelo, Daniel J
Tholouli, Eleni
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2026-01-08
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Abstract
Obecabtagene autoleucel (obe-cel) is a CD19-targeted autologous chimeric antigen receptor T-cell therapy (CAR T) with a fast off-rate binding domain, administered as split-dose infusions guided by pre-lymphodepletion tumor burden (low-tumor-burden [TB] group: ≤20%; high-TB group: >20% bone marrow [BM] blasts). Obe-cel treatment in adult relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) was investigated in the phase 1b/2 FELIX trial. Here, we report pharmacokinetics, safety, and efficacy outcomes in patients with low or high tumor burden and discuss the evidence/rationale justifying the spilt-dose strategy and threshold used to classify the groups. Tumor burden at lymphodepletion was a critical driver of CAR T-cell expansion; a 50% increase, e.g., 70% versus 20% BM blasts, was associated with a 1.9-fold increase (95% confidence interval: 1.4-2.6) in maximal expansion of CAR T-cells. Robust CAR T-cell expansion was observed in both tumor burden groups. The incidence of grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was minimal in both the low- and high-TB groups (2% versus 3% and 4% versus 9%, respectively). Although the overall remission rate was higher in the low-TB group (85%), it also remained high in the high-TB group (73%). Evidence from FELIX suggests that use of tumor burden-guided dosing may mitigate the typical effects of immunotoxicity while maintaining substantial efficacy. Although further study is needed to better characterize the effects of the split-dosing strategy, the clinical evidence supports its use when administering obe-cel for the treatment of R/R B-ALL. Trial registration number: NCT04404660 (www.clinicaltrials.gov).
Citation
Jabbour E, Sandhu KS, Shaughnessy P, Logan AC, Abedi M, Shah BD, Bishop MR, Park JH, DeAngelo DJ, Tholouli E, Yallop D, Chaganti S, Hodby K, Barba P, Guerreiro M, Menne T, Shang J, Lao-Sirieix P, Brugger W, Roddie C. Tumor burden-guided dosing contributes to mitigation of immunotoxicities following treatment with obecabtagene autoleucel in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Haematologica. 2026 Jan 8. doi: 10.3324/haematol.2025.288587. Epub ahead of print.
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