Nonrandomized Phase 1b–2 Study: CAR T-cell Therapy Obecabtagene Autoleucel Effective with Low Severe Toxicity in Adult B-cell ALL
4 Dec, 2024 | 12:04h | UTCBackground: Relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in adults has a poor prognosis, with current therapies often requiring allogeneic stem-cell transplantation for durable responses. CAR T-cell therapies targeting CD19 have shown promise but are associated with significant toxic effects.
Objective: To evaluate the efficacy and safety of obecabtagene autoleucel (obe-cel), a novel autologous 41BB-ζ anti-CD19 CAR T-cell therapy designed to reduce toxic effects and improve persistence, in adults with relapsed or refractory B-cell ALL.
Methods: In this nonrandomized, phase 1b–2 multicenter study, 127 adults aged 18 years or older with relapsed or refractory CD19-positive B-cell ALL received at least one infusion of obe-cel. The primary endpoint was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A (patients with morphologic disease). Secondary endpoints included event-free survival, overall survival, and safety assessments.
Results: Among the 94 patients in cohort 2A (median follow-up of 20.3 months), overall remission occurred in 77% (95% CI, 67–85%), with 55% achieving complete remission and 21% achieving complete remission with incomplete hematologic recovery. The prespecified null hypotheses were rejected (P < 0.001). In the total infused population, the median event-free survival was 11.9 months (95% CI, 8.0–22.1), and the median overall survival was 15.6 months (95% CI, 12.9–NE). Grade 3 or higher cytokine release syndrome occurred in 2.4% of patients, and grade 3 or higher immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 7.1%.
Conclusions: Obe-cel demonstrated a high incidence of durable responses with a low incidence of severe immune-related toxic effects in adults with relapsed or refractory B-cell ALL.
Implications for Practice: Obe-cel may offer an effective CAR T-cell therapy option with manageable toxicity for adult patients with relapsed or refractory B-cell ALL. However, long-term benefits and direct comparisons with existing therapies require further investigation. Clinicians should consider the potential advantages but remain cautious given the lack of randomized controlled data.
Study Strengths and Limitations: Strengths include the multicenter design and substantial patient population. Limitations involve the nonrandomized, single-arm design without a control group, and potential bias from patients who did not receive the infusion due to disease progression or manufacturing failures. Additionally, longer follow-up is needed to fully assess durability and late-onset toxicities.
Future Research: Further studies are warranted to compare obe-cel directly with standard therapies in randomized controlled trials, assess long-term outcomes, and explore its efficacy in earlier lines of treatment or in combination with other modalities.