Use of CD19 CAR-T Cells in Adult B-Cell Acute Lymphoblastic Leukemia (B-ALL) with Minimal Residual Disease (MRD) Positivity at First Complete Remission: Preliminary Outcomes from a Phase I Clinical Trial

作者：Marc Schwartz, Navin Pinto, Jonathan A. Gutman, Michael R. Verneris, Andrew Roth, Jason S. Gilbert, Dina Schneider, Terry J. Fry · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-204262 · 被引用次数：3 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、CRISPR and Genetic Engineering

Introduction: While >90% of adults with B-ALL will achieve morphological remission with frontline chemotherapy/TKI-based approaches, long-term survival of patients with minimal residual disease (MRD+) is ~30%, with poor outcomes driven by high rates of relapse. Incorporation of blinatumomab and/or inotuzumab in CR1 may mitigate the negative prognostic significance of MRD, however it is unclear if intensity of standard post-remission therapy can be safely reduced without compromising outcomes. CD19 CAR-T cell therapy results in durable remissions for approximately 20-30% of adult and 40-50% of pediatric patients with relapsed/refractory B-ALL, without additional consolidative therapy. We hypothesized that durability of response might be improved if CAR-T is delivered earlier in the treatment course due to better T-cell fitness, lower disease burden, and less resistant disease. UCD19 is an investigational 4-1BB-based CD19-directed CAR-T cell product with a unique TNFSF19-derived transmembrane domain. We designed a phase I clinical trial to determine safety and tolerability of UCD19 CAR-T cell therapy for adults with B-ALL in MRD+ CR1 who are at high risk for relapse. Methods: Eligible patients include adults (≥18yo) with B-ALL in CR1 after induction therapy, with MRD positivity by either flow cytometry or NGS (Clonoseq). Ph- ALL patients are eligible if MRD+ after day 28 of induction, and Ph+ patients are eligible if MRD+ after day 84. Two dose levels of CAR-T cells (DL1...