Chimeric Antigen Receptor T-Cell Therapy (Car-T) In Adults With B-Cell Acute Lymphoblastic Leukemia (B-All): A Systematic Review And Meta-Analysis

Background Chimeric antigen receptor (CAR)-T therapy has transformed the treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) in children and younger adults. Several groups have carried out early-phase trials of various CAR-T cell constructs in adults with r/r B-ALL. Recognizing that CAR-T outcomes in adult ALL are likely to differ from pediatric reports, we undertook a systematic review and meta-analysis to investigate the efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. Methods We searched MEDLINE, Embase, and the Cochrane Library for prospective, interventional studies of adults with B-ALL treated with CAR-T therapy. We included studies that enrolled ≥5 patients and excluded studies with a median age Results A total of 2566 records were assessed, and 15 studies involving 434 patients were included in the final analysis. All studies were single-arm, prospective clinical trials of patients with r/r B-ALL with 2–4 median prior lines of therapy. The majority of studies (11/15) included both pediatric and adult patients, but four of the studies enrolled only adults. The cumulative CR rate was 82.4% (95% CI:73.2–89.6%), and MRD-negative remission rate was 80.2% (95% CI: 69.4–88.5%) at 4 weeks post-CAR-T infusion. The cumulative 12-month PFS was 38.3% (95% CI: 27–49.5%), and OS was 56% (95% CI: 47–64); 42.9% patients relapsed at any time during follow-up, and antigen-positive relapse was three times more frequent than antigen-negative relapse. The cumulative incidence of any grade CRS was 81.7% (95% CI: 54.1-95–95%) and grade 3 or higher CRS was 27% (95% CI: 17.8–37.5%). The cumulative incidence of any grade neurotoxicity was 28% (95% CI: 13.3–49.1), and grade 3 or higher was 12.1% (95% CI: 0.7–26%). Conclusions CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. However, relapses are common, and durable response remains a challenge. These results will aid clinicians caring for adults with r/r B-ALL and will serve as a benchmark for investigators studying CAR-T cell therapies in adult ALL.