Efficacy and safety of CAR T-cell therapy in hematologic malignancies: A systematic review and meta-analysis.

e18575 Background: CAR T-cell therapy has shown promise in treating relapsed/refractory hematologic malignancies. To comprehensively evaluate its benefits and risks, we performed a systematic review and meta-analysis of published studies. Methods: Literature search identified 47 studies (31 trials, 10 observational, 6 case series; n per study 12–450; median follow-up 18 months). Pooled overall and complete response rates (ORR and CR), along with 12-month progression-free and overall survival (PFS and OS), were estimated. Rates of cytokine release syndrome (CRS), neurotoxicity, cytopenias, infections, hypogammaglobulinemia, and treatment-related mortality were pooled. Between-study heterogeneity (I²) and publication bias were assessed. Results: Pooled ORR was 75% (95% CI 70–80%) and CR 45% (95% CI 40–50%). B-cell malignancies had higher response (ORR 82%, CR 53%) than T-cell (ORR 63%, CR 34%). At 12 months, PFS was 60% (95% CI 55–65%) and OS 72% (95% CI 67–77%). CRS occurred in 85% (grade ≥3: 20%) and neurotoxicity in 40% (grade ≥3: 15%). Other toxicities included cytopenias (70%), infections (35%), hypogammaglobulinemia (25%), and treatment-related mortality (5%). Heterogeneity was high (I² ORR 75%, CR 68%); sensitivity analyses reduced it (65%, 60%). No significant publication bias was detected. Longer follow-up (>24 months) was associated with higher relapse and lower PFS/OS; patients with prior stem-cell transplant had slightly lower ORR and CR. Patient-reported quality of life improved post-therapy despite acute toxicities. Conclusions: This meta-analysis confirms that CAR T-cell therapy achieves high response rates (ORR 75%, CR 45%) and favorable 12-month survival (PFS 60%, OS 72%) in hematologic malignancies. Toxicities were common (CRS 85%; grade ≥3: 20%; neurotoxicity 40%, grade ≥3: 15%), as were cytopenias (70%) and infections (35%), but these were generally manageable. Treatment-related mortality was 5%. Quality of life improved overall despite acute toxicity. Heterogeneity was substantial, but sensitivity analyses and absence of publication bias support the robustness of these findings. Longer follow-up revealed higher relapse rates and reduced survival, and prior stem-cell transplant was linked to marginally lower responses. These results underscore that CAR T-cell therapy offers significant benefits along with considerable toxicity, and highlight the need to optimize patient selection and management.