Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy appears to be effective for treating patients with relapsed or refractory B-cell acute lymphocytic leukemia (ALL), according to a meta-analysis published in The Lancet Haematology.
While ALL treatment has improved over the past several decades, 5-year disease-free survival remains poor in adults, ranging from 10% to 20%. Up to 20% of pediatric patients will experience disease relapse with few treatment options thereafter. CAR-T therapy, which involves the genetic modification of cells ex vivo, has led to significantly improved response rates, with up to 90% of adult and pediatric patients reaching complete remission.
Anti-CD19 CAR-T therapy has been investigated in a number of iterations across clinical trials; for this study, researchers conducted a systemic review and meta-analysis to determine the long-term safety and efficacy of this novel therapy. The researchers “aimed to systematically review the available trials of anti-CD19 CAR T-cell therapy in [ALL] in both pediatric and adult patients, assess clinical outcomes and toxicities, and identify factors associated with differences in outcomes, focusing on [4] main variables: age group, construct type, single-chain variable fragment clone, and T-cell origin.”
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Heterogeneity between studies was calculated using the I2statistic, where low heterogeneity was defined as 25% to 50%, moderate heterogeneity was 50% to 75%, and high heterogeneity was more than 75%.
Of 1160 identified studies, 35 were included in the analysis, representing 953 patients. Overall, the complete remission rate across studies was 80% (95% CI, 75.5-84.8), with a lowest complete remission rate of 11% in a study of 9 patients and a highest complete remission rate of 100% in several studies, the largest of which involved 10 patients. Heterogeneity between studies was moderate (I2 =56.96%).
Of 263 patients in adult studies, 195 patients (75%; 95% CI, 66.9-82.9) reached complete remission, with low heterogeneity between studies (I2 =35.22%). Of 346 patients in pediatric studies, 242 (81%; 95% CI, 72.9-87.2) reached complete remission, with moderate heterogeneity between studies (I2=54.45%).
The overall pooled complete remission rate was not affected by construct type or single-chain variable fragment clone, though it was higher where the T-cell origin was autologous, rather than allogeneic (83% vs 55%; P =.018).
Overall, 26% of patients (242 of 854) with relevant adverse event data developed grade 3 or worse cytokine release syndrome; 12% of patients (92 of 532) developed grade 3 or worse neurotoxicity. These adverse events were not statistically affected by complete remission or cytokine release syndrome/neurotoxicity.
“In conclusion, complete remission for patients with relapsed or refractory B-cell acute lymphocytic [leukemia] who were treated with anti-CD19 CAR T-cell therapy is high, with patients treated with autologous CAR T cells achieving improved complete remission compared with those who received allogeneic infusions,” the investigators noted.
“Additional studies, including comparison trials, are required to further determine differences in efficacy between different anti-CD19 CAR T-cell constructs,” the authors concluded.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
Anagnostou T, Riaz IB, Hashmi SK, Murad MH, Kenderian SS. Anti-CD19 chimeric antigen receptor T-cell therapy in acute lymphocytic leukaemia: a systematic review and meta-analysis. Lancet Haematol. 2020;7(11):e816-e826. doi:10.1016/S2352-3026(20)30277-5
