Efficacy and safety of second-generation CAR T-cell therapy in diffuse large B-cell lymphoma: A meta-analysis.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma (NHL), representing 30% of all lymphoma cases. Within the first 2-3 years following immunochemotherapy, 30-40% of patients will experience a relapse or a refractory disease, thereby exhibiting a poor prognosis. High-dose immunotherapy followed by autologous stem cell transplantation is the standard care for relapsed/refractory (RR) patients with DLBCL. However, >60% of patients are ineligible for a transplant, presenting a therapeutic challenge. Chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in patients with DLBCL, including those with R/R disease. The present study conducted a meta-analysis that showed highly favorable outcomes [objective response rate (ORR): 69%; complete remission (CR): 49%] in B-cell NHL patients (n=419) who were treated with second-generation CAR T cells. The response rate varied in different types of B-cell NHL. In 306 patients with R/R DLBCL eligible for rate evaluation, the ORR and CR rate mean estimates were 68% [95% confidence interval (CI), 55-79%] and 46% (95% CI, 38-54%), respectively. Thus, the findings indicated that immunotherapy with CAR T cells has improved outcomes for patients with R/R DLBCL and other subtypes of B-cell NHL compared with standard chemotherapy regimens. The study revealed that grade ≥3 anemia (34%) and thrombocytopenia (30%) were the most common adverse effects of CAR T-cell therapy. Incidence of grade ≥3 cytokine release syndrome and neurotoxicity associated with CAR T-cell therapy was effectively managed.