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.

Keywords: B-cell non-Hodgkin's lymphoma; chimeric antigen receptor T cells; chimeric antigen receptor T-cell efficacy; chimeric antigen receptor T-cell safety; chimeric antigen receptor T-cell therapy; diffuse large B-cell lymphoma.

Figure 1

Flow diagram of the study selection process.

Figure 2

Forest plot of the ORR of patients with any B-cell lymphoma. Squares represent the event rates (square size reflects the study-specific statistical weight); horizontal lines represent the 95% CI; and diamonds represent the pooled estimate based on a random-effects model. ORR, objective response rate; CI, confidence interval.

Figure 3

Forest plot of the CR rate of patients with any B-cell lymphoma. Squares represent the event rates (square size reflects the study-specific statistical weight); horizontal lines represent the 95% CI; and diamonds represent the pooled estimate based on a random-effects model. CR, complete remission; CI, confidence interval.

Figure 4

Forest plot of the ORR of patients with diffuse large B-cell lymphoma. Squares represent the event rates (square size reflects the study-specific statistical weight); horizontal lines represent the 95% CI; and diamonds represent the pooled estimate based on a random-effects model. ORR, objective response rate; CI, confidence interval.

Figure 5

Forest plot of the CR rate of patients with large B-cell lymphoma. Squares represent the event rates (square size reflects the study-specific statistical weight); horizontal lines represent the 95% CI; and diamonds represent the pooled estimate based on a random-effects model. CR, complete remission; CI, confidence interval

Figure 6

Forest plot of the rates of adverse events (grade ≥3) in patients with any B-cell lymphoma. Squares represent the event rates (square size reflects the study-specific statistical weight); horizontal lines represent the 95% CI; and diamonds represent the pooled estimate based on random-effects model. CRS, cytokine release syndrome; CI, confidence interval.