Real-World Experiences of CAR T-Cell Therapy for Large B-Cell Lymphoma: How Similar Are They to the Prospective Studies?

Abstract

Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment option for highly aggressive B cell malignancies. Clinical trials of CD19 CAR T cells for the management of relapsed and/or refractory non-Hodgkin lymphoma (NHL) have shown markedly improved survival and response rates. The goal of this review is to evaluate whether the results from these clinical trials are reflective of real-world practices through the analysis of published literature of the commercially available CAR T cell products. We have found that despite the significantly different patient characteristics, the adverse events and response rates of real-world patients were similar to those of the clinical trials. Of interest, several groups excluded from the clinical trials, such as patients with HIV infection, chronic viral hepatitis, and secondary CNS (central nervous system) lymphoma, had case reports of promising outcomes.

Keywords: CAR T cell therapy; Non-Hodgkin lymphoma; cellular therapy; chimeric antigen receptor; lymphoma.

Figure 1

Cytokine release syndrome rates in ZUMA-1 and real-world experiences of axicabtagene ciloleucel. ZUMA-1 graded according to Lee et al and CTCAE version 4.03; Nastoupil et al, according to Lee et al; Jacobson et al, according to Lee et al; Pasquini et al, according to ASTCT. CRS: cytokine release syndrome; CTCAE: Common Terminology Criteria for Adverse Events; ASTCT: American Society for Transplantation and Cellular Therapy.

Figure 2

Neurologic adverse events in ZUMA-1 and real-world experiences of axicabtagene ciloleucel. ZUMA-1 graded according to CTCAE version 4.03; Nastoupil et al graded according to CTCAE version 4.03 and CARTOX; Jacobson et al graded according to CTCAE version 4. CTCAE: Common Terminology Criteria for Adverse Events; CARTOX: CAR T-cell-therapy-associated TOXicity.