CAR-T Therapy Safe, Effective for Relapsed or Refractory B-Cell Malignancies
Researchers have deemed chimeric antigen receptor (CAR)-T therapy a promising treatment option that yields tolerable adverse events in patients with relapsed or refractory B-cell malignancies, according to results from a recent study (BMC Cancer. 2018 Sept 26. Epub ahead of print).
Cancer immunotherapy comprising CAR-T cells has evolved rapidly in recent decades, especially for patients with relapsed or refractory B-cell malignancies, explained lead investigator Hui Zhou, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Chengdu, and colleagues, who assessed the efficacy and safety of CAR-T therapy in an analysis of clinical trials gleaned from PUBMED and EMBASE databases.
Analysis of Patients With B-Cell Malignancies
From a total of 463 clinical trials initially identified, 18 were selected for analysis. These studies included 185 patients with B-cell malignancies (126 leukemia and 59 lymphoma) who received CAR-T therapy.
Among the patients with leukemia, 39 had chronic lymphocytic leukemia and 87 had acute lymphocytic leukemia. Among those with lymphoma, 31 had diffuse large B-cell lymphoma, 11 had mantle-cell lymphoma, 7 had non-Hodgkin lymphoma, 4 had follicular lymphoma, and 6 had lymphoma without a detailed subtype.
High Response Rate and Tolerability
Results from the pooled analysis revealed a response rate of 67%. The progression-free survival (PFS) rates at 6 months and 1 year were 65.2% and 44.18%, respectively. Lymphodepletion and high-peak serum IL-2 levels correlated positively with patient response to CAR-T therapy. Dr Zhou and colleagues noted that, similarly, costimulatory domains in second-generation CAR T-cells correlated positively with PFS.
The pooled risk rates for adverse events of all grades and adverse events of grade 3 or higher were 71% and 43%, respectively. The most common adverse events of grade 3 or higher were fatigue (18%), night sweats (14%), hypotension (12%), injection site reaction (12%), leukopenia (10%), and anemia (9%).
“In conclusion, our study demonstrated a high response rate of CAR T therapy in refractory B cell malignancies. The study also showed lymphodepletion regimen and high serum IL-2 level were associated with better clinical responses, and that costimulatory domains was related with better PFS,” Dr Zhou and colleagues concluded.
“Further modifications of CAR structure and optimal therapy strategy in continuing clinical trials are needed to obtain significant improvements,” they said.—Janelle Bradley
