Therapeutic efficacy and infectious complications of CD19-targeted chimeric antigen receptor-modified T cell immunotherapy

Abstract

Lymphocyte depletion chemotherapy CD19-targeted chimeric antigen receptor-modified T (CAR-T) cell immunotherapy is an innovative approach for the treatment of refractory or relapsed B-cell malignancies. This method also has the occurrence of infection, and there has been no systematic analysis of infectious complications. In our study, we intend to analyze the infection in patients between day 0 and day 90 by analyzing the data of 40 patients who received CD19 CAR-T cell therapy collected in our hospital. We assessed risk factors for infection before and after treatment using Poisson and Cox regression, respectively. A cohort study was used, including patients with acute lymphocytic leukemia, chronic lymphocytic leukemia and non-Hodgkin’s lymphoma. 40 patients were infected for the first time occurred at a median of 6 days after CAR-T cell infusion, and 8 (20%) had 10 infections within 28 days after CAR-T cell infusion, on days 29 and 29. The infection density between 90 days was lower at 0.67. This resulted in an infection density of 1.19 infections per 100 days. Two patients (5%) developed invasive fungal infections and two patients (5%) developed life-threatening or fatal infections. In an adjusted model for baseline characteristics, patients with ALL, ≥4 prior antitumor regimens, and receiving the highest CAR-T cell dose had higher infection densities at 28 days. The incidence of infection was comparable to that observed in clinical trials of salvage associated with infection after CAR-T cell infusion.

Broadening the horizon: potential applications of CAR-T cells beyond current indications

“…Detailed investigations into the kinetics of CAR-T-cell persistence have shown correlations between the numbers of CAR-T cells present in the peripheral blood and adverse events like the occurrence of CRS ( 260 ). In line with these findings, patients treated with anti-CD19 CAR-T-cell therapy for CLL have experienced side effects like bacterial, viral, and fungal infections due to myelosuppression similar to patients suffering from other hematological malignancies ( 261 ). Through the comprehensive analysis of 47 patients with CLL or Richter transformation receiving anti-CD19 CAR-T-cell therapy, Liang et al.…”