Combinational therapy of CAR T-cell and HDT/ASCT demonstrates impressive clinical efficacy and improved CAR T-cell behavior in relapsed/refractory large B-cell lymphoma.

in Journal for immunotherapy of cancer by Wei Liu, Hesong Zou, Lianting Chen, Wenyang Huang, Rui Lv, Yan Xu, Huimin Liu, Yin Shi, Kefei Wang, Yi Wang, Wenjie Xiong, Shuhui Deng, Shuhua Yi, Weiwei Sui, Guangxin Peng, Yueshen Ma, Huijun Wang, Lulu Lv, Jianxiang Wang, Jun Wei, Lugui Qiu, Wenting Zheng, Dehui Zou

TLDR

  • The study found that a combination of a special type of chemotherapy and a special type of blood cell therapy called CAR T-cell therapy was effective in treating a type of cancer called large B-cell lymphoma. The study also found that the combination therapy was safe and had fewer side effects than the therapy alone. The study also found that the combination therapy helped the CAR T-cells work better and last longer in the body. This study is important because it shows that combining different types of cancer treatments can be more effective than using just one type of treatment. The study also highlights the importance of using a special type of chemotherapy and a special type of blood cell therapy to treat this type of cancer.

Abstract

Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL. Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells. A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy. The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile. ChiCTR1900025419 and NCT04690192.

Overview

  • The study aimed to evaluate the safety and efficacy of combining anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy with myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL).
  • The study enrolled 25 patients with R/R LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy. The primary objective was to evaluate the overall response and complete response rates, as well as the 2-year progression-free survival rate and overall survival after a median follow-up of 27.0 months. The study also compared the in vivo behavior of CNCT19 cells in patients receiving the combinational therapy versus those receiving CNCT19 monotherapy. The study was conducted under the clinical trial numbers ChiCTR1900025419 and NCT04690192.

Comparative Analysis & Findings

  • The study found that the overall response rate was 92.0%, and the complete response rate was 72.0%. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy. The combinational therapy of HDT/ASCT and CNCT19 demonstrated impressive efficacy, improved CNCT19 behavior, and a favorable safety profile.

Implications and Future Directions

  • The study's findings suggest that the combinational therapy of HDT/ASCT and CNCT19 is an effective and safe treatment option for patients with R/R LBCL. The study's results also highlight the importance of intensified lymphodepletion and hematological stem cell infusion in promoting adoptively transferred T-cell expansion, enhancing antitumor effects. Future research should focus on expanding the use of this combinational therapy to other types of lymphomas and exploring the potential benefits of combining CAR T-cell therapy with other immunotherapies. The study's findings also highlight the need for further research to identify the optimal dosing and timing of CNCT19 therapy in combination with HDT/ASCT to maximize its efficacy and minimize toxicity.
Read Full Article