KEY TAKEAWAYS
- The phase 1/2 trial aimed to administer CNCT19 post-HDT/ASCT in patients with R/R LBCL.
- The HDT/ASCT and CNCT19 combination therapy showed remarkable efficacy, enhanced CNCT19 performance, and a favorable safety profile.
About two-thirds of individuals with relapsed or refractory large B-cell lymphoma (R/R LBCL) fail to respond to or relapse following anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, resulting in unfavorable outcomes. Prior research indicates that intensified lymphodepletion and hematopoietic stem cell infusion may stimulate adoptively transferred T-cell proliferation, thereby augmenting antitumor responses.
Wei Liu and the team aimed to administer CNCT19 post-HDT/ASCT in patients with R/R LBCL.
The study enrolled transplant-eligible patients with LBCL who were refractory to initial immunochemotherapy or experiencing R/R status after salvage chemotherapy. They aimed to assess the safety and efficacy of this combination therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were utilized to evaluate the combination therapy’s impact on the in vivo behavior of CNCT19 cells.
The results revealed that 25 patients with R/R LBCL were enrolled, with overall response and complete response rates of 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed, with all cases of cytokine release syndrome being of low grade.
About 8% of cases experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. Comparison of CNCT19 in vivo behavior indicated that patients in the combination therapy group showed enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation compared to those receiving CNCT19 monotherapy.
The combination therapy involving HDT/ASCT and CNCT19 showcased remarkable efficacy, enhanced CNCT19 behavior, and a favorable safety profile.
The trial was sponsored by the Zou Dehui, Institute of Hematology & Blood Diseases Hospital, China.
Source: https://pubmed.ncbi.nlm.nih.gov/38631712/
Liu W, Liu W, Zou H, et al. (2024). “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.” J Immunother Cancer. 2024 Apr 16;12(4):e008857. doi: 10.1136/jitc-2024-008857. PMID: 38631712; PMCID: PMC11029269.
