Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of Clinical Oncology, 42(17), 2071–2079. https://doi.org/10.1200/JCO.24.00033 Dr. Adam S. Kittai et al.
Points
- This international retrospective study evaluated 69 heavily pre-treated patients with Richter transformation who received anti-CD19 CAR-T therapy after a median of four prior treatment lines.
- The therapy demonstrated an overall response rate of 63 percent, with 46 percent of patients achieving a complete response, indicating significant clinical activity in this hard-to-treat population.
- After a median 24-month follow-up, the median overall survival was 8.5 months, and the 2-year overall survival rate was 38 percent for the entire cohort.
- Patients who achieved a complete response experienced durable benefits, with a median duration of response of 27.6 months, highlighting a clear advantage for this responding subgroup.
- Significant treatment-related toxicities were observed, including grade 3 or higher cytokine release syndrome in 16 percent and severe neurotoxicity in 37 percent of all patients.
Summary
An international, multicenter, retrospective study was conducted to evaluate the efficacy and safety of anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy in patients with Richter transformation (RT). The study analyzed a cohort of 69 patients with a median age of 64 years (range 27-80 years). This was a heavily pre-treated population, with a median of four prior lines of therapy (range, 1-15); 58 patients (84%) had received prior Bruton tyrosine kinase inhibitor and/or BCL2 inhibitor therapy. The CAR-T products administered were axicabtagene ciloleucel (64%), tisagenlecleucel (25%), lisocabtagene maraleucel (10%), and brexucabtagene autoleucel (1%).
The therapy demonstrated significant clinical activity. The overall response rate was 63%, with 46% of patients achieving a complete response (CR). After a median follow-up of 24 months, the median progression-free survival (PFS) for the entire cohort was 4.7 months (95% CI, 2.0-6.9 months), and the 2-year PFS rate was 29% (95% CI, 18-41%). The median overall survival (OS) was 8.5 months (95% CI, 5.1-25.4 months), with a 2-year OS rate of 38% (95% CI, 26-50%). Notably, for patients who achieved a CR, the response was durable, with a median duration of response of 27.6 months (95% CI, 14.5 to not reached).
Regarding safety, the treatment was associated with notable toxicities. Grade 3 or higher cytokine release syndrome (CRS) was observed in 11 patients (16%), while grade 3 or higher immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 25 patients (37%). Despite the modest median survival outcomes for the overall cohort and the significant rates of toxicity, these findings suggest that CAR-T therapy is a clinically effective option that can induce deep and durable responses in a subset of patients with an otherwise poor prognosis.
Link to the article: https://ascopubs.org/doi/10.1200/JCO.24.00033
References Kittai, A. S., Bond, D., Huang, Y., Bhat, S. A., Blyth, E., Byrd, J. C., Chavez, J. C., Davids, M. S., Dela Cruz, J. P., Dowling, M. R., Duffy, C., Ho, C., Jacobson, C., Jaglowski, S., Jain, N., Lin, K. H., Miller, C., McCarthy, C., Omer, Z., … Thompson, P. A. (2024). Anti-cd19 chimeric antigen receptor t-cell therapy for richter transformation: An international, multicenter, retrospective study. Journal of Clinical Oncology, 42(17), 2071–2079. https://doi.org/10.1200/JCO.24.00033
