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Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: A CIBMTR Analysis
Kalyan V Nadiminti1, Kwang W Ahn2, Jinalben Patel3
1Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin, Carbone Cancer Center, Madison, Wisconsin.
Transplantation and Cellular Therapy
|August 3, 2025
Summary
Chimeric antigen receptor T cell (CAR-T) therapy shows effectiveness in treating Richter transformation (RT), a rare and aggressive lymphoma complication. This study highlights CAR-T as a viable option for RT patients, offering improved survival outcomes.
Area of Science:
- Hematology
- Oncology
- Immunotherapy
Background:
- Richter transformation (RT) is a severe complication of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with poor prognosis.
- Limited data exists on the efficacy of chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory RT due to patient exclusion from pivotal trials.
- Existing therapies for RT offer suboptimal outcomes, necessitating exploration of novel treatment strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of anti-CD19 CAR-T therapy in patients with relapsed and/or refractory Richter transformation.
- To identify factors influencing outcomes in RT patients treated with CAR-T therapy.
Main Methods:
- Retrospective analysis of 140 RT patients who received anti-CD19 CAR-T therapy between 2018 and 2023 from the CIBMTR registry.
- Data collected included patient demographics, prior therapies (including BTK inhibitors and venetoclax), CAR-T product used (axi-cel or tisa-cel), adverse events, and survival outcomes.
- Statistical analysis focused on progression-free survival (PFS), overall survival (OS), cumulative incidence of relapse, and non-relapse mortality.
Main Results:
- The 2-year PFS and OS were 32.5% and 46.6%, respectively. The 2-year cumulative incidence of relapse was 58.8%, and non-relapse mortality was 8.7%.
- Commonly used CAR-T products were axicabtagene ciloleucel (65%) and tisagenlecleucel (28%). Grade ≥3 cytokine release syndrome (CRS) and neurotoxicity (ICANS) occurred in 9.4% and 20% of patients, respectively.
- Poor performance status and refractory disease prior to CAR-T infusion were associated with inferior survival and increased risk of disease progression.
Conclusions:
- Anti-CD19 CAR-T therapy demonstrates efficacy in a subset of patients with relapsed/refractory Richter transformation.
- CAR-T therapy offers a potential treatment option for RT patients who have exhausted other therapeutic avenues.
- Further research is warranted to optimize CAR-T therapy selection and management strategies for RT.
