Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
CAR-T therapy can be effective in certain patients with Richter transformation. Patients who respond to CAR-T therapy are more likely to have durable remissions.
Who Performed the Research and Where Was it Presented:
Dr. Paolo Ghia from Università Vita-Salute San Raffaele in Milano, Italy, and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Richter transformation is a rare complication of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL), where the disease turns into an aggressive lymphoma. Richter transformation is difficult to treat and has a poor prognosis. Chimeric antigen receptor T-cell (CAR-T) therapy is approved for use in many types of lymphomas but is not currently approved for Richter transformation. Previous research suggests CAR-T therapy can be effective for a subset of patients with Richter transformation. This study examined outcomes for patients with Richter transformation who received CAR-T therapy.
Methods and Participants:
This retrospective study used patient data from multiple centers across Europe and the United States. It included patients with Richter transformation treated with CD19-targeting CAR-T cells between 2018 and 2024.
Results:
- The study included 54 patients with Richter transformation who received CAR-T therapy.
- Approximately half of the patients received investigational products, and half received products that were already on the market.
- The overall response rate was 65%, and 50% of patients had a complete response three months after receiving CAR-T infusion.
- Among all patients, the median progression-free survival was 56% at 6 months and 41% at 12 months.
- Patients with any type of response (complete or partial) had a median progression-free survival of 2 years.
- Patients who did not respond to treatment had a median progression-free survival of 1 month.
- Response rates for patients with high-risk features (deletion 17p, 13q, 11q, TP53 mutations, IGHV mutational status) were not significantly different.
- Seven, or 13%, of the patients, went on to a transplant to consolidate their response.
- Common side effects included cytokine release syndrome (87%) and immune effector cell-associated neurotoxicity syndrome (22%), both well-known side effects of CAR-T therapy. Infections were seen in 41%.
Conclusions:
CAR-T therapy can be effective in certain patients with Richter transformation. Patients who respond to CAR-T therapy are more likely to have durable remissions, while patients who do not respond have short progression-free survival. It is still unclear what determines whether a patient will respond or not. Still, it does not appear related to high-risk genetic features such as deletion 17p, TP53 mutations, or IGHV mutational status.
Links and Resources:
Watch the interview on the abstract here:
You can read the ASH abstract here: CD19 CAR-T Cell Therapy Is Effective in Richter Transformation: A Multicenter Retrospective Analysis By the European Research Initiative on Chronic Lymphocytic Leukemia.
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