Medically reviewed by Dr. Brian Koffman
The Bottom Line:
Chimeric antigen receptor T-cell (CAR-T) therapy can provide durable remissions in a subset of patients with Richter’s transformation. Side effects, including cytokine release syndrome and neurotoxicity, were common but usually manageable.
Who Performed the Research and Where Was it Presented:
Dr. Adam Kittai and colleagues from Ohio State University presented the results at the American Society for Hematology (ASH) Annual Meeting in 2023.
Background:
Richter’s transformation is when chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) turns into an aggressive lymphoma known as diffuse large B-cell lymphoma (DLBCL). Only 1-5% of CLL patients will develop Richter’s transformation, but it is associated with worse outcomes, including a median overall survival time of less than 12 months. Clinical trials testing new therapies for Richter’s transformation are sorely needed because, currently, available therapies do not provide durable remissions. CAR-T therapy has successfully treated certain types of lymphomas, including DLBCL, but these trials largely excluded patients with Richter’s transformation.
Methods and Participants:
This was an international multicenter retrospective study of patients with Richter’s transformation who received CD19 CAR-T therapy.
Results:
- The study included 69 patients, which is a lot for a Richter’s transformation study because it is a relatively rare disease.
- Patients were heavily pretreated with a median of two prior therapies for CLL and two prior therapies for Richter’s transformation for a total of four prior lines of therapy.
- Eighty-four percent of patients had previously received a Bruton tyrosine kinase (BTK) inhibitor or BCL2 inhibitor for CLL or Richter’s transformation.
- Patients were treated with one of four FDA-approved CAR-T products: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), or brexucabtagene autoleucel (brexu-cel).
- The overall response rate was 65%, and the median overall survival was 8.5 months.
- Forty percent of patients had a complete response, and the duration of that response was about two years.
- CAR-T therapy is well-known to have certain immune-related side effects, including cytokine release syndrome and neurotoxicity, but these can usually be managed with medication.
- About 15% of patients experienced cytokine release syndrome, which was grade 3 or higher (required hospitalization and medication).
- About 35% of patients experienced neurotoxicity that was grade 3 or higher.
- About 20% of patients experienced an infection that was grade 3 or higher.
- These side effect rates are slightly higher than what is normally seen with CAR-T therapy, so it is important to discuss the potential risks and benefits with your doctor.
Conclusions:
This study demonstrates that CAR-T therapy can provide durable remissions in a subset of patients with Richter’s transformation. Side effects, including cytokine release syndrome and neurotoxicity, were common but usually manageable. However, there is room for improvement, and given that a higher number of prior therapies is associated with worse outcomes, earlier use of CAR-T in the Richter’s transformation disease course may be warranted.
Links and Resources:
Watch the interview on the abstract here:
If you are interested in participating in a clinical trial, there are currently three ongoing clinical trials or CAR-T for Richter’s transformation:
- Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter’s Syndrome at the Ohio State University, Columbus, OH.
- Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter’s Transformation at City of Hope Medical Center, Duarte, CA.
- Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies (ZUMA-25) at multiple locations in the US and worldwide.
You can read the actual ASH abstract here: Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter’s Transformation: An International Multicenter Retrospective Study
Take care of yourself first.
Ann Liu, PhD
