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CAR-T Therapy for Richter’s Transformation

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

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.


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.


  • 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.


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:

CAR-T Therapy for Richter Transformation – Dr. Adam Kittai ASH 2023

If you are interested in participating in a clinical trial, there are currently three ongoing clinical trials or CAR-T for Richter’s transformation:

  1. Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter’s Syndrome at the Ohio State University, Columbus, OH.
  2. Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter’s Transformation at City of Hope Medical Center, Duarte, CA.
  3. 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