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ASH 2021: Dr. Alexey Danilov on Richter’s Transformation After CAR-T Therapy

In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

Richter’s transformation (sometimes called Richter’s syndrome) is a rare complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), where the cancer cells transform into a much more aggressive lymphoma. It occurs in 5-10% of CLL patients and it is associated with very rapid disease progression, limited therapeutic options, and poor survival. The median overall survival rate is less than one year.

At the American Society of Hematology (ASH) 2021, Steven Bloom, CLL Society’s Chairman of the Board and President, interviewed Dr. Alexey Danilov, Associate Director of the Toni Stephenson Lymphoma Center at City of Hope in Duarte, CA. They discussed the development of Richter’s transformation after chimeric antigen receptor T-cell (CAR-T) therapy.

Takeaways:

  • Richter’s transformation is hard to treat because it often does not respond to chemotherapy, which is usually used to treat lymphomas.
  • Some patients treated with CAR-T therapy become resistant to it by developing Richter’s transformation.
  • Paradoxically, in some cases, CAR-T therapy can effectively treat Richter’s transformation.
  • This highlights that we still have a lot to learn about Richter’s transformation, who might be at risk for developing it, and who might benefit from specific treatments.
  • Researchers reviewed charts from patients with relapsed/refractory CLL who had received CD19-targeted CAR-T therapy to look at the characteristics of patients who developed Richter’s transformation.
  • Seven out of 27 patients who received CAR-T therapy subsequently developed Richter’s transformation.
  • Almost all of these patients had responded to CAR-T therapy, and 4 out of 7 had even achieved undetectable measurable residual disease in the blood and bone marrow.
  • The median time to Richter’s transformation after administration of CAR-T was 9.5 months (range 3.5-40 months).
  • Of the patients who developed Richter’s transformation, 5 out of 7 had deletion 17p (del17(p)), 3 out of 7 had TP53 mutation, and 2 out of 7 had NOTCH1 mutation.
  • Patients with specific genetic abnormalities such as del17(p) are at higher risk of developing Richter’s transformation.

Conclusions:

This study found that certain high-risk genetic features are common in patients with relapsed/refractory CLL who went on to develop Richter’s transformation after CAR-T therapy. The next step for researchers will be to compare samples from these patients to samples from patients treated with CAR-T but who did not develop Richter’s transformation. Richter’s transformation is a rare condition that is hard to treat, but there are many emerging experimental options. Therefore, it will be helpful to get a second opinion on your options if you are diagnosed with this condition and consider a clinical trial that can provide access to new experimental treatments.

Please enjoy this interview with Dr. Danilov from the ASH meeting held in December 2021 in Atlanta, GA.

You can read the actual abstract here: Richter’s Transformation after CD-19 Directed CAR-T Cells for Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

You can find more research on Richter’s Transformation on our website here. It remains one of the greatest unmet needs for CLL/SLL patients.

Take care of yourself first.

Ann Liu, PhD