Medically reviewed by Dr. Brian Koffman
Richter’s transformation is a rare complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, where the disease turns into a much more aggressive lymphoma known as diffuse large B cell lymphoma (DLBCL). Richter’s transformation is fast-moving, and current treatments don’t work that well. While Richter’s transformation is difficult to treat, changes in how clinical trials are conducted might help patients access novel therapies. In this interview, Dr. Brian Koffman spoke with Dr. Adam Kittai, an associate professor of medicine at Mount Sinai. They discussed the challenges of treating patients with Richter’s transformation and how changes to the design of research trials for Richter’s transformation might help.
How is Richter’s transformation currently treated?
“Current treatments for Richter’s transformation are modeled on what we use to treat aggressive lymphoma. Multiagent chemoimmunotherapy regimens such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the most commonly used initial treatment for Richter’s transformation, but patients have poor outcomes and the responses are not durable. Additionally, chemoimmunotherapy is also very tough on the bone marrow and immune system. Because patients with Richter’s transformation do so poorly on these chemoimmunotherapy regimens, it brings into question whether it really makes sense to require patients to receive these therapies before trying a novel clinical trial that could potentially work better for them.”
What are the challenges for Richter’s transformation patients who want to participate in a clinical trial?
“Patients with Richter’s transformation have often been required to fail a prior line of therapy (usually chemoimmunotherapy) before entering into clinical trials with novel agents. However, Richter’s transformation is a very fast-moving disease with a median overall survival of only 6-12 months. Richter’s transformation is a very aggressive, fast-moving disease, and waiting for patients to fail on a therapy that doesn’t work very well is wasting precious time.
Additionally, patients who progressed to Richter’s transformation while on targeted therapies such as ibrutinib for CLL had worse outcomes than patients who developed Richter’s transformation while not on treatment. This highlights that patients who are progressing to Richter’s transformation on targeted therapies probably shouldn’t have to fail chemoimmunotherapy regimens before enrolling in clinical trials with novel agents.”
How can things be changed to help patients with Richter’s transformation?
“Things are starting to change in small ways. Most clinical trials for Richter’s transformation are phase 2 clinical trials where the efficacy of a treatment is being tested, but there is no comparator “standard of care” group. In many of the recent clinical trials for Richter’s transformation presented at ASH 2023, there was no requirement that patients had to have failed one prior therapy for Richter’s transformation. In some cases, progressing to Richter’s transformation on a prior CLL therapy was enough. This makes it easier for patients with Richter’s transformation to get into a clinical trial as quickly as possible.
Researchers are also putting together a panel of international experts in Richter’s transformation to develop recommendations for designing Richter’s transformation clinical trials. Clinical trials are a key part of developing new, effective frontline therapies for Richter’s transformation, which are desperately needed.”
Links and Resources:
Watch the interview with Dr. Adam Kittai:
Take care of yourself first.
Ann Liu, PhD
