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Richter’s Transformation (RT) or Richter’s Syndrome (RS) remains a major unmet need in CLL.
For a background on RT, please read this article by Dr. Weistner from the National Institutes of Health (NIH).
Briefly, RT occurs when the usually slow growing CLL/SLL transforms into a more aggressive lymphoma, usually diffuse large B cell lymphoma (DLBCL) and occasionally Hodgkin Lymphoma.
Here we will only discuss the most common DLBCL variation. The rare patient whose CLL transforms to Hodgkin tends to do better.
While DLBCL is quite treatable when it arises “de novo” or on its own, when it evolves from a chronic lymphocytic leukemia clone, the prognosis is too often poor.
Dr. Yucai Wang, MD, PhD is a fellow at the Mayo Clinic in Rochester, MN. I interviewed him at ASH 2018 in San Diego about his research into RT.
- Other indolent (slow growing) lymphomas besides CLL can also develop RT.
- In CLL, the annual transformation rate is 0.5% in untreated patients and 1% in those treated.
- Risk factors for RT include TP53 mutation, 17p deletion and unmutated IGVH. Prior research has also suggested that the Notch1 mutation increases the risk of RT.
- Patients who developed RT and were never treated did better than those who had been treated.
- Genetic abnormalities found in de novo DLBCL that normally would lead to more aggressive disease were not significant in this study.
- As in prior studies, patients whose RT is clonally related to their CLL do worse than those whose DLBCL arose as a secondary cancer, unrelated to the chronic lymphocytic leukemia.
- Most patients were treated with R-CHOP (R = Rituximab, C = Cyclophosphamide, H = Doxorubicin Hydrochloride (Hydroxydaunomycin), O = Vincristine Sulfate (Oncovin), P = Prednisone), a common chemo-immunotherapy cocktail used in lymphomas. For more on R-CHOP from the NIH, please see this.
- Most patients who were treated with other more aggressive chemotherapy cocktails did better than those treated with R-CHOP. This might be because they were better able to tolerate such harsh, but more effective therapies.
- Patients treated with novel therapies, such as checkpoint inhibitors (pembrolizumab), ibrutinib and venetoclax also did better.
- Prior studies have shown that an allogeneic hematopoietic stem cell transplant (bone marrow transplant) often strengthens or “consolidates” the therapy, improving outcome and potentially leading to very durable responses. Again, the results may be biased, as only those patients who respond well to the first treatment and are strong enough to undergo the procedure get transplanted.
Richter’s Transformation remains an unsolved problem in CLL, but progress is being made. Combinations using novel therapies and old school chemotherapy might offer the best options for this aggressive cancer. The good news is that RT is rare and there is active research such as this by Dr. Wang.
Please take a look at our video interview from ASH 2018.
Here is the link to Dr. Wang’s ASH abstract: Clinical Characteristics and Outcomes of Chronic Lymphocytic Leukemia Patients with Richter Transformation
Stay tuned for more promising Richter’s research very soon.
Stay strong. We are all in this together.