What follows is our patient-friendly summary of this research.
The Bottom Line:
Richter’s syndrome (RS), also known as Richter’s transformation, is a rare complication of chronic lymphocytic leukemia (CLL). It transforms into what is usually an aggressive lymphoma with a dismal prognosis.
By whom and where were the research and presentation done:
Maryam Alasfour and her colleagues at the University of Miami Sylvester Cancer Center, Miami, FL, presented the results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago in 2022.
Methods and Participants:
This was a retrospective review of patients diagnosed with confirmed RS who presented at the University of Miami Sylvester Cancer Center between 2011 and 2020.
Results:
- 33 patients with RS, including 87.9% with the most common pathology, diffuse large B-cell lymphoma-type RS, and 12.1% with Hodgkin lymphoma-type RS.
- The median time from CLL diagnosis to RS transformation was 37 months.
- Most patients presented with elevated Lactate Dehydrogenase (LDH) in 75% (a simple blood test that can roughly measure tumor activity), bulky lymph nodes in 66%, and adverse genetic markers, such as
- TP53 disruption in 52%
- Complex karyotype in 81%.
- FISH abnormalities: del(17p) 37%, del(11q) 17%, trisomy 12 58%.
- The overall response rate (ORR) to first-line therapy was a remarkedly good 75.8%, with 55% achieving a complete remission (CR) and 27% partial remission (PR).
- Unfortunately, even among those who achieved a CR, 44% relapsed.
- Median progression free survival (mPFS) was 10 months for the anthracycline-based chemotherapy group (ABC) with a CR of 50%
- mPFS was 15.5 months for the platinum-based chemotherapy group and a CR of 60%.
- Similar overall survival (OS) was observed regardless of the chemotherapy regimen, with median OS of 60 months in the ABC group versus 59.5 months in the platinum-based chemotherapy group.
- Notably, the addition of a BTKi to chemoimmunotherapy markedly improved outcomes with a median OS of
- More than 10 years in BTKi-naïve patients
- 5.1 years in BTKi-exposed patients
- Only 1.8 years in patients who did not receive a BTKi as part of their RS treatment.
Conclusions:
Patients who develop Richter’s syndrome most often develop it in those with high-risk CLL, especially complex cytogenetics.
While in this study, Richter’s syndrome responded surprisingly well to frontline therapy, but almost half relapsed. While median overall survival is similar for the two different chemotherapies, platinum-based chemotherapy can lead to superior complete remissions and progression-free survival.
Adding a BTKi, especially in BTKi-naïve patients, leads to significantly superior median overall survival.
While the overall outcomes, especially those with the addition of BTKi, are encouraging, they seem out of step with the generally much worse outcomes reported with RS. Therefore, I would like to see these findings replicated at other centers.
Links and resources:
Here is the link to the actual ASCO 2022 abstract for more detailed information: Outcomes of Richter’s syndrome in patients with chronic lymphocytic leukemia (CLL) treated with platinum or anthracycline based chemotherapy with or without a BTK inhibitor (BTKi) and to several links to articles on Richter’s Syndrome for more basic and research background of this dreaded CLL complication.
Stay strong. We are all in this together.
Brian
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer, CLL Society, Inc.
