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ASCO 2020 Top 12” #3: A multicenter phase II study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome

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In short videos with accompanying text, Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, takes us through his “Top 12” abstracts from ASCO or the American Society of Clinical Oncology Annual Meeting held virtually in May, 2020.


ASCO 2020: A multicenter phase II study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome

While improvements in CLL treatment have lengthened overall survival (OS) and progression free survival (PFS), the prognosis remains dismal for patients whose CLL turns bad and transforms into Richter’s Syndrome (RS) or Richter’s Transformation.

For more background on RS, please see this review article by Dr. Wiestner.

At ASCO 2020, Dr. Matt Davids from Dana Farber presented an update on a study trying a new combination to try to improve the odds.


  • In a 2017 study, the median overall survival (OS) for those who developed RS after taking a novel agent, such as ibrutinib, was only 3.3 months.
  • Patients whose RS can be controlled are generally recommended to have an allogeneic hematopoietic stem cell (bone marrow) transplant (HSCT) to “consolidate” the response. HSCT can lead to very durable remissions in a lucky few.
  • R-EPOCH is a potent and tough chemo-immunotherapy (CIT) regime with a 20% complete response rate in RS, it includes:
    • R = Rituximab
    • E = Etoposide Phosphate
    • P = Prednisone
    • O = Vincristine Sulfate (Oncovin)
    • C = Cyclophosphamide
    • H = Doxorubicin Hydrochloride (Hydroxydaunorubicin)
  • In a small study, 3 of 7 RS patients responded to single agent venetoclax for a 43% overall response rate (ORR), suggesting venetoclax may be an active therapy in RS.
  • This study combined the two treatments into “VR-EPOCH” in 26 difficult to treat patients.
  • Sadly, 6 of the 26 developed RS having had no prior treatment for their CLL.
  • The protocol started with one cycle of R-EPOCH.
  • Next came the venetoclax and the dosing was unusual:
    • It was started 3 weeks after the first cycle.
    • It was ramped up over 5 days instead of the usual 5 weeks (RS can move very fast, and many patients can’t wait 5 weeks).
    • It was given for only 10 days on, 20 days off to lower the side effects, especially the low neutrophil counts (neutropenia).
  • Serious side effects were common, as would be expected for such a potent mix, including:
    • Significant (grade 3 or higher) neutropenia (58%), anemia (50%), thrombocytopenia (50%)
    • Febrile neutropenia (38%)
    • No tumor lysis syndrome (TLS) occurred, despite the rapid ramp up.
  • The results were encouraging given the grim stats mentioned earlier:
    • 10 patients (pts) died, including 7 from disease progression (2 before even getting a chance to start on the venetoclax), and 1 each due to sepsis, sudden death, and complications post-HCST.
    • In the 21 pts who were able to start the combo therapy, the ORR was 76%, CR rate 62%.
    • Only 1 patient who achieved a complete remission (CR) had progressed when the data were analyzed.
    • 8 pts went on to transplant, with some still in CR up to 2½ years later.

Median PFS and OS are both 16.3 months.

Richter’s Syndrome (RS) is a fast moving, difficult to treat, aggressive lymphoma.  Better treatments are desperately needed.  This trial may the first of a tidal wave of new research that will combine the best old school chemo drugs with the best of the newer novel agents in innovative ways to maximize benefit and minimize toxicity to beat back this killer. CAR-T is being explored as well.

Here is the abstract from ASCO: A multicenter phase II study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome.

RS research is hard because RS is rare and can be rapidly fatal. We think of RS as coming after patients have been beaten up by chemo, and while that can be the case, in this study 23% of the RS patients had received no prior treatment for CLL.

We need more answers and more trials like this.  While this treatment didn’t help everyone, it did give more time to a majority of the patients.

Here is my short video on this important research:

Stay strong and safe, we are all in this together.


Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.