Phase II study of venetoclax plus dose-adjusted R-EPOCH for Richter’s syndrome

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

Abstract Number : 8004

Abstract Type : Oral Abstract Session

Indication : Chronic Lymphocytic Leukemia

Intervention : Venetoclax (VR-EPOCH)

Company : Roche

Technology : Small molecule


As of the data cut on 2/3/2020, the study is fully enrolled with 27 pts. Median age: 63 yrs (range 49-77). CLL features: 26% del(17p); 44% complex karyotype; 48% IGHV unmutated; 41% TP53 and 15% NOTCH1 mutation. Median prior CLL treatments: 2 (range 0-5, prior ibrutinib [n = 8], ven [n = 2], and PI3Ki [n = 2]) with 6 untreated CLL pts. Median # ven + R-EPOCH cycles: 4 (range 0-6). 5 pts had dose de-escalation of R-EPOCH, 1 pt had dose escalation. ≥Gr 3 heme tox: neutropenia (58%), anemia (50%), thrombocytopenia (50%). ≥Gr 3 non-heme tox in > 15% of pts: febrile neutropenia (38%) and hypophosphatemia (23% each). No pts had TLS with daily ven ramp-up. Infections: pneumonia (n = 4), sepsis during C1 of R-EPOCH prior to starting ven (n = 3), enterocolitis (n = 3), sinusitis (n = 2), and 1 pt each with influenza A and norovirus. 10 pts have died, including 7 due to disease progression (2 during C1 before ven), and 1 each due to sepsis, sudden death, and GVHD post-alloHCT. In ITT analysis, 16 responded (ORR 59%); 13/27 (48%) had CR as best response, all with undetectable bone marrow MRD for CLL. Six pts were not evaluable for efficacy of the combo (5 had toxicity in C1 and never started ven, 1 withdrew after C1). In the 21 pts who started combo therapy, the ORR was 76%, CR rate 62%. Only 1 pt with CR has progressed. The pt on longest ven maintenance is in CR 2 years post chemo. 8 pts went to alloHCT, with pts still in CR now up to 2.5 yrs post-alloHCT. With a median follow-up of 9.3 mo (range 0.6-30), median PFS and OS are both 16.3 mo.


VR-EPOCH is active for RS. Expected toxicities from intensive chemoimmunotherapy and ven were seen, but daily ven ramp-up was feasible. The 48% CR rate and median PFS of 16.3 mo are favorable in the context of historical results.


About two-thirds of the patients who started the VR-EPOCH combination achieved complete remission, far higher than the 20% achieved historically with R-EPOCH alone, giving rise to adoption of chemosensitization strategy

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