The standard front line therapy for chronic lymphocytic leukaemia (CLL) is a combination of chemotherapeutic drugs referred to as EPOCH-R. This includes drugs such as etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. However, CLL patients who develop Richter’s Syndrome (RS) are resistant to chemotherapy, with a poor prognosis. When treated with venetoclax (ven) (BCL-2 oral inhibitor), these RS patients had a response rate of 43%. A recent study by Davids et al. has investigated the efficacy of combining venetoclax with dose-adjusted EPOCH-R as a first-line treatment option for RS.
The single-arm, phase 2 enrolled 26 patients (age-49-77 years) to determine the complete response rate (CR) with venetoclax plus EPOCH-R. Patients were administered one cycle of R-EPOCH. Then after count recovery, patients received accelerated daily venetoclax ramp-up (20/50/100/200/400 mg) followed by venetoclax + R-EPOCH for up to 5 more 21-day cycles. Responders received venetoclax (400mg/daily) maintenance or cellular therapy.
At the cutoff date of 2/3/2020, 50% (13/26) patients achieved CR, of which 11 achieved undetectable bone marrow minimal residual disease for CLL. Additionally, partial response was seen in three patients. The observed median progression-free survival and overall survivals were 10.1 and 19.6 months, respectively. The adverse events of grade ≥3 included neutropenia (65%), thrombocytopenia (50%), and febrile neutropenia (38%). Importantly, tumour lysis syndrome was not observed with venetoclax daily ramp-up.
The proposed combination of venetoclax with R-EPOCH demonstrated durable CR in RS patients.