Overall response was strong even in high-risk patients (over age 65, with 17p deletion, with prior ibrutinib therapy, and mutations of BTK and PLCγ2).
A real-world trial of single-agent venetoclax in patients with chronic lymphocytic leukemia (CLL) with 17p deletion showed that response rates and duration of response were similar to those reported in clinical trials.
“These results suggest that the efficacy and safety profile of venetoclax demonstrated in the clinical trials setting are comparable to what has been observed in the real world,” wrote researcher Anthony R. Mato, MD, of Memorial Sloan Kettering Cancer Center, and colleagues in Haematologica.
Venetoclax is an oral second-generation BCL2 inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of patients with CLL with 17p deletion. Clinical trials of venetoclax showed overall responses rates (ORRs) ranging from 65% to 79% in patients with relapsed or refractory disease.
To better understand the use and efficacy of venetoclax in a real-world population, Mato and colleagues conducted a multicenter, retrospective study of all patients with CLL treated with venetoclax across 19 US academic and community cancer centers.
The study included 141 patients with a median age at treatment initiation of 67 years. Patients had received a median of three prior therapies. During dose escalation, the majority (85%) achieved the maximum dose of 400-mg daily.
Overall, 72% of patients responded to venetoclax, with 19.4% of this group achieving a complete response. The ORR was similarly high among several groups of high-risk patients, including those older than 65, with 17p deletion, prior ibrutinib therapy, BTK mutation, and PLCÎ³2 mutation. At a median follow-up of 7 months, the median progression-free survival and overall survival have not yet been reached.
To prevent tumor lysis syndrome (TLS), 93% of patients received allopurinol, 92% received normal saline, and 45% received rasburicase; 35.8% of patients had been considered intermediate-risk and 19.4 % were considered high-risk patients.
“TLS has been suggested as the most critical toxicity with venetoclax, contributing to early treatment-related deaths in clinical trials, particularly before the current dose ramp-up schedule was implemented in trials to minimize TLS risk,” the researchers wrote. “In our study, TLS rates were higher than those reported in most recent trials.”
TLS occurred in 13.4% of patients, with 6.7% of events in high-risk patients. One death from TLS was reported in a patient re-challenged with venetoclax after delayed interruption without utilizing a dose-escalation schedule.
Other adverse events of interest included neutropenia (47.4%), thrombocytopenia (36%), neutropenia fever (11.6%), and diarrhea (7.3%).
Forty-one patients have discontinued therapy and 24 have received subsequent therapy, mostly ibrutinib.
“To date, little is known regarding reasons for venetoclax discontinuation in clinical practice,” the researchers wrote. “In our study, 28% of all patients discontinued therapy; 53.8% of these patients discontinued due to progression of CLL excluding Richter’s transformation (RT), and 20.5% discontinued due to toxicity.
The FDA recently expanded the approval of venetoclax to include combination therapy with rituximab for patients with CLL with or without 17p deletion who have received one prior line of therapy.