Early venetoclax discontinuation impacts survival in CLL
Researchers linked early discontinuation of venetoclax to shorter progression-free survival and impacted overall survival in relapsed or refractory chronic lymphocytic leukemia but interruption of venetoclax was not.
“Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells,” Anthony R. Mato, MD, MSCE, director of the CLL Program at Memorial Sloan Kettering Cancer Center, told Healio about his poster from ASCO20 Virtual Scientific Program. “Some people with relapsed or refectory chronic lymphocytic leukemia who take venetoclax [Venclexta; Genentech, AbbVie] plus rituximab [Rituxan; Genentech, Biogen] experience treatment discontinuation or modification.”
Mato and colleagues presented data from the phase 3 MURANO study, in which they examined the impact of premature venetoclax discontinuation and/or treatment modification on clinical outcomes in patients with relapsed or refectory CLL.
The researchers performed time-dependent Cox proportional hazards regression models (stratified by 17p deletion and risk status) to assess the effect of venetoclax discontinuation/interruption on PFS and OS, according to the abstract. They performed retrospective analyses in intent-to-treat patients with relapsed or refractory CLL from the fixed-duration venetoclax plus rituximab arm of this phase 3 study.
Overall, 140 of 194 patients in the venetoclax plus rituximab arm completed 2 years of therapy. Of these, 54 patients (28%) discontinued treatment early – the most common reasons were due to adverse events (n = 29) and disease progression (n = 12), according to the abstract. The investigators reported that the median venetoclax durations for those who discontinued because of adverse events and disease progression were 11.3 months and 17.1 months (P = .08).
Mato and colleagues observed inferior PFS in patients who discontinued treatment early for any reason, excluding disease progression or adverse events, compared with patients who completed therapy. Further, greater exposure over time to venetoclax treatment significantly decreased the risk for a PFS (HR = 0.93; 95% CI, 0.88–0.99) or OS (HR = 0.85; 95% CI, 0.79–0.92) event.
Overall, 134 of 194 patients interrupted treatment due to adverse events, most commonly because of neutropenia (43%); the median duration of interruption was 9 days. Treatment interruption at any duration did not impact PFS (HR = 0.67; 95% CI, 0.38–1.19) or OS (HR = 0.97; 95% CI, 0.43–2.21), according to the data.
“This study provides the first comprehensive account on how treatment discontinuation or modification of venetoclax plus rituximab impacts clinical outcome measures in people with relapsed or refectory CLL,” Mato told Healio. “Given that treatment modification had no impact on progression-free survival or overall survival, appropriate treatment modification to manage adverse events can allow patients to continue venetoclax treatment and avoid treatment discontinuation, which was associated with shorter progression-free survival.”
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Mato AR, et al. Abstract 8028. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.