As reported in The Lancet Oncology by Michael Wang, MD, and colleagues, the phase III SYMPATICO trial has shown that venetoclax/ibrutinib significantly improved progression-free survival vs placebo/ibrutinib in patients with relapsed or refractory mantle cell lymphoma (MCL).
Michael Wang, MD
Study Details
In the double-blind trial, 267 patients from sites in Europe, North America, and the Asia-Pacific region were randomly assigned between April 2018 and August 2019 to receive ibrutinib at 560 mg once daily concurrently with oral venetoclax at a 5-week ramp-up to 400 mg once daily (n = 134) or matching placebo and single-agent ibrutinib at 560 mg once daily (n = 133) for 2 years, followed by single-agent ibrutinib until disease progression or unacceptable toxicity. The primary endpoint of the trial was investigator-assessed progression-free survival in the intention-to-treat population.
Key Findings
Median follow-up was 51.2 months (interquartile range = 48.2–55.3 months). Median progression-free survival was 31.9 months (95% confidence interval [CI] = 22.8–47.0 months) in the ibrutinib/venetoclax group vs 22.1 months (95% CI = 16.5–29.5 months) in the placebo/ibrutinib group (hazard ratio = 0.65, 95% CI = 0.47–0.88, P = .0052). The rate at 24 months was 57% vs 45%.
At interim analysis for overall survival, estimated 24-month overall survival was 66% in the ibrutinib/venetoclax group vs 61% in the placebo/ibrutinib group.
Grade ≥ 3 adverse events occurred in 83% of patients in the ibrutinib/venetoclax group vs 76% of the placebo/ibrutinib group, with the most common in both groups being neutropenia (31% vs 11%), thrombocytopenia (13% vs 8%), and pneumonia (12% vs 11%). Serious adverse events occurred in 60% vs 60% of patients. Death considered related to treatment occurred in three patients (2%) in the ibrutinib/venetoclax group (from COVID-19 infection, cardiac arrest, and respiratory failure, respectively) and in two patients (2%) in the ibrutinib/placebo group (from cardiac failure and COVID-19–related pneumonia, respectively).
The investigators concluded: “The combination of ibrutinib/venetoclax significantly improved progression-free survival compared with ibrutinib/placebo in patients with relapsed or refractory MCL. The safety profile was consistent with known safety profiles of the individual drugs. These findings suggest a positive benefit-risk profile for ibrutinib/venetoclax treatment.”
Dr. Wang, of The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosures: The study was funded by Pharmacyclics (an AbbVie Company) and Janssen Research and Development. For full disclosures of the study authors, visit thelancet.com.
