Ibrutinib Plus Venetoclax Improves Outcomes in Relapsed Mantle Cell Lymphoma: SYMPATICO Trial
A phase 3 trial has demonstrated that combining ibrutinib with venetoclax significantly extends progression-free survival in patients with relapsed or refractory mantle cell lymphoma (MCL), offering new hope for individuals with this aggressive B-cell malignancy.
Results from the international SYMPATICO trial highlight the benefits of combining two targeted therapies—ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and venetoclax, a BCL-2 inhibitor—in a treatment-resistant patient population. Conducted at 84 centers across Europe, North America, and Asia-Pacific, the double-blind, placebo-controlled study enrolled 267 adult patients with MCL who had previously received up to five lines of therapy.
Patients were randomized to receive either ibrutinib with venetoclax (134) or ibrutinib with placebo (133). After a median follow-up of 51.2 months, median progression-free survival (PFS) in the ibrutinib–venetoclax arm was 31.9 months, compared with 22.1 months in the ibrutinib–placebo group. This translated to a 35% reduction in risk of disease progression or death (HR 0.65, P = .0052).
While the combination therapy was associated with a higher incidence of grade 3-4 neutropenia (31% vs 11%) and thrombocytopenia (13% vs 8%), the overall safety profile was consistent with known effects of the individual agents. Serious adverse events occurred in 60% of patients in both groups, and treatment-related mortality remained low and comparable.
The SYMPATICO trial had three parts, including a safety run-in and an ongoing evaluation of first-line use in treatment-naïve patients. While this report focuses on the relapsed/refractory cohort, data from the first-line setting are anticipated in the near future.
Reference
Wang M, Jurczak W, Trneny M, et al. Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2025;26(2):200-213. doi:10.1016/S1470-2045(24)00682-X
