Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare, incurable hematological malignancy with a heterogenous presentation and clinical course. A wide variety of chemotherapy-based regimens are currently utilized in untreated patients. Several targeted or small molecule therapies have shown efficacy in the relapsed/refractory (R/R) setting over the last several years and have since been explored in the frontline setting. Lenalidomide plus rituximab was explored in a phase II study of 38 untreated patients with MCL ineligible for transplant, where the combination produced durable remissions. We looked to build upon this regimen by adding venetoclax to the combination. We conducted a multi-center, open-label, non-randomized, single arm study to evaluate this combination. We enrolled 28 unselected patients with untreated disease irrespective of age, fitness or risk factors. Lenalidomide was dosed at 20 mg daily on days 1-21 of each 28-day cycle. The dose of venetoclax was determined using the TITE-CRM model. Rituximab was dosed at 375 mg/m2 weekly starting on cycle 1 day 1 until cycle 2 day 1. No DLTs were noted. All patients were treated with venetoclax at the maximum tolerated dose of 400 mg daily. The most common Adverse Events noted were neutropenia and thrombocytopenia. The overall and complete response rates were 96% and 86% respectively. 86% of patients achieved minimal residual disease undetectability by NGS. The median overall and progression-free survivals were not reached. The combination of lenalidomide, rituximab and venetoclax is a safe and effective regimen in patients with untreated MCL. Clinical trial # NCT03523975.