Long-term results from the phase 2 M20-075 study show that the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) provides strong and lasting responses in patients with relapsed or refractory mantle cell lymphoma (MCL).
After a median follow-up of 37.2 months, the overall response rate was 83.3%. Among patients who could be evaluated, 83% achieved a complete response. At 36 months, 90% of responding patients were still in remission, showing durable benefit. The overall survival rate at three years was 76.9%.
The treatment works by targeting the cancer in two ways. Ibrutinib blocks BTK, a protein that helps cancerous B cells survive. Venetoclax blocks BCL-2, a protein that prevents cancer cells from undergoing programmed cell death. Patients received both drugs daily for up to 24 months, followed by ibrutinib alone until disease progression.
The combination was considered well tolerated, with a predictable safety profile. The most common side effects included neutropenia and diarrhea (both 54%), as well as constipation and fever (38%). Severe side effects included neutropenia (46%), leukopenia (23%), and COVID-19 pneumonia (15%). Although many patients needed dose interruptions and over half eventually stopped venetoclax due to side effects, only one patient discontinued the entire study because of an unrelated adverse event.
Overall, the findings suggest that this dual-targeted approach offers durable disease control with manageable toxicity in relapsed or refractory MCL.