Evaluating long-term effectiveness and safety of venetoclax patients with for non-Hodgkin lymphoma

This early study looked at the long-term results of the targeted treatment venetoclax (Venclexta) for patients with relapsed non-Hodgkin lymphoma (NHL). It found that venetoclax is a safe and effective treatment and that some patients have a durable response.

NHL is a group of cancers of a type of white blood cell known as B-cells. NHL survival has been improved by targeted treatments, which specifically kill or reduce B-cells. However, NHL will often become resistant to a treatment over time. Researchers are looking for additional treatments for NHL which has relapsed after previous treatment.

Venetoclax is a targeted treatment that has been approved for some blood cancers including acute myeloid leukemia and small lymphocytic lymphoma. It is not yet approved for all NHLs. Venetoclax works by interfering with the protein B cell lymphoma-2 (BCL-2). This protein is overactive in NHL and prevents the normal death of cells. It is not clear whether long-term treatment with venetoclax is safe and effective for people with relapsed NHL.

This study included 106 patients with NHL which had relapsed after at least one previous treatment. The most common types of NHL in this report were follicular lymphoma (FL) and mantle cell lymphoma (MCL). FL is a slow-growing disease, while MCL grows aggressively. The study also included patients with Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma (MZL). All patients were treated with venetoclax alone until their cancer began to progress (spread). After progression, the patients had the option to increase their dose and add the antibody therapy rituximab (Rituxan). The patients were followed for 38.5 months on average.

Patients were treated for 5.3 months on average with venetoclax alone. Those who responded to treatment had an average venetoclax treatment duration of 19.1 months.

38% of patients with FL responded to venetoclax. 17% of patients with FL had a complete response (cancer no longer detectable). Complete responses lasted 37.6 months on average. For patients who responded to venetoclax but still had signs of cancer (partial response), the response lasted an average of 9.7 months.

75% of patients with MCL responded. There was a complete response for 21% of patients with MCL, which lasted 31.5 months on average. For patients with a partial response, it lasted 10.1 months on average.

Two out of three patients (67%) with MZL responded. There was an average response duration of 20.1 months for patients with MZL, including all treated patients. 

All four patients (100%) with WM responded to treatment. There was a response duration of 25.3 months for patients with WM.

The most common side effects were nausea (47%), diarrhea (43%), and fatigue (40%). The most common severe side effects were low white blood cells (13%) and low red blood cells (11%).

This study found that venetoclax is a safe and effective treatment for relapsed NHL, and that some patients have a long-term response.

This study was funded by AbbVie and Genentech, who are developing Venclexta for NHL. This was a long-term follow-up of an early (Phase I) trial. The number of patients was very small. Larger studies are needed.