Umbralisib A Potential New Treatment for Marginal Zone Lymphoma

PI3K inhibitors are a promising new therapy for the management of b cell lymphomas and are being evaluated in MZL.

by Dr. C.H. Weaver M.D. 6/2019

More than half of the individuals with recurrent marginal zone lymphoma (MZL) treated with the experimental PI3K delta inhibitor umbralisib experienced a response to treatment according to clinical trial results presented at the 2019 American Association for Cancer Research annual meeting.

Marginal zone lymphomas are typically first treated with the anti-CD20 therapy using Rituxan (rituximab) as a single drug or in combination with chemotherapy. Rituxan based therapy has improved outcomes but MZL eventually relapses, and these individuals have limited treatment options.

In January, the FDA granted a breakthrough therapy designation to umbralisib for adults with MZL who have had at least one anti-CD20 treatment.

About Umbralisib

Phosphatidylinositol 3-kinases (PI3K), are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. Umbralisib (TGR-1202) is an orally available PI3K delta inhibitor, targeting the delta isoform selectivity over the alpha, beta, and gamma isoforms of PI3K. The delta isoform of PI3K is strongly expressed in blood cells and is believed to be important in the proliferation and survival of B-cell lymphocytes.

About The UNITY-NHL Clinical Trial

Patients with MZL that had previously received ≥1 prior therapy, including at least one CD20 monoclonal antibody-containing regimen were enrolled in the study evaluating umbralisib. Patients received 800 mg orally once daily until progression or unacceptable toxicity.

Initial results from the found that 55% of treated patients had a complete or partial response at 6 months, and one in five had complete remission. The clinical benefit rate was 84 percent and tumors were reduced in 91 percent of patients with at least one post-baseline assessment.

The most common side effects were diarrhea, nausea, fatigue, headache, cough, and decreased appetite affected between 20-30 percent of patients. Neutropenia occurred in 8% of patients.

The results now need to be confirmed in other studies. Phase III clinical trials are ongoing in MZL and other B-cell malignancies, including follicular lymphoma and chronic lymphocytic leukemia.

Reference: https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1297

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