Umbralisib Approved for Marginal Zone Lymphoma and Follicular Lymphoma

Follicular lymphoma.

The FDA has granted accelerated approval to umbralisib (Ukoniq™, TG Therapeutics) for patients with relapsed/refractory marginal zone lymphoma (MZL) and relapsed/refractory follicular lymphoma (FL).

Umbralisib is a dual inhibitor of phosphatidylinositol-3-kinase (Pi3K) delta and casein kinase-1 epsilon that has achieved meaningful clinical activity in the treatment of patients with relapsed/refractory MZL and relapsed/refractory FL. The safety profile was manageable, with a low incidence of immune-mediated toxicities that are also exhibited by other PI3K inhibitors.

The Phase 2 UNITY-NHL trial (NCT02793583), on which the approval was based, enrolled 69 patients with refractory/relapsed MZL who received at least one prior line of treatment including an anti-CD20–based regimen and 117 patients with refractory/relapsed FL who received at least two prior lines of treatment including an anti-CD20–based regimen and an alkylating agent–based regimen. Patients received 800 mg of umbralisib once daily in 28-day treatment cycles until disease progression or unacceptable toxicity, for a primary end point of overall response rate as assessed by an independent review committee according to the revised International Working Group criteria.

At a median follow-up of 27.8 months, umbralisib produced an overall response rate of 49.3% in patients with MZL, with 15.9% achieving a complete response and a disease control rate––defined as the sum of complete responses, partial responses, and stable disease––of 82.6%. At a median follow-up of 27.5 months, the overall response rate in patients with FL was 45.3%, with 5.1% achieving a complete response, and a disease control rate of 79.5%.

According to the prescribing information, adverse events affecting at least 15% of patients include increased creatinine, diarrhea or colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash.

Serious adverse reactions were experienced by a total 18% of patients and included diarrhea or colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). Fatal adverse reactions, including exfoliative dermatitis, occurred in less than 1% of patients.

“Umbralisib achieved meaningful clinical activity in a heavily pretreated indolent non-Hodgkin lymphoma population,” concluded the study investigators in their abstract presented at the American Society of Hematology Annual Meeting and Exposition this past December, led by Pier Luigi Zinzani, MD, Professor at the Seràgnoli Institute of Hematology of the University of Bologna, Italy. “The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse effect-related discontinuations. These results suggest umbralisib has a favorable benefit-risk profile in this patient population and further development is ongoing.”

The recommended dose of umbralisib is 800 mg, taken orally once daily with food.

For More Information

Zinzani PL, Samaniego F, Jurczak W, et al (2020). Umbralisib, the once daily dual inhibitor of PI3Kd and casein kinase-1 demonstrates clinical activity in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results from the phase 2 global unity-NHL trial. 62nd American Society of Hematology Annual Meeting & Exposition. Abstract 2934. (2021). Study to assess the efficacy and safety of ublituximab + umbralisib with or without bendamustine and umbralisib alone in patients with previously treated non-Hodgkins lymphoma (UNITY-NHL). NCT02793583.

Ukoniq (umbralisib) prescribing information (2021). TG Therapeutics. Available at:

US Food & Drug Administration (2021). FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma. Available at:

Image credit: Nephron. Licensed under CC BY-SA 3.0 

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