FDA Investigates Umbralisib Due to Possible Increased Risk of Death in Lymphomas

Umbralisib is currently under investigation by the FDA regarding a potentially increased risk of death in patients with lymphomas following data from an ongoing trial investigating its use in chronic lymphocytic leukemia.

The FDA has launched an investigation into whether treatment with umbralisib (Ukoniq) results in an increased risk of death for its approved indications in the treatment of lymphomas, according to a press release from the FDA.1

Following an initial evaluation of UNITY clinical trial assessing umbralisib in chronic lymphocytic leukemia (CLL), which is a disease related to both marginal zone and follicular lymphoma for which umbralisib is approved, investigators uncovered a potential increased risk of death among those treated. With respect to these concerns, the FDA sent out a notice to patients and health care providers stating their intention to re-evaluate the therapeutic in its FDA-approved indications.

Part of this process includes continued evaluation of the phase 3 UNITY-CLL trial (NCT02612311), which is examining umbralisib and ublituximab (U2) in a population of patients with treatment-naïve and relapsed/refractory chronic lymphocytic leukemia.2 Exploration of these findings and continued marketing of the drug may be discussed by the FDA at an upcoming meeting. In the interim, ongoing clinical trials utilizing umbralisib have suspended enrollment while findings are reviewed.

In January 2022, the FDA placed a partial clinical hold on U2 as a treatment for patients with CLL and non-Hodgkin lymphoma.3 Presented at the 2022 Virtual Oncology Investor Conference, the developer noted that although the hold was not based on new findings, other concerns would be presented at the Oncologics Drug Advisory Committee meeting in March or April 2022.

A biologics license application for U2 as treatment of CLL was submitted in May 2021 based on the UNITY-CLL trial.4 Umbralisib received accelerated approval in February 2021 as a treatment for patients with marginal zone lymphoma who previously received at least 1 anti-CD20 regimen or follicular lymphoma previously treated with 3 or more lines of therapy.5 The approval was based on findings from the phase 2b UNITY-NHL trial (NCT02793583), examining U2 with or without bendamustine and single-agent umbralisib in previously treated non-Hodgkin lymphoma.


  1. FDA investigating possible increased risk of death with lymphoma medicine Ukoniq (umbralisib). News release. FDA. February 3, 2022. Accessed February 3, 2022. https://bit.ly/3GiKnvO
  2. Gribben JG, Jurczak W, Jacobs R, et al. Umbralisib plus ublituximab (U2) is superior to obinutuzumab plus chlorambucil (O+Chl) in patients with treatment naïve (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): results from the phase 3 Unity-CLL study. Blood. 2020;136(suppl 1):37-39. doi:10.1182/blood-2020-134783
  3. TG Therapeutics falls 30% as CEO discloses partial clinical hold on blood cancer trials. News release. TG Therapeutics. January 28, 2022. Accessed February 3, 2022. https://yhoo.it/3rWhKPL
  4. TG Therapeutics announces FDA acceptance of biologics license application for ublituximab in combination with Ukoniq (umbralisib) as a treatment for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. News release. TG Therapeutics, Inc. May 25, 2021. Accessed January 28, 2022. https://bit.ly/34gxnGj
  5. FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma. News release. FDA. February 5, 2021. Accessed February 3, 2022. https://bit.ly/3roDAwr