Umbralisib: A Dual PI3Kd/CK1 Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma

Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3Kd/casein kinase-1e, exhibits improved selectivity for PI3Kd compared with other PI3K inhibitors. This phase IIb trial was designed to evaluate the efficacy and safety of Umbralisib in patients with R/R iNHL. In this review, Umbralisib achieved meaningful clinical activity in heavily pretreated patients with iNHL. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse event-related discontinuations. The theoretical pharmacokinetic behavior comparison between Idelalisib, Duvelisib, and Parsaclisib correlates favorably with the observation in clinical settings.