Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients with Relapsed or Refractory Indolent Lymphoma
In the May 20,2021 edition of Journal of Clinical Oncology , investigators report on the utility of Umbralisib in relapsed / refractory indolent lymphomas.
Umbralisib is a PI3K inhibitor, with known activity in relapsed / refractory non-Hodgkin’s lymphoma.
In a phase 2 clinical trial, patients with relapsed marginal zone lymphoma, follicular lymphoma or small lymphocytic leukemia, unresponsive to 2 or more lines of therapy, were treated with Umbralisib 800 mg once daily until disease progression, unacceptable toxicity or study withdrawal. The primary endpoint was overall response rate with a secondary endpoint including partial response, duration of response, safety and progression free survival.
After a median follow-up of 27.7 months for efficacy and 21.4 months for safety, the overall response rate was 47.1% with tumor reduction seen in 86.4% of patients. The median times to response was between 2.7 and 4.6 months. The median duration of response was not reached for marginal zone lymphoma.
The median duration of response for follicular lymphoma was 11.1 months and 18.3 months for small lymphocytic leukemia. The median progression free survival was not reached in marginal zone lymphoma, 10.6 months for follicular lymphoma and 20.9 months for small lymphocytic leukemia. Grade 3 or higher treatment emergent adverse events were reported in 53.4% of patients. 32 patients had to discontinue Umbralisib as a result of adverse events. Grade 3 or higher adverse events were seen in more than 10% of patients included neutropenia, diarrhea, as well as elevations in AST and ALT, 11.5%, 10.1%, 6.7, 7.2%, respectively. Nearly 80% of patients experienced elevations in creatinine, but the best majority were clinically negligible.
The authors concluded “Umbralisib achieve meaningful clinical activity in heavily pretreated patients with indolent non-Hodgkin’s lymphoma. The safety profile was manageable, with a relatively low incidence of immune mediated toxicities and adverse event related discontinuations “
Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma