A Phase I Study of Everolimus and Bendamustine in Patients With Relapsed/Refractory Lymphoid Hematologic Malignancies.

Everolimus and bendamustine both have single-agent activity against lymphoid hematologic malignancies. We examined this combination in a group of heavily pretreated patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM).

In this phase I trial, 18 patients (8 with NHL, 6 with MM, and 4 with HL) were treated with bendamustine 90 mg/m² on days 1 and 2 and everolimus from 5 to 10 mg daily on a 28-day cycle, for up to 4 cycles.

Adverse events were generally mild and mostly hematologic in nature. The most frequent grade 3/4 adverse events were lymphopenia (61%), thrombocytopenia (22%), leukopenia (22%), neutropenia (17%), and fatigue (17%). Overall response rate varied by malignancy: diffuse large B-cell lymphoma, 20% (1 of 5 patients); HL (2 of 4 patients), 50%; MM, 80% (4 of 5 patients); and indolent lymphomas, 100% (3 of 3 patients). The maximum tolerated dose of everolimus was determined to be 7.5 mg daily.The combination of everolimus and bendamustine appeared to be well-tolerated and relatively efficacious.