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

This is the first study to examine the combination of everolimus and bendamustine in the treatment of lymphoid hematologic malignancies. Eighteen patients with relapsed/refractory lymphoma and multiple myeloma were treated. Toxicities were mainly hematologic. Response rates varied by malignancy from 20% to 100%. Introduction: 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). Patients and Methods: In this phase I trial, 18 patients (8 with NHL, 6 with MM, and 4 with HL) were treated with bendamustine 90 mg/m(2) on days 1 and 2 and everolimus from 5 to 10 mg daily on a 28-day cycle, for up to 4 cycles. Results: 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. Conclusion: The combination of everolimus and bendamustine appeared to be well-tolerated and relatively efficacious. (C) 2020 Elsevier Inc. All rights reserved.