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/m² 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.

Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using venetoclax in combination with decitabine or azacitidine, which is not otherwise widely evaluated in the current literature. Our patients come from a large, socioeconomically and geographically diverse area including the majority of Northern California. Most had ELN Adverse Risk (52%) or Intermediate Risk (44%) AML, and most had an ECOG Performance Status of 1 (64%). Over half (52%) had prior hypomethylating agent exposure, and 40% had Secondary AML. We observed an overall response rate of 52%, with eight patients (32%) achieving composite complete remission. Median overall survival was 5.5 months, and for patients achieving composite complete remission this was 21.6 months. One-year estimated overall survival was 38%. Three patients were able to proceed directly to stem cell transplant for consolidation, and all three were alive at last follow-up, ranging 13.8-24.0 months. We found venetoclax in combination with hypomethylating agents to be well tolerated and potentially efficacious in securing long-term remissions for patients with relapsed/refractory AML.