A Novel Combination of the mTORC1 Inhibitor Everolimus and the Immunomodulatory Drug Lenalidomide Produces Durable Responses in Patients with Heavily Pretreated Relapsed Lymphoma

Publication date: Available online 15 June 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Leslie Padrnos, Brenda Ernst, Amylou C. Dueck, Heidi E. Kosiorek, Brenda F. Ginos, Angela Toro, Patrick B. Johnston, Thomas M. Habermann, Jose F. Leis, Joseph R. Mikhael, Grzegorz S. Nowakowski, Joseph Colgan, Luis Porrata, Stephen M. Ansell, Thomas E. Witzig, Craig ReederSummaryTreatment outcomes have improved in lymphoid malignancies but relapse remains inevitable in most patients. Everolimus (RAD) and lenalidomide (LEN) have shown clinical activity as single agents in patients with relapsed and refractory (R/R) Hodgkin and non-Hodgkin lymphomas. This Phase I/II trial for patients with R/R lymphoid malignancy opened at Mayo Clinic between January 2011 and May 2013 utilized a standard cohort of 3+3 design to determine the Maximum Tolerated Dose(MTD) of the combination. Twenty-seven (49%) of the patients had failed stem cell transplantation, 63% had stage IV disease and 78% had failed 3 or more prior therapies. Fifty-five patients were evaluable for analysis. The MTD was determined to be RAD 5mgdaily + LEN 10 mg/d X21d. The most common Gradeā‰„3 toxicities were hematologic including neutropenia (56%), leucopenia (38%), and thrombocytopenia (33%). Seven patients discontinued study due to adverse events. One death occurred due to disease progression. The ORR was 27% (15/55) with 38% (21/55) having stable disease. This phase I/II trial of everolimus and lenalidomide in relapse...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research