FDA Approval: Idelalisib Monotherapy for the Treatment of Patients with Follicular Lymphoma and Small Lymphocytic Lymphoma

摘要

Abstract On July 23, 2014, the FDA granted accelerated approval to idelalisib (Zydelig tablets; Gilead Sciences, Inc.) for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma or relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. In a multicenter, single-arm trial, 123 patients with relapsed indolent non-Hodgkin lymphomas received idelalisib, 150 mg orally twice daily. In patients with follicular lymphoma, the overall response rate (ORR) was 54%, and the median duration of response (DOR) was not evaluable; median follow-up was 8.1 months. In patients with SLL, the ORR was 58% and the median DOR was 11.9 months. One-half of patients experienced a serious adverse reaction of pneumonia, pyrexia, sepsis, febrile neutropenia, diarrhea, or pneumonitis. Other common adverse reactions were abdominal pain, nausea, fatigue, cough, dyspnea, and rash. Common treatment-emergent laboratory abnormalities were elevations in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, absolute lymphocytes, and triglycerides. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials. Introduction Although there are several active combinations of cytotoxic chemotherapeutics or radioimmunotherapeutics that can be used for the treatment of relapsed follicular lymphoma (FL) or small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL), response rates range from 40% to 90% with varying durations of response (1, 2). Moreover, repeated administration of intravenous combination chemotherapy is associated with myelosuppression that may limit the amount of treatment that can be given. Therapies currently used for the treatment of patients with relapsed FL or SLL/CLL include single-agent rituximab or combination regimens; for example, bendamustine, rituximab (BR); rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP); rituximab, cyclophosphamide, vincristine sulfate, prednisone (RCVP; ref. 3). SEER 5-year relative survival rates for patients with FL and SLL/CLL are estimated to be 86% and 79%, respectively (4).