ABSTRACT
The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Neoplasm Recurrence, Local/drug therapy , Rituximab/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Drug Resistance, Neoplasm , Female , Follow-Up Studies , France/epidemiology , Humans , Lymphoma, Follicular/mortality , Lymphoma, Follicular/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Progression-Free Survival , Prospective Studies , Rituximab/pharmacology , Time-to-TreatmentABSTRACT
INTRODUCTION: Owing to improved lymphoma cure rates, preserving fertility has received attention. MATERIAL AND METHODS: Women under 40 years at diagnosis of lymphoma, treated with >/=3 chemotherapy cycles including alkylating agents and no pelvic or total body irradiation were selected. A total of 84 women fullfiled these criteria with a median age at diagnosis at 27.4 years, the duration of first-line chemotherapy ranged from 3 to 36 months (median: 7 months) and 17 women received consolidation with high-dose therapy (HDT). After complete remission, 16 women relapsed and received second-line regimen followed by HDT for 9 months. RESULTS: With a median follow-up of 100 months, 31 women became pregnant, 34 women had primary ovarian failure (POF) and 19 women retained relative fertility. While women with preserved or relative fertility had the same clinical characteristics those with POF were older at diagnosis (30.6 versus 24.3 years), relapsed more often (34 versus 8%) and received HDT more often (54 versus 16%). After HDT (n=26), only three women (25-27 years) became pregnant. CONCLUSION: Women given alkylating agents have a high risk of POF if they are older than 30 years at diagnosis and older than 25 years at the time of HDT. For these women with a high chance of cure and who wish to be pregnant after treatment, regimens with fewer alkylating agents should be proposed or cryopreservation of embryos when possible.
