Abstract
Idelalisib is a first-in-class, selective, orally available, phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor. High efficacy in double refractory indolent B-cell non Hodgkin lymphoma has been demonstrated based on results of a phase 2 study (101-09).
Idelalisib was given orally, 150mg twice daily, until progressive disease or unacceptable toxicity. The overall response rate was achieved in 71/125 patients (57 %), including 7 complete remissions (6 %), 63 partial remissions (59 %) and one minor response in patient with Waldenström macroglobulinaemia.
The median duration of response in responding patients was 12.5 months and the median progressionfree survival 11 months. Based on results of 101-09 trial idelalisib was approved by EMEA agency in Europe for the treatment of patients with follicular lymphoma refractory to 2 lines of previous therapy.
Despite high clinical efficacy, some important side effects were recorded. Most frequent adverse events (all grades of toxicity) were: diarrhea (43 %), fatigue (30 %), nausea (30 %), cough (29 %) and pyrexia (28 %).
Clinically signifiant grade toxicities were: diarrhoea (13 %) and pneumonitis (7 %). Most frequent laboratory findings grade3 were neutropenia (27 %) and elevation of ALT or AST (13 %).
Due to severity of adverse events during idelalsib treatment, the American Food and Drug Administration issued black box warning for fatal and/or severe diarrhoea or colitis, hepatotoxicity, pneumonitis and intestinal perforation in the prescribing information. More data regarding clinical significance of these adverse events are needed from results of ongoing clinical randomized trials.