The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study.

Autor: Zelenetz AD; Memorial Sloan Kettering Cancer Center New York New York USA., Jurczak W; Maria Sklodowska-Curie National Research Institute of Oncology Krakow Poland., Ribrag V; Gustave Roussy Cancer Villejuif France., Linton K; The Christie NHS Foundation Trust and Manchester Cancer Research Centre Manchester UK., Collins GP; GenesisCare Cancer and Radiotherapy Centre Oxford UK., Jiménez JL; University Hospital Ramon y Cajal Madrid Spain., Bishton M; Translational Medical Sciences University of Nottingham and Nottingham University Hospitals NHS Trust Nottingham UK., Dholaria B; Vanderbilt School of Medicine Nashville Tennessee USA., Mengarelli A; IRCCS Regina Elena National Cancer Institute Rome Italy., Phillips TJ; University of Michigan Health System Ann Arbor Michigan USA.; Present address: City of Hope, Duarte California USA., Sungala N; Liverpool Hospital Sydney New South Wales Australia., Musuraca G; Istituto Scientifico Romagnolo per lo Studio et la Cura dei Tumori Meldola Italy., Sheehy O; Belfast HSC Trust Belfast United Kingdom., Van Den Neste E; Cliniques Universitaires Saint-Luc Bruxelles Belgium., Odera M; Kyowa Kirin Co. Ltd. Tokyo Japan., Miao L; MEI Pharma San Diego California USA., Gold DP; MEI Pharma San Diego California USA., Ghalie RG; MEI Pharma San Diego California USA., Zinzani PL; IRCCS Azienda Ospedaliero-Universitaria di Bologna Bologna Italy.
Jazyk: angličtina
Zdroj: HemaSphere [Hemasphere] 2024 Aug 06; Vol. 8 (8), pp. e138. Date of Electronic Publication: 2024 Aug 06 (Print Publication: 2024).
DOI: 10.1002/hem3.138
Abstrakt: In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2-8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9-80.4), the complete response (CR) rate was 38% (95% CI, 29.3-47.3), and the median DOR was 16.4 months (95% CI, 9.5-not reached). With a median follow-up of 14.3 months (range, 1-30.5), the median progression-free survival was 11.6 months (95% CI, 8.3-not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3-4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies.
(© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)
Databáze: MEDLINE
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