BACKGROUND: Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell malignancies. This phase 2 study (CITADEL-203; NCT03126019, EudraCT 2017-001624-22) assessed efficacy and safety of parsaclisib monotherapy in patients with R/R follicular lymphoma (FL). METHODS: Patients ≥18 years of age with histologically confirmed R/R FL (grade 1-3a) and prior treatment with ≥2 systemic therapies received parsaclisib 20 mg once daily (QD) for 8 weeks then parsaclisib 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg QD for 8 weeks then parsaclisib 2.5 mg QD (daily dosing group [DG]); DG was selected for further assessment. Primary endpoint was objective response rate (ORR). FINDINGS: At data cut-off (January 15, 2021), 126 patients had been treated (WG: n = 23; DG: n = 103). ORR (95% confidence interval [CI]) was 77.7% (68.4-85.3) with a complete response rate (95% CI) of 19.4% (12.3-28.4) in DG; median (95% CI) duration of response was 14.7 months (10.4-not estimable [NE]), median progression-free survival was 15.8 months (11.0-NE), and median overall survival was not reached. The most common any-grade treatment-emergent adverse events (TEAEs) among all treated patients included diarrhoea (n = 48, 38.1%), nausea (n = 31, 24.6%), and cough (n = 28, 22.2%); the most common grade ≥3 TEAEs were diarrhoea (n = 15, 11.9%), neutropenia (n = 13, 10.3%), and colitis (n = 7, 5.6%). Dose interruption, reduction, and discontinuation from TEAEs occurred in 46.8% (n = 59), 17.5% (n = 22), and 23.8% (n = 30) of patients, respectively. INTERPRETATION: Treatment with parsaclisib demonstrated rapid and durable responses, and a manageable safety profile in patients with R/R FL. FUNDING: Incyte Corporation.

1st Department of Medicine Hematology Charles University General Hospital Prague Czech Republic

4th Department of Internal Medicine Hematology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Department of Haematology and Stem Cell Transplantation Birmingham Heartlands Hospital Birmingham UK

Division of Hemathology and Stem Cell Transplantation IRCCS Istituto Nazionale Tumori Milan Italy

Division of Hematologic Malignancies and Cellular Therapy Department of Medicine Duke Cancer Institute Durham NC USA

Forrest General Hospital and Hattiesburg Clinic of Hematology and Oncology Hattiesburg MS USA

Hematology Department Hospital General Universitario Gregorio Marañón Madrid Spain

Hospital Universitario La Paz Madrid Spain

Incyte Corporation Wilmington DE USA

Institute of Hematology Sheba Medical Center Ramat Gan Israel

Karolinska Institutet Department of Medicine Huddinge and Karolinska University Hospital Unit for Hematology Stockholm Sweden

Royal Marsden Hospital NHS Foundation Trust London and Surrey UK

Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Sheffield Teaching Hospital NHS Foundation Trust Sheffield and London UK

University of Washington School of Medicine Fred Hutch Cancer Center Seattle WA USA

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