Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.

Center for Cancer and Blood Disorders Bethesda Maryland USA

Clinical Hematology Department Institut Català d'Oncologia Hospital Germans Trias i Pujol IJC Barcelona Spain

Clinical Research Alliance Inc Westbury New York USA

Department of Haematology and Phase 1 Unit Rigshospitalet Copenhagen Denmark

Department of Haematooncology University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università di Bologna Bologna Italy

Division of Hematology and Oncology Medical College of Wisconsin Milwaukee Wisconsin USA

Incyte Corporation Wilmington Delaware USA

Instituto de Investigación Sanitaria Gregorio Marañón Madrid Spain

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

Lymphoma Unit Department of Hematology Fundación Jimenez Diaz University Hospital Madrid Spain

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