Parsaclisib for the treatment of primary autoimmune hemolytic anemia: Results from a phase 2, open-label study.

Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).