Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia: Phase 2, multicenter, open-label study

Abstract

Patients with relapsed warm antibody autoimmune hemolytic anemia (wAIHA) have limited treatment options. Fostamatinib is a potent, orally administered spleen tyrosine kinase inhibitor approved in the United States and Europe for the treatment of adults with chronic immune thrombocytopenia (ITP). This phase 2 study evaluated the response to fostamatinib, administered at 150 mg BID orally with or without food in adults with wAIHA and active hemolysis with hemoglobin (Hgb) <10 g/dL who had failed at least one prior treatment. Hemoglobin levels and safety assessments were performed at visits every 2 weeks. The primary endpoint was Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by week 24 without rescue therapy or red blood cell transfusion. Eleven of 24 (46%) patients achieved the primary endpoint. Increases in median Hgb were detected at week 2 and sustained over time. Median lactate dehydrogenase levels and reticulocyte counts generally declined over time with little change in median haptoglobin levels. The most common adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). AEs were manageable and consistent with the fostamatinib safety database of over 3900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and ITP). No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, phase 3 study is nearing completion.

Trial registration: ClinicalTrials.gov NCT02612558.

Conflict of interest statement

David J. Kuter has received research funding from Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, and Takeda (Bioverativ) UCB; and has served in a consulting role for Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa‐Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Platelet Disorder Support Association, Principia, Protalex, Protalix, Rigel, Sanofi, Genzyme, Shionogi, Shire, Takeda (Bioverativ), UCB, Up‐To‐Date, and Zafgen. Kerry A. Rogers has received research funding from Genentech, AbbVie, Novartis, and Janssen; has served in a consulting role for Acerta Pharma, AbbVie, Genentech, Pharmacyclics, AstraZeneca, and Innate Pharma; and has received travel funding from AstraZeneca. Michael A. Boxer has served on speaker's bureaus for Sanofi and Pharmacosmos. Michael Choi has received research funding from Pharmacyclics, Rigel, Sunesis, TG Therapeutics, and Velosbio. Donald Arnold has received research funding from Novartis and BMS; and has served in a consulting role for Rigel, Novartis, Amgen, UCB, and Principia. Catherine M. Broome has served in a consulting role for Alexion, Argenx, Sanofi, and Appelis. Robert Numerof and Sandra Tong are employees of Rigel Pharmaceuticals. The remaining authors declare no competing financial interests.

© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.

Figures

FIGURE 1

Study flow diagram. *Six patients completed the study at 12 weeks prior to the protocol amendment that extended the initial treatment period to 24 weeks

FIGURE 2

Fostamatinib improved markers of red cell hemolysis. (A) Median Hgb in the efficacy evaluable population (n = 24) categorized by response. (B) Median change in Hgb from baseline in the efficacy evaluable population (n = 24) categorized by response. (C) Median change in LDH from baseline categorized by response. (D) Median change in reticulocytes from baseline categorized by response. Hgb, hemoglobin; LDH, lactate dehydrogenase