PMID- 30784097 OWN - NLM STAT- MEDLINE DCOM- 20200127 LR - 20231012 IS - 1096-8652 (Electronic) IS - 0361-8609 (Print) IS - 0361-8609 (Linking) VI - 94 IP - 5 DP - 2019 May TI - Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. PG - 546-553 LID - 10.1002/ajh.25444 [doi] AB - Two randomized, double-blind, placebo-controlled studies demonstrated responses (>/=50 000/muL) to fostamatinib in adults with long-standing immune thrombocytopenia (ITP). The long-term safety and efficacy of fostamatinib were evaluated in a follow-on, open-label extension (OLE) study. Patients received double-blind fostamatinib in the randomized trials, and responders continued the same dose, 100 to 150 mg BID, in the OLE study. Nonresponders received 100 mg BID for 4 weeks and could escalate to 150 mg BID at week 4. Endpoints included stable response, platelet count >/=50 000/muL at 4/6 biweekly (randomized trials) or 2/3 monthly visits (OLE), and overall response, >/=1 platelet count >/=50 000/muL during weeks 1 to 12. A total of 146 patients received fostamatinib including 123 in the OLE study. Median treatment duration was 6.7 months. Baseline median ITP duration was 8 years and median platelet count was 16 000/muL; prior treatments included thrombopoietic (TPO) agents (47%), splenectomy (35%), and rituximab (32%). Twenty-seven (18%) patients achieved a stable response with median duration of >28 months and a median platelet count of 89 000/muL. Sixty-four (44%) patients achieved an overall response (including stable responders) with a median platelet count of 63 000/muL and a median response duration of >28 months. Twenty-four of 71 (34%) patients who had failed TPO agents achieved overall responses to fostamatinib. The most common adverse events (AEs) were diarrhea, hypertension, nausea, epistaxis, and abnormal liver function tests. Most AEs were mild/moderate and resolved or were managed with dose reduction, dose interruption, and/or secondary medication. Almost half of the patients achieved an overall response, and most of these maintained their responses for >2 years. No new or increased frequency of AEs was seen at up to 31 months of treatment. CI - (c) 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc. FAU - Bussel, James B AU - Bussel JB AD - Division of Pediatric Hematology/Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, New York. FAU - Arnold, Donald M AU - Arnold DM AD - Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, and McMaster Centre for Transfusion Research, Hamilton Health Sciences, Hamilton, Ontario, Canada. AD - Canadian Blood Services, Hamilton, Ontario, Canada. FAU - Boxer, Michael A AU - Boxer MA AD - Arizona Oncology Associates, Tucson, Arizona. FAU - Cooper, Nichola AU - Cooper N AD - Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom. FAU - Mayer, Jiri AU - Mayer J AD - Fakultni nemocnice Brno, Brno, Czech Republic. FAU - Zayed, Hany AU - Zayed H AD - Rigel Pharmaceuticals Inc., South San Francisco, California. FAU - Tong, Sandra AU - Tong S AD - Rigel Pharmaceuticals Inc., South San Francisco, California. FAU - Duliege, Anne-Marie AU - Duliege AM AD - Rigel Pharmaceuticals Inc., South San Francisco, California. LA - eng GR - Rigel Pharmaceuticals, Inc/International PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190313 PL - United States TA - Am J Hematol JT - American journal of hematology JID - 7610369 RN - 0 (Aminopyridines) RN - 0 (Morpholines) RN - 0 (Oxazines) RN - 0 (Pyridines) RN - 0 (Pyrimidines) RN - SQ8A3S5101 (fostamatinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Aminopyridines MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Morpholines MH - *Oxazines/administration & dosage/adverse effects MH - Platelet Count MH - Purpura, Thrombocytopenic, Idiopathic/blood/*drug therapy MH - *Pyridines/administration & dosage/adverse effects MH - Pyrimidines MH - Time Factors PMC - PMC6594140 COIS- JB has received research support from Rigel, Novartis, and Amgen, and has participated on advisory boards for Rigel, Novartis, Amgen, Momenta, and Protalex. DMA has received research support from Novartis, Amgen, and Bristol Meyers Squibb, and has been a consultant for Rigel, Amgen, Novartis, and UCB. MB has participated in speakers' bureaus for Rigel, Incyte, and Abbvie. NC has participated in a consultancy or advisory committee for Amgen and Novartis. JM has received research funding from Rigel. HZ, ST and AMD are employees of Rigel Pharmaceuticals. EDAT- 2019/02/21 06:00 MHDA- 2020/01/28 06:00 PMCR- 2019/06/26 CRDT- 2019/02/21 06:00 PHST- 2018/11/25 00:00 [received] PHST- 2019/02/13 00:00 [revised] PHST- 2019/02/19 00:00 [accepted] PHST- 2019/02/21 06:00 [pubmed] PHST- 2020/01/28 06:00 [medline] PHST- 2019/02/21 06:00 [entrez] PHST- 2019/06/26 00:00 [pmc-release] AID - AJH25444 [pii] AID - 10.1002/ajh.25444 [doi] PST - ppublish SO - Am J Hematol. 2019 May;94(5):546-553. doi: 10.1002/ajh.25444. Epub 2019 Mar 13.