BRIEF REPORTSerious Adverse Events During Ruxolitinib Treatment Discontinuation in Patients With Myelofibrosis
Section snippets
RUXOLITINIB
Ruxolitinib (INCB018424) is an ATP mimetic JAK1 and JAK2 inhibitor.9 In healthy volunteers, the drug, given in single oral 25-mg doses, was rapidly absorbed with mean time to reach maximal drug concentration of less than 1 hour and mean half-life of 2 to 6 hours.11 The drug is metabolized by CYP3A4.12 Ruxolitinib was the first JAK inhibitor to be evaluated in patients with MF and has already undergone phase 1, 2, and 3 studies. The first phase 1/2 MF study using ruxolitinib was conducted at the
DISCUSSION
Our experience with ruxolitinib therapy for patients with MF suggests a remarkable and prompt activity in alleviating constitutional symptoms such as night sweats, pruritus, fatigue, and cachexia.9 The effect on splenomegaly was also notable. However, these benefits come with tradeoffs, including drug-induced anemia, thrombocytopenia, and, as we have described in the current report, potentially catastrophic adverse events during drug discontinuation. We speculate that the underlying mechanism
REFERENCES (15)
How I treat myelofibrosis
Blood
(2011)Myelofibrosis with myeloid metaplasia
N Engl J Med
(2000)- et al.
Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms
Leukemia
(2008) Pathogenesis of myelofibrosis with myeloid metaplasia
J Clin Oncol
(2005)- et al.
Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study
J Clin Oncol
(2011) - et al.
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
Nature
(2005) Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1
Leukemia
(2010)
Cited by (189)
JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study
2024, Journal of Allergy and Clinical ImmunologySevere ARDS due to Ruxolitinib discontinuation syndrome: case presentation and literature review
2022, HeliyonCitation Excerpt :By inhibiting cytokine signaling, JAK inhibitors decrease inflammatory and hematopoietic reactions, leading to symptom reduction in myelofibrosis [2, 3, 4, 5]. After sudden cessation of JAK-inhibitor therapy, a withdrawal syndrome can occur, presenting with symptoms of a cytokine storm, such as acute respiratory distress syndrome (ARDS), septic-like shock and disseminated intravascular coagulation (DIC)-like syndrome [6, 7, 8]. Although rare, more cases are being reported due to the growing use of RUX [6, 7, 8].
Myeloproliferative Neoplasms
2022, Encyclopedia of Cell Biology: Volume 1-6, Second Edition
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Dr Tefferi has served as Principal Investigator/coinvestigator for clinical trials that received institutional support (free drug and funds) from Incyte, Sanofi-Aventis, TargeGen, YM BioSciences, Cytopia, Bristol-Myers Squibb, Celgene, and Novartis. TargeGen, Cytopia, and YM BioSciences have also provided support for laboratory studies relevant to clinical trials. Dr Pardanani has served as Principal Investigator/coinvestigator for clinical trials that received institutional support (free drug and funds) from Incyte, Sanofi-Aventis, TargeGen, YM BioSciences, Cytopia, Bristol-Myers Squibb, Celgene, and Novartis. TargeGen and Cytopia have also provided support for laboratory studies relevant to clinical trials.