Case Report Features Potential Link Between JAK2 Inhibition and CLL
Posted: Friday, August 21, 2020
Patients with myeloproliferative neoplasms may have a higher risk of developing a lymphoproliferative disorder compared with the general population, yet the molecular and clinical factors remain unknown. Adam J. Mead, MRCP, PhD, of MRC Weatherall Institute of Molecular Medicine, University of Oxford, UK, and colleagues recently published the case of a patient with postpolycythemia vera myelofibrosis who was treated with the JAK2 inhibitor fedratinib. The patient rapidly developed chronic lymphocytic leukemia (CLL) with an aggressive disease course. The case study was published in HemaSphere, a journal powered by the European Hematology Association.
A 72-year-old male patient presented with secondary myelofibrosis 18 years after being diagnosed with postpolycythemia vera myelofibrosis. He was later enrolled in a study to test the efficacy of fedratinib. Within 4 weeks of beginning treatment, the patient showed significant improvement, yet along with this response, his white blood cell counts rapidly increased. Blood film evaluation and immunophenotyping confirmed the patient had CLL.
Following the discontinuation of fedratinib, the patient experienced recurrence of splenomegaly and systemic symptoms. He completed six cycles of immunochemotherapy and continued on ibrutinib due to disease progression. After 1 year, the patient developed severe headaches and was diagnosed with subdural hematomas. He was moved to palliative care and died 1 month later.
“The very clear temporal relationship between JAK2 inhibition and emergence of CLL in this case, including reversibility when JAK2 inhibition was withdrawn, strongly supports a direct link between JAK2 inhibition and CLL progression, although the exact mechanism remains uncertain,” explained the researchers. “Our case highlights the necessity to carefully evaluate myeloproliferative neoplasm patients for [the] presence of coexisting lymphoproliferative disease, which may be subclinical, and counsel patients in relation to the potential risks of progression of lymphoproliferative disease with JAK2 inhibitor therapy.”
Disclosure: For full disclosures of the study authors, visit journals.lww.com.
