Does ruxolitinib prolong the survival of patients with myelofibrosis?

Abstract

Case presentation A 73-year-old man was diagnosed with primary myelofibrosis (PMF) after the incidental discovery of abnormalities in a blood test performed for the control of diabetes mellitus. The patient was asymptomatic. The spleen was palpable at 6 cm below the left costal margin. Hemoglobin was 10.9 g/dL; white blood cell count was 13.2 3 10 9 /L, with a leukoerythroblastic blood picture and 2% blasts, platelet count of 387 3 10 9 /L, and serum lactic dehydrogenase level of 1087 U/L. BCR/ABL was negative, and the JAK2 V617F mutation was found. Bone marrow cytogenetic study disclosed a normal 46,XY karyotype, and the marrow biopsy was typical of myelofibrosis. According to the International Prognostic Scoring System (IPSS), 1 the patient had intermediate-2 risk PMF, because of age over 65 years and blood blasts $1%. Median survival of patients with intermediate-2 risk PMF is 4 years. Because the patient was asymptomatic and not eligible for allogeneic stem cell transplantation, should he receive ruxolitinib to try to prolong his survival? Methods We searched the Medline database for references on ruxolitinib treatment. We considered only full published articles analyzing the effect of the drug on survival and including a comparator, either historical controls, placebo, or BAT. Because of this, studies on patients with intermediate-1 risk MF were not considered, as

Traffic lights for ruxolitinib

“…1 M acromolecular traffic in and out of the eukaryotic cell nucleus is facilitated by carrier proteins (karyopherins) that interact with cargo, chaperones, nucleoporins, and other components of nuclear pore complexes. 2 chromosome region maintenance 1 (CRM1), exportin 1, or XPO1, is uniquely required for the export of .200 different proteins to the cytoplasm, including nucleophosmin, survivin, p27, APC, BRCA1, and p53. 3 The effects of shuttled proteins often depend on their location; for example, in the nucleus, survivin helps attach centromeres to mitotic spindles, whereas in the cytoplasm, it interacts with caspases to inhibit apoptosis.…”

Allogeneic stem cell transplantation for myelofibrosis patients aged ≥65 years

“…With a median age of 67 at diagnosis, MF is predominantly a disease of the elderly: only 13% of patients are younger than 50 years of age . Ruxolitinib is the only approved JAK 1/2 inhibitor therapy for MF, conferring clear benefit in reducing spleen size and constitutional symptoms, nevertheless, the issue of improvement on survival is controversial and even the effect on JAK2 allele burden, which is considered as a surrogate marker of expanded malignant clone, is modest …”

Survival outcomes in myelofibrosis patients treated with ruxolitinib: A population‐based cohort study in Sweden and Norway

“…Results from clinical studies suggest that the JAK-1/2 inhibitor ruxolitinib is effective in reducing symptoms of MF, which also has translated into improved quality of life. 1 Ruxolitinib was approved based on the results of two phase-III studies that compared ruxolitinib with placebo or best available care. The US Food and Drug Administration approved ruxolitinib for intermediate and high-risk MF, 7,8 while the European Medicines Agency approved ruxolitinib for treatment of splenomegaly and/or constitutional symptoms of MF, irrespective of risk group.…”

“…The US Food and Drug Administration approved ruxolitinib for intermediate and high-risk MF, 7,8 while the European Medicines Agency approved ruxolitinib for treatment of splenomegaly and/or constitutional symptoms of MF, irrespective of risk group. 1 There is limited evidence to show that ruxolitinib improves survival outcomes by modifying the disease course, although its effect on metabolic and nutritional variables may translate into survival benefits. 9 Eventually, most patients discontinue treatment due to adverse events or lack of efficacy.…”