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Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing.

Mesa RA, Cortes J - J Hematol Oncol (2013)

Bottom Line: Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients.In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies.Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation.

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ABSTRACT
Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit.

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Changes in platelet count and hemoglobin in COMFORT-I. (Reprinted from Verstovsek S, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther [published by Dove Press] [22]). Shown are mean percentage changes from baseline (BL) with standard errors in (A) platelet count and (B) hemoglobin over time. Final titrated dose was defined as the average daily dose during weeks 21–24. BID, twice a day.
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Figure 2: Changes in platelet count and hemoglobin in COMFORT-I. (Reprinted from Verstovsek S, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther [published by Dove Press] [22]). Shown are mean percentage changes from baseline (BL) with standard errors in (A) platelet count and (B) hemoglobin over time. Final titrated dose was defined as the average daily dose during weeks 21–24. BID, twice a day.

Mentions: Anemia and thrombocytopenia were the most common adverse events associated with ruxolitinib treatment and typically occurred early in the course of therapy [16,17,21]. As shown in Figure 1A and 1B, grade 3 or 4 anemia and thrombocytopenia were greatest in the first 8–12 weeks of treatment [16]. Similarly, hemoglobin levels and platelet counts decreased during the same time frame (Figure 2A and 2B) [22].


Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing.

Mesa RA, Cortes J - J Hematol Oncol (2013)

Changes in platelet count and hemoglobin in COMFORT-I. (Reprinted from Verstovsek S, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther [published by Dove Press] [22]). Shown are mean percentage changes from baseline (BL) with standard errors in (A) platelet count and (B) hemoglobin over time. Final titrated dose was defined as the average daily dose during weeks 21–24. BID, twice a day.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4222119&req=5

Figure 2: Changes in platelet count and hemoglobin in COMFORT-I. (Reprinted from Verstovsek S, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther [published by Dove Press] [22]). Shown are mean percentage changes from baseline (BL) with standard errors in (A) platelet count and (B) hemoglobin over time. Final titrated dose was defined as the average daily dose during weeks 21–24. BID, twice a day.
Mentions: Anemia and thrombocytopenia were the most common adverse events associated with ruxolitinib treatment and typically occurred early in the course of therapy [16,17,21]. As shown in Figure 1A and 1B, grade 3 or 4 anemia and thrombocytopenia were greatest in the first 8–12 weeks of treatment [16]. Similarly, hemoglobin levels and platelet counts decreased during the same time frame (Figure 2A and 2B) [22].

Bottom Line: Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients.In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies.Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit.

Show MeSH
Related in: MedlinePlus