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EFFECT OF RUXOLITINIB ON MARKERS OF IRON DEFICIENCY: AN ANALYSIS OF THE RESPONSE TRIAL
Author(s): ,
Srdan Verstovsek
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Claire N. Harrison
Affiliations:
Haematology/Oncology and Cellular Pathology,Guy’s and St Thomas’ NHS Foundation Trust,London,United Kingdom
,
Jean-Jacques Kiladjian
Affiliations:
Department of Hematology,Hôpital Saint-Louis et Université Paris Diderot,Paris,France
,
Carole Miller
Affiliations:
Saint Agnes Cancer Institute,Baltimore, MD,United States
,
Ahmad B. Naim
Affiliations:
Incyte Corporation,Wilmington, DE,United States
,
Dilan C. Paranagama
Affiliations:
Incyte Corporation,Wilmington, DE,United States
,
Dany Habr
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover, NJ,United States
Alessandro M. Vannucchi
Affiliations:
Department of Experimental and Clinical Medicine,University of Florence,Florence,Italy
(Abstract release date: 05/21/15) EHA Library. Verstovsek S. 06/13/15; 100814; P673
Dr. Srdan Verstovsek
Dr. Srdan Verstovsek
Contributions
Abstract
Abstract: P673

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Patients with polycythemia vera (PV) often rely on phlebotomy to control their hematocrit. Frequent phlebotomies may result in a state of iron deficiency, which can be associated with various complications, such as restless leg syndrome and cognitive dysfunction. The RESPONSE trial demonstrated that ruxolitinib lowers hematocrit and reduces the need for phlebotomy in patients with PV who have had an inadequate response to or are intolerant of hydroxyurea (HU).

Aims
A subanalysis of the RESPONSE trial data was conducted to evaluate the effect of ruxolitinib on markers of iron deficiency. 

Methods
Total iron binding capacity (TIBC), ferritin, mean corpuscular volume (MCV), and serum iron were Total iron binding capacity (TIBC), ferritin, mean corpuscular volume (MCV), and serum iron were measured at baseline and over time in patients randomized to ruxolitinib and best available therapy (BAT); in the BAT group, these measures were assessed before and after crossover to ruxolitinib. Transferrin iron saturation (TS) was calculated based on observed iron and TIBC. Patients within each arm were stratified into 2 groups: patients with baseline values within the normal range and patients with baseline values outside of the normal range; this was determined for each patient based on the normal ranges for each of the study sites. Values outside of the normal ranges indicative of iron deficiency included TIBC above the upper limit of normal; and ferritin, MCV, serum iron, and TS below the lower limits of normal.

Results
The majority of patients (in both study arms) had laboratory values outside of normal limits at baseline: TIBC, n=54 (24.3%); ferritin n=141 (63.5%); MCV, n=137 (61.7%); serum iron, n=181 (81.5%); MCV + iron, n=127 (57.2%); TS, n=197 (88.7%). Among patients with evidence of iron deficiency at baseline, use of iron supplementation was infrequent (<20% of patients) and balanced between treatment arms. Changes in TIBC over time are shown in Figure 1 and Table 1. In patients with elevated TIBC at baseline, mean TIBC improved (ie, lowered) to levels within the normal range during ruxolitinib treatment (in patients randomized to ruxolitinib and after crossover from BAT), but remained above the normal limit during BAT treatment. Consistent with these findings, ferritin, MCV, serum iron, and TS improved (ie, increased) in patients with low baseline levels during ruxolitinib therapy, but remained outside of the normal limits during BAT treatment (Table 1). Similar patterns were also observed when evaluating these markers by gender. Mean values for patients with normal iron status at baseline remained within normal ranges during ruxolitinib therapy.

Table 1.  Values for Markers of Iron Deficiency at Baseline and Week 32 in Patients with Evidence of Iron Deficiency at Baseline

Mean(SD)

Ruxolitinib (randomized)

BAT (randomized)

Baseline

Week 32

Baseline

Week 32

Ferritin, pMol/L

19.7 (8.0)

134.1 (99.2)

21.7 (7.2)

43.2 (64.0)

Serum Iron, μMoL/L

3.7 (1.2)

16.4 (7.5)

3.9 (1.1)

6.4 (5.4)

MCV, FL

70.3 (6.5)

81.1 (8.9)

70.6 (6.6)

73.1 (10.6)

TS, %

6.00 (2.9)

31.1 (14.9)

6.6 (3.4)

10.6 (9.6)

TIBC, μMol/L

82.5 (6.3)

60.2 (4.2)

79.8 (3.6)

75.5 (6.2)

Increases in ferritin, iron, MCV, and TS = improvement; decreases in TIBC = improvement.



Summary
In patients with PV who have had an inadequate response to or are intolerant of HU, normalization of 5 markers of iron deficiency was observed with ruxolitinib therapy, while in the BAT arm, there was little or no change in these parameters.

Keyword(s): Anemia, Iron deficiency, Kinase inhibitor, Polycythemia vera



Session topic: Myeloproliferative neoplasms - Clinical 3
Abstract: P673

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Patients with polycythemia vera (PV) often rely on phlebotomy to control their hematocrit. Frequent phlebotomies may result in a state of iron deficiency, which can be associated with various complications, such as restless leg syndrome and cognitive dysfunction. The RESPONSE trial demonstrated that ruxolitinib lowers hematocrit and reduces the need for phlebotomy in patients with PV who have had an inadequate response to or are intolerant of hydroxyurea (HU).

Aims
A subanalysis of the RESPONSE trial data was conducted to evaluate the effect of ruxolitinib on markers of iron deficiency. 

Methods
Total iron binding capacity (TIBC), ferritin, mean corpuscular volume (MCV), and serum iron were Total iron binding capacity (TIBC), ferritin, mean corpuscular volume (MCV), and serum iron were measured at baseline and over time in patients randomized to ruxolitinib and best available therapy (BAT); in the BAT group, these measures were assessed before and after crossover to ruxolitinib. Transferrin iron saturation (TS) was calculated based on observed iron and TIBC. Patients within each arm were stratified into 2 groups: patients with baseline values within the normal range and patients with baseline values outside of the normal range; this was determined for each patient based on the normal ranges for each of the study sites. Values outside of the normal ranges indicative of iron deficiency included TIBC above the upper limit of normal; and ferritin, MCV, serum iron, and TS below the lower limits of normal.

Results
The majority of patients (in both study arms) had laboratory values outside of normal limits at baseline: TIBC, n=54 (24.3%); ferritin n=141 (63.5%); MCV, n=137 (61.7%); serum iron, n=181 (81.5%); MCV + iron, n=127 (57.2%); TS, n=197 (88.7%). Among patients with evidence of iron deficiency at baseline, use of iron supplementation was infrequent (<20% of patients) and balanced between treatment arms. Changes in TIBC over time are shown in Figure 1 and Table 1. In patients with elevated TIBC at baseline, mean TIBC improved (ie, lowered) to levels within the normal range during ruxolitinib treatment (in patients randomized to ruxolitinib and after crossover from BAT), but remained above the normal limit during BAT treatment. Consistent with these findings, ferritin, MCV, serum iron, and TS improved (ie, increased) in patients with low baseline levels during ruxolitinib therapy, but remained outside of the normal limits during BAT treatment (Table 1). Similar patterns were also observed when evaluating these markers by gender. Mean values for patients with normal iron status at baseline remained within normal ranges during ruxolitinib therapy.

Table 1.  Values for Markers of Iron Deficiency at Baseline and Week 32 in Patients with Evidence of Iron Deficiency at Baseline

Mean(SD)

Ruxolitinib (randomized)

BAT (randomized)

Baseline

Week 32

Baseline

Week 32

Ferritin, pMol/L

19.7 (8.0)

134.1 (99.2)

21.7 (7.2)

43.2 (64.0)

Serum Iron, μMoL/L

3.7 (1.2)

16.4 (7.5)

3.9 (1.1)

6.4 (5.4)

MCV, FL

70.3 (6.5)

81.1 (8.9)

70.6 (6.6)

73.1 (10.6)

TS, %

6.00 (2.9)

31.1 (14.9)

6.6 (3.4)

10.6 (9.6)

TIBC, μMol/L

82.5 (6.3)

60.2 (4.2)

79.8 (3.6)

75.5 (6.2)

Increases in ferritin, iron, MCV, and TS = improvement; decreases in TIBC = improvement.



Summary
In patients with PV who have had an inadequate response to or are intolerant of HU, normalization of 5 markers of iron deficiency was observed with ruxolitinib therapy, while in the BAT arm, there was little or no change in these parameters.

Keyword(s): Anemia, Iron deficiency, Kinase inhibitor, Polycythemia vera



Session topic: Myeloproliferative neoplasms - Clinical 3

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