ASH Clinical News April 2017 New | Page 15

For intermediate-2 – risk and high-risk myelofibrosis

Jakafi data include spleen , symptoms , and overall survival

COMFORT-I * primary end point : At 24 weeks , 42 % of patients receiving Jakafi achieved a ≥35 % reduction in spleen volume vs 0.7 % of patients receiving placebo ( P < 0.0001 ) 1 , 2
COMFORT-II † primary end point : At 48 weeks , 29 % of patients receiving Jakafi achieved a ≥35 % reduction in spleen volume vs 0 % of patients receiving best available therapy ‡ ( P < 0.0001 ) 1 , 3
Prespecified Secondary End Point : Overall Survival Kaplan-Meier Curves by Treatment Group in COMFORT-I 1
1.0
0.9
Jakafi Placebo
0.8
0.7
0.6
0.5
0.4
Median crossover :
9 months
Jakafi
( n = 155 )
Placebo
( n = 154 )
0.3
% 1-year survival
91 %
84 %
0.2
% 2-year survival
80 %
69 %
0.1
% 3-year survival
70 %
61 %
0.0
0
6
12
18
24
30
36
42
Time ( Months )
Number of patients at risk
Jakafi
155
145
134
122
111
102
29
0
Placebo
154
142
117
101
92
82
32
0
Survival Probability
* COMFORT-I ( COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-I ) was a randomized , double-blind , placebo-controlled phase 3 study with 309 total patients . The primary end point was the proportion of subjects achieving a ≥35 % reduction in spleen volume from baseline to week 24 as measured by computed tomography or magnetic resonance imaging . A secondary end point was the proportion of subjects with a ≥50 % reduction in Total Symptom Score from baseline to week 24 as measured by the daily patient diary , the modified Myelofibrosis Symptom Assessment Form . 1 , 2
COMFORT-I secondary end point : At 24 weeks , 46 % of patients receiving Jakafi achieved a ≥ 50 % improvement in Total Symptom Score § vs 5 % of patients receiving placebo ( P < 0.0001 ) 1 , 2
Prespecified Secondary End Point : Overall Survival Kaplan-Meier Curves by Treatment Group in COMFORT-II 1
Survival Probability
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1
Jakafi
146
135
BAT
73
58
126 50
Median crossover : 17 months
0.0
0
6
12
18
24
30
36
42
Time ( Months )
Number of patients at risk
BAT , best available therapy .
115 47
107 42
104 33
Jakafi
BAT
( n = 146 )
( n = 73 )
% 1-year survival 96 % 94 % % 2-year survival 86 % 81 % % 3-year survival 79 % 59 %
33 9
Jakafi BAT
COMFORT-II ( COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-II ) was a randomized , open-label phase 3 study with 219 patients . The primary end point was the proportion of patients achieving a ≥35 % reduction in spleen volume from baseline at week 48 as measured by computed tomography or magnetic resonance imaging . 1 , 3
Best available therapy in COMFORT-II included hydroxyurea ( 46.6 %) and glucocorticoids ( 16.4 %), as well as no medication , anagrelide , epoetin alfa , thalidomide , lenalidomide , mercaptopurine , thioguanine , danazol , peginterferon alfa-2a , interferon-α , melphalan , acetylsalicylic acid , cytarabine , and colchicine . 4
§
Total Symptom Score was captured by a daily patient diary , the Myelofibrosis Symptom Assessment Form . Total Symptom Score encompasses debilitating symptoms of myelofibrosis : abdominal discomfort , early satiety , pain under left ribs , pruritus , night sweats , and bone / muscle pain . Symptom scores ranged from 0 to 10 , with 0 representing symptoms “ absent ” and 10 representing symptoms “ worst imaginable .” These scores were added to create the daily total score , which has a maximum of 60 . At baseline , mean Total Symptom Score was 18.0 in the group receiving Jakafi and 16.5 in the group receiving placebo . 1 , 2
0 0

Spleen . Symptoms . Overall survival .

When discontinuing Jakafi , myeloproliferative neoplasm-related symptoms may return within one week . After discontinuation , some patients with myelofibrosis have experienced fever , respiratory distress , hypotension , DIC , or multi-organ failure . If any of these occur after discontinuation or while tapering Jakafi , evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi . Instruct patients not to interrupt or discontinue Jakafi without consulting their physician . When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia , consider gradual tapering rather than abrupt discontinuation
Non-melanoma skin cancers including basal cell , squamous cell , and Merkel cell carcinoma have occurred . Perform periodic skin examinations
Treatment with Jakafi has been associated with increases in total cholesterol , low-density lipoprotein cholesterol , and triglycerides . Assess lipid parameters 8-12 weeks after initiating Jakafi . Monitor and treat according to clinical guidelines for the management of hyperlipidemia
The three most frequent non-hematologic adverse reactions ( incidence > 10 %) were bruising , dizziness and headache
A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or fluconazole or in patients with renal or hepatic impairment . Patients should be closely monitored and the dose titrated based on safety and efficacy
Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus . Women taking Jakafi should not breast-feed
Please see Brief Summary of Full Prescribing Information for Jakafi on the following pages .
To learn more about intervening with Jakafi , visit Jakafi . com / HCP .
References : 1 . Jakafi Prescribing Information . Wilmington , DE : Incyte Corporation . 2 . Verstovsek S , Mesa RA , Gotlib J , et al . A double-blind , placebo-controlled trial of ruxolitinib for myelofibrosis . N Engl J Med . 2012 ; 366 ( 9 ): 799-807 . 3 . Harrison C , Kiladjian J-J , Al-Ali HK , et al . JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis . N Engl J Med . 2012 ; 366 ( 9 ): 787-798 . 4 . Data on file . Incyte Corporation . Wilmington , DE .