ASH Clinical News December 2016 | Page 111

Significantly more patients receiving Jakafi achieved the composite primary * and key secondary end points 1 , 2 †

Components of Primary End Point at Week 32 1
Patients (%)
80
60
40
20
0
Composite Primary End Point
( P < 0.0001 )
23 % a
( n = 25 )
< 1 % b
( n = 1 )
Hct Control + Spleen Volume Reduction
60 %
( n = 66 )
Hct Control Without Phlebotomy
Individual Components of Primary End Point
19 %
( n = 21 )
40 %
( n = 44 )
Jakafi ( n = 110 )
BAT ( n = 112 )
< 1 %
( n = 1 )
≥35 % Spleen Volume Reduction
BAT , best available therapy ; CI , confidence interval ; Hct , hematocrit .
a
95 % CI , 15 % -32% b
95 % CI , 0 % -5%
* The composite primary end point was defined as hematocrit ( Hct ) control without phlebotomy and a ≥35 % spleen volume reduction as measured by CT or MRI . To achieve the Hct control end point , patients could not become eligible for phlebotomy between weeks 8 and 32 . Phlebotomy eligibility was defined as Hct > 45 % that is ≥3 percentage points higher than baseline or Hct > 48 % ( lower value ). 1 , 2
The RESPONSE ( Randomized Study of Efficacy and Safety in Polycythemia Vera with JAK Inhibitor Ruxolitinib versus Best Available Care ) trial was a randomized , open-label , active-controlled phase 3 trial comparing Jakafi with best available therapy in 222 patients with polycythemia vera . Patients enrolled in the study were resistant to or intolerant of hydroxyurea , required phlebotomy for Hct control , and had splenomegaly . All patients entered into a Hct control period , during which time Hct levels were maintained between 40 % and 45 % for 28 days before patients were randomized to Jakafi or best available therapy . Best available therapy included hydroxyurea ( 60 %), interferon / pegylated interferon ( 12 %), anagrelide ( 7 %), pipobroman ( 2 %), lenalidomide / thalidomide ( 5 %), and observation ( 15 %). Patients had been diagnosed with polycythemia vera for at least 24 weeks , had an inadequate response to or were intolerant of hydroxyurea , required phlebotomy , and exhibited splenomegaly . After week 32 , patients were able to cross over to Jakafi treatment . An updated analysis was performed at week 80 only in patients originally randomized to Jakafi .
Patients Achieving Complete Hematologic Remission 1a
Patients (%)
60
40
20
0
24 % b
( n = 26 )
( P = 0.0016 )
8 % c
( n = 9 )
Complete Hematologic Remission at Week 32
Jakafi ( n = 110 ) BAT ( n = 112 )

Durable response at week 80 1

19 of 25 patients ( 76 %) who achieved a primary response at week 32 in the Jakafi arm maintained their response
51 of 66 patients ( 77 %) who achieved Hct control at week 32 in the Jakafi arm maintained their response
43 of 44 patients ( 98 %) who achieved a ≥35 % spleen volume reduction at week 32 in the Jakafi arm maintained their response
15 of 26 patients ( 58 %) who achieved complete hematologic remission at week 32 in the Jakafi arm maintained their response
BAT , best available therapy ; CI , confidence interval . a
Complete hematologic remission was defined as achieving hematocrit control ( as specified in the primary end point ), platelet count ≤400 × 10 9 / L , and white blood cell count ≤10 × 10 9 / L . 1 , 2 b
95 % CI , 16 % -33 % c 95 % CI , 4 % -15 %

Durable count control

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 . Vannucchi AM , Kiladjian JJ , Griesshammer M , et al . Ruxolitinib versus standard therapy for the treatment of polycythemia vera . N Engl J Med . 2015 ; 372 ( 5 ): 426-435 .