Jakafi Efficacy:
Clinical Trial Results in
Patients with Intermediate-2
or High-Risk Myelofibrosis
...ruxolitinib as a treatment option for patients with myelofibrosis (MF)1
Jakafi is indicated for treatment of patients with intermediate or high-risk MF including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.
In COMFORT-I,* significantly more patients receiving Jakafi achieved the primary end point compared with those who received placebo.2,3
*COMFORT-I (COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-I) was a randomized, double-blind, placebo-controlled phase 3 study with 309 patients with intermediate-2–risk or high-risk myelofibrosis. The primary end point was the proportion of subjects achieving a ≥35% reduction in spleen volume from baseline to week 24 as measured by CT or MRI. 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.2
In COMFORT-I at week 24, 46% of patients receiving Jakafi achieved a ≥50% improvement in Total Symptom Score* vs 5% of patients receiving placebo (P<0.0001)2,3
COMFORT-I 5-year overall survival probability data4: Jakafi and placebo
At 3 years, survival probability was 70% for patients originally randomized to Jakafi and 61% for those originally randomized to placebo.2
Overall survival was a prespecified secondary end point in COMFORT-I.2
Adapted with permission from the Journal of Hematology & Oncology.
aThe 5-year overall survival analysis is not included in the Full Prescribing Information for Jakafi. Although the 3-year overall survival analysis is presented in the Full Prescribing Information, P values and hazard ratios are omitted from the overall survival Kaplan-Meier curves.5
b COMFORT-I was not designed to compare survival probabilities between Jakafi and placebo at 3 or 5 years.5
cPatients randomized to placebo were eligible to cross over to receive Jakafi because of progression-driven events or at the physician’s discretion; however, these patients continued to be grouped within their original randomized assignment for analysis purposes.5
In COMFORT-II,† significantly more patients receiving Jakafi achieved the primary end point compared with those who received best available therapy (BAT). 2,6‡
BAT=best available therapy.
†COMFORT-II (COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-II) was a randomized, open-label phase 3 study with 219 patients with intermediate-2–risk or high-risk myelofibrosis. 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 (CT) or magnetic resonance imaging (MRI).5
‡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.5
COMFORT-II 5-year overall survival probability data7: Jakafi and best available therapy
At 3 years, survival probability was 79% for patients originally randomized to Jakafi and 59% for those originally randomized to BAT.2
Overall survival was a prespecified secondary end point in COMFORT-II.2
Adapted with permission from Leukemia.
BAT=best available therapy.
a The 5-year overall survival analysis is not included in the Full Prescribing Information for Jakafi. Although the 3-year overall survival analysis is presented in the Full Prescribing Information, P values and hazard ratios are omitted from the overall survival Kaplan-Meier curves.5
bCOMFORT-II was not designed to compare survival probabilities between Jakafi and best available therapy at 3 or 5 years.5
cPatients randomized to best available therapy were eligible to cross over to receive Jakafi because of progression-driven events or at the physician’s discretion; however, these patients continued to be grouped within their original randomized assignment for analysis purposes.5
Video
In this video, Salman Fazal, MD, discusses the COMFORT I and COMFORT II trials. In addition to reviewing the study design for each, Dr Fazal highlights important efficacy and safety data in these trials. The data show efficacy and safety results of Jakafi® (ruxolitinib) in patients with intermediate-2 risk and high-risk myelofibrosis.
§COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment
References
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.1.2019. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed September 4, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
- Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
- 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.
- Verstovsek S, Mesa RA, Gotlib J, et al; for the COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017;10(1):55.
- Data on file. Incyte Corporation. Wilmington, DE.
- 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.
- Harrison CN, Vannucchi AM, Kiladjian J-J, et al; on behalf of the COMFORT-II Investigators. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701-1707.
References
-
Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
-
Verstovsek S, Mesa RA, Gotlib J, et al. Engl J Med. 2012;366:799-807. [also supplementary appendix: http://www.nejm.org/action/showSupplements?doi=10.1056%2FNEJMoa1110557&viewType=Popup&viewClass=Suppl]
Jakafi significantly reduced spleen volume and improved symptoms of myelofibrosis
Superior reductions in spleen volume and improvements in Total Symptom Score (TSS) vs placebo in COMFORT-I1,2
-
41.9% of patients receiving Jakafi achieved a ≥35% reduction in spleen volume (primary end point) at week 24 vs 0.7% of patients receiving placebo (P <0.0001) 1,2
-
45.9% of patients receiving Jakafi achieved a ≥50% improvement in TSS (secondary end point) at week 24 vs 5.3% of patients receiving placebo (P <0.0001) 1,2
- TSS captured in daily patient diary, including abdominal discomfort, early satiety, pain under left ribs, pruritus, night sweats and bone/muscle pain. Symptom scores ranged from 1 to 10. These scores were added to create the daily total score, with a maximum of 601,3
- At baseline, mean TSS was 18.0 in the Jakafi group and 16.5 in the placebo group1
A subgroup analysis of final titrated dose from the COMFORT-I trial
- The starting dose of Jakafi is based on patient’s baseline platelet count1:
- Greater than 200 X 109/L: 20 mg given orally twice daily
- 100 X 109/L to 200 X 109/L: 15 mg given orally twice daily
- 50 X 109/L to less than 100 X 109/L: 5 mg given orally twice daily
References
-
Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
-
Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis.N Engl J Med. 2012;366:799-807.
-
Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(suppl):1-38.
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Verstovsek S, Gotlib J, Gupta V, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther. 2013;7:13-21.
Primary End Point Results
Each bar represents an individual patient's response.
Adapted with permission from the Massachusetts Medical Society.
JAK=Janus-associated kinase.
99% of patients receiving Jakafi experienced some reduction in spleen volume, while most patients receiving placebo experienced an increase in spleen volume.1,2
References
-
Data on file. Incyte Corporation. Wilmington, DE.
-
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.
-
Deisseroth A, Kaminskas E, Grillo J, et al. US Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212-3217.
References
-
Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
-
Data on file. Incyte Corporation. Wilmington, DE.
-
Harrison C, Kiladjian JJ, Al-Ali HK, et al. N Engl J Med. 2012;366:787-798.