Targeted Therapy of Myelofibrosis

OYu Vinogradova1,3,4, VA Shuvaev2, IS Martynkevich2, MM Pankrashkina1,3, MS Fominykh2, EV Efremova2, KYu Krutikova2, LB Polushkina2, NN Sharkunov1, SV Voloshin2, AV Chechetkin2

1SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

2Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

3Dmitrii Rogachev National Medical Pediatric Hematology, Oncology and Immunology Research Center, 1 Samory Mashela str., Moscow, Russian Federation, 117198

4NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Ol’ga Yur’evna Vinogradova, MD, PhD, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284; Tel.: 8(495)945-97-61; e-mail:

For citation: Vinogradova OYu, Shuvaev VA, Martynkevich IS, et al. Targeted Therapy of Myelofibrosis. Clinical oncohematology. 2017;10(4):471–8 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-471-478


Background. Myelofibrosis (primary myelofibrosis, post-essential trombocythemia myelofibrosis, post-polycythemia myelofibrosis) is the most complex and pressing problem among all Ph-negative myeloproliferative diseases. The present article summarizes the author’s experience of using new Janus kinase inhibitors in routine clinical practice, and compares the data with the results of other clinical research.

Aim. To evaluate the use of ruxolitinib in patients with myelofibrosis.

Materials & Methods. Our analysis includes 48 patients (21 men and 27 women) with histologically verified myelofibrosis (primary myelofibrosis in 36 cases, post-essential trombocythemia myelofibrosis in 10 cases, and post-polycythemia myelofibrosis in 2 cases) in a chronic stage. All patients received ruxolitinib. Median age at the start of therapy was 60 years (range from 35 to 79). Massive splenomegaly (≥ 10 cm below the costal margin) was found in 34 (71 %) of 48 patients. The initial dose of ruxolitinib was determined by the platelet level. The efficacy of the therapy was evaluated in accordance with ELN 2013 criteria.

Results. Median duration of treatment was 18 months (range from 1 to 50 months). Symptoms of intoxication were relieved in 33 of 37 patients (89 %). The spleen size decreased in 64 % of patients. In 33 % of cases spleen size did not change, whereas an increase was observed in 3 % of patients. In the majority of patients hemoglobin level remained stable through the course of treatment. Three of 14 transfusion dependent patients did not require blood transfusions after 3 months of therapy. In patients with high thrombocyte levels prior to ruxolitinib therapy the mean level was approaching normal by the end of the 1st month of treatment. The median JAK2V617F mutant allele burden at the beginning treatment was 56.5 % (n = 20; 22.5–126.1 %). After 6 moths of treatment it accounted for 62.3 % (n = 11; 25.4–79.7 %) and in 12 months accounted for 47.4 % (n = 12; 14.2–102.2 %). By the time of the analysis 42 of 48 patients continued the ruxolitinib treatment (88 %). Death occurred in 4 patients. Overall 1-year (92 %) and 2-year (87 %) survival corresponds to the data of COMFORT-I, COMFORT-II and JUMP clinical trials.

Conclusion. Ruxolitinib showed to be an effective treatment for myelofibrosis. The most pronounced and rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. The tolerability of ruxolitinib was satisfactory in the majority of patients. According to the author’s data, ruxolitinib had a small impact on the JAK2V617F mutant allele burden. The overall survival rate in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was similar to that of in the clinical trials.

Keywords: primary myelofibrosis, post-essential trombocythemia myelofibrosis, post-polycythemia myelofibrosis, JAK2V617F, ruxolitinib, clinical practice, targeted therapy.

Received: February 11, 2017

Accepted: May 22, 2017

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  1. Абдулкадыров К.М., Шуваев В.А., Мартынкевич И.С. Миелопролиферативные новообразования. М.: Littera, 2016. 304 с.[Abdulkadyrov KM, Shuvayev VA, Martynkevich IS. Mieloproliferativnye novoobrazovaniya. (Myeloproliferative Neoplasms.) Moscow: Littera Publ.; 2016. 304 p. (In Russ)]
  2. Абдулкадыров К.М., Шуваев В.А., Мартынкевич И.С. Первичный миелофиброз: собственный опыт и новое в диагностике и лечении. Онкогематология. 2015;10(2):25–35. doi: 10.17650/1818-8346-2015-10-2-26-36.[Abdulkadyrov KM, Shuvayev VA, Martynkevich IS. Primary myelofibrosis: own experience and news from diagnostic and treatment. Oncohematology. 2015;10(2):25–35. doi: 10.17650/1818-8346-2015-10-2-26-36. (In Russ)]
  3. Shuvaev V, Martynkevich I, Abdulkadyrova A, et al. Ph-Negative Chronic Myeloproliferative Neoplasms–Population Analysis, a Single Center 10-years’ Experience. Blood (56th ASH Annual Meeting Abstracts). 2014;124(21): Abstract 5556.
  4. Shuvaev V, Udaleva V, Golovchenko R, et al. Primary myelofibrosis–a survey based on the 20-years’ experience of a single center. Haematologica. 2013;98(Suppl 1):624.
  5. Cervantes F, Passamonti F, Barosi G. Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia. 2008;22(5):905–14. doi: 10.1038/leu.2008.72.
  6. Абдулкадыров К.М., Шуваев В.А., Мартынкевич И.С. Критерии диагностики и современные методы лечения первичного миелофиброза. Вестник гематологии. 2013;9(3):44–78.[Abdulkadyrov KM, Shuvayev VA, Martynkevich IS. Diagnostic criteria and current methods of primary myelofibrosis treatment. Vestnik gematologii. 2013;9(3):44–78. (In Russ)]
  7. Gupta V, Hari P, Hoffman R. Allogeneic hematopoietic cell transplantation for myelofibrosis in the era of JAK inhibitors. Blood. 2012;120(7):1367–79. doi: 10.1182/blood-2012-05-399048.
  8. Vannucchi AM, Kantarjian HM, Kiladjian J-J, et al. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139–45. doi: 10.3324/haematol.2014.119545.
  9. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2008;113(13):2895–901. doi: 10.1182/blood-2008-07-170449.
  10. Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2009;115(9):1703–8. doi: 10.1182/blood-2009-09-245837.
  11. Gangat N, Caramazza D, Vaidya R, et al. DIPSS Plus: A Refined Dynamic International Prognostic Scoring System for Primary Myelofibrosis That Incorporates Prognostic Information from Karyotype, Platelet Count, and Transfusion Status. J Clin Oncol. 2011;29(4):392–7. doi: 10.1200/jco.2010.32.2446.
  12. Vannucchi AM, Rotunno G, Pascutto C, Pardanani A. Mutation-Enhanced International Prognostic Scoring System (MIPSS) for Primary Myelofibrosis: An AGIMM & IWG-MRT Project. (56th ASH Annual Meeting and Exposition, San-Francisco, December 6–9, 2014) Blood. 2014;2014:P405.
  13. Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395. doi: 10.1182/blood-2013-03-488098.
  14. Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701–7. doi: 10.1038/leu.2016.148.
  15. Verstovsek S, Mesa RA, Gotlib J, et al. 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. doi: 10.1186/s13045-017-0417-z.
  16. Al-Ali HK, Griesshammer M, le Coutre P, et al. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016;101(9):1065–73. doi: 10.3324/haematol.2016.143677.