Quality of life and symptom profile in patients with myelofibrosis undergoing treatment: Data of clinical practice

The aim of the study was to evaluate the quality of life (QoL) and symptoms in patients with myelofibrosis (MF). 93 patients with MF who participated in the multicenter observational study “Quality of life and symptoms in myelofibrosis: validation of the symptom assessment tool for patients with myelofibrosis” (2014–2015) were enrolled in the analysis. 62 patients received best available treatment (BAT) and 31 patients received ruxolitinib. All the patients filled out the SF-36, CSP-Myelofibrosis Module and Patient Global Impression of Change (PGIC) tools. In the real-world study in MF patients QoL was demonstrated to be significantly worse than in healthy controls; more than one third of patients had significant or severe QoL impairment. Patients treated with ruxolitinib had better QoL and lower symptom severity as compared to BAT patients. Decline of activity appeared to be the major symptom which significantly reduced QoL in MF patients. QoL and symptom data in MF patients during treatment in a real world setting may be a solid supplement to clinical variables and may contribute to better disease control in accordance with the principles of risk-adaptive therapy.

1. Melikyan A.L., Turkina A.G., Abdulkadyrov K.M., Zaritsky A.Yu., Afanasyev B.V., Shuvaev V.A., Lomaia E.G., Morozova E.V., Baikov V.V., Golenkov A.K., Subortseva I.N., Sokolova M.A., Kovrigina A.M., Martynkevich I.S., Gritsaev S.V., Sudarikov A.B., Sukhanova G.A., Ivanova V.L., Kaplanov K.D., Konstantinova T.S., Pospelova T.I., Ageeva T.A., Shatokhin Yu.V., Savchenko V.G. Clinical recommendations for diagnosis and therapy of Рh-negative myeloproliferative diseases (polycythemia vera, essential thrombocythemia, primary myelofbrosis). Hematology and Transfusiology. Russian Journal (Gematologiya i transfusiologiya). 2014; 4: 31–56. (in Russian)

2. Reilly J.T., McMullin M.F., Beer P.A., Butt N., Conneally E., Duncombe A. et al.; Writing group: British Committee for Standards in Haematology. Guideline for the diagnosis and management of myelofbrosis. Br. J. Haematol. 2012; 158(4): 453–71. doi: 10.1111/j.1365-2141.2012.09179.x.

3. Novik A., Salek S., Ionova T., eds. Guidelines. Patient-Reported Outcomes in Hematology. Genoa: Forum service editore; 2012.

4. Tefferi A., Cervantes F., Mesa R., Passamonti F., Verstovsek S., Vannucchi A.M., et al. Revised response criteria for myelofbrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013; 122(8): 1395–98. doi: 10.1182/blood-2013-03-488098.

5. Mesa R.A., Gotlib J., Gupta V., Catalano J.V., Deininger M.W., Shields A.L., et al. Effect of Ruxolitinib therapy on myelofbrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. J. Clin. Oncol. 2013; 31(10): 1285–92. doi: 10.1200/JCO.2012.44.4489.

6. Yacoub A., Odenike O., Verstovsek S. Ruxolitinib: long-term management of patients with myelofbrosis and future directions in the treatment of myeloproliferative neoplasms .Curr. Hematol. Malig. Rep. 2014; 9(4): 350–9. doi: 10.1007/s11899-014-0229-y.

7. Cervantes F., Vannucch A.M., Kiladjian J.J., Al-Ali H.K., Sirulnik A., Stalbovskaya V., et al. Three-year effcacy, safety, and survival fndings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofbrosis. Blood. 2013; 122(25): 4047–53

8. Mesa R.A., Kiladjian J.J., Verstovsek S., Gotlib J., Gisslinger H., Levy R., et al. Comparison of placebo and best available therapy for the treatment of myelofbrosis in the phase 3 COMFORT studies. Haematologica. 2014; 99(2): 292–8.

9. Verstovsek S., Almomen A.K., Newberry K.J., Aleem A. Development of ruxolitinib as a myelofbrosis therapy. J. Appl. Hematol. 2013; 4(3): 89–95.

10. Verstovsek S., Mesa R.A., Gotlib J., Levy R.S., Gupta V., DiPersio J.F., et al. Effcacy, safety, and survival with ruxolitinib in patients with myelofbrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015; 100(4): 479–88.

11. Mead A., Milojkovic D., Knapper S., Garg M., Chacko J., Farquharson M., et al. Response to ruxolitinib in patients with intermediate-1, intermediate-2 and high-risk myelofbrosis: results of the UK ROBUST trial. Br. J. Haematol. 2015; 170(1): 29–39.

12. Harrison C., Kiladjian J.J., Al-Ali H.K., Gisslinger H., Waltzman R., Stalbovskaya V., et al. JAK inhibition with ruxolitinib versus best available therapy for myelofbrosis. N. Engl. J. Med. 2012; 366(9):787–98.

13. Mesa R.A., Kantarjian H., Tefferi A., Dueck A., Levy R., Vaddi K., et al. Evaluating the serial use of the Myelofbrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofbrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Cancer. 2011; 117(21): 4869–77. doi: 10.1002/cncr.26129.

14. Harrison C.N., Mesa R.A., Kiladjian J.J., Al-Ali H.K., Gisslinger H., Knoops L., et al. Health-related quality of life and symptoms in patients with myelofbrosis treated with ruxolitinib versus best available therapy. Br. J. Haematol. 2013; 162(2): 229–39. doi: 10.1111/bjh.12375.

15. Kiladjian J.J., Gisslinger H., Passamonti F., Niederwieser D., Mendelson E., Sirulnik L.A., et al. Health-related quality of life and symptom burden in patients with myelofbrosis in the COMFORT-II study. J. Clin. Oncol. 2012; 30 (Suppl): Abstr. 6626.

16. Vargas-Viveros P., Hurtado-Monroy R., Candelaria-Hernández M. Signifcant Improvement in Quality of Life (QoL) in Patients with Chronic Myeloproliferative Neoplasms (CMPN) and Myelofbrosis Treated with JAK-1 and JAK-2 Inhibitor Ruxolitinib. Clin. Lymph. Myeloma Leuk. 2014; 14 (Suppl): S155–6.

17. Meshcheryakova L.M., Porotkova O.V., Kovaleva L.G., Kolosova L.Yu. L.M. Patients with primary myelofbrosis: treatment and quality of life. Oncogematology. Russian journal (Onkogematologiya). 2012; 2: 6–13. (in Russian) http://www.hematology.ru/journals/oncohematology/2012/2/oncohematology_0212.pdf

18. Porotkova O.V. Patients with primary myelofbrosis: treatment and quality of life. Dis. Moscow; 2012. Available at http://medical-diss.com/docreader/539980/a#?page=1

19. Common Terminology Criteria for Adverse Evens (CTCAE 3) Version 3.0 12.12.2003. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

20. Hays R.D., Sherbourne C.D., Mazel R.M. User’s Manual for Medical Outcomes Study (MOS) Core measures of health-related quality of life. RAND Corporation, MR-162-RC. Available at: http://www.rand.org.

21. Novik A.A., Ionova T.I., Kishtovich A.V., Tsepkova A.A., Mylnikov S.V. Stratifcation of patients using QoL parametrs by the method of integral profles. Quality Life Res. 2003; 12(7): 770.

22. Novik A.A., Ionova T.I. Integral indicator of quality of life – a new category in the concept of quality of life research. Bulletin of the international centre for the study of quality of life. Bulletin of the Multinational Center of Quality of Life Research. Russian jour nal (Vestnik Mezhnatsional’nogo tsentra issledovaniya kachestva zhizni). 2006; 7–8. http://www.quality-life.ru/gyrnstat0124.php

23. Hurst H., Bolton J. Assessing the clinical signifcance of changes cores recorded on subjective outcome measures. J. Manipulative Physiol. Ther. 2004; 27(1): 26–35.

24. Mesa R.A., Harrison C.N., Cervantes F., Dean J.P., Wang L., Granston T., et al. Relationship between Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) and effcacy in patients with myelofbrosis in the phase III persist-1 trial of Pacritinib vs. Best Available Therapy (BAT). Blood. 2015; 126(23): Abstr. 1609. http://www.bloodjournal.org/content/126/23/1609?sso-checked=true

25. Fauble V., Emanuel R.M., Geyer H.L., Dueck A.C., Kroeger N., Scott B.L., et al. Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group: Observational Study of quality of life and symptomatic response in myelofbrosis patients receiving undergoing treatment with conventional therapy, the measures trial and allogeneic stem cell transplant, the symptoms trial. Blood. 2013; 122 (21): 4090. https://ash.confex.com/ash/2013/webprogram/Paper65062.html

26. Davis K.L., Côté I., Kaye J.A., Mendelson E., Gao H., Ronco J.P. Real-world assessment of clinical outcomes in lower-risk myelofbrosis patients receiving treatment with Ruxolitinib. Adv. Hematol. 2015; 2015. Article ID 848473. doi:10.1155/2015/848473. http://dx.doi.org/10.1155/2015/848473

27. Emanuel R.M., Geyer H.L., Mesa R.A. Ruxolitinib as an emerging treatment in myelofbrosis. Blood Lymph. Cancer: Targets Ther. 2013; 3: 11–8. http://dx.doi.org/10.2147/BLCTT.S24926

28. Mesa R.A., Schwager S., Radia D., Cheville A., Hussein K., Niblack J., et al. The Myelofbrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofbrosis. Leuk. Res. 2009; 33(9): 1199–203. doi: 10.1016/j.leukres.2009.01.035.

29. Mitra D., Kaye J.A., Piecoro L.T., Brown J., Reith K., Mughal T.I., Sarlis N.J. Symptom burden and splenomegaly in patients with myelofbrosis in the United States: a retrospective medical record review. Cancer Med. 2013; 2(6): 889–98. doi: 10.1002/cam4.136.