Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=icmo20 Current Medical Research and Opinion ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: https://www.tandfonline.com/loi/icmo20 Chronic myeloproliferative disorders: is quality-of- life the new goal? Elisabetta Abruzzese, Pasquale Niscola, Malgorzata Monika Trawinska & Paolo de Fabritiis To cite this article: Elisabetta Abruzzese, Pasquale Niscola, Malgorzata Monika Trawinska & Paolo de Fabritiis (2018) Chronic myeloproliferative disorders: is quality- of-life the new goal?, Current Medical Research and Opinion, 34:7, 1345-1347, DOI: 10.1080/03007995.2018.1473245 To link to this article: https://doi.org/10.1080/03007995.2018.1473245 Published online: 01 Jun 2018. Submit your article to this journal Article views: 805 View related articles View Crossmark data Citing articles: 2 View citing articles
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Chronic myeloproliferative disorders: is quality-of-life the new goal?Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=icmo20
Current Medical Research and Opinion
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: https://www.tandfonline.com/loi/icmo20
Chronic myeloproliferative disorders: is quality-of- life the new goal?
Elisabetta Abruzzese, Pasquale Niscola, Malgorzata Monika Trawinska & Paolo de Fabritiis
To cite this article: Elisabetta Abruzzese, Pasquale Niscola, Malgorzata Monika Trawinska & Paolo de Fabritiis (2018) Chronic myeloproliferative disorders: is quality- of-life the new goal?, Current Medical Research and Opinion, 34:7, 1345-1347, DOI: 10.1080/03007995.2018.1473245
To link to this article: https://doi.org/10.1080/03007995.2018.1473245
Published online: 01 Jun 2018.
Submit your article to this journal
Article views: 805
View related articles
View Crossmark data
Elisabetta Abruzzese , Pasquale Niscola , Malgorzata Monika Trawinska and Paolo de Fabritiis
Hematology, St. Eugenio Hospital, Tor Vergata University, Rome, Italy
Chronic myeloproliferative neoplasms (MPN) are a group of hematologic malignancies that include a variety of different illnesses1. Chronic myeloid leukemia (CML) has been the pri- mary illness for targeted therapy since the advent of tyrosine kinase inhibitors (TKI), and plays a separate role among MPN. Other MPN include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), all of which share common features and a common pathogenetic path- way. Disease presentation and complaints, such as abdominal pain/discomfort and microvascular-related symptoms (e.g. headache, fatigue, insomnia, concentration difficulties, and dizziness) can overlap across MPN, making presentation a mix between the three statuses1.
Different studies have showed increased plasma levels of inflammatory cytokines, such as IL-1, IL-2, IL-6, IL-8, IL-12, TNFa, interferon (IFN)g, and growth factors, including gran- ulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) in MPNs that can be responsible, in total or in part, of pathogenesis and/or symptoms of the disease2.
The symptom burden of MPN, its impact on quality-of-life (QoL), and ability to work, as well as disease management strategies, have been recently addressed by the online survey of almost 700 patients and over 200 physicians conducted in Australia, Canada, Germany, Japan, Italy, and the United Kingdom. That study confirmed that the majority of patients experience severe debilitating symptoms, reduced QoL, and impaired productivity, requiring the need of therapies that reduce systemic complaints and improve everyday life3. The results of that study also showed that 64% of patients with MPN suffer from some degree of sexual dysfunction, with 43% experiencing severe symptoms. Sexual problems were more severe in the elderly, and were associated with depres- sion, microvascular-related symptoms, and a reduced QoL4. The contributing role of gender to the phenotypic profile and symptom expression has also been claimed, with females more affected than males, although the QoL scores in both sexes are similar5. Fatigue, fever, night sweats, bone and muscle pain, abdominal discomfort/pain, anorexia, and inco- ercible pruritus attributable to progressive cytopenias repre- sent a formidable symptom profile in either primary or secondary MF6. The mix of those manifestations (systemic symptoms can be found also in less severe PV and ET) dra- matically affects daily activities and is not relieved by
conventional therapy. Although the prognosis of MF may be variable6, it is generally considered a chronic disorder, with a relatively long disease trajectory. Ninety per cent of MF patients, including those with low symptom burden or low risk score, have difficulty controlling systemic symptoms, especially fatigue, resulting in a reduced QoL3. Therefore, improving QoL should be considered a crucial issue in the MF management.
The recent discovery of the first Janus kinase inhibitor (Ruxolitinib) approved for the treatment of MF with spleno- megaly has changed the treatment scenario of this disease7,8. As reported by two phase III, multi-center, randomized con- trolled trials (COMFORT-I and COMFORT-II), patients reported an immediate and significant relief of systemic manifesta- tions9,10. These studies demonstrated that Ruxolitinib trig- gered a significant reduction of spleen size, as well as an improvement in myelofibrosis-associated symptoms and QoL, compared with the best available treatment or placebo9–11. Two anecdotes support the findings of these studies. The first involves a 70-year-old patient who, the day after taking the drug for the first time, reported that he had carried two heavy grocery bags up two flights of stairs without fatigue, muscular pain, or dyspnoea for the first time in years. The second anecdote concerned a young woman who could finally take a bath, a simple enjoyable event for most people, but which she had avoided for years for fear of pruritus!
The interesting paper by Oritani et al.12 presents the same revolutionary situation: the improvement of QoL in patients with MF treated with Ruxolitinib in Japan. The authors reported a pooled analysis regarding QoL and symptoms bur- den over a 24-week period in 81 Japanese patients with intermediate or high-risk MF who had received Ruxolitinib after their enrolment in the Asian and Japanese clinical trials, which substantially confirmed the clinical results of the COMFORT-I and COMFORT-II studies13,14. Their pooled ana- lysis included the entire cohort of the Japanese study, adding the Japanese patients previously included in the Asian clin- ical trial. QoL was measured using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ- C30, scoring from 0–100), and symptoms burden profile was determined using the 7-day MF Symptom Assessment form (MFSAF, 0–10 scale)15,16. The majority of patients reported >50% reduction of the MFSAF at 24 weeks, and an increase in QoL. Notably, improvements in QoL and symptoms relief were associated with reduction of splenomegaly; in
CONTACT Paolo de Fabritiis [email protected] Hematology, St. Eugenio Hospital, Piazzale Umanesimo 10, 00144 Rome, Italy 2018 Informa UK Limited, trading as Taylor & Francis Group www.cmrojournal.com
CURRENT MEDICAL RESEARCH AND OPINION 2018, VOL. 34, NO. 7, 1345–1347 https://doi.org/10.1080/03007995.2018.1473245 Article ST-0015.R1/1473245 All rights reserved: reproduction in whole or part not permitted
particular, patients who achieved a reduction in spleen size greater than one third compared to baseline experienced the largest improvements of QoL and symptoms relief. The great- est clinical benefits correlated with higher dosages of admin- istered drug, such as 20 or 25mg BID of Ruxolitinib, although favorable results were recorded in all groups receiv- ing the drug. The authors concluded that Ruxolitinib allowed for substantial improvements in symptoms and QoL in Japanese MF patients, and that higher Ruxolitinib doses were associated with better responses, confirming the clinical ben- efits of this JAK-2 inhibitor in previous studies9,10.
The reduction of symptoms burden that impacts QoL in patients chronically treated for hematological malignancies has become a critical issue, and one of the major goals of treatment17. In particular, the improvement in survival seen in CML after the use of targeted drugs, now approaching that of general population18, has brought up the need for investigators to explore QoL, because it directly affects patient compliance to lifelong treatment. In this context, even low-grade adverse effects can substantially impair daily life of CML patients and, therefore, negatively affect adher- ence to therapy and clinical response19,20. From this perspec- tive, the role of the patient is becoming increasingly relevant, and the patient’s reported outcome assessment (PRO) is rap- idly changing clinical and research practice in the setting of hematologic neoplasms. For example, the use of self-reported QoL in patients with Myelodysplastic Syndromes (MDS) has improved prognostic accuracy and the development of new prognostic models21, with significant advances in the clinical daily MDS management22. The contribution of PRO in the treatment of MF has been critical in determining the most effective strategies for these patients, and this area of research now represents a focus of active investigations. By using disease-specific PRO measures such as MF-SAF, improvement in key symptoms, including fatigue, was dem- onstrated in patients treated with Ruxolitinib, compared to those who received a placebo. These improvements were also noted in patients who did not achieve the spleen size reduction of 35%, which represented the primary end-point of this controlled study. The placebo group, in contrast, reported worsening of MF-related symptoms and other PRO symptoms over time. These results significantly supported the FDA approval of Ruxolitinib for MF patients23.
In conclusion, MF is a challenging disease for which clin- ical management until now consisted only of supportive care for the vast majority of MF patients not eligible for allogeneic stem cell transplantation (SCT), the only treatment able to modify the natural course of the disease1,6. Given the histor- ically limited therapeutic choices, Ruxolitinib, through its pro- ven inhibition of the JAK-2/STAT pathway, has represented a breakthrough treatment, although its effects appear limited to symptoms palliation and reduction of the spleen size7,8. Target treatments in the setting of MF and other Ph negative MPN are less effective compared to CML, because of the complex pathways and multiple molecular lesions that sus- tain neoplastic activity. The impressive clinical results observed in the setting of CML, including treatment discon- tinuation in some patients24, have not been observed in MF by JAK-2 inhibitor therapy. It is hoped that newer effective
treatments will be developed for MF patients, the majority of whom are not eligible for allogeneic SCT. Inhibitors such as Pacritinib and Momelotinib are potentially attractive in cyto- penic patients; furthermore, there is interest in combining JAK inhibitors with traditional and/or experimental agents, with the aim of improving survival and QoL25.
The relief of constitutional and debilitating symptoms and the maintenance of the best possible QoL are currently the key issues in MF management, as outlined by Oritani et al.12. Meanwhile, new research on PRO assessment and QoL in the MF setting is strongly anticipated to improve disease man- agement and QoL in these patients.
Transparency
Declaration of financial/other interests
The authors have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this manuscript have no rele- vant financial or other relationships to disclose.
Acknowledgements
References
1. Meier B, Burton JH. Myeloproliferative disorders. Hematol Oncol Clin North Am 2017;3:1029-44
2. Lussana F, Rambaldi A. Inflammation and myeloproliferative neo- plasms. J Autoimmun 2017;85:58-63
3. Harrison CN, Koschmieder S, Foltz L, et al. The impact of myelo- proliferative neoplasms (MPNs) on patient quality of life and productivity: results from the international MPN Landmark survey. Ann Hematol 2017;96:1653–65
4. Geyer HL, Andreasson B, Kosiorek HE, et al. The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: an analysis by the MPN QOL International Study Group. Cancer 2016;122:1888-96
5. Geyer HL, Kosiorek H, Dueck AC, et al. Associations between gen- der, disease features and symptom burden in patients with myelo- proliferative neoplasms: an analysis by the MPN QOL International Working Group. Haematologica 2017;102:85-93
6. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk- stratification, and management. Am J Hematol 2016;91:1262-71
7. Kuykendall AT, Talati C, Al Ali N, et al. The treatment landscape of myelofibrosis before and after ruxolitinib approval. Clin Lymphoma Myeloma Leuk 2017;17:e45–e53
8. Harrison CN, Mesa RA, Kiladjian JJ, et al. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Br J Haematol 2013;162: 229-39
1346 E. ABRUZZESE ET AL.
9. Mesa RA, Gotlib J, Gupta V, et al. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported out- comes in COMFORT-I: a randomized, double-blind, placebo-con- trolled trial. J Clin Oncol 2013;31:1285-92
10. Verstovsek S, Mesa RA, Gotlib J, et al. A double blind, placebo-con- trolled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807
11. Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 2013;122:4047-53
12. Oritani K, Ohishi K, Okamoto S, et al. Effect of Ruxolitinib therapy on the quality of life of Japanese patients with myelofibrosis. Curr Med Res Opin 2017;9:1-16
13. Jung CW, Shih LY, Xiao Z, et al. Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis. Leuk Lymphoma 2015;56: 2067-74
14. Kirito K, Okamoto S, Ohishi K, et al. Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis. Int J Hematol 2018;107:92-7
15. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality of life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76
16. Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res 2009;33:1199-203
17. Efficace F, Gaidano G, Lo-Coco F. Patient-reported outcomes in hematology: is it time to focus more on them in clinical trials and hematology practice? Blood 2017;130:859-66
18. Bower H, Bj€orkholm M, Dickman PW, et al. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 2016;34:2851-7
19. Gambacorti-Passerini C, Antolini L, Mahon FX, et al. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst 2011;103:553-61
20. Efficace F, Cannella L. The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibi- tors. Hematology (Am Soc Hematol Educ Program) 2016;1:170–9
21. Efficace F, Gaidano G, Breccia M, et al. Prognostic value of self- reported fatigue on overall survival in patients with myelodysplas- tic syndromes: a multicentre, prospective, observational, cohort study. Lancet Oncol 2015;16:1506-14
22. Niscola P, Mandelli F, Efficace F. Improving accuracy of prognosis in patients with myelodysplastic syndromes using self-reported quality of life data. Opportunities for a new research agenda in developing prognostic models. Expert Rev Hematol 2016;9:415-17
23. Deisseroth A, Kaminskas E, Grillo J, et al. U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res 2012;18:3212-17
24. Abruzzese E. The DESTINY of chronic myeloid leukeamia. Lancet Haematol 2017;4:e303-e304
25. Vannucchi AM, Harrison CN. Emerging treatments for classical myeloproliferative neoplasms. Blood 2017;129:693-703
CHRONIC MYELOPROLIFERATIVE DISORDERS 1347
Current Medical Research and Opinion
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: https://www.tandfonline.com/loi/icmo20
Chronic myeloproliferative disorders: is quality-of- life the new goal?
Elisabetta Abruzzese, Pasquale Niscola, Malgorzata Monika Trawinska & Paolo de Fabritiis
To cite this article: Elisabetta Abruzzese, Pasquale Niscola, Malgorzata Monika Trawinska & Paolo de Fabritiis (2018) Chronic myeloproliferative disorders: is quality- of-life the new goal?, Current Medical Research and Opinion, 34:7, 1345-1347, DOI: 10.1080/03007995.2018.1473245
To link to this article: https://doi.org/10.1080/03007995.2018.1473245
Published online: 01 Jun 2018.
Submit your article to this journal
Article views: 805
View related articles
View Crossmark data
Elisabetta Abruzzese , Pasquale Niscola , Malgorzata Monika Trawinska and Paolo de Fabritiis
Hematology, St. Eugenio Hospital, Tor Vergata University, Rome, Italy
Chronic myeloproliferative neoplasms (MPN) are a group of hematologic malignancies that include a variety of different illnesses1. Chronic myeloid leukemia (CML) has been the pri- mary illness for targeted therapy since the advent of tyrosine kinase inhibitors (TKI), and plays a separate role among MPN. Other MPN include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), all of which share common features and a common pathogenetic path- way. Disease presentation and complaints, such as abdominal pain/discomfort and microvascular-related symptoms (e.g. headache, fatigue, insomnia, concentration difficulties, and dizziness) can overlap across MPN, making presentation a mix between the three statuses1.
Different studies have showed increased plasma levels of inflammatory cytokines, such as IL-1, IL-2, IL-6, IL-8, IL-12, TNFa, interferon (IFN)g, and growth factors, including gran- ulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) in MPNs that can be responsible, in total or in part, of pathogenesis and/or symptoms of the disease2.
The symptom burden of MPN, its impact on quality-of-life (QoL), and ability to work, as well as disease management strategies, have been recently addressed by the online survey of almost 700 patients and over 200 physicians conducted in Australia, Canada, Germany, Japan, Italy, and the United Kingdom. That study confirmed that the majority of patients experience severe debilitating symptoms, reduced QoL, and impaired productivity, requiring the need of therapies that reduce systemic complaints and improve everyday life3. The results of that study also showed that 64% of patients with MPN suffer from some degree of sexual dysfunction, with 43% experiencing severe symptoms. Sexual problems were more severe in the elderly, and were associated with depres- sion, microvascular-related symptoms, and a reduced QoL4. The contributing role of gender to the phenotypic profile and symptom expression has also been claimed, with females more affected than males, although the QoL scores in both sexes are similar5. Fatigue, fever, night sweats, bone and muscle pain, abdominal discomfort/pain, anorexia, and inco- ercible pruritus attributable to progressive cytopenias repre- sent a formidable symptom profile in either primary or secondary MF6. The mix of those manifestations (systemic symptoms can be found also in less severe PV and ET) dra- matically affects daily activities and is not relieved by
conventional therapy. Although the prognosis of MF may be variable6, it is generally considered a chronic disorder, with a relatively long disease trajectory. Ninety per cent of MF patients, including those with low symptom burden or low risk score, have difficulty controlling systemic symptoms, especially fatigue, resulting in a reduced QoL3. Therefore, improving QoL should be considered a crucial issue in the MF management.
The recent discovery of the first Janus kinase inhibitor (Ruxolitinib) approved for the treatment of MF with spleno- megaly has changed the treatment scenario of this disease7,8. As reported by two phase III, multi-center, randomized con- trolled trials (COMFORT-I and COMFORT-II), patients reported an immediate and significant relief of systemic manifesta- tions9,10. These studies demonstrated that Ruxolitinib trig- gered a significant reduction of spleen size, as well as an improvement in myelofibrosis-associated symptoms and QoL, compared with the best available treatment or placebo9–11. Two anecdotes support the findings of these studies. The first involves a 70-year-old patient who, the day after taking the drug for the first time, reported that he had carried two heavy grocery bags up two flights of stairs without fatigue, muscular pain, or dyspnoea for the first time in years. The second anecdote concerned a young woman who could finally take a bath, a simple enjoyable event for most people, but which she had avoided for years for fear of pruritus!
The interesting paper by Oritani et al.12 presents the same revolutionary situation: the improvement of QoL in patients with MF treated with Ruxolitinib in Japan. The authors reported a pooled analysis regarding QoL and symptoms bur- den over a 24-week period in 81 Japanese patients with intermediate or high-risk MF who had received Ruxolitinib after their enrolment in the Asian and Japanese clinical trials, which substantially confirmed the clinical results of the COMFORT-I and COMFORT-II studies13,14. Their pooled ana- lysis included the entire cohort of the Japanese study, adding the Japanese patients previously included in the Asian clin- ical trial. QoL was measured using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ- C30, scoring from 0–100), and symptoms burden profile was determined using the 7-day MF Symptom Assessment form (MFSAF, 0–10 scale)15,16. The majority of patients reported >50% reduction of the MFSAF at 24 weeks, and an increase in QoL. Notably, improvements in QoL and symptoms relief were associated with reduction of splenomegaly; in
CONTACT Paolo de Fabritiis [email protected] Hematology, St. Eugenio Hospital, Piazzale Umanesimo 10, 00144 Rome, Italy 2018 Informa UK Limited, trading as Taylor & Francis Group www.cmrojournal.com
CURRENT MEDICAL RESEARCH AND OPINION 2018, VOL. 34, NO. 7, 1345–1347 https://doi.org/10.1080/03007995.2018.1473245 Article ST-0015.R1/1473245 All rights reserved: reproduction in whole or part not permitted
particular, patients who achieved a reduction in spleen size greater than one third compared to baseline experienced the largest improvements of QoL and symptoms relief. The great- est clinical benefits correlated with higher dosages of admin- istered drug, such as 20 or 25mg BID of Ruxolitinib, although favorable results were recorded in all groups receiv- ing the drug. The authors concluded that Ruxolitinib allowed for substantial improvements in symptoms and QoL in Japanese MF patients, and that higher Ruxolitinib doses were associated with better responses, confirming the clinical ben- efits of this JAK-2 inhibitor in previous studies9,10.
The reduction of symptoms burden that impacts QoL in patients chronically treated for hematological malignancies has become a critical issue, and one of the major goals of treatment17. In particular, the improvement in survival seen in CML after the use of targeted drugs, now approaching that of general population18, has brought up the need for investigators to explore QoL, because it directly affects patient compliance to lifelong treatment. In this context, even low-grade adverse effects can substantially impair daily life of CML patients and, therefore, negatively affect adher- ence to therapy and clinical response19,20. From this perspec- tive, the role of the patient is becoming increasingly relevant, and the patient’s reported outcome assessment (PRO) is rap- idly changing clinical and research practice in the setting of hematologic neoplasms. For example, the use of self-reported QoL in patients with Myelodysplastic Syndromes (MDS) has improved prognostic accuracy and the development of new prognostic models21, with significant advances in the clinical daily MDS management22. The contribution of PRO in the treatment of MF has been critical in determining the most effective strategies for these patients, and this area of research now represents a focus of active investigations. By using disease-specific PRO measures such as MF-SAF, improvement in key symptoms, including fatigue, was dem- onstrated in patients treated with Ruxolitinib, compared to those who received a placebo. These improvements were also noted in patients who did not achieve the spleen size reduction of 35%, which represented the primary end-point of this controlled study. The placebo group, in contrast, reported worsening of MF-related symptoms and other PRO symptoms over time. These results significantly supported the FDA approval of Ruxolitinib for MF patients23.
In conclusion, MF is a challenging disease for which clin- ical management until now consisted only of supportive care for the vast majority of MF patients not eligible for allogeneic stem cell transplantation (SCT), the only treatment able to modify the natural course of the disease1,6. Given the histor- ically limited therapeutic choices, Ruxolitinib, through its pro- ven inhibition of the JAK-2/STAT pathway, has represented a breakthrough treatment, although its effects appear limited to symptoms palliation and reduction of the spleen size7,8. Target treatments in the setting of MF and other Ph negative MPN are less effective compared to CML, because of the complex pathways and multiple molecular lesions that sus- tain neoplastic activity. The impressive clinical results observed in the setting of CML, including treatment discon- tinuation in some patients24, have not been observed in MF by JAK-2 inhibitor therapy. It is hoped that newer effective
treatments will be developed for MF patients, the majority of whom are not eligible for allogeneic SCT. Inhibitors such as Pacritinib and Momelotinib are potentially attractive in cyto- penic patients; furthermore, there is interest in combining JAK inhibitors with traditional and/or experimental agents, with the aim of improving survival and QoL25.
The relief of constitutional and debilitating symptoms and the maintenance of the best possible QoL are currently the key issues in MF management, as outlined by Oritani et al.12. Meanwhile, new research on PRO assessment and QoL in the MF setting is strongly anticipated to improve disease man- agement and QoL in these patients.
Transparency
Declaration of financial/other interests
The authors have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this manuscript have no rele- vant financial or other relationships to disclose.
Acknowledgements
References
1. Meier B, Burton JH. Myeloproliferative disorders. Hematol Oncol Clin North Am 2017;3:1029-44
2. Lussana F, Rambaldi A. Inflammation and myeloproliferative neo- plasms. J Autoimmun 2017;85:58-63
3. Harrison CN, Koschmieder S, Foltz L, et al. The impact of myelo- proliferative neoplasms (MPNs) on patient quality of life and productivity: results from the international MPN Landmark survey. Ann Hematol 2017;96:1653–65
4. Geyer HL, Andreasson B, Kosiorek HE, et al. The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: an analysis by the MPN QOL International Study Group. Cancer 2016;122:1888-96
5. Geyer HL, Kosiorek H, Dueck AC, et al. Associations between gen- der, disease features and symptom burden in patients with myelo- proliferative neoplasms: an analysis by the MPN QOL International Working Group. Haematologica 2017;102:85-93
6. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk- stratification, and management. Am J Hematol 2016;91:1262-71
7. Kuykendall AT, Talati C, Al Ali N, et al. The treatment landscape of myelofibrosis before and after ruxolitinib approval. Clin Lymphoma Myeloma Leuk 2017;17:e45–e53
8. Harrison CN, Mesa RA, Kiladjian JJ, et al. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Br J Haematol 2013;162: 229-39
1346 E. ABRUZZESE ET AL.
9. Mesa RA, Gotlib J, Gupta V, et al. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported out- comes in COMFORT-I: a randomized, double-blind, placebo-con- trolled trial. J Clin Oncol 2013;31:1285-92
10. Verstovsek S, Mesa RA, Gotlib J, et al. A double blind, placebo-con- trolled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807
11. Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 2013;122:4047-53
12. Oritani K, Ohishi K, Okamoto S, et al. Effect of Ruxolitinib therapy on the quality of life of Japanese patients with myelofibrosis. Curr Med Res Opin 2017;9:1-16
13. Jung CW, Shih LY, Xiao Z, et al. Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis. Leuk Lymphoma 2015;56: 2067-74
14. Kirito K, Okamoto S, Ohishi K, et al. Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis. Int J Hematol 2018;107:92-7
15. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality of life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76
16. Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res 2009;33:1199-203
17. Efficace F, Gaidano G, Lo-Coco F. Patient-reported outcomes in hematology: is it time to focus more on them in clinical trials and hematology practice? Blood 2017;130:859-66
18. Bower H, Bj€orkholm M, Dickman PW, et al. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 2016;34:2851-7
19. Gambacorti-Passerini C, Antolini L, Mahon FX, et al. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst 2011;103:553-61
20. Efficace F, Cannella L. The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibi- tors. Hematology (Am Soc Hematol Educ Program) 2016;1:170–9
21. Efficace F, Gaidano G, Breccia M, et al. Prognostic value of self- reported fatigue on overall survival in patients with myelodysplas- tic syndromes: a multicentre, prospective, observational, cohort study. Lancet Oncol 2015;16:1506-14
22. Niscola P, Mandelli F, Efficace F. Improving accuracy of prognosis in patients with myelodysplastic syndromes using self-reported quality of life data. Opportunities for a new research agenda in developing prognostic models. Expert Rev Hematol 2016;9:415-17
23. Deisseroth A, Kaminskas E, Grillo J, et al. U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res 2012;18:3212-17
24. Abruzzese E. The DESTINY of chronic myeloid leukeamia. Lancet Haematol 2017;4:e303-e304
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