Quality of life and symptom profile in patients with chronic myeloid leukemia receiving dasatinib as а second-line therapy due to intolerance or resistance to imatinib

The article is focused on preliminary results of the observational study “Quality of life and symptom profile in imatinib-resistant or intolerant patients with chronic myeloid leukemia during disease-modifying treatment” (2011–2012). 56 imatinib-resistant or intolerant patients with chronic myeloid leukemia in chronic phase were included in the preliminary analysis. It was shown that prior to treatment with dasatinib more than one third of patients had severe or critical quality of life deterioration. Patients treated with standard doses of imatinib during the first-line treatment reported better quality of life than patients treated with high doses of imatinib. After 12 months of treatment with dasatinib, the majority of patients showed complete or partial cytogenetic response (62 %); most of the patients with complete cytogenetic response were treated with standard doses of imatinib during the first-line treatment (19 % vs 8 %). During treatment with dasatinib, stabilization of quality of life parameters was recorded with a slight trend towards improved vitality, mental health, and pain scales. In the majority of patients (68 %), the treatment response as improved or stabilized quality of life was observed. During treatment with dasatinib, severity of the most frequent disease- or treatment-specific symptoms decreased. In this observational study, it was shown that dasatinib therapy in the real-world practice is effective both in terms of clinical parameters and patient-reported outcomes, and characterized by good tolerability.

• T.I. Ionova N.I. Pirogov National Medico-surgical Center, Moscow, Russian Federation; International Center for Quality of Life Studies, Saint-Petersburg, Russian Federation ; Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Российская Федерация; Межнациональный центр исследования качества жизни, Санкт-Петербург, Российская Федерация
• D.A. Fedorenko N.I. Pirogov National Medico-surgical Center, Moscow, Russian Federation; International Center for Quality of Life Studies, Saint-Petersburg, Russian Federation ; Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Российская Федерация; Межнациональный центр исследования качества жизни, Санкт-Петербург, Российская Федерация
• T.P. Nikitina N.I. Pirogov National Medico-surgical Center, Moscow, Russian Federation ; Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Российская Федерация
• K.A. Kurbatova N.I. Pirogov National Medico-surgical Center, Moscow, Russian Federation ; Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Российская Федерация

1. Baccarani M., Pileri S., Steegmann J.-L. et al. Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncology 2012; 23(7): vii72–7. DOI: https://doi.org/10.1093/annonc/mds228
2. Saglio G. New approaches to treatment of chronic myeloid leukemia. Hematology Education: the education program for the annual congress of the European Hematology Association. 2012; 6: 129–36.
3. Hochhaus A. Management of newly diagnosed chronic myeloid leukemia patients. Hematology Education: the education program for the annual congress of the European Hematology Association. 2011; 5: 120–6.
4. Голенков А.К., Высоцкая Л.Л., Трифонова Е.В. и др. Эффективность лечения больных хроническим миелолейкозом иматинибом в широкой клинической практике. Онкогематология 2012; 3: 17–21. [Golenkov A.K., Vysotskaya L.L., Trifonova E.V. i dr. Effectivnost lecheniya bolnikh khronicheskim miyeloleykozom imatinibom v shirokoy klinicheskoy practike (Efficacy of imatinib therapy for chronic myeloid leukemia in routine clinical practice). Onkogematologia 2012; 3: 17–21.]
5. Практические аспекты терапии хронического миелолейкоза в хро- нической фазе (по материалам выступлений на конгрессе гематологов. Москва, 3 июля 2012 г.). Онкогематология 2012; 3: 8–16. [Practicheskiye aspecty terapii khronicheskogo miyeloleykoza v khronicheskoy faze (po materialam vystupleniy na kongresse gematologov. Moskva, 3 iulya 2012 g.) (Practical aspects of therapy for chronic myeloid leukemia in chronic phase (adapted from presentations at the hematologists’ congress. Moscow, July 3, 2012)). Onkogematologia 2012; 3: 8–16.]
6. De Lavallade H., Apperley J.F., Khorashad J.S. et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J. Clin. Oncol. 2008; 26: 3358–63. DOI: https://doi.org/10.1200/JCO.2007.15.8154
7. Волкова М.А. Новые возможности в терапии хронического миелолей- коза: дазатиниб. Клин. онкогематол. 2008; 1(3): 218–25. [Volkova M.A. Novyye vozmozhnosti v terapii khronicheskogo miyeloleykoza: dazatinib (New possibilities in dasatinib therapy for chronic myeloid leukemia). Klin. onkogematol. 2008; 1(3): 218–25.]
8. Guilhot F., Apperley J., Kim D.-W. et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 2007; 109: 4143–50. DOI: https://doi.org/10.1182/blood-2006-09-046839
9. Hochhaus A., Kantarjian H.M., Baccarani M. et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007; 109: 2303–9. DOI: https://doi.org/10.1182/blood-2006-09-047266
10. Kantarjian H., Pasquini R., Hamerschlak N. et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 2007; 109(12): 5143–50. DOI: https://doi.org/10.1182/blood-2006-11-056028
11. Hochhaus A., Baccarani M., Deininger M. et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 2008: 1–7. DOI: https://doi.org/10.1038/leu.2008.84
12. Ottmann O., Dombret H., Martinelli G. et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood 2007; 110: 2309–15. DOI: https://doi.org/10.1182/blood-2007-02-073528
13. Guidelines. Patient-reported outcomes in hematology. The EHA SWG «Quality of life and Symptoms». Forum Service Editore. Genoa, Forum service editore. 2012.
14. Ionova T., Nikitina T., Gritsenko T. et al. Quality of life and symptom profile in patients with Imatinib-resistant or intolerant chronic myeloid leukemia. Haematologica 2012; 97(1): 368.
15. Новик А.А., Ионова Т.И. Руководство по исследованию качества жизни в медицине, 3-е изд., перераб. и доп. Под ред. Ю.Л. Шевченко. М.: РАЕН, 2012. [Novik A.A., Ionova T.I. Rukovodstvo po issledovaniyu kachestva zhizni v meditsine, 3-e izd., pererab. i dop. Pod. red. Yu.L. Shevchenko (Manual on quality of life assessment in medicine, 3rd ed., revised and amended. Ed. by Yu.L. Shevchenko). M.: RAEN, 2012.]
16. Efficace F., Baccarani M., Breccia M. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood 2011; 118(17): 4554–60. DOI: https://doi.org/10.1182/blood-2011-04-347575
17. Efficace F., Cocks K., Breccia M. et al. GIMEMA and EORTC Quality of Life Group. Time for a new era in the evaluation of targeted therapies for patients with chronic myeloid leukemia: Inclusion of quality of life and other patientreported outcomes. Crit. Rev. Oncol. Hematol. 2012; 81(2): 123–35. DOI: https://doi.org/10.1016/j.critrevonc.2011.02.007
18. Guilhod J., Baccarani M., Clark R.E. et al. Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European Leukemia Net. Blood 2012; 119: 5963–71. DOI: https://doi.org/10.1182/blood-2011-10-383711
19. 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: www.rand.org.
20. Efficace F., Cocks K., Breccia M. et al. GIMEMA and EORTC Quality of Life Group. Time for a new era in the evaluation of targeted therapies for patients with chronic myeloid leukemia: Inclusion of quality of life and other patientreported outcomes. Crit. Rev. Oncol. Hematol. 2012; 81(2): 123–35. DOI: https://doi.org/10.1016/j.critrevonc.2011.02.007
21. Bevans M.F., Mitchell S.A., Barrett A.J. et al. Function, Adjustment, Quality of Life and Symptoms (FAQS) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Survivors: A Study Protocol. Health and Quality of Life Outcomes 2011; 9: 24. doi: 10.1186/1477-7525-9-24. DOI: https://doi.org/10.1186/1477-7525-9-24