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Published in: Annals of Hematology 6/2020

Open Access 01-06-2020 | Chronic Myeloid Leukemia | Original Article

Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia

Authors: Tim H. Brümmendorf, Carlo Gambacorti-Passerini, Andrew G. Bushmakin, Joseph C. Cappelleri, Andrea Viqueira, Arlene Reisman, Susanne Isfort, Carla Mamolo

Published in: Annals of Hematology | Issue 6/2020

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Abstract

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR.

Literature
  1. Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM (2016) Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 34(24):2851–2857. https://​doi.​org/​10.​1200/​JCO.​2015.​66.​2866 View ArticlePubMed
  2. Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, Dyagil I, Glushko N, Milojkovic D, le Coutre P, Garcia-Gutierrez V, Reilly L, Jeynes-Ellis A, Leip E, Bardy-Bouxin N, Hochhaus A, Brummendorf TH (2018) Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol 36(3):231–237. https://​doi.​org/​10.​1200/​JCO.​2017.​74.​7162 View ArticlePubMed
  3. Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boque C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M (2010) Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362(24):2260–2270. https://​doi.​org/​10.​1056/​NEJMoa1002315 View ArticlePubMed
  4. Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, ENESTnd Investigators (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362(24):2251–2259. https://​doi.​org/​10.​1056/​NEJMoa0912614
  5. Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P, Intergroupe Francais des Leucemies Myeloides C (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11(11):1029–1035. https://​doi.​org/​10.​1016/​S1470-2045(10)70233-3 View ArticlePubMed
  6. Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, Janssen J, Mayer J, Koskenvesa P, Panayiotidis P, Olsson-Stromberg U, Martinez-Lopez J, Rousselot P, Vestergaard H, Ehrencrona H, Kairisto V, Machova Polakova K, Muller MC, Mustjoki S, Berger MG, Fabarius A, Hofmann WK, Hochhaus A, Pfirrmann M, Mahon FX, EURO-SKI investigators (2018) Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol 19(6):747–757. https://​doi.​org/​10.​1016/​S1470-2045(18)30192-X
  7. De Marchi F, Medeot M, Fanin R, Tiribelli M (2017) How could patient reported outcomes improve patient management in chronic myeloid leukemia? Expert Rev Hematol 10(1):9–14. https://​doi.​org/​10.​1080/​17474086.​2017.​1262758 View ArticlePubMed
  8. Trask PC, Cella D, Besson N, Kelly V, Masszi T, Kim DW (2012) Health-related quality of life of bosutinib (SKI-606) in imatinib-resistant or imatinib-intolerant chronic phase chronic myeloid leukemia. Leuk Res 36(4):438–442. https://​doi.​org/​10.​1016/​j.​leukres.​2011.​10.​011 View ArticlePubMed
  9. Whiteley J, Reisman A, Shapiro M, Cortes J, Cella D (2016) Health-related quality of life during bosutinib (SKI-606) therapy in patients with advanced chronic myeloid leukemia after imatinib failure. Curr Med Res Opin 32(8):1325–1334. https://​doi.​org/​10.​1185/​03007995.​2016.​1174108 View ArticlePubMed
  10. Kantarjian HM, Mamolo CM, Gambacorti-Passerini C, Cortes JE, Brummendorf TH, Su Y, Reisman AL, Shapiro M, Lipton JH (2018) Long-term patient-reported outcomes from an open-label safety and efficacy study of bosutinib in Philadelphia chromosome-positive chronic myeloid leukemia patients resistant or intolerant to prior therapy. Cancer 124(3):587–595. https://​doi.​org/​10.​1002/​cncr.​31082 View ArticlePubMed
  11. Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, Milojkovic D, le Coutre P, Garcia-Gutierrez V, Crescenzo R, Mamolo C, Reisman A, Hochhaus A, Brummendorf TH, BFORE Study Investigators (2019) Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia. J Cancer Res Clin Oncol 145(6):1589–1599. https://​doi.​org/​10.​1007/​s00432-019-02894-3
  12. Brümmendorf TH, Mamolo CM, Reisman A, Bushmakin AG, Cappelleri JC, Crescenzo RJ, DeAnnuntis L, Viquiera A, Cortes JE (2018) Impact of diarrhea on health-related quality of life: analysis of the phase 3 BFORE trial of bosutinib vs imatinib for newly diagnosed chronic phase chronic myeloid leukemia. Blood 132(Suppl 1):4264. https://​doi.​org/​10.​1182/​blood-2018-99-110152
  13. Cortes JE, Mauro MJ, Deininger MWN, Chuah C, Kim D-W, Kota V, Lipton JH, Rousselot PH, Milojkovic D, Coutre PDL, Gutierrez VG, Crescenzo RJ, Leip E, An F, Bouxin N, Hochhaus A, Brümmendorf TH, Gambacorti-Passerini C (2018) Bosutinib vs imatinib for newly diagnosed chronic myeloid leukemia in the BFORE trial: 24-month follow-up. J Clin Oncol 36(15_suppl):7002. https://​doi.​org/​10.​1200/​JCO.​2018.​36.​15_​suppl.​7002 View Article
  14. Khoury HJ, Gambacorti-Passerini C, Brummendorf TH (2018) Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. Ann Oncol 29(3):578–587. https://​doi.​org/​10.​1093/​annonc/​mdy019 View ArticlePubMedPubMed Central
  15. Steegmann JL, Baccarani M, Breccia M, Casado LF, Garcia-Gutierrez V, Hochhaus A, Kim DW, Kim TD, Khoury HJ, Le Coutre P, Mayer J, Milojkovic D, Porkka K, Rea D, Rosti G, Saussele S, Hehlmann R, Clark RE (2016) European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia 30(8):1648–1671. https://​doi.​org/​10.​1038/​leu.​2016.​104 View ArticlePubMedPubMed Central
  16. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, Baccarani M, Cortes J, Cross NC, Druker BJ, Gabert J, Grimwade D, Hehlmann R, Kamel-Reid S, Lipton JH, Longtine J, Martinelli G, Saglio G, Soverini S, Stock W, Goldman JM (2006) Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108(1):28–37. https://​doi.​org/​10.​1182/​blood-2006-01-0092 View ArticlePubMedPubMed Central
  17. Cella D, Jensen SE, Webster K, Hongyan D, Lai JS, Rosen S, Tallman MS, Yount S (2012) Measuring health-related quality of life in leukemia: the Functional Assessment of Cancer Therapy--Leukemia (FACT-Leu) questionnaire. Value Health 15(8):1051–1058. https://​doi.​org/​10.​1016/​j.​jval.​2012.​08.​2210 View ArticlePubMed
  18. FACIT.​org FACT-Leu (Version 4). https://​www.​facit.​org/​FACITOrg/​Questionnaires. Accessed 23 Aug 2019
  19. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Muller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saussele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6):872–884. https://​doi.​org/​10.​1182/​blood-2013-05-501569 View ArticlePubMedPubMed Central
  20. Fairclough DL (2010) Design and analysis of quality of life studies in clinical trials, 2nd edn. Chapman & Hall/CRC, Boca RatonView Article
  21. Fitzmaurice GM, Laird NM, Ware JH (2011) Applied longitudinal analysis, 2nd edn. Wiley, HobokenView Article
  22. Cohen J (1988) Statistical power analysis for the behavioral sciences. Lawrence Erlbaum Associates, Hillsdale
  23. Cappelleri JC, Zou KH, Bushmakin AG, Alvir JMJ, Alemayehu D, Symonds T (2013) Patient-reported outcomes: measurement, implementation and interpretation. CRC Press, Boca RatonView Article
  24. Norman GR, Sloan JA, Wyrwich KW (2003) Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 41(5):582–592. https://​doi.​org/​10.​1097/​01.​MLR.​0000062554.​74615.​4C View ArticlePubMed
  25. Efficace F, Cannella L (2016) The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitors. Hematol Am Soc Hematol Educ Program 2016(1):170–179. https://​doi.​org/​10.​1182/​asheducation-2016.​1.​170 View Article
  26. Gambacorti-Passerini C, Cortes JE, Lipton JH, Kantarjian HM, Kim DW, Schafhausen P, Crescenzo R, Bardy-Bouxin N, Shapiro M, Noonan K, Leip E, DeAnnuntis L, Brummendorf TH, Khoury HJ (2018) Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Haematologica 103(8):1298–1307. https://​doi.​org/​10.​3324/​haematol.​2017.​171249 View ArticlePubMedPubMed Central
  27. Cortes J (2004) Natural history and staging of chronic myelogenous leukemia. Hematol Oncol Clin North Am 18(3):569–584, viii. https://​doi.​org/​10.​1016/​j.​hoc.​2004.​03.​011 View ArticlePubMed
  28. King MT, Stockler MR, Cella DF, Osoba D, Eton DT, Thompson J, Eisenstein AR (2010) Meta-analysis provides evidence-based effect sizes for a cancer-specific quality-of-life questionnaire, the FACT-G. J Clin Epidemiol 63(3):270–281. https://​doi.​org/​10.​1016/​j.​jclinepi.​2009.​05.​001 View ArticlePubMed
  29. Efficace F, Baccarani M, Breccia M, Alimena G, Rosti G, Cottone F, Deliliers GL, Barate C, Rossi AR, Fioritoni G, Luciano L, Turri D, Martino B, Di Raimondo F, Dabusti M, Bergamaschi M, Leoni P, Simula MP, Levato L, Ulisciani S, Veneri D, Sica S, Rambaldi A, Vignetti M, Mandelli F, Gimema (2011) Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood 118(17):4554–4560. https://​doi.​org/​10.​1182/​blood-2011-04-347575 View ArticlePubMed
  30. Phillips KM, Pinilla-Ibarz J, Sotomayor E, Lee MR, Jim HS, Small BJ, Sokol L, Lancet J, Tinsley S, Sweet K, Komrokji R, Jacobsen PB (2013) Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison. Support Care Cancer 21(4):1097–1103. https://​doi.​org/​10.​1007/​s00520-012-1630-5 View ArticlePubMed
  31. Aziz Z, Iqbal J, Aaqib M, Akram M, Saeed A (2011) Assessment of quality of life with imatinib mesylate as first-line treatment in chronic phase-chronic myeloid leukemia. Leuk Lymphoma 52(6):1017–1023. https://​doi.​org/​10.​3109/​10428194.​2011.​560310 View ArticlePubMed
  32. Hahn EA, Glendenning GA, Sorensen MV, Hudgens SA, Druker BJ, Guilhot F, Larson RA, O’Brien SG, Dobrez DG, Hensley ML, Cella D, IRIS Investigators (2003) Quality of life in patients with newly diagnosed chronic phase chronic myeloid leukemia on imatinib versus interferon alfa plus low-dose cytarabine: results from the IRIS study. J Clin Oncol 21(11):2138–2146. https://​doi.​org/​10.​1200/​JCO.​2003.​12.​154
  33. Efficace F, Castagnetti F, Martino B, Breccia M, D’Adda M, Angelucci E, Stagno F, Cottone F, Malato A, Trabacchi E, Capalbo SF, Gobbi M, Visani G, Salvucci M, Capodanno I, Tosi P, Tiribelli M, Scortechini AR, Levato L, Maino E, Binotto G, Gugliotta G, Vignetti M, Baccarani M, Rosti G (2018) Health-related quality of life in patients with chronic myeloid leukemia receiving first-line therapy with nilotinib. Cancer 124(10):2228–2237. https://​doi.​org/​10.​1002/​cncr.​31323 View ArticlePubMed
  34. Sacha T, Gora-Tybor J, Wasak-Szulkowska E, Kyrcz-Krzemien S, Medras E, Becht R, Bober G, Kotowska A, Waclaw J, Hellmann A (2017) Quality of life and adherence to therapy in patients with chronic myeloid leukemia treated with nilotinib as a second-line therapy: a multicenter prospective observational study. Clin Lymphoma Myeloma Leuk 17(5):283–295. https://​doi.​org/​10.​1016/​j.​clml.​2017.​01.​001 View ArticlePubMed
  35. Mahon FX, Etienne G (2014) Deep molecular response in chronic myeloid leukemia: the new goal of therapy? Clin Cancer Res 20(2):310–322. https://​doi.​org/​10.​1158/​1078-0432.​CCR-13-1988 View ArticlePubMed
  36. Efficace F, Baccarani M, Breccia M, Cottone F, Alimena G, Deliliers GL, Barate C, Specchia G, Di Lorenzo R, Luciano L, Turri D, Martino B, Stagno F, Dabusti M, Bergamaschi M, Leoni P, Simula MP, Levato L, Fava C, Veneri D, Sica S, Rambaldi A, Rosti G, Vignetti M, Mandelli F (2013) Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib. Leukemia 27(7):1511–1519. https://​doi.​org/​10.​1038/​leu.​2013.​51 View ArticlePubMed
  37. Guerin A, Chen L, Ionescu-Ittu R, Marynchenko M, Nitulescu R, Hiscock R, Keir C, Wu EQ (2014) Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase. Curr Med Res Opin 30(11):2317–2328. https://​doi.​org/​10.​1185/​03007995.​2014.​944973 View ArticlePubMed
  38. Kekale M, Peltoniemi M, Airaksinen M (2015) Patient-reported adverse drug reactions and their influence on adherence and quality of life of chronic myeloid leukemia patients on per oral tyrosine kinase inhibitor treatment. Patient Prefer Adherence 9:1733–1740. https://​doi.​org/​10.​2147/​PPA.​S92125 View ArticlePubMedPubMed Central
  39. Efficace F, Rosti G, Breccia M, Cottone F, Giesinger JM, Stagno F, Iurlo A, Russo Rossi A, Luciano L, Martino B, Galimberti S, Turri D, Bergamaschi M, Tiribelli M, Fava C, Angelucci E, Mandelli F, Baccarani M (2016) The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia. Ann Hematol 95(2):211–219. https://​doi.​org/​10.​1007/​s00277-015-2541-6 View ArticlePubMed
  40. Jiang Q, Wang HB, Yu L, Gale RP (2017) Variables associated with patient-reported outcomes in persons with chronic myeloid leukemia receiving tyrosine kinase-inhibitor therapy. J Cancer Res Clin Oncol 143(6):1013–1022. https://​doi.​org/​10.​1007/​s00432-017-2353-2 View ArticlePubMed
  41. Yu L, Wang H, Milijkovic D, Huang X, Jiang Q (2018) Achieving optimal response at 12 months is associated with a better health-related quality of life in patients with chronic myeloid leukemia: a prospective, longitudinal, single center study. BMC Cancer 18(1):782. https://​doi.​org/​10.​1186/​s12885-018-4699-5 View ArticlePubMedPubMed Central
Metadata
Title
Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia
Authors
Tim H. Brümmendorf
Carlo Gambacorti-Passerini
Andrew G. Bushmakin
Joseph C. Cappelleri
Andrea Viqueira
Arlene Reisman
Susanne Isfort
Carla Mamolo
Publication date
01-06-2020
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 6/2020
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-020-04018-1

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