Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia

Annals of Hematology

Volumn 94, Issue 2, 2015, Pages 149-158

  Rea, Delphine ^a  

^a SAINT LOUIS HOSPITAL   (France)

Author keywords

Chronic myeloid leukemia; Tyrosine kinase inhibitors

Indexed keywords

ANTIHISTAMINIC AGENT; CORTICOSTEROID; PROTEIN TYROSINE KINASE INHIBITOR; STEROID; ANTINEOPLASTIC AGENT; BCR ABL PROTEIN; BCR-ABL1 FUSION PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR;

ARTERY OCCLUSION; BONE MARROW SUPPRESSION; CARDIOTOXICITY; CHRONIC MYELOID LEUKEMIA; CONGESTIVE HEART FAILURE; CYTOPENIA; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG TOLERABILITY; ENDOCRINE DISEASE; FLUID RETENTION; GASTROINTESTINAL SYMPTOM; HUMAN; HYPERTENSION; LIVER DISEASE; LUNG TOXICITY; METABOLIC DISORDER; MUSCULOSKELETAL DISEASE; PANCREAS DISEASE; PATIENT CARE; PRIORITY JOURNAL; QT PROLONGATION; REVIEW; RISK ASSESSMENT; SKIN MANIFESTATION; ADVERSE EFFECTS; ANTAGONISTS AND INHIBITORS; DRUG MONITORING; ENZYMOLOGY; EVIDENCE BASED MEDICINE; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MOLECULARLY TARGETED THERAPY; PERSONALIZED MEDICINE;

ANTINEOPLASTIC AGENTS; DRUG MONITORING; EVIDENCE-BASED MEDICINE; FUSION PROTEINS, BCR-ABL; HUMANS; INDIVIDUALIZED MEDICINE; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS;

EID: 84925947209     PISSN: 09395555     EISSN: 14320584     Source Type: Journal    
DOI: 10.1007/s00277-015-2318-y     Document Type: Review

References (70)

1. Gambacorti-Passerini C, Antolini L, Mahon FX, Guilhot F, Deininger M, Fava C, Nagler A, Della Casa CM, Morra E, Abruzzese E, D'Emilio A, Stagno F, le Coutre P, Hurtado-Monroy R, Santini V, Martino B, Pane F, Piccin A, Giraldo P, Assouline S, Durosinmi MA, Leeksma O, Pogliani EM, Puttini M, Jang E, Reiffers J, Valsecchi MG, Kim DW (2011) Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst 103:553–561
2. Huang X, Cortes J, Kantarjian H (2012) Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer 118:3123–3127
3. 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, Müller 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 122:872–884
4. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ, IRIS Investigators (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994–1004
5. Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM, Hughes TP, Muller MC, Ezzeddine R, Countouriotis AM, Shah NP (2007) Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 109:2303–2309
6. Shah NP, Kantarjian HM, Kim DW, Réa D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A (2008) Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 26:3204–3212
7. Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boqué 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 362:2260–2270
8. Kantarjian HM, Giles FJ, Bhalla KN, Pinilla-Ibarz J, Larson RA, Gattermann N, Ottmann OG, Hochhaus A, Radich JP, Saglio G, Hughes TP, Martinelli G, Kim DW, Shou Y, Gallagher NJ, Blakesley R, Baccarani M, Cortes J, le Coutre PD (2011) Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood 117:1141–1145
9. 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 362:2251–2259
10. Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R, Wang J, Leip E, Gambacorti-Passerini C (2011) Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 118:4567–4576
11. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Müller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H, PACE Investigators (2013) A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 369:1783–1796
12. Bantscheff M, Eberhard D, Abraham Y, Bastuck S, Boesche M, Hobson S, Mathieson T, Perrin J, Raida M, Rau C, Reader V, Sweetman G, Bauer A, Bouwmeester T, Hopf C, Kruse U, Neubauer G, Ramsden N, Rick J, Kuster B, Drewes G (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 25:1035–1044
13. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G (2009) Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia 23:477–485
14. Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, Zhu X, Cai L, Wen D, Liu S, Romero J, Qi J, Chen I, Banda G, Lentini SP, Das S, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Zhou T, Commodore L, Narasimhan NI, Mohemmad QK, Iuliucci J, Rivera VM, Dalgarno DC, Sawyer TK, Clackson T, Shakespeare WC (2010) Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-Abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J Med Chem 53:4701–4719
15. Gugliotta G, Castagnetti F, Fogli M, Cavo M, Baccarani M, Rosti G (2013) Impact of comorbidities on the treatment of chronic myeloid leukemia with tyrosine-kinase inhibitors. Expert Rev Hematol 6:563–574
16. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA, IRIS Investigators (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417
17. Sneed TB, Kantarjian HM, Talpaz M, O'Brien S, Rios MB, Bekele BN, Zhou X, Resta D, Wierda W, Faderl S, Giles F, Cortes JE (2004) The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase. Cancer 100:116–121
18. Quintas-Cardama A, Kantarjian H, O'Brien S, Garcia-Manero G, Rios MB, Talpaz M, Cortes J (2004) Granulocyte-colony-stimulating factor (filgrastim) may overcome imatinib-induced neutropenia in patients with chronic-phase chronic myelogenous leukemia. Cancer 100:2592–2597
19. Cortes J, O'Brien S, Quintas A, Giles F, Shan J, Rios MB, Talpaz M, Kantarjian H (2004) Erythropoietin is effective in improving the anemia induced by imatinib mesylate therapy in patients with chronic myeloid leukemia in chronic phase. Cancer 100:2396–2402
20. Cortes JE, Hochhaus A, le Coutre PD, Rosti G, Pinilla-Ibarz J, Jabbour E, Gillis K, Woodman RC, Blakesley RE, Giles FJ, Kantarjian HM, Baccarani M (2011) Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib. Blood 117:5600–5606
21. Amitay-Laish I, Stemmer SM, Lacouture ME (2011) Adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib. Dermatol Ther 24:386–395
22. Brazzelli V, Grasso V, Borroni G (2013) Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience. J Eur Acad Dermatol Venereol 27:1471–1480
23. Tanaka C, Yin OQ, Sethuraman V, Smith T, Wang X, Grouss K, Kantarjian H, Giles F, Ottmann OG, Galitz L, Schran H (2010) Clinical pharmacokinetics of the BCR-ABL tyrosine kinase inhibitor nilotinib. Clin Pharmacol Ther 87:197–203
24. Quintás-Cardama A, Kantarjian H, Ravandi F, O'Brien S, Thomas D, Vidal-Senmache G, Wierda W, Kornblau S, Cortes J (2009) Bleeding diathesis in patients with chronic myelogenous leukemia receiving dasatinib therapy. Cancer 115:2482–2490
25. Patodi N, Sagar N, Rudzki Z, Langman G, Sharma N (2012) Haemorrhagic colitis caused by dasatinib. Case Rep Hematol 2012:417106
26. Quintás-Cardama A, Han X, Kantarjian H, Cortes J (2009) Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia. Blood 114:261–263
27. Deininger MW, O'Brien SG, Ford JM, Druker BJ (2003) Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol 21:1637–1647
28. Singer JB, Shou Y, Giles F, Kantarjian HM, Hsu Y, Robeva AS, Rae P, Weitzman A, Meyer JM, Dugan M, Ottmann OG (2007) UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia 21:2311–2315
29. Rosti G, Castagnetti F, Gugliotta G, Palandri F, Baccarani M (2012) Physician’s guide to the clinical management of adverse events on nilotinib therapy for the treatment of CML. Cancer Treat Rev 38:241–248
30. Palandri F, Castagnetti F, Soverini S, Poerio A, Gugliotta G, Luatti S, Amabile M, Martinelli G, Rosti G, Baccarani M (2009) Pancreatic enzyme elevation in chronic myeloid leukemia patients treated with nilotinib after imatinib failure. Haematologica 94:1758–1761
31. Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, Clackson T, Turner CD, Haluska FG, Druker BJ, Deininger MW, Talpaz M (2012) Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med 367:2075–2088
32. Hohenegger M (2012) Drug induced rhabdomyolysis. Curr Opin Pharmacol 12:335–339
33. Breccia M, D'Elia GM, D'Andrea M, Latagliata R, Alimena G (2005) Pleural-pericardic effusion as uncommon complication in CML patients treated with Imatinib. Eur J Haematol 74:89–90
34. Esmaeli B, Prieto VG, Butler CE, Kim SK, Ahmadi MA, Kantarjian HM, Talpaz M (2002) Severe periorbital edema secondary to STI571 (Gleevec). Cancer 95:881–887
35. Moore JC, Dennehey CF, Anavim A, Kong KM, Tiong Ong S (2006) Multiple joint effusions associated with high-dose imatinib therapy in a patient with chronic myelogenous leukaemia. Eur J Haematol 76:444–446
36. Bergeron A, Réa D, Levy V, Picard C, Meignin V, Tamburini J, Bruzzoni-Giovanelli H, Calvo F, Tazi A, Rousselot P (2007) Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series. Am J Respir Crit Care Med 176:814–818
37. Goldblatt M, Huggins JT, Doelken P, Gurung P, Sahn SA (2009) Dasatinib-induced pleural effusions: a lymphatic network disorder? Am J Med Sci 338:414–417
38. Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O'Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354:2531–2541
39. Shah NP, Kim DW, Kantarjian H, Rousselot P, Llacer PE, Enrico A, Vela-Ojeda J, Silver RT, Khoury HJ, Müller MC, Lambert A, Matloub Y, Hochhaus A (2010) Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica 95:232–240
40. Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, Wang J, Ipiña JJ, Kim DW, Ogura M, Pavlovsky C, Junghanss C, Milone JH, Nicolini FE, Robak T, Van Droogenbroeck J, Vellenga E, Bradley-Garelik MB, Zhu C, Hochhaus A (2012) Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 119:1123–1129
41. Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boqué C, Chuah C, Pavlovsky C, Mayer J, Cortes J, Baccarani M, Kim DW, Bradley-Garelik MB, Mohamed H, Wildgust M, Hochhaus A (2014) Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood 123:494–500
42. Porkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE (2010) Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer 116:377–386
43. de Lavallade H, Punnialingam S, Milojkovic D, Bua M, Khorashad JS, Gabriel IH, Chaidos A, Olavarria E, Goldman JM, Apperley JF, Marin D (2008) Pleural effusions in patients with chronic myeloid leukaemia treated with dasatinib may have an immune-mediated pathogenesis. Br J Haematol 141:745–747
44. Quintás-Cardama A, Kantarjian H, O'brien S, Borthakur G, Bruzzi J, Munden R, Cortes J (2007) Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol 25:3908–3914
45. Latagliata R, Breccia M, Fava C, Stagno F, Tiribelli M, Luciano L, Gozzini A, Gugliotta G, Annunziata M, Cavazzini F, Ferrero D, Musto P, Capodanno I, Iurlo A, Visani G, Crugnola M, Calistri E, Castagnetti F, Vigneri P, Alimena G (2013) Incidence, risk factors and management of pleural effusions during dasatinib treatment in unselected elderly patients with chronic myelogenous leukaemia. Hematol Oncol 31:103–109
46. Rousselot P, Mollica L, Guerci-Bresler A, Nicolini FE, Etienne G, Legros L, Charbonnier A, Coiteux V, Dartigeas C, Escoffre-Barbe M, Roy L, Cony-Makhoul P, Dubruille V, Gardembas M, Berthou C, Huguet F, Deau B, Jourdan E, Fouillard L, Malak S, Rea D, Busque L, Guilhot F, Molimard M, Guilhot J, Cayuela JM, Bouchet S, Mahon FX (2014) Dasatinib daily dose optimization based on residual drug levels resulted in reduced risk of pleural effusions and high molecular response rates: final results of the randomized OPTIM Dasatinib trial. Haematologica (EHA congress). Abstract S678
47. Montani D, Bergot E, Günther S, Savale L, Bergeron A, Bourdin A, Bouvaist H, Canuet M, Pison C, Macro M, Poubeau P, Girerd B, Natali D, Guignabert C, Perros F, O'Callaghan DS, Jaïs X, Tubert-Bitter P, Zalcman G, Sitbon O, Simonneau G, Humbert M (2012) Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 125:2128–2137
48. Montani D, Seferian A, Savale L, Simonneau G, Humbert M (2013) Drug-induced pulmonary arterial hypertension: a recent outbreak. Eur Respir Rev 22:244–250
49. des Guetz G, Uzzan B, Chouahnia K, Morère JF (2011) Cardiovascular toxicity of anti-angiogenic drugs. Target Oncol 6:197–202
50. Kerkelä R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12:908–916
51. Breccia M, Cannella L, Frustaci A, Stefanizzi C, Levi A, Alimena G (2008) Cardiac events in imatinib mesylate-treated chronic myeloid leukemia patients: a single institution experience. Leuk Res 32:835–836
52. Atallah E, Durand JB, Kantarjian H, Cortes J (2007) Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 110:1233–1237
53. Cortes JE, Kim D-W, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio JF, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Müller MC, Gambacorti-Passerini C, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes TP, Goldman JM, Shah NP, Kantarjian HM (2013) Ponatinib in patients (pts) with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR-ABL mutation: 2-year follow-up of the PACE trial. Blood 122: abstract 650
54. Saglio G, Hochhaus A, Hughes TP, Clark RE,, Lipton JH, Pasquini R, Moiraghi B, Kemp C, Fan X, Menssen HD, Kantarjian HM, Larson RA. ENESTnd update: nilotinib (NIL) vs imatinib (IM) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and the impact of early molecular response (EMR) and Sokal risk at diagnosis on long-term outcomes. Blood. 2013; 122: abstract 92.
55. Cortes JE, Hochhaus A, Kim D-W, Shah NP, Mayer J, Rowlings P, Nakamae H, Bradley-Garelik M.B, Mohamed H, Kantarjian HM, Saglio G (2013) Four-year (yr) follow-up of patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) receiving dasatinib or imatinib: efficacy based on early response. Blood 122: abstract 653
56. Cortes JE, Kantarjian HM, Khoury HJ, Brümmendorf TH, Conlan MG, Wang K, Fly KD, Shapiro M, Lipton JH, Durand J-B, Gambacorti-Passerini C (2014) Long-term evaluation of vascular toxicity in patients with Ph+ leukemias treated with bosutinib. J Clin Oncol 32(suppl; abstr 7060):5s
57. Aichberger KJ, Herndlhofer S, Schernthaner GH, Schillinger M, Mitterbauer-Hohendanner G, Sillaber C, Valent P (2011) Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol 86:533–539
58. Le Coutre P, Rea D, Abruzzese E, Dombret H, Trawinska MM, Herndlhofer S, Dörken B, Valent P (2011) Severe peripheral arterial disease during nilotinib therapy. J Natl Cancer Inst 103:1347–1348
59. Berman E, Nicolaides M, Maki RG, Fleisher M, Chanel S, Scheu K, Wilson BA, Heller G, Sauter NP (2006) Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med 354:2006–2013
60. O'Sullivan S, Horne A, Wattie D, Porteous F, Callon K, Gamble G, Ebeling P, Browett P, Grey A (2009) Decreased bone turnover despite persistent secondary hyperparathyroidism during prolonged treatment with imatinib. J Clin Endocrinol Metab 94:1131–1136
61. Alemán JO, Farooki A, Girotra M (2014) Effects of tyrosine kinase inhibition on bone metabolism: untargeted consequences of targeted therapies. Endocr Relat Cancer 21:R247–R259
62. Narayanan KR, Bansal D, Walia R, Sachdeva N, Bhansali A, Varma N, Marwaha RK (2013) Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis. Pediatr Blood Cancer 60:1148–1153
63. Breccia M, Loglisci G, Salaroli A, Serrao A, Alimena G (2012) Nilotinib-mediated increase in fasting glucose level is reversible, does not convert to type 2 diabetes and is likely correlated with increased body mass index. Leuk Res 36:e66–e67
64. Racil Z, Razga F, Drapalova J, Buresova L, Zackova D, Palackova M, Semerad L, Malaskova L, Haluzik M, Mayer J (2013) Mechanism of impaired glucose metabolism during nilotinib therapy in patients with chronic myelogenous leukemia. Haematologica 98:e124–e126
65. Rea D, Mirault T, Cluzeau T, Gautier JF, Guilhot F, Dombret H, Messas E (2014) Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia. Haematologica 99:1197–1203
66. Veneri D, Franchini M, Bonora E (2005) Imatinib and regression of type 2 diabetes. N Engl J Med 352:1049–1050
67. Gottardi M, Manzato E, Gherlinzoni F (2005) Imatinib and hyperlipidemia. N Engl J Med 353:2722–2723
68. Kim TD, Schwarz M, Nogai H, Grille P, Westermann J, Plöckinger U, Braun D, Schweizer U, Arnold R, Dörken B, le Coutre P (2010) Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia. Thyroid 20:1209–1214
69. de Groot JW, Zonnenberg BA, Plukker JT, van Der Graaf WT, Links TP (2005) Imatinib induces hypothyroidism in patients receiving levothyroxine. Clin Pharmacol Ther 78:433–438
70. Marcolino MS, Boersma E, Clementino NC, Macedo AV, Marx-Neto AD, Silva MH, van Gelder T, Akkerhuis KM, Ribeiro AL (2011) Imatinib treatment duration is related to decreased estimated glomerular filtration rate in chronic myeloid leukemia patients. Ann Oncol 22:2073–2079