Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: A subanalysis of the randomized CML-Study IV

Annals of Hematology

Volumn 93, Issue 7, 2014, Pages 1167-1176

  Proetel, Ulrike ^a   Pletsch, Nadine ^a   Lauseker, Michael ^b   Müller, Martin C ^a   Hanfstein, Benjamin ^a   Krause, Stefan W ^c   Kalmanti, Lida ^a   Schreiber, Annette ^a   Heim, Dominik ^d   Baerlocher, Gabriela M ^e   Hofmann, Wolf Karsten ^a   Lange, Elisabeth ^f   Einsele, Hermann ^g   Wernli, Martin ^h   Kremers, Stephan ⁱ   Schlag, Rudolf ^j   Müller, Lothar ^h   Hänel, Mathias ^k   Link, Hartmut ^l   Hertenstein, Bernd ^m   Pfirrmann, Markus ^b   Hochhaus, Andreas ⁿ   Hasford, Joerg ^b   Hehlmann, Rüdiger ^a   Saußele, Susanne ^a   more..

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^d UNIVERSITY HOSPITAL BASEL   (Switzerland)

^e UNIVERSITY OF BERN   (Switzerland)

^f EVANGELISCHES KRANKENHAUS   (Germany)

^g UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^h Onkologie/Hämatologie Kantonsspital ^*  (Germany)

ⁱ Onkologisches Zentrum   (Germany)

^j Hämatologisch onkologische Schwerpunktpraxis Würzburg   (Germany)

^k Klinikum   (Germany)

^l Westpfalz Klinikum GmbH   (Germany)

^m Klinikum Mitte   (Germany)

ⁿ JENA UNIVERSITY HOSPITAL   (Germany)

more..

Author keywords

Chronic myeloid leukemia; Different imatinib dose regimens; Early applied higher imatinib dosages; Older patients

Indexed keywords

BCR ABL PROTEIN; CYTARABINE; IMATINIB; INTERFERON;

ADOLESCENT; ADULT; AGE DISTRIBUTION; ALLERGY; ARTHRALGIA; ARTICLE; CANCER FATIGUE; CANCER GRADING; CANCER GROWTH; CANCER SURVIVAL; CANCER THERAPY; CHEMOTHERAPY INDUCED ANEMIA; CHRONIC MYELOID LEUKEMIA; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG MEGADOSE; DRUG TOLERABILITY; EDEMA; FEMALE; GASTROINTESTINAL DISEASE; GROUPS BY AGE; HUMAN; INFECTION; LEUKEMIA REMISSION; LEUKOPENIA; MAJOR CLINICAL STUDY; MALE; MYALGIA; NEUROLOGIC DISEASE; OPTIMAL DRUG DOSE; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SKIN DISEASE; THROMBOCYTOPENIA;

ADOLESCENT; ADULT; AGE FACTORS; AGED; AGED, 80 AND OVER; BENZAMIDES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MALE; MIDDLE AGED; PIPERAZINES; PROTEIN KINASE INHIBITORS; PYRIMIDINES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84902684699     PISSN: 09395555     EISSN: 14320584     Source Type: Journal    
DOI: 10.1007/s00277-014-2041-0     Document Type: Article

References (30)

1. Rohrbacher M, Berger U, Hochhaus A, Metzgeroth G, Adam K, Lahaye T, Saussele S, Müller MC, Hasford J, Heimpel H, Hehlmann R (2009) Clinical trials underestimate the age of chronic myeloid leukemia (CML) patients. Incidence and median age of Ph/BCR-ABL-positive CML and other chronic myeloproliferative disorders in a representative area in Germany. Leukemia 23(3):602-604. doi:10.1038/leu.2008.245
2. Björkholm M,OhmL, Eloranta S, Derolf A,Hultcrantz M, Sjöberg J, Andersson T, Höglund M, Richter J, Landgren O, Kristinsson SY, Dickman PW (2011) Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol 29(18):2514-2520. doi:10.1200/jco.2011.34.7146
3. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK (eds) (based on November 9 SEER data submission, posted to the SEER web site, 2010) SEER cancer statistics review, 1975-2007: median age of cancer patients at diagnosis, 2003-2007 by primary cancer site, race and sex. http://seer.cancer.gov/csr/1975-2007/results- single/sect-01-table.11-2pgs.pdf, National Cancer Institute, Bethesda, MD
4. Rohrbacher M, Hasford J (2009) Epidemiology of chronic myeloid leukaemia (CML). Best Pract Res Clin Haematol 22(3):295-302. doi:10.1016/j.beha.2009.07. 007
5. 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, or the IRIS Investigators (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355(23):2408-2417. doi:10.1056/ NEJMoa062867 (Pubitemid 44903745)
6. Berger U, Engelich G, Maywald O, Pfirrmann M, Hochhaus A, Reiter A, Metzgeroth G, Gnad U, Hasford J, Heinze B, Heimpel H, Hossfeld DK, Kolb HJ, Loffler H, Pralle H, Queisser W, Hehlmann R, and the German CML-Study Group (2003) Chronic myeloid leukemia in the elderly: long-term results from randomized trials with interferon alpha. Leukemia 17(9):1820-1826. doi:10.1038/sj.leu.2403042 (Pubitemid 37185258)
7. Rosti G, Iacobucci I, Bassi S, Castagnetti F, Amabile M, Cilloni D, Poerio A, Soverini S, Palandri F, Rege Cambrin G, Iuliano F, Alimena G, Latagliata R, Testoni N, Pane F, Saglio G, Baccarani M, Martinelli G (2007) Impact of age on the outcome of patients with chronic myeloid leukemia in late chronic phase: results of a phase II study of the GIMEMA CMLWorking Party. Haematologica 92(1): 101-105. doi:10.3324/haematol.10239 (Pubitemid 46232662)
8. Latagliata R, Breccia M, Carmosino I, Cannella L, De Cuia R, Diverio D, Frustaci A, Loglisci G, Mancini M, Santopietro M, Stefanizzi C, Volpicelli P, Vozella F, Alimena G (2010) "Real- life" results of front-line treatment with Imatinib in older patients (≥65 years) with newly diagnosed chronic myelogenous leukemia. Leuk Res 34(11):1472-1475. doi:10.1016/j.leukres. 2010.07.001
9. Cortes J, Talpaz M, O'Brien S, Giles F, Beth Rios M, Shan J, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, Kantarjian H (2003) Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer 98(6):1105-1113. doi:10.1002/cncr.11629 (Pubitemid 37099894)
10. Gugliotta G, Castagnetti F, Palandri F, Breccia M, Intermesoli T, Capucci A, Martino B, Pregno P, Rupoli S, Ferrero D, Gherlinzoni F, Montefusco E, Bocchia M, Tiribelli M, Pierri I, Grifoni F, Marzocchi G, AmabileM, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M, Rosti G, and on behalf of the Gruppo Italiano Malattie Ematologiche dell'Adulto CMLWorking Party (2011) Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party. Blood 117(21):5591-5599. doi:10.1182/blood-2010-12-324228
11. Cortes JE, Kantarjian HM, Goldberg SL, Powell BL, Giles FJ, Wetzler M, Akard L, Burke JM, Kerr R, Saleh M, Salvado A, McDougall K, Albitar M, Radich J, on behalf of the Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) Trial Study Group (2009) High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses. J Clin Oncol 27(28):4754-4759. doi:10.1200/jco.2008.20.3869
12. Rousselot P, Cony-Makhoul P, Nicolini F, Mahon FX, Berthou C, Réa D, Reiffers J, Bornand A, Saint-Jean O, Guilhot J, Guilhot F, on behalf of the French Intergroup For ChronicMyelogenous Leukemia (Fi-LMC) (2013) Long-term safety and efficacy of imatinib mesylate (Gleevec®) in elderly patients with chronic phase chronic myelogenous leukemia: Results of the AFR04 study. Am J Hematol 88(1):1-4. doi:10.1002/ajh.23330
13. Sánchez-Guijo FM, Durán S, Galende J, Boqué C, Nieto JB, Balanzat J, Gracia A, García I, Avellaneda-Molina C, Moreno M-V, Luño-Fernandez E, Hermosilla M, Sanchez-Varela JM, Dios A, Lopez-Garrido P, Giraldo P, Bargay J, Domingo JM, Soler A, Salinas R, del Cañizo MC (2011) Evaluation of tolerability and efficacy of imatinib mesylate in elderly patients with chronic phase CML: ELDERGLI study. Leuk Res 35(9):1184-1187. doi:10.1016/j.leukres.2011.01.017
14. Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Mueller MC, Pletsch N, Proetel U, Haferlach C, Schlegelberger B, Balleisen L, HänelM, PfirrmannM, Krause SW, Nerl C, Pralle H, Gratwohl A, Hossfeld DK, Hasford J, Hochhaus A, Saussele S, (2011) Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol 29(12):1634-1642. doi:10.1200/jco.2010.32.0598
15. Hehlmann R, Müller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, Proetel U, Pletsch N, Pfirrmann M, Haferlach C, Schnittger S, Einsele H, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Ehninger G, Heim D, Heimpel H, Nerl C, Krause SW, Hossfeld DK, Kolb HJ, Hasford J, Saußele S, Hochhaus A (2014) Deep molecular response (MR4.5) is reached by the majority of imatinib-treated patients, predicts survival, and is achieved faster by optimized high-dose imatinib-results from the randomized CML-Study IV. J Clin Oncol 32(5):415- 423. doi:10.1200/JCO.2013.49.9020
16. Fabarius A, Leitner A, Hochhaus A, Müller MC, Hanfstein B, Haferlach C, Göhring G, Schlegelberger B, Jotterand M, Reiter A, Jung-Munkwitz S, Proetel U, Schwaab J, HofmannWK, Schubert J, Einsele H, Ho AD, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Lauseker M, Pfirrmann M, Hasford J, Saussele S, Hehlmann R, and for the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) and the German CML Study Group (2011) Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood 118(26):6760-6768 doi:10.1182/blood-2011-08-373902
17. Hanfstein B, Müller MC, Hehlmann R, Erben P, Lauseker M, Fabarius A, Schnittger S, Haferlach C, Göhring G, Proetel U, Kolb HJ, Krause SW, Hofmann WK, Schubert J, Einsele H, Dengler J, Hänel M, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Branford S, Hughes TP, Spiekermann K, BaerlocherGM, Pfirrmann M, Hasford J, Saußele S, Hochhaus A, for the SAKK and the German CML Study Group (2012) Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 26(9):2096-2102. doi:10.1038/leu.2012.85
18. Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, Kolb HJ, Ho AD, Falge C, Holler E, Schlimok G, Zander AR, Arnold R, Kanz L, Dengler R, Haferlach C, Schlegelberger B, Pfirrmann M, Müller MC, Schnittger S, Leitner A, Pletsch N, Hochhaus A, Hasford J, Hehlmann R, and for the German CML-Study Group (2010) Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood 115(10):1880-1885. doi:10.1182/blood-2009-08-237115
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 F-X,Martinelli G, Mayer J,MüllerMC, 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. doi:10.1182/blood-2013-05- 501569
20. Cross NCP, White HE, Müller MC, Saglio G, Hochhaus A (2012) Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 26(10):2172-2175. doi:10.1038/leu.2012.104
21. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, Alimena G, Steegmann JL, Ansari H (1998) A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 90(11):850-858. doi:10.1093/jnci/90.11.850 (Pubitemid 28280552)
22. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, Guilhot F, Porkka K, Ossenkoppele G, Lindoerfer D, Simonsson B, Pfirrmann M, Hehlmann R (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118(3):686-692. doi:10.1182/blood-2010-12-319038
23. Gooley TA, LeisenringW, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18(6):695-706 (Pubitemid 29126745)
24. Pfirrmann M, Hochhaus A, Lauseker M, Saußele S, Hehlmann R, Hasford J (2011) Recommendations to meet statistical challenges arising from endpoints beyond overall survival in clinical trials on chronic myeloid leukemia. Leukemia 25(9):1433-1438. doi:10.1038/leu.2011.116
25. Gray RJ (1988) A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16(3):1141-1154. doi:10.1214/aos/ 1176350951
26. Hughes T, DeiningerM, Hochhaus A, Branford S, Radich J, Kaeda J, BaccaraniM, 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 doi:10.1182/blood-2006-01-0092 (Pubitemid 43990609)
27. Müller MC, Cross NC, Erben P, Schenk T, Hanfstein B, Ernst T, Hehlmann R, Branford S, Saglio G, Hochhaus A (2009) Harmonization of molecular monitoring of CML therapy in Europe. Leukemia 23(11):1957-1963. doi:10.1038/leu.2009.168
28. Statistical Yearbook for the Federal Republic of Germany including "International tables" (2011) Federal Statistical Office, Wiesbaden
29. Cortes JE, BaccaraniM, Guilhot F, Druker BJ, Branford S, Kim DW, Pane F, Pasquini R, Goldberg SL, Kalaycio M, Moiraghi B, Rowe JM, Tothova E, De Souza C, Rudoltz M, Yu R, Krahnke T, Kantarjian HM, Radich JP, Hughes TP (2010) Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 28(3):424-430. doi:10.1200/JCO.2009.25.3724
30. Kantarjian HM, Keating MJ, McCredie KB, Walters R, Talpaz M, Smith TL, Freireich EJ (1987) Old age: a sign of poor prognosis in patients with chronic myelogenous leukemia. South Med J 80(10): 1228-1232 (Pubitemid 17160779)