First-line therapy for chronic phase CML: selecting the optimal BCR-ABL1-targeted TKI

References

• Baccarani M, Rosti G, de Vivo A, et al. A randomized study of interferon-alpha versus interferon-alpha and low-dose arabinosyl cytosine in chronic myeloid leukemia. Blood. 2002;99:1527–1535.
   PubMed Web of Science ®Google Scholar
• Guilhot F, Chastang C, Michallet M, et al. French Chronic Myeloid Leukemia Study Group. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. N Engl J Med. 1997;337:223–229.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Giles FJ, O'Brien SM, et al. Clinical course and therapy of chronic myelogenous leukemia with interferon-alpha and chemotherapy. Hematol Oncol Clin North Am. 1998;12:31–80.
   PubMed Web of Science ®Google Scholar
• O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004.
   PubMed Web of Science ®Google Scholar
• Gleevec (imatinib) [prescribing information]. East Hanover, NJ: Novartis; 2015.
   Google Scholar
• Sprycel (dasatinib) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2015.
   Google Scholar
• Tasigna (nilotinib) [prescribing information]. East Hanover, NJ: Novartis; 2015.
   Google Scholar
• Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-year study results of DASISION: the Dasatinib Versus Imatinib Study in treatment-naive chronic myeloid leukemia patients trial. JCO. 2016;34:2333–2340.
   PubMed Web of Science ®Google Scholar
• Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30:1044–1054.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376:917–927.
   PubMed Web of Science ®Google Scholar
• Baccarani M, Druker BJ, Branford S, et al. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study. Int J Hematol. 2014;99:616–624.
   PubMed Web of Science ®Google Scholar
• de Lavallade H, Apperley JF, Khourashad JS, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. JCO. 2008;26:3358–3363.
   PubMed Web of Science ®Google Scholar
• Kalmanti L, Saussele S, Lauseker M, et al. Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV. Leukemia. 2015;29:1123–1132.
   PubMed Web of Science ®Google Scholar
• Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26:2096–2102.
   PubMed Web of Science ®Google Scholar
• Pemmaraju N, Kantarjian H, O'Brien S, et al. Phase II Clinical Trial Results of Dasatinib for Frontline Therapy in Patients with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP). Poster presented at: American Society of Hematology; 2014 Dec 6–9; San Francisco, CA. Abstract 4565.
   Google Scholar
• Radich JP, Kopecky KJ, Appelbaum FR, et al. A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. Blood. 2012;120:3898–3905.
   PubMed Web of Science ®Google Scholar
• Hughes TP, Saglio G, Kantarjian HM, et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014;123:1353–1360.
   PubMed Web of Science ®Google Scholar
• Wang J, Shen ZX, Saglio G, et al. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood. 2015;125:2771–2778.
   PubMed Web of Science ®Google Scholar
• George SG, Kantarjian H, Garcia-Manero G, et al. Seven-year follow up of chronic myeloid leukemia (CML) patients treated with Nilotinib 400 mg twice daily – a single center study at MDACC. Poster presented at: American Society of Hematology; 2015 Dec 5–8; Orlando, FL. Poster 2796.
   Google Scholar
• Gugliotta G, Castagnetti F, Breccia M, et al. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia. Haematologica. 2015;100:1146–1150.
   PubMed Web of Science ®Google Scholar
• Brummendorf TH, Cortes JE, de Souza CA, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br J Haematol. 2015;168:69–81.
   PubMed Web of Science ®Google Scholar
• Lipton JH, Chuah C, Guerci-Bresler A, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:612–621.
   PubMed Web of Science ®Google Scholar
• Kwak JY, Kim H, Kim JA, et al. Efficacy and Safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia patients: 12 months result of phase 3 clinical trial. Blood. 2015;126:Abstract 476.
   Web of Science ®Google Scholar
• Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–2270.
   PubMed Web of Science ®Google Scholar
• O'Brien SG, Hedgley C, Adams S, et al. Spirit 2: An NCRI Randomised Study Comparing Dasatinib with Imatinib in Patients with Newly Diagnosed CML. Presented at: American Society of Hematology Annual Meeting; [cited 2014 Dec 6–9]; San Francisco, California, USA. Abstract 517.
   Google Scholar
• O'Brien S, Hedgley C, Foroni L, et al. SPIRIT 2: An NCRI Randomised Study comparing dasatinib with imatinib in patients with newly diagnosed chronic myeloid leukaemia: 2 year Follow-up. Presented at: European Hematology Association; [cited 2015 Jun 11–14]; Vienna, Austria. Abstract S489.
   Google Scholar
• Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–2259.
   PubMed Web of Science ®Google Scholar
• Takahashi K, Kantarjian HM, Yang Y, et al. A propensity score matching analysis of dasatinib and nilotinib as a frontline therapy for patients with chronic myeloid leukemia in chronic phase. Cancer. 2016;122:3336–3343.
   PubMed Web of Science ®Google Scholar
• Pfizer: News and Media [Internet]. New York (NY): Pfizer Inc; c2002–2017. Pfizer and Avillion Announce Positive Top-Line Results for Phase 3 BFORE Study of BOSULIF for FIrst-Line Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia; [cited 2016 Dec 2016]. Available from: http://www.pfizer.com/news/press-release/press-release-detail/pfizer_and_avillion_announce_positive_top_line_results_for_phase_3_bfore_study_of_bosulif_for_first_line_treatment_of_philadelphia_chromosome_positive_chronic_myeloid_leukemia
   Google Scholar
• Iclusig (ponatinib) [prescribing information]. Cambridge, MA: ARIAD; 2016.
   Google Scholar
• Xia L, Qian W, Yang M, et al. Comparison of the utility and applicability of the Sokal, Hasford, and EUTOS scores in a population of Chinese patients with chronic-phase chronic myeloid leukemia undergoing imatinib therapy. Onco Targets Ther. 2015;8:2485–2492.
   PubMed Web of Science ®Google Scholar
• Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63:789–799.
   PubMed Web of Science ®Google Scholar
• Hasford J, Pfirrmann M, Hehlmann R, et al. Writing committee for the collaborative CML prognostic factors project group. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst. 1998;90:850–858.
   PubMed Web of Science ®Google Scholar
• Hasford J, Baccarani M, Hoffmann V, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118:686–692.
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Chronic Myeloid Leukemia V.2. 2017. NCCN website. 2017 [cited 2017 Mar 31]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf
   Google Scholar
• Shah NP, Saglio G, Hochhaus A, et al. Achievement of early molecular response in patients (Pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with dasatinib (DAS) or imatinib (IM) from DASISION. Poster presented at: American Society of Clinical Oncology. [cited 2016 Jun 2–7] Chicago, IL. Poster 7055.
   Google Scholar
• Jabbour E, Cortes J, Nazha A, et al. EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience. Blood. 2012;119:4524–4526.
   PubMed Web of Science ®Google Scholar
• Marin D, Ibrahim AR, Goldman JM. European treatment and outcome study (EUTOS) score for chronic myeloid leukemia still requires more confirmation. JCO. 2011;29:3944–3945.
   PubMed Web of Science ®Google Scholar
• Pfirrmann M, Baccarani M, Saussele S, et al. Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia. 2016;30:48–56.
   PubMed Web of Science ®Google Scholar
• Castagnetti F, Gugliotta G, Breccia M, et al. The EUTOS Long-term survival score is predictive for response and outcome in CML patients treated frontline with nilotinib-based regimens. Oral presentation at: The European Hematology Association Annual Meeting; [cited 2016 Jun 9–12]; Copenhagen, Denmark. Abstract S434.
   Google Scholar
• Than H, Ley WK, Seow CH, et al. Genetic profiling augments prognostic value of the EUTOS long-term survival score for disease-specific mortality in imatinib-treated Asian chronic myeloid leukaemia patients. Presented at the American Society of Hematology Annual Meeting; [2016 cited Dec 3–6], San Diego, California. Abstract 3077.
   Google Scholar
• Jain P, Kantarjian H, Patel KP, et al. Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors. Blood. 2016;127:1269–1275.
   PubMed Web of Science ®Google Scholar
• Ernst T, Schafer V, White HE, et al. Assessment of molecular response in CML patients with atypical BCR-ABL transcripts. Recommendations by the EUTOS collaboration. poster presented at the American Society of Hematology Annual Meeting. [2016 cited Dec 3–6] San Diego, California. Abstract 1918.
   Google Scholar
• Guilhot F. Cytogenetics in CML: more important than you think. Blood. 2016;127:2661–2662.
   PubMed Web of Science ®Google Scholar
• Fabarius A, Leitner A, Hochhaus A, et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood. 2011;118:6760–6768.
   Google Scholar
• Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–884.
   PubMed Web of Science ®Google Scholar
• Bosulif (bosutinib) [prescribing information]. New York, NY: Pfizer; 2015.
   Google Scholar
• Saussele S, Kraub M-P, Hehlmann R, et al. Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML Study IV. Blood. 2015;126:42–49.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian H, O'Brien S, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. JCO. 2007;25:3908–3914.
   PubMed Web of Science ®Google Scholar
• de Lavallade H, Punnialingam S, Milojkovic D, et al. Pleural effusions in patients with chronic myeloid leukaemia treated with dasatinib may have an immune-mediated pathogenesis. Br J Haematol. 2008;141:734–747.
   PubMed Web of Science ®Google Scholar
• Goldberg S, Michallet M, Hehlmann R, et al. Tyrosine kinase inhibitor (TKI) switching patterns during the first 12 months in simplicity, an observational study of chronic-phase chronic myeloid leukemia (CP-CML) patients (Pts) in routine clinical practice. Presented at the American Society of Hematology Annual Meeting; [cited 2016 Dec 3–6], San Diego, California. Abstract 937.
   Google Scholar
• 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;103:553–561.
   PubMed Web of Science ®Google Scholar
• Efficace F, Baccarani M, Breccia M, et al. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011;118:4554–4560.
   PubMed Web of Science ®Google Scholar
• Kim DW, Cleeland CS, Saussele S, et al. Dasatinib in patients with chronic phase chronic myeloid leukemia (CML-CP) with persistent, low-grade nonhematologic toxicity to imatinib: results from dasperse (CA180-400). Presented at: American Society of Hematology; [cited 2015 Dec 5–8]; Orlando, FL. Poster 1575.
   Google Scholar
• Cortes JE, Lipton JH, Miller CB, et al. Evaluating the impact of a switch to nilotinib on imatinib-related chronic low-grade adverse events in patients with CML-CP: the ENRICH study. Clin Lymphoma Myeloma Leuk. 2016;16:286–296.
   PubMed Web of Science ®Google Scholar
• de Almeida MH, Fogliatto L, Couto D. Importance of adherence to BCR-ABL tyrosine-kinase inhibitors in the treatment of chronic myeloid leukemia. Rev Bras Hematol Hemoter. 2014;36:54–59.
   PubMedGoogle Scholar
• Ibrahim AR, Eliasson L, Apperley JF, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. Blood. 2011;117:3733–3736.
   PubMed Web of Science ®Google Scholar
• Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. JCO. 2010;28:2381–2388.
   PubMed Web of Science ®Google Scholar
• Wu EQ, Johnson S, Beaulieu N, et al. Healthcare resource utilization and costs associated with non-adherence to imatinib treatment in chronic myeloid leukemia patients. Curr Med Res Opin. 2010;26:61–69.
   PubMed Web of Science ®Google Scholar
• Hirji I, Gupta S, Goren A, et al. Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient's perspective. Health Qual Life Outcomes. 2013;11:167.
   PubMed Web of Science ®Google Scholar
• Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. Am J Hematol. 2016;91:252–265.
   PubMed Web of Science ®Google Scholar
• Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Kantarjian HM, Goldberg SL, et al. High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses. JCO. 2009;27:4754–4759.
   PubMed Web of Science ®Google Scholar
• Hughes TP, Branford S, White DL, et al. Impact of early dose intensity on cytogenetic and molecular responses in chronic-phase CML patients receiving 600 mg/day of imatinib as initial therapy. Blood. 2008;112:3965–3973.
   PubMed Web of Science ®Google Scholar
• Hehlmann R, Muller MC, Lauseker M, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. JCO. 2014;32:415–423.
   PubMed Web of Science ®Google Scholar
• Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. JCO. 2011;29:1634–1642.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Baccarani M, Guilhot F, et al. 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. JCO. 2010;28:424–430.
   PubMed Web of Science ®Google Scholar
• Russo D, Martinelli G, Malagola M, et al. Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia. Blood. 2013;121:5138–5144.
   PubMed Web of Science ®Google Scholar
• Rousselot P, Mollica L, Guerci-Bresler A, et al. 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. 2014;99(s1):Abstract S678.
   Web of Science ®Google Scholar
• Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib. ClinicalTrials.gov. [cited 2017 Mar 21]. Available from: https://clinicaltrials.gov/ct2/show/NCT02689440?term=NCT02689440&rank=1
   Google Scholar
• Hughes TP, Salvino MA, Chuan OT, et al. Dose-optimized nilotinib (NIL) in patients (Pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): final results from ENESTxtnd study. Blood. 2016;126. Abstract 344.
   PubMed Web of Science ®Google Scholar
• De-escalation and stopping treatment of imatinib, nilotinib, or sprYcel in chronic myeloid leukaemia (DESTINY) trial. ClinicalTrials.gov. 2015 [cited 2017 Jan 3]. Available from: https://clinicaltrials.gov/ct2/show/NCT01804985.
   Google Scholar
• Hughes T, White D. Which TKI? An embarrassment of riches for chronic myeloid leukemia patients. Hematology Am Soc Hematol Educ Program. 2013;2013:168–175.
   PubMed Web of Science ®Google Scholar
• Balducci L, Dolan D. Chronic myelogenous leukemia (CML) in the elderly. Mediterr J Hematol Infect Dis. 2014;6:e2014037.
   PubMedGoogle Scholar
• Khera N, Zeliadt SB, Lee SJ. Economics of hematopoietic cell transplantation. Blood. 2012;120:1545–1551.
   PubMed Web of Science ®Google Scholar
• The National CML Society. Stem cell transplant. National CML Society website. 2010 [cited 2016 Aug 31]. Available at: http://www.nationalcmlsociety.org/stem-cell-transplant.
   Google Scholar
• Padula WV, Larson RA, Dusetzina SB, et al. Cost-effectiveness of Tyrosine kinase inhibitor treatment strategies for chronic myeloid leukemia in chronic phase after generic entry of imatinib in the United States. JNCIJ. 2016;108:pii: djw003. doi: 10.1093/jnci/djw003.
   Web of Science ®Google Scholar
• Nelson R. Two generic versions of imatinib launched but will prices drop? Medscape. 2016 [cited 2017 Mar 21]. Available at: www.medscape.com/viewarticle/867272_print.
   Google Scholar
• Hill A, Gotham D, Fortunak J, et al. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment. BMJ Open. 2016;6:e009586.
   PubMed Web of Science ®Google Scholar
• Madhav D. Generic imatinib in chronic myeloid leukemia: survival of the cheapest. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]. San Diego, CA. Poster 630.
   Google Scholar
• Sacha T, Gora-Tybor J, Szarejko M, et al. Imatinib generics in treatment of chronic myeloid leukemia: a prospective observation in Large Cohort of Patients from Polish (PALG) Imatinib Generics Registry. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]. San Diego, CA. Poster 629.
   Google Scholar
• Darkow T, Henk HJ, Thomas SK, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics. 2007;25:481–496.
   PubMed Web of Science ®Google Scholar
• Esposti LD, Saragoni S, Buda S, et al. Medication adherence in patients with chronic myelogenous leukemia using tyrosine-kinase inhibitors: a retrospective analysis. Blood. 2014;124:Abstract 1808.
   Web of Science ®Google Scholar
• R&D Pipelines: 18th Korea’s New Drug – SUPer + effECT treatment ‘SUPECT’. IL-Yang Pharm website. 2015. [cited 2017 Jan 18]. Available at: https://www.ilyang.co.kr/english/rnd/rnd03.asp.
   Google Scholar
• Radotinib trials. ClinicalTrials.gov. [cited 2017 May 2]. Available at: https://clinicaltrials.gov/ct2/results?term=&type=&rslt=&recr=&age_v=&gndr=&cond=chronic+myeloid+leukemia&intr=radotinib&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&rcv_s=&rcv_e=&lup_s=&lup_e=
   Google Scholar
• Leukemia ECM. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121:4439–4442.
   PubMed Web of Science ®Google Scholar
• Hughes TP, Goh YT, Ottmann OG, et al. Expanded phase-1 study of ABL001, a potent, allosteric inhibitor of BCR-ABL, reveals significant and durable responses in patients with CML-chronic phase with failure of prior TKI therapy. Presented at: American Society of Hematology; [cited 2016 Dec 3–6]; San Diego, CA. Abstract 625. http://www.bloodjournal.org/content/128/22/625
   Google Scholar
• Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010;363:2511–2521.
   PubMed Web of Science ®Google Scholar
• Talpaz M, Hehlmann R, Quintas-Cardama A, et al. Re-emergence of interferon-α in the treatment of chronic myeloid leukemia. Leukemia. 2013;27:803–812.
   PubMed Web of Science ®Google Scholar
• Hjorth-Hansen H, Stentoft J, Richter J, et al. Safety and efficacy of the combination of pegylated interferon-alpha2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients. Leukemia. 2016;30:1853–1860.
   PubMed Web of Science ®Google Scholar
• Combination of dasatinib and peg-interferon alpha 2b in first line for chronic myeloid leukemia in chronic phase (NCT01872442). ClinicalTrials.gov. 2016 [cited 2017 Mar 3]. Available at: https://clinicaltrials.gov/ct2/show/NCT01872442.
   Google Scholar
• Porkka K, Mauro MJ, Lipton JH, et al. An open-label, phase 1b, dose-escalation study (CA180-373) of dasatinib plus nivolumab, an investigational anti-programmed cell death 1 (PD-1) antibody, in patients (pts) with previously treated chronic myeloid leukemia (CML). Presented at: American Society of Clinical Oncology; 2014 May 30–June 3; Chicago, IL. Abstract TPS7119.
   Google Scholar
• Nilotinib and IFN studies. ClinicalTrials.gov. [cited 2017 Jan 3]. Available from: https://clinicaltrials.gov/ct2/results?term=interferon±and±nilotinib&type=&rslt=&recr=&age_v=&gndr=&cond=chronic±myelogenous±leukemia&intr=&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&phase=1&phase=2&rcv_s=&rcv_e=&lup_s=&lup_e=
   Google Scholar
• Gallipoli P, Cook A, Rhodes S, et al. JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo. Blood. 2014;124:1492–1501.
   PubMed Web of Science ®Google Scholar
• Mahon FX, Richter J, Guilhot J, et al. Cessation of tyrosine kinase inhibitors treatment in chronic myeloid leukemia patients with deep molecular response: results of the Euro-Ski Trial. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]; San Diego, CA. Poster 787.
   Google Scholar
• Richter J, Mahon FX, Guilhot F, et al. Stopping tyrosine kinase inhibitors in a very large cohort of European chronic myeloid leukemia patients: results of the EURO-SKI Trial. Presented at: European Hematology Association; [cited 2016 Jun 9–12]; Copenhagen, Denmark. Abstract S145.
   Google Scholar
• The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study). ClinicalTrials.gov. 2016 [cited 2017 Jan 18]. Available at: https://clinicaltrials.gov/ct2/show/NCT02269267?term=NCT02269267&rank=1.
   Google Scholar
• Clark RE, Polydoros F, Apperley JF, et al. Chronic myeloid leukaemia patients with stable molecular responses (at least MR3) may safely decrease the dose of their tyrosine kinase inhibitor: Data from the British Destiny Study. Presented at: American Society of Hematology; [2016 Dec 3–6]; San Diego, CA. Abstract 938.
   Google Scholar
• Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129:846–854.
   PubMed Web of Science ®Google Scholar
• Imagawa J, Tanaka H, Okada M, et al. Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. Lancet Haematol. 2015;2:e528–e535.
   PubMed Web of Science ®Google Scholar
• Shah NP, Paquette R, Muller MC, et al. Treatment-free remission (TFR) in patients with chronic phase chronic myeloid leukemia (CML-CP) and in stable deep molecular response (DMR) to dasatinib – the Dasfree Study. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]. San Diego, CA. Poster 1895.
   Google Scholar
• UMIN.ac.jp. Dasatinib treatment discontinuation study implementation plan for initial chronic phase chronic myelogenous leukemia with 1 year complete molecular genetic effect. 2013 [cited 2017 Mar 22]. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000012999&language=J.
   Google Scholar
• Kumagai T, Nakaseko C, Nishiwaki K, et al. Discontinuation of dasatinib after deep molecular response for over 2 years in patients with chronic myelogenous leukemia and the unique profiles of lymphocyte subsets for successful discontinuation: a prospective, multicenter Japanese trial (D-STOP Trial). Blood. 2016;128:Abstract 791.
   Web of Science ®Google Scholar
• Kim DDH, Bence-Bruckler I, Forrest DL, et al. Treatment-free remission accomplished by dasatinib (TRAD): preliminary results of the Pan-Canadian tyrosine kinase inhibitor discontinuation trial. Blood. 2016;128:Abstract 1922.
   Web of Science ®Google Scholar
• Etienne G, Rea D, Guilhot F, et al. Long-term follow-up of the French 1 Stop Imatinib Study (STIM1) in chronic myeloid leukemia patients. Blood. 2015;126:Abstract 345.
   Google Scholar
• Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122:515–522.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with front line nilotinib: results from the ENESTFreedom study. Presented at: American Society of Clinical Oncology; [cited 2016 June 3–7]; Chicago, IL. Abstract 7001.
   Google Scholar
• Ritchie EK, Catchatourian R, Klisovic RB, et al. ENESTgoal treatment-free remission study: updated preliminary results and digital polymerase chain reaction analysis in patients with chronic myeloid leukemia in chronic phase who switched from imatinib to nilotinib. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]; San Diego, CA. Poster 3090.
   Google Scholar
• Rea D, Rosti G, Cross NCP, et al. ENESTPath: A phase-3 study to assess the effect of nilotinib treatment duration on treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with imatinib: 24-month analysis of the first 300 patients in the induction/consolidation phase. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]; San Diego, CA. Poster 3094.
   Google Scholar
• Mahon FX, Boquimpani C, Takahashi N, et al. Patient-reported quality of life before and after stopping treatment in the ENESTop trial of treatment-free remission for patients with chronic myeloid leukemia in chronic phase. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–8]; San Diego, CA. Poster 1891.
   Google Scholar
• Kadowaki N, Kawaguchi T, Kuroda J, et al. Discontinuation of nilotinib in patients with chronic myeloid leukemia who have maintained deep molecular responses for at least 2 years: a multicenter phase 2 stop nilotinib (Nilst) trial. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]; San Diego, CA. Poster 790.
   Google Scholar
• Takahashi N, Nakaseko C, Nishiwaki K, et al. Two-year consolidation by nilotinib is associated with successful treatment free remission in chronic myeloid leukemia with MR: Subgroup Analysis from STAT2 Trial in Japan. Poster presented at: American Society of Hematology; [cited 2016 Dec 3–6]; San Diego, CA. Poster 1889.
   Google Scholar
• Treatment-free remission studies. ClinicalTrials.gov. [cited 2017 Jan 3]. Available from: https://clinicaltrials.gov/ct2/results?term=treatment±free±remission&type=&rslt=&recr=&age_v=&gndr=&cond=chronic±myelogenous±leukemia&intr=&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&rcv_s=&rcv_e=&lup_s=&lup_e=
   Google Scholar
• Saussele S, Richter J, Hochhaus A, et al. The concept of treatment-free remission in chronic myeloid leukemia. Leukemia. 2016;30:1638–1647.
   PubMed Web of Science ®Google Scholar