Making Treatment-Free Remission (TFR) Easier in Chronic Myeloid Leukemia: Fact-Checking and Practical Management Tools.
Journal
Targeted oncology
ISSN: 1776-260X
Titre abrégé: Target Oncol
Pays: France
ID NLM: 101270595
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
accepted:
20
07
2021
pubmed:
19
10
2021
medline:
3
5
2022
entrez:
18
10
2021
Statut:
ppublish
Résumé
In chronic-phase chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are the standard of care, and treatment-free remission (TFR) following the achievement of a stable deep molecular response (DMR) has become, alongside survival, a primary goal for virtually all patients. The GIMEMA CML working party recently suggested that the possibility of achieving TFR cannot be denied to any patient, and proposed specific treatment policies according to the patient's age and risk. However, other international recommendations (including 2020 ELN recommendations) are more focused on survival and provide less detailed suggestions on how to choose first and subsequent lines of treatment. Consequently, some grey areas remain. After literature review, a panel of Italian experts discussed the following controversial issues: (1) early prediction of DMR and TFR: female sex, non-high disease risk score, e14a2 transcript and early MR achievement have been associated with stable DMR, but the lack of these criteria is not sufficient to exclude any patient from TFR; (2) criteria for first and subsequent line therapy choice: a number of patient and drug characteristics have been proposed to make a personalized decision; (3) monitoring of residual disease after discontinuation: after the first 6 months, the frequency of molecular tests can be reduced based on MR4.5 persistence and short turnaround time; (4) prognosis of TFR: therapy and DMR duration are important to predict TFR; although immunological control of CML plays a role, no immunological predictive phenotype is currently available. This guidance is intended as a practical tool to support physicians in decision making.
Identifiants
pubmed: 34661826
doi: 10.1007/s11523-021-00831-4
pii: 10.1007/s11523-021-00831-4
pmc: PMC8613078
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
823-838Informations de copyright
© 2021. The Author(s).
Références
Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966–84.
pubmed: 32127639
pmcid: 7214240
Mahon F-X, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. 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. 2010;11:1029–35.
pubmed: 20965785
Etienne G, Guilhot J, Rea D, Rigal-Huguet F, Nicolini F, Charbonnier A, et al. Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia. J Clin Oncol. 2017;35:298–305.
pubmed: 28095277
Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol. 2014;32:424–30.
pubmed: 24323036
Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122:515–22.
pubmed: 23704092
Hehlmann R, Müller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, 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. J Clin Oncol. 2014;32:415–23.
pubmed: 24297946
Mori S, Vagge E, le Coutre P, Abruzzese E, Martino B, Pungolino E, et al. Age and dPCR can predict relapse in CML patients who discontinued imatinib: the ISAV study. Am J Hematol. 2015;90:910–4.
pubmed: 26178642
Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333–40.
pubmed: 27217448
pmcid: 5118045
Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim D-W, Issaragrisil S, 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;30:1044–54.
pubmed: 26837842
pmcid: 4858585
Lee S-E, Choi SY, Song H-Y, Kim S-H, Choi M-Y, Park JS, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016;101:717–23.
pubmed: 26888022
pmcid: 5013960
Mahon F-X, Nicolini FE, Noël M-P, Escoffre M, Charbonnier A, Rea D, et al. Preliminary report Of The STIM2 study: a multicenter stop imatinib trial for chronic phase chronic myeloid leukemia de novo patients on imatinib. Blood. 2013;122(21):654.
Takahashi N, Tauchi T, Kitamura K, Miyamura K, Saburi Y, Miyata Y, et al. Around 70% of Japanese CML patients could stop imatinib according to a-STIM criteria: the JALSG-STIM213 Study. Blood. 2015;126(23):4035.
Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, et al. 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. 2018;19:747–57.
pubmed: 29735299
Breccia M, Foà R. Current Information and Recommendations on the Discontinuation of TKI Inhibitors in Chronic Myeloid Leukemia. Curr Oncol Rep. 2018;20:23.
pubmed: 29511948
Rea D, Nicolini FE, Tulliez M, Guilhot F, Guilhot J, Guerci-Bresler A, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129(7):846–54.
Okada M, Imagawa J, Tanaka H, Nakamae H, Hino M, Murai K, et al. Final 3-year results of the dasatinib discontinuation trial in patients with chronic myeloid leukemia who received dasatinib as a second-line treatment. Clin Lymphoma Myeloma Leuk. 2018;18:353-360.e1.
pubmed: 29610029
Kumagai T, Nakaseko C, Nishiwaki K, Yoshida C, Ohashi K, Takezako N, 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(22):791.
Shah NP, Paquette R, Müller MC, Saussele S, Garcìa-Gutiérrez V, Jiménez-Velasco A, 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. Blood.2016;128(22):1895.
Shah NP, García-Gutiérrez V, Jiménez-Velasco A, Larson S, Saussele S, Rea D, et al. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study. Leuk Lymphoma. 2020;61:650–9.
pubmed: 31647335
Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gómez Casares MT, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31:1525–31.
pubmed: 28218239
pmcid: 5508077
Ross DM, Masszi T, Gómez Casares MT, Hellmann A, Stentoft J, Conneally E, et al. Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study. J Cancer Res Clin Oncol. 2018;144:945–54.
pubmed: 29468438
pmcid: 5916993
Giles FJ, Masszi T, Gómez Casares MT, Hellmann A, Stentoft J, Conneally E, et al. Treatment-free remission (TFR) following frontline (1L) nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): 192-week data from the ENESTfreedom study. J Clin Oncol. 2019;37(15_Suppl):7013.
doi: 10.1200/JCO.2019.37.15_suppl.7013
Mahon F-X, Boquimpani C, Kim D-W, Benyamini N, Clementino NCD, Shuvaev V, et al. Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase: results from a single-group, phase 2, open-label Study. Ann Intern Med. 2018;168:461–70.
pubmed: 29459949
Hughes TP, Boquimpani C, Takahashi N, Benyamini N, Clementino NCD, Shuvaev V, et al. ENESTop 192-week results: Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after stopping second-line (2L) nilotinib (NIL). J Clin Oncol. 2019;37(15_Suppl):7005.
doi: 10.1200/JCO.2019.37.15_suppl.7005
Fava C, Rege-Cambrin G, Dogliotti I, Cerrano M, Berchialla P, Dragani M, et al. Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice. Haematologica. 2019;104(8):1589–96.
Kwok M, Shenouda A, Duncan N, Hasan Y, Ewing J, Raghavan M, et al. Outcomes following treatment discontinuation iN CML: real-world experience from 3 regional UK centres: PB1946. HemaSphere. 2019;3:884.
Abruzzese E, Bosi A, Breccia M, D’Adda M, Di Renzo N, Liberati AM, et al. Treatment patterns in patients with chronic-phase chronic myeloid leukaemia in routine clinical practice: the SIMPLICITY Italian Population. Mediterr J Hematol Infect Dis. 2019;11:e2019025.
pubmed: 31205629
pmcid: 6548212
Dengler J, Tesch H, Jentsch-Ullrich K, Gerhardt A, Schulte C, Lipke J, et al. Treetment-free remission in real-world chronic myeloid leukemia patients: Insights from German clinical hematology practices. EHA Library. Kiani A. 06/14/19; 266218; PF418. https://library.ehaweb.org/eha/2019/24th/266218/alexander.kiani.treatment-free.remission.in.real-world.chronic.myeloid.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dkiani .
Ross DM, Hughes TP. Treatment-free remission in patients with chronic myeloid leukaemia. Nat Rev Clin Oncol. 2020;17:493–503.
pubmed: 32377005
Ross DM, Pagani IS, Shanmuganathan N, Kok CH, Seymour JF, Mills AK, et al. Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells. Leukemia. 2018;32:2572–9.
pubmed: 30315232
Rea D, Nicolini FE, Tulliez M, Rousselot P, Gardembas M, Etienne G, et al. Prognostication of molecular relapses after dasatinib or nilotinib discontinuation in chronic myeloid leukemia (CML): a FI-LMC STOP 2G-TKI study update. Blood. 2019;134(1_Suppl):30.
Saglio G, Kim D-W, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.
pubmed: 20525993
Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.
pubmed: 20525995
Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim D-W, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE Trial. J Clin Oncol. 2018;36:231–7.
pubmed: 29091516
Gruppo Italiano Malattie EMatologiche dell’Adulto. Sustained Treatment-free Remission in BCR-ABL+ Chronic Myeloid Leukemia: a Prospective Study Comparing Nilotinib Versus Imatinib With Switch to Nilotinib in Absence of Optimal Response. SUSTRENIM Study-GIMEMA CLM1415 [Internet]. clinicaltrials.gov; 2017 Oct. Report No.: NCT02602314. https://clinicaltrials.gov/ct2/show/NCT02602314 .
Radich JP, Deininger M, Abboud CN, Altman JK, Berman E, Bhatia R, et al. Chronic myeloid leukemia, Version 1.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:1108–35.
pubmed: 30181422
Baccarani M, Abruzzese E, Accurso V, Albano F, Annunziata M, Barulli S, et al. Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP. Blood Adv. 2019;3:4280–90.
Shah NP, García Gutiérrez JV, Jiménez-Velasco A, Larson S, Saussele S, Rea D, et al. Updated 18-month results from dasfree: a study evaluating dasatinib discontinuation in patients (Pts) with chronic myeloid leukemia in chronic phase (CML-CP) and deep molecular response (DMR). Blood. 2018;132:4253.
Cross NCP, White HE, Müller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 2012;26:2172–5.
pubmed: 22504141
Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. 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. 2006;108:28–37.
pubmed: 16522812
pmcid: 1895821
Breccia M, Molica M, Colafigli G, Massaro F, Quattrocchi L, Latagliata R, et al. Prognostic factors associated with a stable MR4.5 achievement in chronic myeloid leukemia patients treated with imatinib. Oncotarget. 2018;9:7534–40.
pubmed: 29484130
Branford S, Yeung DT, Ross DM, Prime JA, Field CR, Altamura HK, et al. Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML. Blood. 2013;121:3818–24.
pubmed: 23515925
Castagnetti F, Gugliotta G, Breccia M, Stagno F, Specchia G, Levato L, et al. The use of EUTOS long-term survival score instead of Sokal score is strongly advised in elderly chronic myeloid leukemia Patients. Blood. 2018;132(1_Suppl):44.
doi: 10.1182/blood-2018-99-117409
Sato E, Iriyama N, Tokuhira M, Takaku T, Ishikawa M, Nakazato T, et al. The EUTOS long-term survival score predicts disease-specific mortality and molecular responses among patients with chronic myeloid leukemia in a practice-based cohort. Cancer Med. 2020;9:8931–9.
pubmed: 33037866
pmcid: 7724301
Hochhaus A, Saussele S, Rosti G, Mahon F-X, Janssen JJWM, Hjorth-Hansen H, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv41-51.
pubmed: 28881915
Baccarani M, Castagnetti F, Gugliotta G, Rosti G, Soverini S, Albeer A, et al. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview. Leukemia. 2019;33:1173–83.
pubmed: 30675008
Dragani M, Rege-Cambrin G, Gottardi E, Daraio F, Caocci G, Aguzzi C, et al. Treatment free remission in chronic myeloid leukemia patients harboring atypical BCR-ABL1 transcripts. EHA Library. Dragani M. 06/15/19; 266796; PS1179
Schäfer V, White HE, Gerrard G, Möbius S, Saussele S, Franke G-N, et al. Assessment of individual molecular response in chronic myeloid leukemia patients with atypical BCR-ABL1 fusion transcripts: recommendations by the EUTOS cooperative network. J Cancer Res Clin Oncol. 2021;147(10):3081–89.
Bonifacio M, Scaffidi L, Binotto G, De Marchi F, Maino E, Calistri E, et al. Predictive factors of stable deep molecular response in chronic myeloid leukemia patients treated with imatinib standard dose: a study from the Gruppo Triveneto LMC. Blood. 2015;126(23):597.
Jain P, Kantarjian H, Patel KP, Gonzalez GN, Luthra R, Kanagal Shamanna R, et al. Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors. Blood. 2016;127:1269–75.
pubmed: 26729897
pmcid: 4786836
Castagnetti F, Gugliotta G, Breccia M, Iurlo A, Levato L, Albano F, et al. The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib. Am J Hematol. 2017;92:797–805.
pubmed: 28466557
Claudiani S, Apperley JF, Gale RP, Clark R, Szydlo R, Deplano S, et al. E14a2 BCR-ABL1 transcript is associated with a higher rate of treatment-free remission in individuals with chronic myeloid leukemia after stopping tyrosine kinase inhibitor therapy. Haematologica. 2017;102:e297–9.
pubmed: 28495914
pmcid: 5541883
Pagnano KBB, Miranda EC, Delamain MT, Duarte GO, de Paula EV, Lorand-Metze I, et al. Influence of BCR-ABL transcript type on outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib. Clin Lymphoma Myeloma Leuk. 2017;17:728–33.
pubmed: 28822797
Shanmuganathan N, Branford S, Yong ASM, Hiwase DK, Yeung DT, Ross DM, et al. The e13a2 BCR-ABL1 transcript is associated with higher rates of molecular recurrence after treatment-free remission attempts: retrospective analysis of the adelaide cohort. Blood. 2018;132(1_Suppl):1731.
D’Adda M, Farina M, Schieppati F, Borlenghi E, Bottelli C, Cerqui E, et al. The e13a2 BCR-ABL transcript negatively affects sustained deep molecular response and the achievement of treatment-free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors. Cancer. 2019;125:1674–82.
pubmed: 30707758
Genthon A, Nicolini FE, Huguet F, Colin-Gil C, Berger M, Saugues S, et al. Influence of major BCR-ABL1 transcript subtype on outcome in patients with chronic myeloid leukemia in chronic phase treated frontline with nilotinib. Oncotarget. 2020;11:2560–70.
pubmed: 32655840
pmcid: 7335668
Machova Polakova K, Salmon M, Zizkova H, Gottschalk A, Motlova E, Jurcek T, et al. Individual molecular response evaluation on both DNA and mRNA BCR-ABL1 level diminished differences in time to molecular response achievement between CML patients with E13A2 vs E14A2 transcript type. HemaSphere. 2020;4:351.
Kjaer L, Skov V, Andersen MT, Aggerholm A, Clair P, Gniot M, et al. Variant-specific discrepancy when quantitating BCR-ABL1 e13a2 and e14a2 transcripts using the Europe Against Cancer qPCR assay. Eur J Haematol. 2019;103:26–34.
pubmed: 30985947
Bernardi S, Bonifacio M, Iurlo A, Zanaglio C, Tiribelli M, Binotto G, et al. “Variant-specific discrepancy when quantitating BCR-ABL1 e13a2 and e14a2 transcripts using the Europe Against Cancer qPCR assay.” Is dPCR the key? Eur J Haematol. 2019;103:272–3.
pubmed: 31233644
Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.
pubmed: 23803709
pmcid: 4915804
Hochhaus A, Rosti G, Cross NCP, Steegmann JL, le Coutre P, Ossenkoppele G, et al. Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study. Leukemia. 2016;30:57–64.
pubmed: 26437782
Marin D, Hedgley C, Clark RE, Apperley J, Foroni L, Milojkovic D, et al. Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first-line dasatinib. Blood. 2012;120:291–4.
pubmed: 22645182
Breccia M, Molica M, Colafigli G, Massaro F, Alimena G. Early molecular response in chronic myeloid leukemia and halving time: Latest evidences. Leuk Res. 2016;48:20–5.
pubmed: 27442893
Hanfstein B, Müller MC, Hehlmann R, Erben P, Lauseker M, Fabarius A, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26:2096–102.
pubmed: 22446502
Branford S, Yeung DT, Parker WT, Roberts ND, Purins L, Braley JA, et al. Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood. 2014;124:511–8.
pubmed: 24859364
Iriyama N, Fujisawa S, Yoshida C, Wakita H, Chiba S, Okamoto S, et al. Shorter halving time of BCR-ABL1 transcripts is a novel predictor for achievement of molecular responses in newly diagnosed chronic-phase chronic myeloid leukemia treated with dasatinib: Results of the D-first study of Kanto CML study group. Am J Hematol. 2015;90:282–7.
pubmed: 25530131
Fava C, Rege-Cambrin G, Dogliotti I, Gottardi E, Berchialla P, Di Gioacchino B, et al. Early BCR-ABL1 reduction is predictive of better event-free survival in patients with newly diagnosed chronic myeloid leukemia treated with any tyrosine kinase inhibitor. Clin Lymphoma Myeloma Leuk. 2016;16(Suppl):S96-100.
pubmed: 27131622
Pennisi MS, Stella S, Vitale SR, Puma A, Di Gregorio S, Romano C, et al. BCR-ABL1 doubling-times and halving-times may predict CML response to tyrosine kinase inhibitors. Front Oncol. 2019;9:764.
pubmed: 31456947
pmcid: 6700306
Shanmuganathan N, Pagani IS, Ross DM, Park S, Yong AS, Braley JA, et al. Early BCR-ABL1 kinetics are predictive of subsequent achievement of treatment-free remission in chronic myeloid leukemia. Blood. 2020;137(9):1196–207.
Pinto RZ, Ferreira ML, Oliveira VC, Franco MR, Adams R, Maher CG, et al. Patient-centred communication is associated with positive therapeutic alliance: a systematic review. J Physiother. 2012;58:77–87.
pubmed: 22613237
Villemagne Sanchez LA, O’Callaghan C, Gough K, Hall K, Kashima Y, Seymour JF, et al. Patient perceptions of treatment-free remission in chronic myeloid leukemia. Leuk Lymphoma. 2018;59:406–15.
pubmed: 28617066
Sanford D, Kyle R, Lazo-Langner A, Xenocostas A, Chin-Yee I, Howson-Jan K, et al. Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia. Curr Oncol. 2014;21:e241-249.
pubmed: 24764709
pmcid: 3997457
Breccia M, Efficace F, Sica S, Abruzzese E, Cedrone M, Turri D, et al. Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients. Leuk Res. 2015;39:1055–9.
pubmed: 26282944
Goldberg SL, Savona M, Mauro MJ. Considerations for successful treatment-free remission in chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2018;18:98–105.
pubmed: 29274688
Lou J, Huang J, Wang Z, Wen B, Tu C, Huang W, et al. Chronic myeloid leukemia patients and treatment-free remission attitudes: a multicenter survey. Patient Prefer Adherence. 2018;12:1025–32.
pubmed: 29942119
pmcid: 6007199
Boquimpani CM, Szczudlo T, Mendelson E, Benjamin K, Masszi T. Attitudes and perceptions of patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) toward treatment-free remission (TFR). Blood. 2014;124(21):4547.
Sogawa R, Kimura S, Yakabe R, Mizokami Y, Tasaki M, Sueoka-Aragane N, et al. Anxiety and depression associated with tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia. Int J Clin Oncol. 2018;23(5):974–9.
Uemura M, Imataki O, Kawachi Y, Kawakami K, Hoshijima Y, Matsuoka A, et al. Charlson comorbidity index predicts poor outcome in CML patients treated with tyrosine kinase inhibitor. Int J Hematol. 2016;104:621–7.
pubmed: 27492732
Steegmann JL, Baccarani M, Breccia M, Casado LF, García-Gutiérrez V, Hochhaus A, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30:1648–71.
pubmed: 27121688
pmcid: 4991363
Copland M. Is there a role for dose modification of TKI therapy in CML? Curr Hematol Malig Rep. 2019;14:337–45.
pubmed: 31197525
pmcid: 6647386
Kunbaz A, Eskazan AE. An alternative way—tyrosine kinase inhibitor (TKI) de-escalation—to discontinue TKIs in order to achieve treatment-free remission. Expert Rev Hematol. 2019;12:477–80.
pubmed: 31166812
Cayssials E, Torregrosa-Diaz J, Gallego-Hernanz P, Tartarin F, Systchenko T, Maillard N, et al. Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study. Cancer. 2020;126:3438–47.
pubmed: 32459375
Clark RE, Polydoros F, Apperley JF, Milojkovic D, Rothwell K, Pocock C, et al. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematol. 2019;6:e375–83.
pubmed: 31201085
DANTE study. A phase II, Single-arm, Multicenter study of full treatment-free remission in patients with chronic myeloid leukemia in chronic phase treated with nilotinib in first-line therapy who have achieved a sustained, deep molecular response for at least 1 year [Internet]. clinicaltrials.gov; 2020 Jun. Report No.: NCT03874858. https://clinicaltrials.gov/ct2/show/NCT03874858 .
Rousselot P, Loiseau C, Delord M, Cayuela JM, Spentchian M. Late molecular recurrences in patients with chronic myeloid leukemia experiencing treatment-free remission. Blood Adv. 2020;4:3034–40.
Rea D, Mahon F-X. How I manage relapse of chronic myeloid leukaemia after stopping tyrosine kinase inhibitor therapy. Br J Haematol. 2018;180:24–32.
pubmed: 29048128
Tasigna SPC. Tasigna [Internet]. European Medicines Agency. [cited 2020 Nov 20]. https://www.ema.europa.eu/en/medicines/human/EPAR/tasigna .
Shanmuganathan N, Braley JA, Yong AS, Hiwase DK, Yeung DT, Ross DM, et al. Modelling the safe minimum frequency of molecular monitoring for CML patients attempting treatment-free remission. Blood. 2019;134(1):85–9.
Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016;128:17–23.
pubmed: 27013442
Bernardi S, Malagola M, Zanaglio C, Polverelli N, Dereli Eke E, D’Adda M, et al. Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation. Cancer Med. 2019;8:2041–55.
pubmed: 30950237
pmcid: 6536984
Machova Polakova K, Zizkova H, Zuna J, Motlova E, Hovorkova L, Gottschalk A, et al. Analysis of chronic myeloid leukaemia during deep molecular response by genomic PCR: a traffic light stratification model with impact on treatment-free remission. Leukemia. 2020;34:2113–24.
Diral E, Mori S, Antolini L, Abruzzese E, le Coutre P, Martino B, et al. Increased tumor burden in Chronic Myeloid Leukemia patients after 36 months of imatinib discontinuation. Blood. 2020;136(19):2237–40.
Alikian M, Whale AS, Akiki S, Piechocki K, Torrado C, Myint T, et al. RT-qPCR and RT-digital PCR: a comparison of different platforms for the evaluation of residual disease in chronic myeloid leukemia. Clin Chem. 2017;63:525–31.
pubmed: 27979961
Cortés AA, Olmedillas S, Serrano-López J, Lainez-González D, Castaño T, Iñiguez R, et al. Comparison of droplet digital pcr versus qPCR measurements on the international scale for the molecular monitoring of chronic myeloid leukemia patients. Mol Diagn Ther. 2020;24:593–600.
pubmed: 32875515
Kockerols CCB, Valk PJM, Levin M-D, Pallisgaard N, Cornelissen JJ, Westerweel PE. Digital PCR for BCR-ABL1 quantification in CML: current applications in clinical practice. Hemasphere. 2020;4:e496.
pubmed: 33283168
pmcid: 7710259
Atallah E, Schiffer CA, Radich JP, Weinfurt KP, Zhang M-J, Pinilla-Ibarz J, et al. Assessment of outcomes after stopping tyrosine kinase inhibitors among patients with chronic myeloid leukemia: a nonrandomized clinical trial. JAMA Oncol. 2021;7:42–50.
pubmed: 33180106
Coccaro N, Tota G, Anelli L, Zagaria A, Specchia G, Albano F. Digital PCR: a reliable tool for analyzing and monitoring hematologic malignancies. Int J Mol Sci. 2020;21(9):3141.
Radich JP, Hochhaus A, Giles FJ, Ross DM, Saglio G, Hughes TP, et al. Analyses of predictors of durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline or second-line nilotinib. Blood. 2019;134(1_Suppl):2932.
Claudiani S, Metelli S, Kamvar R, Szydlo R, Khan A, Byrne J, et al. Introducing a predictive score for successful treatment free remission in chronic myeloid leukemia (CML). Blood. 2019;134(1_Suppl):26.
Hughes A, Yong ASM. Immune effector recovery in chronic myeloid leukemia and treatment-free remission. Front Immunol. 2017;8:469.
pubmed: 28484463
pmcid: 5402174
Galimberti S, Petrini M, Baratè C, Ricci F, Balducci S, Grassi S, et al. Tyrosine kinase inhibitors play an antiviral action in patients affected by chronic myeloid leukemia: a possible model supporting their use in the fight against SARS-CoV-2. Front Oncol. 2020;10:1428.
pubmed: 33014780
pmcid: 7493657
Houshmand M, Blanco TM, Circosta P, Yazdi N, Kazemi A, Saglio G, et al. Bone marrow microenvironment: The guardian of leukemia stem cells. World J Stem Cells. 2019;11:476–90.
pubmed: 31523368
pmcid: 6716085
Bocchia M, Sicuranza A, Abruzzese E, Iurlo A, Sirianni S, Gozzini A, et al. Residual peripheral blood CD26+ leukemic stem cells in chronic myeloid leukemia patients during TKI therapy and during treatment-free remission. Front Oncol. 2018;8:194.
pubmed: 29900128
pmcid: 5988870
Irani YD, Hughes A, Clarson J, Kok CH, Shanmuganathan N, White DL, et al. Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells. Br J Haematol. 2020;191:433–41.
Hähnel T, Baldow C, Guilhot J, Guilhot F, Saussele S, Mustjoki S, et al. Model-based inference and classification of immunologic control mechanisms from TKI cessation and dose reduction in patients with CML. Cancer Res. 2020;80:2394–406.
pubmed: 32041835
Söderlund S, Persson I, Ilander M, Guilhot J, Hjorth-Hansen H, Koskenvesa P, et al. Plasma proteomics of biomarkers for inflammation or cancer cannot predict relapse in chronic myeloid leukaemia patients stopping tyrosine kinase inhibitor therapy. Leuk Res. 2020;90:106310.
pubmed: 32058176
Pagani IS, Dang P, Saunders VA, Grose R, Shanmuganathan N, Kok CH, et al. Lineage of measurable residual disease in patients with chronic myeloid leukemia in treatment-free remission. Leukemia. 2020;34:1052–61.
pubmed: 31768016