Interruption or Discontinuation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukaemia: A Retrospective Cohort Study (SPARKLE) in Belgium.
[en] Objectives: To assess interruptions/discontinuations of tyrosine kinase inhibitor (TKI) treatment in Belgian patients with
chronic myeloid leukaemia (CML). Methods: This retrospective study included patients with TKI interruptions/discontinuations of ≥4 continuous weeks (no clinical trial context)
between May 2013 and May 2016. Data collection took place
between October 2016 and February 2017. Results: All 60
participants (69 interruptions/discontinuations) had chronic-phase CML and 75% had at least a major molecular response (≥MMR) at interruption/discontinuation. Most interruptions/discontinuations occurred while on imatinib
(36/69; 49%) and dasatinib (20/69; 29%). Most interruptions/
discontinuations occurred due to side effects/intolerance
(46/69; 67%); other reasons included a wish to conceive
(6/69; 9%) and attempts to achieve treatment-free remission
(TFR) (6/69; 9%). Interruptions due to side effects occurred
later for imatinib- or dasatinib-treated patients than for
those on nilotinib or ponatinib. Treatment was re-initiated in
62% (43/69) of cases. Most interruptions caused by side effects/intolerance were followed by treatment changes. All 4
patients with ≥MR 4.5 at interruption/discontinuation and
≥11-month follow-up who had not restarted treatment
maintained the response. Conclusion: Although TKIs are
used for long-term CML treatment, physicians sometimes
recommend interruptions/discontinuations. In this study,
interruptions/discontinuations were mainly caused by side
effects or intolerance, rather than TFR attempts.
Disciplines :
Hématologie
Auteur, co-auteur :
Devos T.
Verhoef G.
Steel E.
Mazure D.
Lewalle P.
Bron D.
Berneman Z.
Benghiat FS.
MIneur P.
Theunissen K.
Zachée P.
Doyen C.
Put N.
LEJEUNE, Marie ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'hématologie clinique
Interruption or Discontinuation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukaemia: A Retrospective Cohort Study (SPARKLE) in Belgium.
Chopade P, Akard LP. Improving Outcomes in Chronic Myeloid Leukemia over Time in the Era of Tyrosine Kinase Inhibitors. Clin Lymphoma Myeloma Leuk. 2018 Nov; 18(11): 710-23.
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 Aug; 30(8): 1648-71.
Rea D. Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia. Ann Hematol. 2015 Apr; 94(S2 Suppl 2):S149-58.
Palani R, Milojkovic D, Apperley JF. Managing pregnancy in chronic myeloid leukaemia. Ann Hematol. 2015 Apr; 94(S2 Suppl 2):S167-76.
Jiang Q, Liu ZC, Zhang SX, Gale RP. Young age and high cost are associated with future preference for stopping tyrosine kinase inhibitor therapy in Chinese with chronic myeloid leukemia. J Cancer Res Clin Oncol. 2016 Jul; 142(7): 1539-47.
Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010 May; 28(14): 2381-8.
Noens L, van Lierde MA, De Bock R, Verhoef G, Zachée P, Berneman Z, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009 May; 113(22): 5401-11.
Cortes J, O'Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood. 2004 Oct; 104(7): 2204-5.
Mauro MJ, Druker BJ, Maziarz RT. Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission. Leuk Res. 2004 May;
Suppl 1:S71-3.
Merante S, Orlandi E, Bernasconi P, Calatroni S, Boni M, Lazzarino M. Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation. Haematologica. 2005 Jul; 90(7): 979-81.
Mahon FX, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al.; Intergroupe Français des Leucémies Myéloïdes Chroniques. 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 Nov; 11(11): 1029-35.
Mahon FX, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini FE, et al. Discontinuation of Imatinib in Patients with Chronic Myeloid Leukemia Who Have Maintained Complete Molecular Response: Update Results of the STIM Study. American Society of Hematology 53rd Annual Meeting; 2011 Dec 10-13; San Diego, CA, USA. Blood. 2011; 118(21): 603.
Mahon FX, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini FE, et al. Long-Term Follow-Up after Imatinib Cessation for Patients in Deep Molecular Response: The Update Results Of The STIM1 Study. American Society of Hematology 55th Annual Meeting; 2013 Dec 7-13; New Orleans, LA, USA. Blood. 2013; 122(21): 255.
Ross M, Branford S, Seymour J, Arthur C, Schwarer A, Dang P, et al. Frequent and sustained drug-free remission in the Australian CML8 trial of imatinib withdrawal. 17th Congress of the European Hematology Association; 2012 Jun 14-17; Amsterdam, The Netherlands [abstract 0189]. Haematologica. 2012;
Suppl 1: 74.
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 Jul; 122(4): 515-22.
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 Feb; 32(5): 424-30.
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 Jul; 31(7): 1525-31.
Mahon FX, Boquimpani C, Kim DW, Benyamini N, Clementino NC, 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. 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 Apr; 168(7): 461-70.
Rea D, Nicolini FE, Tulliez M, Rousselot P, Guilhot F, Gardembas M, et al. Dasatinib or nilotinib discontinuation in chronic phase (CP)-chronic myeloid leukemia (CML) patients (pts) with durably undetectable BCRABL transcripts: interim analysis of the STOP 2G-TKI study with a minimum follow-up of months-on behalf of the French CML Group Filmc. Blood. 2014; 124(21). Abstract no. 811.
Imagawa J, Tanaka H, Okada M, Nakamae H, Hino M, Murai K, et al.; DADI Trial Group. 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 Dec; 2(12): e528-35.
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.
Breccia M, Foà R. Current Information and Recommendations on the Discontinuation of TKI Inhibitors in Chronic Myeloid Leukemia. Curr Oncol Rep. 2018 Mar; 20(3): 23.
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 Aug; 122(6): 872-84.
Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016 Jul; 128(1): 17-23.
Pallera A, Altman JK, Berman E, Abboud CN, Bhatnagar B, Curtin P, et al. NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017. J Natl Compr Canc Netw. 2016 Dec; 14(12): 1505-12.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul; 114(5): 937-51.
Benghiat F, Beguin Y, Dessars B, Devos T, Lewalle P, Mineur P, et al. Practical management of chronic myeloid leukaemia in Belgium. Belgian J Hematol. 2015; 6(1): 16-32.
Vrijens B, De Geest S, Hughes DA, Przemyslaw K, Demonceau J, Ruppar T, et al; ABC Project Team. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012 May; 73(5): 691-705.
Shash E, Bassi S, Cocorocchio E, Colpi GM, Cinieri S, Peccatori FA. Fatherhood during imatinib. Acta Oncol. 2011 Jun; 50(5): 734-5.
Oweini H, Otrock ZK, Mahfouz RA, Bazarbachi A. Successful pregnancy involving a man with chronic myeloid leukemia on dasatinib. Arch Gynecol Obstet. 2011 Jan; 283(1): 133-4.
