Vol 11, Supp. B (2020)
Case report
Published online: 2021-02-08

open access

Page views 484
Article views/downloads 302
Get Citation

Connect on Social Media

Connect on Social Media

Treatment-free remission in clinical practice: nilotinib treatment discontinuation in six chronic myelogenous leukemia patients — single-center experience

Joanna Niesiobędzka-Krężel1

Abstract

In the last 20 years major goals of therapy of chronic myelogenous leukemia (CML) have changed. This leukemia, which was previously a fatal disease, has indeed become a chronic disease thanks to the use of tyrosine kinase inhibitors (TKIs), with life expectancy close to that in the general population. Excellent treatment effectiveness with the achievement of long-term, stable, deep molecular response was the motivation for attempts to stop the therapy with the intention of maintaining remission (TFR, treatment-free remission). Based on many clinical trials with over 3,000 patients and several years of follow-up, it is known that 40–60% of patients will maintain molecular remission and remain untreated, while the rest of them will require TKI to be restarted. Information on the procedure to be followed appeared in scientific societies’ recommendations and some centers treating CML patients have made attempts to stop the therapy. This work describes a group of six patients in the TFR phase after discontinuation of nilotinib used in the first-line treatment.

Article available in PDF format

View PDF (Polish) Download PDF file

References

  1. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013; 122(6): 872–884.
  2. Hochhaus A, Saussele S, Rosti G, et al. ESMO Guidelines Committee. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(Suppl_4): iv41–iv51.
  3. Rosti G, Castagnetti F, Gugliotta G, et al. Tyrosine kinase inhibitors in chronic myeloid leukaemia: which, when, for whom? Nat Rev Clin Oncol. 2017; 14(3): 141–154.
  4. Brunner AM, Campigotto F, Sadrzadeh H, et al. Trends in all-cause mortality among patients with chronic myeloid leukemia: a Surveillance, Epidemiology, and End Results database analysis. Cancer. 2013; 119(14): 2620–2629.
  5. Shah NP. Front-line treatment options for chronic-phase chronic myeloid leukemia. J Clin Oncol. 2018; 36(3): 220–224.
  6. Efficace F, Baccarani M, Breccia M, et al. GIMEMA. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011; 118(17): 4554–4560.
  7. Efficace F, Baccarani M, Breccia M, et al. Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib. Leukemia. 2013; 27(7): 1511–1519.
  8. Jiang Q, Wang H, Yu Lu, et al. Higher out-of-pocket expenses for tyrosine kinase-inhibitor therapy is associated with worse health-related quality-of-life in persons with chronic myeloid leukemia. J Cancer Res Clin Oncol. 2017; 143(12): 2619–2630.
  9. Mahon FX. Treatment-free remission in CML: who, how, and why? Hematology Am Soc Hematol Educ Program. 2017; 2017(1): 102–109.
  10. Cortes J, O'Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood. 2004; 104(7): 2204–2205.
  11. 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; 28 Suppl 1: S71–S73.
  12. Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007; 109(1): 58–60.
  13. Annunziata M, Bonifacio M, Breccia M, et al. Current strategies and future directions to achieve deep molecular response and treatment-free remission in chronic myeloid leukemia. Front Oncol. 2020; 10: 883.
  14. Chen KK, Du TF, Xiong PS, et al. Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia with losing major molecular response as a definition for molecular relapse: a systematic review and meta-analysis. Front Oncol. 2019; 9: 372.
  15. Cortes J, Rea D, Lipton JH. Treatment-free remission with first- and second-generation tyrosine kinase inhibitors. Am J Hematol. 2019; 94(3): 346–357.
  16. Radich JP, Deininger M, Abboud CN, et al. Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018; 16(9): 1108–1135.
  17. Shah NP. NCCN Guidelines Updates: discontinuing TKI therapy in the treatment of chronic myeloid leukemia. J Natl Compr Canc Netw. 2019; 17(5.5): 611–613.
  18. Charakterystyka produktu leczniczego Tasigna (data zatwierdzenia lub częściowej zmiany tekstu charakterystyki produktu leczniczego 07/2018). https://ec.europa.eu/health/documents/community-register/2018/20180426140910/anx_140910_pl.pdf (November 13, 2020).
  19. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020; 34(4): 966–984.
  20. Etienne G, Guilhot J, Rea D, et al. Long-term follow-up of the French Stop Imatinib (STIM1) Study in patients with chronic myeloid leukemia. J Clin Oncol. 2017; 35(3): 298–305.
  21. 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(4): 515–522.
  22. Rousselot P, Charbonnier A, Cony-Makhoul P, 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(5): 424–430.
  23. Richter J, Mahon FX, Guilhot J, et al. Stopping tyrosine kinase inhibitors in a very large cohort of European chronić myeloid leukemia patients. Results of the EURO-SKI trial. Haematologica. 2016; 101: S145.
  24. Saussele S, Richter J, Guilhot J, et al. EURO-SKI investigators. 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(6): 747–757.
  25. Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016; 128(1): 17–23.
  26. Rea D, Nicolini FE, Tulliez M, et al. France Intergroupe des Leucémies Myéloïdes Chroniques. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017; 129(7): 846–854.
  27. Okada M, Imagawa J, Tanaka H, et al. DADI Trial Group, Japan. 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(5): 353–360.e1.
  28. Rousselot P, Etienne G, Coiteux V, et al. Attempt to early discontinue dasatinib first line in chronic phase CML patients in early molecular response and included in the prospective OPTIM-dasatinib trial. Haematologica. 2015; 1000: P599.
  29. Shah NP, García-Gutiérrez V, Jiménez-Velasco A, et al. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study. Leuk Lymphoma. 2019; 61(3): 650–659.
  30. Radich JP, Masszi T, Górmez Casares MT, et al. ENESTfreedom 144-week update. Long-term treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase (CML-CP). Clin Lymphoma Myeloma Leuk. 2018; 18(1): S226.
  31. Ritchie EK, Catchatourian R, Klisovic R, 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. Blood. 2016; 128(22): 3090–3090.
  32. Hughes TP, Boquimpani C, Takahashi N, 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): 7005–7005.
  33. A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML. (ENESTPath). https://clinicaltrials.gov/ct2/show/NCT01743989 (November 11, 2020).
  34. Hjorth-Hansen H, Stenke L, Söderlund S, et al. Nordic CML Study Group. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006). Eur J Haematol. 2015; 94(3): 243–250.
  35. Benjamini O, Kantarjian H, Rios MB, et al. Patient-driven discontinuation of tyrosine kinase inhibitors: single institution experience. Leuk Lymphoma. 2014; 55(12): 2879–2886.
  36. Saussele S, Guilhot JG. Duration of deep moleculare response has most impact on the success of cessation of tyrosine kinase inhibitor treatment in chronic myeloid leukemia. Results from the EURO-SKI trial. Blood. 2017; 130: 313.
  37. Chamoun K, Kantarjian H, Rios M, et al. CML Patients Outcome after TKI Discontinuation: A Single Institution Experience in the US. Blood. 2016; 128(22): 1923–1923.
  38. Etienne G, Guilhot J, Rea D, et al. Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia. J Clin Oncol. 2017; 35(3): 298–305.



Hematology in Clinical Practice