Rapid molecular recurrence after nilotinib therapy cessation
Abstract
Introduction of imatinib and then second-generation tyrosine kinase inhibitors (TKI) has resulted in the near-normal life expectancy of patients with chronic myeloid leukemia in chronic phase. Currently, treatment-free remission might be a therapeutic goal for a significant group of patients. Results of numerous clinical trials show that 40% up to 50% of patients who discontinue treatment after having achieved a stable deep molecular response (DMR) may remain treatment-free for an as-yet undefined period. It is important to underline that the patients with molecular relapse after discontinuation do not progress, and are almost all able to achieve DMR again upon retreatment. Here, we present a patient with CML, who was switched to nilotinib due to imatinib intolerance. After a few years of sustaining DMR nilotinib was stopped. 4 weeks after TKI discontinuation the patient lost major molecular response. Nilotinib was swiftly reintroduced and after 3 months the patient regained DMR.
Keywords: CMLTKInilotinibtreatment-free remission
References
- Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0, 2017. https://www.ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf (July 18, 2019).
- Hochhaus A, Larson RA, Guilhot F, et al. IRIS Investigators. Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia. 2013; 27(1): 107–112.
- Saglio G, Kim DW, Issaragrisil S, et al. ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010; 362(24): 2251–2259.
- Kantarjian HM, Shah N, Cortes J, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012; 119(5): 1123–1129.
- 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.
- Saussele S, Richter J, Guilhot J, 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. The Lancet Oncology. 2018; 19(6): 747–757.
- Hochhaus A, Masszi T, Giles FJ, 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(7): 1525–1531.
- Rea D, Nicolini F, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017; 129(7): 846–854.
- Baccarani M, Abruzzese E, Accurso V, et al. Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP. Blood Adv. 2019; 3(24): 4280–4290.
- Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020; 34(4): 966–984.
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. Version 3, 2020. https://www.nccn.org/patients/guidelines/content/PDF/cml-patient.pdf (September 20, 2020).
