Relevance of treatment‐free remission recommendations in chronic phase chronic leukemia patients treated with frontline tyrosine kinase inhibitors

Abstract

Background Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia (CP‐CML) patients who had achieved a sustained deep molecular response. Based on the results of discontinuation trials, recommendations regarding patient selection for a treatment‐free remission (TFR) attempt had been proposed. The aims of this study were to evaluate the rate of patients eligible for TKI discontinuation and molecular recurrence‐free survival (MRFS) after stop according to recommendations. Methods Over a 10‐year period, newly diagnosed CP‐CML patients and treated with first‐line TKI in the nine French participating centers were included. Eligibility to treatment discontinuation and MRFS were analyzed and compared according to selection criteria defined by recommendations and first‐line treatments. Results From January 2006 to December 2015, 398 patients were considered. Among them, 73% and 27% of patients received imatinib or either second or third generation tyrosine kinase inhibitors as frontline treatment, respectively. Considering the selection criteria defined by recommendations, up to 55% of the patients were selected as optimal candidates for treatment discontinuation. Overall 95/398 (24%) discontinued treatment. MRFS was 51.8% [95% CI 41.41–62.19] at 2 years and 43.8% [31.45–56.15] at 5 years. Patients receiving frontline second‐generation TKI and fulfilling the eligibility criteria suggested by recommendations had the lowest probability of molecular relapse after TKI stop when compare to others. Conclusion One third of CP‐CML patients treated with TKI frontline fulfilled the selection criteria suggested by European LeukemiaNet TFR recommendations. Meeting selection criteria and second‐generation TKI frontline were associated with the highest MRFS.

Importance of TKI treatment duration in treatment-free remission of chronic myeloid leukemia: results of the D-FREE study

“…The National Comprehensive Cancer Network (NCCN) guidelines describe criteria for TKI discontinuation as being the duration of approved TKI therapy for at least 3 years and stable MR4 for ≥ 2 years [ 12 ], which is less strict than the ELN recommendations. Etienne et al published the results of their evaluation of the rate of patients eligible for TKI discontinuation and MRFS after stopping according to several recommendations/guidelines, including the ELN and the NCCN [ 23 ]. They found that the MRFS of patients who fulfilled the selection criteria proposed by the ELN was significantly different from that of those who did not, whereas no difference in MRFS was observed regarding the criteria proposed by the NCCN.…”

Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid Leukemia: eligibility criteria and predictors of success

“…48 The Sokal score strongly influences the probability of achieving a sustained DMR rather than the risk of relapse after TKI discontinuation. 52,53 One survey reported that 19% of patients who meet discontinuation criteria are not interested in stopping TKI treatment. 54 In particular, patients with a good quality of life, not experiencing significant side effects from TKI, could be uncomfortable with the interruption of their life-saving therapy.…”

“…Recent guidelines do not include the Sokal risk score, while it is mentioned in the European Society for Medical Oncology (ESMO) guidelines, 50 Australian indications for clinical practice, 51 and the above‐cited MDACC update 48 . The Sokal score strongly influences the probability of achieving a sustained DMR rather than the risk of relapse after TKI discontinuation 52,53 …”

Questions concerning tyrosine kinase-inhibitor therapy and transplants in chronic phase chronic myeloid leukaemia

“…There is controversy on how to best use TKIs. Which are the best and most cost-effective strategies to achieve TFR, to optimize survival and improve QoL [ 2 , 7 – 9 , 35 , 36 , 38 , 41 – 46 ]? Which strategy(ies) should be used when someone does not meet proposed TKI stopping criteria or fails because of molecular, cytogenetic and/or haematologic leukaemia recurrence?…”

“…Expert consensus statements and clinical practice guidelines recommend >5 years of imatinib and >3 to 5 years of a 2G-TKI, with a response ≥ MR 4 for ≥2 years [ 2 , 7 – 9 , 38 , 44 , 46 , 48 , 49 ]. Convincing data supporting these recommendations are lacking [ 10 ].…”