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.

Keywords: molecular recurrence-free survival; recommendations; tyrosine kinase inhibitor discontinuation.

FIGURE 1

Eligibility to treatment free remission according to selection criteria proposed in Hughes et al., ⁶ Rea et al., ⁷ Radich et al., ⁸ and Hochhaus et al. ⁹ in de novo CP‐CML patients (N = 398 pts)

FIGURE 2

Molecular recurrence‐free survival after TKI cessation according to eligibility criteria proposed in Hughes et al., ⁶ Rea et al., ⁷ Radich et al., ⁸ and Hochhaus et al., ⁹ (N = 95 pts)

FIGURE 3

Molecular recurrence‐free survival after TKI cessation according eligibility criteria proposed in Rea et al., ⁷ Hochhaus et al., ⁹ and TKI frontline (IMA vs second‐generation TKI) (N = 95 pts)

FIGURE 4

Cumulative incidence of second major molecular response, MR4 log and MR4.5 log after TKI resumption in patients experienced molecular recurrence after TKI stop (N = 43 pts)