Recent studies suggest that some patients can achieve sustained molecular responses after TKI discontinuation (major molecular response for 2 years or longer) but that for many—perhaps most—other patients, discontinuation entails significant relapse risks. A retrospective single-institutional study of 95 patients with CML who achieved CCyR and major molecular response at a median of 3 and 9 months, respectively, at the University of Texas MD Anderson Cancer Center in Houston concluded that patients with lower than MR4.5 at the time of discontinuation have elevated risks of relapse compared to patients with MR4.5.1

Late relapse (relapse after a year or longer) was also noted, cautioned the study authors.

Relapse among patients who achieved sustained MR4.5 for more than 2 years was 32%, vs 82% among patients who had not achieved that benchmark. Patients on imatinib had lower relapse rates than second-generation agents, probably because of their longer TKI treatment duration before discontinuation, the authors noted.

Sokol scores, TKI treatment duration, depth of achieved molecular response, and natural killer T-cell presence are potential predictive markers of treatment-free remission.

An interim analysis of STOP 2G-TKI study outcomes suggest that among patients on second-generation-agent dasatinib or nilotinib TKI therapy, resistance or suboptimal response predicts significantly worse rates of treatment-free remission.4

RELATED: Second Generation TKIs Can Be Safely Stopped in CML

Until more research is done, it is unclear which patients will relapse after TKI discontinuation.

“Although the majority of patients who lose their response after discontinuation respond to re-treatment, treatment discontinuation is still not recommended outside clinical trials,” the MD Anderson Cancer Center team concluded.

References

  1. Chamoun K, Kantarjian HM, Rios MB, et al. CML patients outcome after TKI discontinuation: a single institution experience in the US. Poster presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.
  2. Bhalla S, Tremblay D, Mascarenhas J. Discontinuing tyrosine kinase inhibitor therapy in chronic myelogenous leukemia: current understanding and future directions. Clin Lymphoma Myeloma Leuk. 2016;16(9):488-94. doi: 10.1016/j.clml.2016.06.012
  3. Caldemeyer L, Dugan M, Edwards J, Akard L. Long-term side effects of tyrosine kinase inhibitor in chronic myeloid leukemia. Curr Hematol Malig Rep. 2016;11(2):71-9. doi: 10.1007/s11899-016-0309-2
  4. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2016 Dec 8. doi: 10.1182/blood-2016-09-742205 [Epub ahead of print]