Discontinuation of Tyrosine Kinase Inhibitor Therapy and Treatment-Free Remission in Chronic-Phase Chronic Myeloid Leukemia: An Observational Retrospective Multi-Center Study

Introduction: Discontinuation of tyrosine kinase inhibitor (TKI) therapy and achievement of treatment-free remission (TFR) in chronic-phase chronic myeloid leukemia (CP-CML) patients is feasible and can be implemented in clinical practice. We conducted a retrospective study at 3 tertiary care centers in Riyadh, Saudi Arabia of all CP-CML patients who discontinued TKI therapy.

Methods: All CP-CML patients being followed at participating centers who discontinued TKI, were eligible. TKI discontinuation was carried out as per clinical practice guidelines. Criterion to restart TKI therapy in relapsed patients was loss of major molecular response (MMR; BCR-ABL > 0.1). We collected data on gender, age, prognostic risk-score, type(s) of TKI therapy, type and duration of last TKI before discontinuation, total duration of TKI therapy and response, time to achieve MMR, relapse data including time to relapse and response to re-initiation of TKI therapy, and analyzed the risk factors for relapse. Study was approved by the institutional review boards of all participating centers.

Results: Fifty-five patients (35 females) with a median age of 40 years (range 16-74) were included in the study. Median age at TKI stop was 48 years (range 21-80). Majority of the patients (48; 87.27%) received imatinib as first line therapy; 29 (53.74) patients were receiving imatinib at TKI-stop, and 26 (47.27) a second-generation TKI (dasatinib or nilotinib). Fifty-two (94.5%) patients discontinued TKI as per clinical practice (shared decision between treating physician and the patient), and 3 (5.5%) stopped because of pregnancy; 2 patients fulfilled the criteria to stop post-delivery as they remained in deep MR, they were offered to continue stopping. One patient refused to restart TKI (dasatinib) after delivery although she had only 24 months of deep response but continues to have deep remission after 91 months of follow up. Median time to achieve MMR after diagnosis was 12 (range 2-164) months. All the patients had achieved MR4.5 or better (complete molecular response) before stop. Median time from diagnosis to TKI stop was 86 months (IQR 60;132) and median time of last TKI before stop was 66 months (IQR 47;114). After a median follow up of 42 months (IQR 12.5;69) post TKI-discontinuation, 15 (28%) patients relapsed. Median time to relapse was 5 months (range 3-38). Most of the relapses occurred during the first 6 months, except 3 patients who relapsed after 10, 11, and 38 months. Most of the relapsed patients had intermediate or high risk Sokal score. All the relapsed patients achieved MMR after a median of 3 months (range 2-6) after restarting TKI. None of the patients progressed to advanced phase.

Conclusion: In real-life practice, TKI discontinuation was possible without relapse for CP-CML patients in deep molecular response, with over two-third of patients continuing in TFR. Majority of the relapsed patients belonged to the intermediate/high-risk score Sokal category at diagnosis. Although this study has the limitation of a retrospective study, our experience in this population confirms that discontinuation of TKI therapy in CP-CML patients is feasible and safe in clinical practice.

Alfayez:Celgene: Research Funding; AstraZeneca: Honoraria, Research Funding; Johnson & Johnson: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Astellas: Honoraria; Amgen: Honoraria; AbbVie: Honoraria, Research Funding.