How Many Chronic Myeloid Leukemia (CML) Patients in Chronic Phase (CP) Benefit from Treatment Free Remission? a Single Center Real-Life Experience
Authors: D'Adda Mariella , Cancelli Valeria , Terlizzi Sofia , Pelizzari Annamaria , Ferrari Samantha , Bertoli Diego , Bottelli Chiara , Bianchetti Nicola , Peli Annalisa , Accarino Ilaria , Giupponi Carlotta , Tucci Alessandra 
Published: December 2024

Background: Treatment free remission (TFR) is currently one of the main goals of CML therapy and data of literature show that 40-60% of patients (pts) that discontinue tyrosine kinase inhibitors (TKI) after a sustained deep molecular response (sDMR) of at least 2 years remain in TFR. Few data are available about second TFR for pts that fail a first TKI discontinuation and another topic not so clear is how many pts with newly diagnosed CML will achieve a successful TFR.
Aim: To describe the TFR theme in CML-CP pts followed in our center
Methods: We evaluated all consecutive CP-CML pts treated with TKI in our center from 2000 to mid 2024. The main criteria for 1st TKI discontinuation were at least 5 years of TKI therapy and at least 2 years of sDMR. Even for 2nd TKI discontinuation a sDMR of at least 2 years was required.
Results: The total number of CP-CML pts referred to our center was 311. From 2000 to the present date, 60 (19%) pts died, 10 of them for CML related cause; 11 pts were lost at follow up and 240 pts are presently in follow up (in TKI treatment or in TFR). Among these 240 pts, 123 were male and 117 were female; the median age at CML diagnosis was 53 (13-86) years (y), median follow up from the beginning of TKI therapy to the last follow up 103 (1-270) months (mo). 1 hundred sixty-three out of 240 pts had TKI treatment of 5 y or more; 115/163 (70%) pts reached a sDMR of at least 2 y, that is the other criteria for TKI discontinuation, and they stopped treatment. Imatinib and 2nd generation TKI (2GTKI) represented 1st line therapy respectively in 73 and 42 of the pts that entered 1st TKI discontinuation attempt, but 19/73 (26%) of pts initially treated with imatinib and 11/42 (26%) of pts initially treated with 2GTKI were on 2nd or 3rd line therapy at the moment of TFR. At the time of 1st TKI discontinuation median age was 63 years (20-85), median time from TKI start 113 months (60-172), median duration of sDMR 60 months (24-153). After a median follow up of 82 mo from 1st TKI discontinuation, 70/115 (61%) pts remain in TFR without treatment, while 45/115 (39%) pts lost major molecular response. The relapsed pts resumed TKI treatment and in 42/45 cases regained DMR: 17 (40%) of these 42 pts, with a median 2nd sDMR of 62 (32-86) mo, entered a 2nd TKI discontinuation. Thirteen out of 17 (76%) pts that attempted a 2nd TKI withdraw, remained in TFR after a median follow up of 14 (2-47) mo from 2nd TKI discontinuation. Overall, among 163 pts with a newly diagnosed CP-CML treated with TKI for at least 5 y, 70 (43%) achieved a successful durable 1st TFR and 13 (8%) were in 2nd TFR. No pts in 1st and 2nd TFR progressed to accelerated/blast phase.
Conclusion: Our experience shows that in real-life setting, TFR appears an achievable goal for about half of newly diagnosed CP-CML pts.