DP131 | TREATMENT-FREE REMISSION AFTER PONATINIB: AN ITALIAN CAMPUS CML EXPERIENCE

Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) approved in Italy for treatment of Chronic Myeloid Leukemia (CML) previously treated with one or multiple TKIs. Data on ponatinib discontinuation are limited and further studies are needed to assess its potential for treatment free remission (TFR). We collected data of 33 pts from 15 Italian centers who attempted TFR after ponatinib treatment. Median age at diagnosis was 44 yo, 56 yo at ponatinib discontinuation. Sokal score was available for 28 pts: 10, 6 and 12 pts were low, intermediate and high risk respectively. 12 pts were treated with ponatinib in 2nd, 13 in 3rd, 7 in 4th, 1 in 5th line. Reason to start ponatinib was intolerance for 10 pts, resistance for 22 pts and loss of major molecular response (MMR) after TFR attempt for 1 pt. At ponatinib start, response was MR1 for 8 pts, MR2 for 15, MR3 for 4 and DMR for 3; 5 pts had a single mutation (F359V, M244V, T315I, E450G, G250E) while 2 pts carried 2 mutations each (Y253H and E499E,Q252R and T267A). Pts received ponatinib for a median time of 48 mos (IQR 37-64). Starting dose was 45 mg for 12 pts, 30 mg for 15 pts and 15 mg for 6 pts. Median time to DMR was 6 mos (IQR3-23). 9 pts had a CV adverse event (1 stroke, 3 myocardial infarction, 1 cardiac angina, 1 venous thrombosis, 2 carotid stenosis, 1 hypertension ), with no correlation with starting dose. Ponatinib dose before discontinuation was 15 mg for all but 2 pts: 1 was dose reduced from 45 to 30 mg, 1 remained on 45 mg. 1 pt discontinued in MR3, 11 pts in MR4, 10 in MR4.5 and 11 in MR5. Median duration of DMR was 35.5 mos (IQR 21.6-47). Reasons for discontinuation were: shared choice (17 pts), intolerance (12 pts), 2ndneoplasia (2 pts), pregnancy (1 pt) and self-suspension (1 pt). 24/33 (72,7%) pts were in TFR at the last follow-up. 9 pts had to resume treatment after a median time of 4 mos (IQR 4-9); of them, 6 were intolerant to ponatinib due to CV adverse events. 8/9 pts reobtained DMR after a median time of 3 mos (IQR 1-3); 1 pt maintained a stable MMR. All pts were alive at last follow-up except for 4 pts, died for non-haematological cancer and heart failure. No pt progressed. After 12 months TFR rate was 70%.(Figure 1) We showed that TFR may be feasible for some pts treated with ponatinib in second or subsequent lines, not only for intolerance. Additional data are needed to better define the characteristics of pts who might benefit from ponatinib with the purpose of TFR.