PS1183 THE POTENTIAL IMPACT OF SWITCH TO SECOND GENERATION TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA PATIENTS IN CHRONIC PHASE WHO HAD NO OPTIMAL RESPONSE TO 3 MONTHS OF INITIAL IMATINIB THERAPY

Background: Studies have demonstrated that administration of second generation tyrosine kinase inhibitors (2 nd gen TKIs) in chronic myeloid leukemia (CML) patients (pts) in chronic phase (CP‐CML) had allowed to obtain deeper remissions than with the use of imatinib (IM). Yet with less side effects and being more accessible for pts, IM became a TKI of choice for 1 st line CML therapy. It was also shown that pts with optimal response to 3 months (mo) of TKI therapy ( BCR/ABL1 ≤ 10% on the International Scale (IS) and/or ≤ 35% of Ph‐positive metaphases) have an improved probability of deep molecular responses and superior progression‐free and overall survival (PFS and OS). Still, there are a few data supporting change from IM therapy to 2 nd gen TKI therapy when no optimal response to 3 mo of IM treatment had been achieved. Aims: To evaluate the potential benefits of switching from IM to 2 nd gen TKIs in CP‐CML pts without optimal response to 3 mo of IM therapy. Methods: We conducted open prospective observational study during which CP‐CML pts at Moscow City Hematology Center with full hematological response but with no optimal response ( BCR‐ABL1 > 10% IS and/or Ph‐positive metaphases of > 35%) after 3 mo of IM 400 mg once daily were switched to 2 nd gen TKIs. IM therapy must have been started within 6 mo of the initial CML‐CP diagnosis (dx). A particular 2 nd gen TKI selection was based on a BCR/ABL1 mutational status, patient comorbidity and a drug toxicity profile. A primary endpoint was the rate of major molecular response (MMR) ( BCR‐ABL1 <0.1% IS) at 12 mo after initiation of IM treatment. Secondary endpoints included rates of MMR at 24 and at 36 mo of TKI therapy; and rates of MR 4 , MR 4,5 , PFS and OS at 12, 24 and 36 mo of TKI therapy. Results: Study included 76 CP‐CML pts with no optimal response to 3 mo of IM therapy. Group 1 (G1) included 33 pts (43%) who were switched to 2 nd gen TKIs (dasatinib: n = 19; nilotinib: n = 12, bosutinib: n = 2), while the rest of pts (group 2 – G2) (n = 43, 57%) continued with IM. In G1, 17 (52%) were males и 16 (48%) – females, median age at CML dx was 55 (range 20 – 82) years, median follow‐up time at the time of analysis was 39 mo. G2 comprised of 21 (49%) males и 22 (51%) females, median age at CML dx was 57 (range 22 – 81) years, median follow‐up time was 56 mo. At 12, 24 and 36 mo of TKI therapy: Respective rates of MMR were: 39%, 67% and 76% in G1 pts, and 12%, 19% and 35% in G2 pts ( P  < 0.05). Respective rates of MR 4 were: 21%, 39% and 48% in G1 pts, and 7%, 12% and 16% in G2 pts ( P  < 0.05). Respective rates of MR 4,5 were: 12%, 21%, and 36 % in G1 pts, and 5%, 7% and 14% in G2 pts ( P  < 0.05). At the same time points, PFS in G1 pts was 91% (at each time point), and in G2 pts ‐ 95%, 93% and 91%, respectively. At 12 and 24 mo of therapy, OS at both groups was the same (100%). At 36 mo of therapy, 97% of G1 pts and 92% of G2 pts remained alive. Summary/Conclusion: Switch to 2 nd gen TKIs of CP‐CML pts who had no optimal response to 3 months of initial imatinib therapy has improved their rates of MMR, MR 4 and MR 4,5 . After 36 mo follow‐up, no statistically significant differences were seen in PFS and OS. Longer follow‐up and larger number of pts enrolled are required to fully assess the potential benefits of such treatment change.