The Clinical Impact of Time to Response in De Novo Accelerated Phase Chronic Myeloid Leukemia (CML-AP)

Abstract 72 [][1] Background: Early (3-month) response is important in chronic phase chronic myeloid leukemia (CML-CP). Whether this applies also to CML in accelerated phase (CML-AP) has not been analyzed. Aim: To describe the impact of time to response on the outcome of patients (pts) with CML-AP. Methods: Frontline tyrosine kinase inhibitor (TKI) therapy was administered on consecutive or parallel clinical trials to 58 CML pts presenting with features of AP at the time of diagnosis, defined as blasts ≥15% (n=8), basophils ≥20%, (n=22), platelets <100×109/L (n=3), cytogenetic clonal evolution (n=22), or more than 1 feature (n=3). 36 pts received imatinib. 22 pts received a 2nd generation TKI (2GTKI) (dasatinib, n = 5 or nilotinib, n= 17).We analyzed the impact of various degrees of molecular and cytogenetic responses at 3, 6, and 12-months on rates of major molecular response (MMR), MR4.5, overall survival (OS), event free survival (EFS), and transformation (to blast phase) free survival (TFS). Results: After a median follow-up of 73 months (range 3 to 142) the overall rate of CCyR was 81% (imatinib 75%, 2GTKI 91%), and MMR 69% (imatinib 64%, 2GTKI 77%). At 3 yrs, TFS was 92%, EFS 90% and OS 87%. At 3 months 43 (81%) out of 53 evaluable pts had achieved a major cytogenetic response (MCyR) (71% of pts treated with imatinib, 95% of pts treated with 2GTKI); BCR-ABL/ABL <10% was achieved in 27 (96%) out of 28 evaluable pts (100% with imatinib, 95% with 2GTKI). At 6 months, 44 (86%) out of 51 evaluable pts had achieved a MCyR (83% of pts treated with imatinib, 90% of pts treated with 2GTKI); BCR-ABL/ABL <10% was achieved in 26 (93%) out of 28 evaluable pts (100% with imatinib, 90% with 2GTKI). The probability of achieving various outcomes: MMR, MR4.5, OS, EFS, and TFS by response at 3 and 6 months are shown in [Table 1][2] and 2. The number of pts evaluable for both cytogenetic and molecular responses at 3 and 6 months were 44 and 45 respectively. Conclusion: Pts with de novo CML-AP have an excellent outcome with TKIs, particularly 2GTKIs. As for chronic phase, pts with deep responses at 3 months (MCyR or BCR-ABL <10%) have the best probability of a favorable long-term outcome, although a few have not achieved MCyR at 3 months. TKIs should be standard for all pts with AP features at the time of diagnosis. | | Ph ≤35% | Ph >35% | |:------- | --------- | -------- | | No. | 41 | 3 | | MMR % | 88 (n=36) | 33 (n=1) | | MR4.5 % | 66 (n=27) | 33 (n=1) | | TFS % | 97 | 67 | | EFS % | 94 | 67 | | OS % | 97 | 67 | Table 1. Outcome probability at 36 months by response at 3 months for pts evaluable by both molecular and cytogenetic responses | | Ph ≤35% | Ph >35% | |:------- | --------- | -------- | | No. | 40 | 5 | | MMR % | 90 (n=36) | 40 (n=2) | | MR4.5 % | 68 (n=27) | 40 (n=2) | | TFS % | 97 | 100 | | EFS % | 97 | 75 | | OS % | 100 | 75 | Table 2. Outcome probability at 36 months by response at 6 months for pts evaluable by both molecular and cytogenetic responses Disclosures: Kantarjian: Novartis Pharmaceuticals Corp: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding. Jabbour: BMS: Honoraria; Novartis: Honoraria; Pfizer: Consultancy. Ravandi: BMS: Honoraria, Research Funding; Novartis: Honoraria. Cortes: Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. [1]: #fn-2 [2]: #T1