Bosutinib (BOS) for chronic phase (CP) chronic myeloid leukemia (CML) after imatinib (IMA) failure: ≥8-y update of a phase I/II study.

Abstract

7549 Background: BOS is approved for newly diagnosed CP CML and CML resistant/intolerant to prior therapy. In a phase I/II study, BOS showed durable efficacy and manageable toxicity in patients (pts) with CP CML after IMA failure. We report an ≥8-y update of this phase I/II and ongoing extension study. Methods: Pts with CP CML resistant/intolerant to IMA (CP2L) or IMA + dasatinib and/or nilotinib (CP3L) or with accelerated/blast phase (AP/BP) CML or Philadelphia chromosome+ acute lymphoblastic leukemia with prior tyrosine kinase inhibitor (TKI) therapy (ADV) received BOS starting at 500 mg/d. Results: 54/284 (19%) CP2L pts were still on BOS after ≥9 y and 8/119 (7%) CP3L and 5/167 (3%) ADV pts after ≥8 y; 61 CP2L pts discontinued BOS since y 5 and 21 CP3L and 12 ADV pts since y 4. Overall, the most common reason for discontinuation was disease progression/lack of efficacy in CP2L (27%), CP3L (42%) and ADV (50%) pts; last dose before discontinuation was ≥500 mg/d in 59 (21%), 28 (24%) and 46 (28%) pts, respectively. In CP2L pts, median (range) of follow-up was 54 (1–155) mo, treatment duration 26 (<1–155) mo and dose intensity 438 (87–599) mg/d; responses were durable (Table) and overall survival (OS) at 9 y was 74% vs 84% at 5 y. OS at 8 y was 69% in CP3L, 54% in AP CML and 23% in BP CML pts vs 78%, 59% and 23% at 4 y. 55 CP2L, 29 CP3L and 98 ADV pts died on study (10, 3 and 2 since the 4/5-y reports); 15, 5 and 3 had on-treatment transformations to AP/BP. Most common new treatment-emergent adverse events since y 5 in CP2L pts were pleural effusion (n=13), arthralgia (n=12) and increased blood creatinine (n=11). Conclusions: After ≥8 y, BOS continued to show durable efficacy and no new safety signals in pts with CP CML on long-term treatment, providing further support for BOS use after prior TKIs. Clinical trial information: NCT00261846 and NCT01903733 . [Table: see text]