Second-Line Bosutinib In Elderly Cml Patients: Final Results Of Best Study

Introduction: The median age of CML patients failing a first-line TKI because of resistance or intolerance is higher than 60 years Bosutinib (BOS), dasatinib (DAS) and nilotinib (NIL) have similar second-line efficacy, but in elderly patients DAS and NIL toxicity is more frequent and more clinically relevant BOS safety profile may be an added value in this setting, but the approved initial dose of 500 mg OAD may be higher than necessary Aims: All TKIs have been tested in CML patients at a fixed initial dose, with dose reductions in case of toxicity On the contrary, the aim of our study was to evaluate the efficacy and the tolerability of low-dose second-line BOS in elderly CML patients, using the molecular response at given timepoints to increase the dose only in selected patients, thus finding the minimum effective dose Methods: A prospective phase 2 single-arm multicenter study has been designed by the GIMEMA CML Working Party (NCT02810990) Study design: All patients started BOS 200 mg OAD for 2 weeks (ârun-inâ period), then the dose was increased to 300 mg OAD;after 3 months, patients with BCR-ABLIS transcript ≤ 1% continued 300 mg OAD, while in patients with transcript \u003e 1% the dose is furtherly increased to 400 mg OAD, in absence of relevant toxicity The primary endpoint was the rate of MR3 at 12 months Key inclusion criteria: \u003e 60 yrs old, chronic phase CML, intolerance or failure of any first-line TKI (2013 ELN criteria), absence of T315I or V299L mutation Results: Sixty-three patients have been enrolled Median age: 73 yrs (range 60-90) Reasons for switching to BOS: Intolerance 63%, resistance 37% First-line TKI: Imatinib 83%, DAS 11%, NIL 6% All patients reached at least 1-year observation Due to the emergency situation caused by SARS CoV2 spread in Italy, few data are still missing, but final results will be presented onsite Maximum BOS dose: 400 mg OAD, 19%;300 mg OAD, 76%;200 mg OAD, 5% At baseline, 17% of patients were already in MR3;MR3 rates at 3, 6 and 12 months were 44%, 54% and 59%, respectively The cumulative rate of patients achieving or maintaining a MR3 by 12 months was 67%;patients achieving MR4 or MR4 5 by 12 months were 44% and 24%, respectively Overall, 30%, 29% and 8% of patients had 1 log, 2 logs or \u003e 3 logs reduction from baseline BCR-ABLIS transcript level (67% of patients had a molecular improvement from baseline) Selected adverse events: Acute coronary syndromes, 4 patients;pericarditis, 2 patients;peripheral arterial thrombosis, 1 patient;no pleural effusions were observed Events leading to permanent treatment discontinuation: 2 unrelated deaths, 7 adverse events, 4 unsatisfactory responses (without progressions), 1 second neoplasia Fourty-nine patients are still on BOS at the last contact: 10% of them on 400 mg OAD, 61% on 300 mg OAD, 29% on 200 mg OAD Conclusions: These results trial showed that in elderly patients intolerant to or failing a first-line TKI BOS may be highly effective and better tolerated at a dose lower than 500 mg OAD, namely at 300 mg OAD