How many chronic myeloid leukemia patients who started a frontline second-generation tyrosine kinase inhibitor have to switch to a second-line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA).

Massimo Breccia,Marcello Cuomo,Lucia Gozzo,Alessia Cirilli,The Aifa’s Monitoring Registries Group ,Paolo Foggi,Fabrizio Pane,Pier Paolo Olimpieri,Valentina Summa,Paolo Corradini,Odoardo Olimpieri,Pierluigi Russo,Antonietta Colatrella,Alessandra Iurlo

doi:10.1002/cam4.3071

Abstract

ABSTRACTThe frequency of patients who switch to a second‐line therapy from a frontline second‐generation (2gen) tyrosine kinase inhibitor (TKI) such as dasatinib and nilotinib, is still substantially unknown. We retrospectively investigated a large series of chronic phase chronic myeloid leukemia (CP‐CML) patients initially treated with 2gen TKIs monitored through the Italian Medicines Agency (AIFA Agenzia Italiana del farmaco) registries. Overall, 2420 patients were analyzed over a period of 6 years. One hundred and fifty‐seven patients (16.3%) treated with dasatinib and 164 treated with nilotinib (11.3%) have switched to another drug, with an overall frequency of 13.2%. In the dasatinib cohort, 39.4% of patients changed treatment for failure and 36.3% for intolerance as compared to 45.7% and 27.4% respectively in the nilotinib cohort. Overall, the median time to switch due to resistance was 293 days, whereas it was 317 days in case of intolerance. Resistance was observed mainly in younger male patients with high‐risk features, while intolerance was not related to any baseline parameter. After resistance/intolerance to nilotinib, the majority of patients switched to dasatinib (53.8%) whereas in case of frontline dasatinib to ponatinib (43.2%). To the best of our knowledge these data provide the first report on the frequency of discontinuation of frontline 2gen TKIs and on the main causes and pattern of choice to a second‐line therapy in the real‐life setting.

Highlights

The treatment of chronic myeloid leukemia (CML) has drastically changed since the introduction of imatinib, the first-generation tyrosine kinase inhibitor (TKI)
We retrospectively investigated a large series of chronic phase chronic myeloid leukemia (CP-CML) patients initially treated with 2gen TKIs monitored through the Italian Medicines Agency (AIFA Agenzia Italiana del farmaco) registries
According to the only published experience on the outcome of patients resistant/intolerant to a frontline 2gen TKI reported by MD Anderson Cancer Center (MDACC) out of 218 patients treated with dasatinib or nilotinib after a median follow-up of 23 months, 40 patients (18%) discontinued therapy, 25 initially treated with nilotinib (21% of all treated with nilotinib) and 15 (15%) initially treated with dasatinib

Summary

Introduction

The treatment of chronic myeloid leukemia (CML) has drastically changed since the introduction of imatinib, the first-generation tyrosine kinase inhibitor (TKI). Eleven subjects received imatinib as second-line therapy and only two patients switched to third-generation ponatinib.[6] Considering the still persisting paucity of data on frequency and causes of discontinuation from frontline 2gen TKIs and on second-line therapy selection, the aim of this study is to provide a real-life picture on these crucial issues based on a large series of Italian patients from AIFA registries

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Results

Conclusion