Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice.

Abstract

It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P<0.001). Eighty-eight percent of patients discontinued as per clinical practice, and reasons for stopping treatment were: toxicity (20%), pregnancy (6%), and shared decision between treating physician and patient (62%). After a median follow up of 34 months (range, 12-161) overall estimated TFR was 62% (95%CI: 56;68). At 12 months, TFR was 68% (95%CI: 62;74) for imatinib, 73% (95%CI: 64;83) for second generation TKI. Overall median time to restart treatment was six months (IQR 4;11). No progressions occurred. Although our study has the limitation of a retrospective study, our experience within the Italian population confirms that discontinuation of imatinib and second generation TKI is feasible and safe in clinical practice.

• Authors: Carmen Fava, Giovanna Rege-Cambrin, Irene Dogliotti, Marco Cerrano, Paola Berchialla, Matteo Dragani, Gianantonio Rosti, Fausto Castagnetti, Gabriele Gugliotta, Bruno Martino, Carlo Gambacorti-Passerini, Elisabetta Abruzzese, Chiara Elena, Patrizia Pregno, Antonella Gozzini, Isabella Capodanno, Micaela Bergamaschi, Monica Crugnola, Monica Bocchia, Sara Galimberti, Davide Rapezzi, Alessandra Iurlo, Daniele Cattaneo, Roberto Latagliata, Massimo Breccia, Michele Cedrone, Marco Santoro, Mario Annunziata, Luciano Levato, Fabio Stagno, Francesco Cavazzini, Nicola Sgherza, Valentina Giai, Luigia Luciano, Sabina Russo, Pellegrino Musto, Giovanni Caocci, Federica Sorà, Francesco Iuliano, Francesca Lunghi, Giorgina Specchia, Fabrizio Pane, Dario Ferrero, Michele Baccarani, Giuseppe Saglio
• Journal: Haematologica (Haematologica) Vol. 104 Issue 8 Pg. 1589-1596 (08 2019) ISSN: 1592-8721 [Electronic] Italy
• PMID: 30819917 (Publication Type: Journal Article, Observational Study)
• Copyright: Copyright© 2019 Ferrata Storti Foundation.

Chemical References

• Protein Kinase Inhibitors
• Imatinib Mesylate
• Protein-Tyrosine Kinases

Topics

• Adult
• Disease Progression
• Female
• Humans
• Imatinib Mesylate (therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
• Leukemia, Myeloid, Chronic-Phase (drug therapy)
• Male
• Middle Aged
• Pregnancy
• Protein Kinase Inhibitors (therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Retrospective Studies
• Safety-Based Drug Withdrawals
• Treatment Outcome