Treatment-free remission in chronic myeloid leukemia patients treated front-line with nilotinib: 10-year followup of the GIMEMA CML 0307 study

• Published in: Haematologica (Roma) Vol. 107; no. 10; pp. 2356 - 2364
• Main Authors: Gugliotta, Gabriele, Castagnetti, Fausto, Breccia, Massimo, Levato, Luciano, Intermesoli, Tamara, D'Adda, Mariella, Salvucci, Marzia, Stagno, Fabio, Rege-Cambrin, Giovanna, Tiribelli, Mario, Martino, Bruno, Bocchia, Monica, Cedrone, Michele, Trabacchi, Elena, Cavazzini, Francesco, Porretto, Ferdinando, Sorà, Federica, Simula, Maria Pina, Albano, Francesco, Soverini, Simona, Foà, Robin, Pane, Fabrizio, Cavo, Michele, Saglio, Giuseppe, Baccarani, Michele, Rosti, Gianantonio
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.10.2022
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Humans; Leukemia, Myeloid, Chronic-Phase - drug therapy; Middle Aged; Progression-Free Survival; Pyrimidines - adverse effects; Treatment Outcome; Young Adult
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2021.280175

We report the final analysis, with a 10-year follow-up, of the phase II study GIMEMA CML 0307 (NCT 00481052), which enrolled 73 adult patients (median age 51 years; range, 18-83) with newly diagnosed chronic-phase chronic myeloid leukemia to investigate the efficacy and the toxicity of front-line treatment with nilotinib. The initial dose was 400 mg twice daily; the dose was reduced to 300 mg twice daily as soon as this dose was approved and registered. The 10-year overall survival and progression- free survival were 94.5%. At the last contact, 36 (49.3%) patients were continuing nilotinib (22 patients at 300 mg twice daily, 14 at lower doses), 18 (24.7%) patients were in treatment-free remission, 14 (19.2%) were receiving other tyrosinekinase inhibitors and four (5.5%) patients have died. The rates of major and deep molecular responses by 10 years were 96% and 83%, respectively. The median times to major and deep molecular response were 6 and 18 months, respectively. After a median duration of nilotinib treatment of 88 months, 24 (32.9%) patients discontinued nilotinib while in stable deep molecular response. In these patients, the 2-year estimated treatment-free survival was 72.6%. The overall treatment-free remission rate, calculated on all enrolled patients, was 24.7% (18/73 patients). Seventeen patients (23.3%), at a median age of 69 years, had at least one arterial obstructive event. In conclusion, the use of nilotinib front-line in chronic phase chronic myeloid leukemia can induce a stable treatment-free remission in a relevant number of patients, although cardiovascular toxicity remains of concern.