Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia
Gianantonio Rosti, Francesca Palandri, Fausto Castagnetti, Massimo Breccia, Luciano Levato, Gabriele Gugliotta, Adele Capucci, Michele Cedrone, Carmen Fava, Tamara Intermesoli, Giovanna Rege Cambrin, Fabio Stagno, Mario Tiribelli, Marilina Amabile, Simona Luatti, Angela Poerio, Simona Soverini, Nicoletta Testoni, Giovanni Martinelli, Giuliana Alimena, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, GIMEMA CML Working Party, Gianantonio Rosti, Francesca Palandri, Fausto Castagnetti, Massimo Breccia, Luciano Levato, Gabriele Gugliotta, Adele Capucci, Michele Cedrone, Carmen Fava, Tamara Intermesoli, Giovanna Rege Cambrin, Fabio Stagno, Mario Tiribelli, Marilina Amabile, Simona Luatti, Angela Poerio, Simona Soverini, Nicoletta Testoni, Giovanni Martinelli, Giuliana Alimena, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, GIMEMA CML Working Party
Abstract
Nilotinib has a higher binding affinity and selectivity for BCR-ABL with respect to imatinib and is an effective treatment of chronic myeloid leukemia (CML) after imatinib failure. In a phase 2 study, 73 early chronic-phase, untreated, Ph(+) CML patients, received nilotinib at a dose of 400 mg twice daily. The primary endpoint was the complete cytogenetic response (CCgR) rate at 1 year. With a median follow-up of 15 months, the CCgR rate at 1 year was 96%, and the major molecular response rate 85%. Responses were rapid, with 78% CCgR and 52% major molecular response at 3 months. During the first year, the treatment was interrupted at least once in 38 patients (52%). The mean daily dose ranged between 600 and 800 mg in 74% of patients, 400 and 599 mg in 18% of patients, and was less than 400 mg in 8% of patients. Dose interruptions were mainly due to nonhematologic and biochemical side effects. Myelosuppression was irrelevant. One patient progressed to blastic crisis after 6 months; one went off-treatment for lipase increase grade 4 (no pancreatitis). Nilotinib is safe and very active in early chronic-phase CML. These data support a role for nilotinib for the frontline treatment of CML. This study was registered at ClinicalTrials.gov as NCT00481052.
Source: PubMed