Nilotinib for the frontline treatment of Ph+ chronic myeloid leukemia

• Published in: Blood 2009-12, Vol.114 (24), p.4933-4938
• Main Authors: Rosti, Gianantonio, Palandri, Francesca, Castagnetti, Fausto, Breccia, Massimo, Levato, Luciano, Gugliotta, Gabriele, Capucci, Adele, Cedrone, Michele, Fava, Carmen, Intermesoli, Tamara, Cambrin, Giovanna Rege, Stagno, Fabio, Tiribelli, Mario, Amabile, Marilina, Luatti, Simona, Poerio, Angela, Soverini, Simona, Testoni, Nicoletta, Martinelli, Giovanni, Alimena, Giuliana, Pane, Fabrizio, Saglio, Giuseppe, Baccarani, Michele, GIMEMA CML Working Party
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Female; Fusion Proteins, bcr-abl - drug effects; Hematologic and hematopoietic diseases; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Pyrimidines - therapeutic use; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-07-232595

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.