Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib

• Published in: Blood 2014-07, Vol.124 (5), p.729-736
• Main Authors: Hughes, Timothy P., Lipton, Jeffrey H., Spector, Nelson, Cervantes, Francisco, Pasquini, Ricardo, Clementino, Nelma Cristina D., Dorlhiac Llacer, Pedro Enrique, Schwarer, Anthony P., Mahon, Francois-Xavier, Rea, Delphine, Branford, Susan, Purkayastha, Das, Collins, LaTonya, Szczudlo, Tomasz, Leber, Brian
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Benzamides - administration & dosage; Benzamides - adverse effects; Drug Substitution; Female; Fusion Proteins, bcr-abl - antagonists & inhibitors; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Time Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-12-544015

Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials–Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1IS ≤0.0032%; MR4.5) and those without major molecular response at study start, MR4.5 by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877. •Nilotinib induced deeper molecular responses than continued imatinib in patients with minimal residual disease on long-term imatinib.•These deeper responses may enable more patients to benefit from treatment-free remission trials.