RE-NICE: In Early Chronic-Phase CML With Suboptimal Response to Imatinib, Switching to Nilotinib or High-Dose Imatinib Is Feasible
• RE-NICE: randomized, multicenter, open-label phase III study[1]
Summary of Key Conclusions
• In patients with early chronic-phase chronic myeloid leukemia (CML) and suboptimal response to standard-dose imatinib, cumulative major molecular response (MMR) rates were similar when patients were switched to either nilotinib, high-dose imatinib, or standard-dose imatinib
• Nilotinib treatment showed nonsignificant trend toward increased cumulative MMR rates vs standard dose imatinib
• Intolerable adverse effects associated with high-dose imatinib
o Resulted in 3 patients crossing over to nilotinib
• All patients, regardless of treatment group, maintained a complete cytogenetic response (CCyR) with 100% survival
• Further studies necessary to assess safety and efficacy of early switching to nilotinib or high-dose imatinib in individuals with chronic-phase CML and suboptimal response to imatinib
Background
• IRIS study suggested increased event-free survival in patients who attain MMR to imatinib by Month 18 after treatment vs achieving CCyR with no MMR[2]
• In addition, studies suggest imatinib 400 mg/day produces suboptimal (< 20%) cumulative MMR
• Current study compared the efficacy of nilotinib 400 mg twice daily (BID) or high-dose imatinib 400 mg BID with continued standard-dose imatinib treatment (400 mg once daily [QD]) in patients with early chronic-phase CML and suboptimal response to imatinib
Schematic of Study Design
Eligibility
• Patients with chronic-phase CML who attained CCyR but not MMR after 18-24 months treatment with imatinib 400 mg QD
Baseline Characteristics
Description of Current Analysis
• Primary objective: cumulative MMR by 12 months posttreatment
• Secondary objectives
o Cumulative rate of complete molecular response at 12 months posttreatment
o Time to onset and duration of MMR, MR4.0, and undetectable molecular residual disease (UMRD)
o Rate of loss of MMR and UMRD
o Safety of high-dose imatinib and nilotinib over time
o OS and PFS during 3 years following treatment
• Exploratory secondary objectives
o Identify the presence of BCR-ABL1 mutations before and after respective treatments
• Assess ≥ 20 metaphases with banding techniques to determine cytogenic response
• Enumerate BCR-ABL transcripts by real-time quantitative-polymerase chain reaction (3 log reduction = .1% International Scale) to determine molecular response
• Use sequencing to assess mutational status
• Individuals who were unresponsive (MMR negative by 12 months or loss of MMR at any time) or intolerant crossed over to the opposite treatment
Main Findings
• Early switching from standard-dose imatinib to nilotinib or high-dose imatinib is feasible
• MMR rates increased over time in each treatment group
• CCyR rates remained high with no patient experiencing progressive disease
• Nilotinib treatment showed nonsignificant trend toward increased cumulative MMR rates vs high-dose imatinib
• By Month 36, 90% of patients in the nilotinib arm had achieved MMR
• Significant toxicity observed with high-dose imatinib, causing 4 patients in the imatinib 400-mg BID arm to cross over to nilotinib after 12 months
Other Outcomes
• Grade 3/4 adverse events were infrequent
References
1. Choi SY, Lee SE, Oh YJ, et al. Nilotinib or high-dose imatinib compared with standard-dose imatinib in early chronic phase CML patients who have suboptimal molecular responses to standard-dose imatinib: including updated data from RE-NICE Study. Program and abstracts of the 55th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2013; New Orleans, Louisiana. Abstract 1499.
2. Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010;116:3758-3765.
