Treatment patterns and deep molecular response in chronic phase – chronic myeloid leukemia patients treated with second-line nilotinib or dasatinib: a multi-country retrospective chart review study

Abstract

Achievement of MR4.5 (BCR-ABL1 ≤ 0.0032% on international scale) is an important goal of tyrosine kinase inhibitor (TKI) treatment for patients with chronic myeloid leukemia (CML). This study describes treatment patterns by region and assesses time to achieve MR4.5 in patients with CML – chronic phase (CP) treated with second-line nilotinib or dasatinib in 10 countries. A multivariate Cox proportional hazards model was used to assess time to MR4.5 for nilotinib versus dasatinib. The model accounted for the competing-risk event of TKI resistance, included random effects for country clustering, and was adjusted for baseline covariates. The study included 280 patients treated with either nilotinib (N = 135 [48%]) or dasatinib (N = 145 [52%]) as second-line TKI with median treatment durations of 19.1 and 18.7 months, respectively. Nilotinib was observed to be better in achieving MR4.5 than dasatinib (adjusted hazard ratio = 1.37, 95% CI [1.11, 1.69]) suggesting second-line nilotinib may perform better in achieving MR4.5 than dasatinib.

Keywords:

• Chronic myeloid leukemia
• tyrosine kinase inhibitor
• targeted therapies
• nilotinib
• deep molecular response

Acknowledgments

The authors thank Giuliana Zaccardelli for her analytical support and Camara Sharperson and Jessica Marden for their writing and editorial support to the study.

Author contributions

LH, MD, and SN made substantial contributions to the analysis and interpretation of data and drafting the manuscript. MSD made substantial contributions to study conception and design, analysis and interpretation of data, and revising the manuscript critically for important intellectual content. EM, PB, DD, and DC made substantial contributions to study conception and design, interpretation of data, and revising the manuscript critically for important intellectual content. JC made substantial contributions to study conception and design, interpretation of data, and revising the manuscript critically for important intellectual content. All authors have given final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Disclosure statement

JC has received consulting fees from Novartis Pharmaceuticals Corporation. LH, MD, SN, and MSD are employees of Analysis Group, Inc., a consultancy that has received research funding from Novartis Pharmaceuticals Corporation for this and other studies. PB, DD, DC, and EM are employees and stock holders of Novartis Pharmaceuticals Corporation.

Additional information

Funding

This research was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, US.