Association between molecular monitoring and long-term outcomes in chronic myelogenous leukemia patients treated with first line imatinib

Abstract

Objective:

Molecular monitoring using quantitative polymerase chain reaction (qPCR) of BCR-ABL mRNA transcripts using the international scale (IS) is recommended by the National Comprehensive Cancer Network and the European LeukemiaNet for patients with chronic myelogenous leukemia in chronic phase (CML-CP). This study assessed the impact of the frequency of qPCR testing on progression-free survival (PFS).

Research design and methods:

This retrospective chart review of 402 CML-CP patients on first line imatinib therapy, performed by 38 community-based US physicians, analyzed the impact of the frequency of molecular monitoring on the risk of progression and PFS.

Main outcome measures:

Time to progression and progression-free survival.

Results:

Over the 3 year study, 13.2% of patients did not have any qPCR monitoring and 46.3% had 3–4 qPCR tests per year; 5.7% of CML-CP patients progressed to accelerated/blast phase or died. Compared to patients with no qPCR monitoring, those with 3–4 qPCR tests per year had a lower risk of progression (HR = 0.085; p = 0.001) and longer PFS (HR = 0.088; p = 0.001) after adjusting for potential confounders, as did those patients with 1–2 qPCR tests per year (both p < 0.02). Results were consistent after adjusting for Sokal score when available.

Conclusion:

This is the first study to document the clinical impact of frequent molecular monitoring, and the findings underscore the importance of regular molecular monitoring in delivering quality care for CML. These findings could be subject to unobserved confounders.

Keywords::

• Chronic myelogenous leukemia
• Progression-free survival
• Quantitative real time polymerase chain reaction
• Tyrosine kinase inhibitor

Transparency

Declaration of funding

This study was sponsored by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

S.L.G. is a consultant for and receives research support from Novartis Pharmaceuticals Corporation. L.C. and S.G.E. are employees of Novartis Pharmaceuticals Corporation. A.G., A.R.M., N.L., M.K., and E.Q.W. are employees of Analysis Group Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation.

CMRO peer reviewers on this manuscript have received an honorarium for their review work, but have no other relevant financial or other relationships to disclose.

Acknowledgments

We thank Sarah King, an employee of Analysis Group Inc., who contributed to the preparation and editing of the manuscript.

Previous presentation: This study has been presented in part at the 54th ASH Annual Meeting and Exposition, Atlanta, GA, USA, December 8–11, 2012.