Differentiating factors in treatment-free remission trials: impact of study design on results and clinical applications

Abstract

For patients with chronic myeloid leukemia in chronic phase with sustained deep molecular responses on long-term tyrosine kinase inhibitor (TKI) therapy, treatment-free remission (TFR) feasibility has been established. TFR is now a treatment goal for patients meeting specific criteria; NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for CML have developed criteria for attempting TFR outside clinical trials, and TFR was added to the US Food and Drug Administration–approved nilotinib label. Importantly, TFR studies vary in design and characteristics of participating patients. We discuss key study design elements to consider when assessing results from TFR trials, including criteria for attempting TFR, characteristics of enrolled patients, use of a consolidation phase (whereby patients continue TKI treatment on study before attempting TFR), and criteria for restarting TKI therapy. Finally, we review the criteria outlined in the NCCN Guidelines^® for TFR outside clinical trials and compare to criteria used in TFR studies.

Keywords:

• Chronic myeloid leukemia
• clinical trial
• imatinib
• nilotinib
• treatment-free remission
• tyrosine kinase inhibitor

Acknowledgments

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Christopher Edwards, PhD, and Karen Kaluza Smith, PhD, of ArticulateScience LLC for their medical editorial assistance with this manuscript. The author had full control of the content and made the final decision for all aspects of this article.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1535114.

Additional information

Funding

Novartis: personal fees during the conduct of the study; Incyte: personal fees outside the submitted work; Pfizer: grants and personal fees outside the submitted work; Jazz: grants outside the submitted work; Agios: personal fees outside the submitted work; Celgene: personal fees outside the submitted work.