Format

Send to

Choose Destination
Clin Cancer Res. 2017 Aug 1;23(15):3980-3993. doi: 10.1158/1078-0432.CCR-16-2895. Epub 2017 Apr 20.

The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. kenneth_anderson@dfci.harvard.edu.
2
Multiple Myeloma Research Foundation, Norwalk, Connecticut.
3
Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
4
CCS Associates, Inc., San Jose, California.
5
Laboratoire d'Hématologie, Pôle Biologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
6
Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
7
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
8
Memorial Sloan Kettering Cancer Center, New York, New York.
9
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
10
Seragnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy.
11
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
12
Translational Medicine, Oncology, Takeda Pharmaceuticals, Cambridge, Massachusetts.
13
Division of Molecular Genetics and Pathology, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiologic Health, U.S. Food and Drug Administration, Silver Spring, Maryland.
14
Illumina, Inc., San Diego, California.
15
Department of Hematology, Morsini College of Medicine, University of South Florida, Tampa, Florida.
16
Scientific Collaborations, Celgene Corporation, Summit, New Jersey.
17
Precision Cancer Care Program, Inova Schar Cancer Institute, Falls Church, Virginia.
18
Translational Medicine, Adaptive Biotechnologies, Seattle, Washington.
19
Medical Sciences, Amgen Inc., Thousand Oaks, California.
20
Central Nebraska Myeloma Support Group, Grand Island, Nebraska.
21
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
22
US Medical Oncology, Bristol-Myers Squibb, Princeton, New Jersey.
23
Translational Research, Oncology, Janssen Research & Development, Spring House, Pennsylvania.
24
BioOncology, Genentech Inc., South San Francisco, California.

Abstract

Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next-generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10-5 to 10-6 cells. These technologies may be combined with functional imaging to detect MRD outside of bone marrow. Moreover, immune profiling methods are being developed to better understand the immune environment in myeloma and response to immunomodulatory agents while methods for molecular profiling of myeloma cells and circulating DNA in blood are also emerging. With the continued development and standardization of these methodologies, MRD has high potential for use in gaining new drug approvals in myeloma. The FDA has outlined two pathways by which MRD could be qualified as a surrogate endpoint for clinical studies directed at obtaining accelerated approval for new myeloma drugs. Most importantly, better understanding of MRD should also contribute to better treatment monitoring. Potentially, MRD status could be used as a prognostic factor for making treatment decisions and for informing timing of therapeutic interventions. Clin Cancer Res; 23(15); 3980-93. ©2017 AACR.

PMID:
28428191
DOI:
10.1158/1078-0432.CCR-16-2895
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center