CCS Associates’ Caroline Sigman, Howard Higley, and Lata Mukundan are co-authors on an article first published in April 2017 in Clinical Cancer Research: The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications.
Dr. Caroline Sigman is CEO and President of CCS Associates. She has extensive experience in strategic planning for drug biomarker development and management of drug development efforts. Dr. Sigman has specialized knowledge of carcinogenesis, cancer chemoprevention, cancer biomarkers, structure-activity relationships, literature search, critical evaluation of health effects data on chemicals, and research and development strategies for biomedical products.
Dr. Howard Higley is Director of Scientific Affairs at CCS Associates. He has extensive knowledge of clinical/regulatory/intellectual property requirements for successful medical product registration. Dr. Higley has been the study director/principal investigator on more than 125 pilot and good laboratory practice in vivo research studies designed and performed in industry.
Dr. Lata Mukundan is a senior scientist at CCS Associates. She is an immunologist with expertise in multiparametric flow cytometry and its application to minimal residual disease measurement in various hematological malignancies.
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.
The full paper can be found here.