ASH Clinical News July 2017 V2 - Page 44

Drawing First Blood We invite two experts to debate controversial topics in hematology and health care. Is MRD Testing Worthwhile in Myeloma? Faith Davies, MD Saad Z. Usmani, MD Disclaimer: The following positions were assigned to the participants and do not necessarily reflect ASH opinions, the participants’ opinions, or what they do in daily practice. Agree? Disagree? We want to hear from you! Send your thoughts and opinions on this controversial issue to 42 ASH Clinical News With the clinically effective treatment regimens now available for myeloma, more patients can achieve deep and sustained responses. The ability to measure minimal residual disease (MRD) during and after treatment has the potential to help guide treatment decisions and predict patients’ likelihood of relapse, but is MRD monitoring ready to be used in routine clinical practice? ASH Clinical News invited Faith Davies, MD, and Saad Z. Usmani, MD, to debate the question, “Is measuring MRD worthwhile in myeloma?” Dr. Davies, professor of medicine and deputy director of the Myeloma Institute at the University of Arkansas for Medical Sciences, will argue on the “pro” side; Dr. Usmani, chief of the Plasma Cell Disorders Program and director of clinical research in hematologic malignancies at Levine Cancer Institute/ Carolinas HealthCare System, will argue on the “con” side. Faith Davies, MD: Recently, a number of new myeloma treatment options have become available, with four new agents receiving U.S. Food and Drug Administration (FDA) approval since 2015: the monoclonal antibodies daratumumab and elotuzumab, the histone deacetylase inhibitor panobinostat, and the proteasome inhibitor ixazomib. This proliferation of options has helped more patients with myeloma achieve a complete response (CR) and, along with these new treatment options, the technology for detecting low levels of disease has also improved to the point that we are able to monitor patients’ MRD effectively. Measuring MRD is informative because patients who achieve an MRD-negative state have a much better prognosis. In a recent meta-analysis of 21 studies that assessed MRD status and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed myeloma, the authors found that patients who achieved MRD- negative status had a PFS nearly twice as long as patients who were MRD- positive (54 vs. 26 months; p<0.001). 1 MRD-negative patients also had longer OS (98 vs. 82 months; p<0.001), and the association between MRD status and survival persisted among patients who achieved CR. There’s no doubt that it is worthwhile for clinicians to measure MRD as a signal of how well patients are responding to treatment and to serve as a guide as to their overall prognosis. Saad Z. Usmani, MD: In principle, yes, MRD testing is a fantastic idea. My concern is that we haven’t fully vetted the available platforms. Even among patients who achieve CR, we don’t know the true measure of underlying residual disease because we still haven’t figured out the op- timal technique for collecting these data. The most common method for detecting MRD in bone marrow (BM) is flow cytometry. However, with this method, we can only obtain a finite number of samples, and the depth of detectable MRD negativity is not optimal. The estimated sensitivity is only 10 -4 ; other methods allow us to detect myeloma cells down to 10 -6 . There is a lot of interest in developing next-generation sequencing (NGS) techniques to measure MRD, with the hope that they will overcome some of the limitations of flow cytometry and polymerase chain reaction assays. This technique isn’t ready to be used routinely in clinical practice and the company producing the only commercially available NGS testing kit is trying to keep pace with the growing sample volumes. And these are just the samples being analyzed from clinical trials, leaving us to wonder what will happen when that workload grows as physicians start incorporating NGS techniques more regularly in their practices. These are the two methodologies of greatest interest right now, but companies are also actively developing other platforms. July 2017