Outcomes for patients with multiple myeloma have improved drastically, not least because of the availability of novel triplet, and now quadruplet regimens. In this OncLive® Peer Exchange discussion today I am joined by a superb panel of experts in the field of myeloma research. Today we will discuss modern approaches to management and we’ll reflect from the latest data, including information from the ASH [American Society of Hematology] 2019 annual meeting.

My name is Dr Paul Richardson, and I’m the R.J. Corman professor of medicine and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.

It’s truly my pleasure to welcome and participating today on our distinguished panel:

Dr Ajai Chari, associate professor of medicine and director of clinical research at the Multiple Myeloma Program in the Icahn School of Medicine at Mount Sinai in New York, New York;

Dr Amrita Krishnan, who directs the Judy and Bernard Briskin Center for Multiple Myeloma Research and Stem Cell Transplantation in the City of Hope Comprehensive Cancer Center in Duarte, California;

Dr Sagar Lonial, professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta, Georgia;

Dr Nina Shah, hematologist at the Hematology and Blood and Marrow Transplant Clinic and associate professor at the University of California San Francisco in San Francisco, California;

And last but not least, Dr Ken Shain, assistant member in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida.

Thank you so much for joining us, and please let’s begin.

In our first segment we’re going to talk today about newly diagnosed multiple myeloma, and it’s really my pleasure to ask Dr Sagar Lonial to lead this discussion. Let’s start with the emerging data about high-risk asymptomatic myeloma, and should these patients receive treatment?

Sagar Lonial, MD, FACP: Smoldering myeloma is an area where there’s been intense interest of late, and I think part of this is recognition of the fact that not all smolders are the same, and being able to more adequately risk stratify patients into groups of patients that are low risk, intermediate risk and high risk. Now a lot of the interest in trials in smoldering was started almost 6 years ago now when the Spanish group published data on LEN/DEX [lenalidomide, dexamethasone] versus observation and demonstrated PFS [progression-free survival] benefit as well as overall survival [OS] benefit. Despite that OS benefit, it was not widely adopted because I think they used older imaging techniques, so we were concerned that some of those patients had myeloma as opposed to smoldering. We were waiting on additional data.

The ECOG [Eastern Cooperative Oncology Group] group published recently lenalidomide versus observation where every patient had modern imaging. The take-home message was the same hazard ratio for PFS benefit was shown in the ECOG trial. It’s too early for overall survival. I think most importantly what we did in that trial was go back and try to identify who were the highest risk of people. If you look at the current Mayo Clinic 2018, 20/2/20 criteria: 20% plasma cells, M protein greater than 2, and free light chain ratio greater than 20.

If you look at just those patients who fit the high risk, the hazard ratio for lenalidomide versus observation was 0.09. A 91% risk reduction in that trial, which I think has introduced us to an era now where it’s reasonable to consider early therapy with either lenalidomide or lenalidomide, dexamethasone, and limited duration. Both our trial and the Spanish trial recommend 2 years of therapy and then discontinuation.

Dr Jesus San Miguel MD, PhD on behalf of the IMF [International Myeloma Foundation] presented an updated risk stratification piece at ASCO [the American Society of Clinical Oncology annual meeting] last year where it’s basically a scoring system. There are 11 criteria, and you add up the points and you figure out where you are. There was a higher-risk group than the 20/2/20 criteria that the Mayo Clinic has published. To be honest with you, I can’t remember all the things that get points. I think it’s not as easily usable, it’s not as practical as the 20/2/20 criteria are. It is a little bit more accurate at predicting the highest-risk group of patients. At least from my view I think it’s a little bit more challenging.

Paul G. Richardson, MD: Nina Shah, I’d love your comments on that because I agree absolutely, Sagar, the challenge with smoldering myeloma is the dissection of real risk. In my experience, one of the most important aspects is the evolution of disease over time. A key aspect apart from just the hard information, 20/2/20, is monitoring the patient over a period of time and then determining where you think the patient is going. Nina, in your practice, how do you embrace the risk stratification criteria?

Nina Shah, MD: I think Sagar brought up some good points. One thing I like about the 20/2/20 is that it’s easy, at the end of the day we just want to do the best in the shortest amount of time, so that’s the good thing.

We’re still having a little bit of difficulty understanding, because overall survival data have not been matured, who is really going to, if we use the 20/2/20 and treat people, are those people going to benefit in overall survival? That’s just the limitation of time. Other things that have been interesting and I think are coming through, for example, isatuximab, potentially to have a little bit of way to reduce disease. All of the studies that looked at smoldering myeloma with some treatment, with the exception of GEM-CESAR, use treatment that’s not “therapy” that we get from myeloma, like single agent, stuff like that, non-triplet. Looking at response rates is not relevant in that way. You’re comparing apples to oranges, and you really do need to look at the long-term curve. I’m looking forward to seeing the longer-term follow-up from the ECOG data, and understanding if maybe quality of life, which was looked at, we have more information on.

Transcript Edited for Clarity