The Changing Landscape of Multiple Myeloma Treatment

Few disease states have experienced an increase in available therapeutic options occurring as rapidly as multiple myeloma. Four new agents have been approved for the disease state since 2015,1 and available clinical data show a variety of exciting doublet and triplet combinations available for patients with newly diagnosed, relapsed, or refractory disease. The 5-year survival rate for patients with multiple myeloma has increased from 34% in 2000 to 49% in 2016.2

To gain a better understanding of the newly available options for patients with this hematologic malignancy, Journal of Clinical Pathways spoke with Natalie S Callander, MD, professor of hematology/oncology at University of Wisconsin School of Medicine and Public Health (Madison, WI). Dr Callander contextualized the onslaught of new treatments, and discussed how a practicing hematologist or oncologist should best decide what treatment to use for each individual patient. She offered further insight into the continued use of long-existing treatments, such as autologous stem cell transplantation.

Patients with multiple myeloma frequently relapse or become refractory to treatment. What are some of the considerations that clinicians need to take into account for further treatment following a relapse or the development of refractory disease?

There are some basic rules that many people know. There are lots of talking points out there about how to treat patients with relapsed multiple myeloma, and I think that is a reflection on how complicated this has become, in part because we are doing so much better and people are living so much longer. It also has to do with the fact that we have a lot more treatment choices than we ever used to have, but it can be confusing for people to try and figure out what we should be doing. The first consideration is what kind of relapse you are dealing with. The International Myeloma Working Group put out some guidelines that basically tried to define relapse for myeloma, and used some pretty standard definitions for clinical relapse. That would be a new bone lesion or a fracture, or if the patient has a plasma cytoma; if they present with hyperkalemia or new anemia, or other symptoms that suggest progressive myeloma, such as renal failure. Those are very straightforward, in the sense that patients are clearly having a relapse.

Beyond that, there are more subtle relapses, which people are now terming “biochemical progression.” These are situations where patients really are asymptomatic, but they are starting to show elevations of their monoclonal proteins or their light chains, and you wonder whether you should do something or not. There are some considerations for both groups. Certainly people who have clinical relapse with a new event needs a new intervention — I don’t think that is something to be debated. With a biochemical relapse, there are some more considerations about whether or not the patient can actually be watched for a while. I think that is appropriate when people appear to have a more indolent relapse.

The other question of what is appropriate is, what was their myeloma like in the beginning? Patients who have the revised International Staging System3 stage III disease, or who have bad cytogenetics, or plasma cell leukemia tend to relapse with very aggressive disease. Those are not the patients you are going to watch. Those are certainly the patients that you are going to intervene upon, even if you just have a biochemical response, because they tend to be so refractory. The other considerations can be: are they healthy? Are there other issues? Are they still recovering from side effects from previous treatments? Apart from biochemical vs clinical relapse, a lot of people really pay attention to how long it has been since last treatment. If someone is progressing while in the middle of receiving an aggressive triplet treatment, that is definitely a different situation from someone who was just on observation or low-dose maintenance.

On top of all this, I live and work in a quite rural state, and there are questions I need to ask about this when I am planning treatment. Can the patient get to clinic? Do they have insurance coverage for some of the more expensive oral agents? What is their frailty like—are they what we would consider a frail patient vs a robust patient? And maybe the most important question is, what is the availability for a clinical research trial that might be most appropriate for the patient? This is something of a long list, but I think all of these have to be taken into account.

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