When should risk stratification occur? Should risk stratification be redone at relapse?
Generally, risk is assessed at the time of diagnosis. That's really the most important time to understand the underlying biology of the myeloma and whether our assessment is that this is going to be more challenging or less challenging and easier to control.
Having said that, myeloma is not a static disease. It evolves over time. The myeloma you start with may not be the myeloma that you have at three, five, ten, or fifteen years. The myeloma cells, when they're treated, can mutate. You can select out, killing all the easy-to-kill myeloma cells, and what you leave behind are the hard-to-kill myeloma cells. It's a genetically unstable disease, so they'll develop new chromosomal abnormalities, and the risk will actually increase over time. Most people understand that the disease can be harder to treat if you've failed multiple prior exposures to effective anti-myeloma medications.
Can a person start as high risk and become standard risk over time?
People can be extremely sensitive to treatment, so you can eradicate the myeloma to the point where you can't even find it anymore. But generally, that doesn't mean that the risk really changes. It's just that your disease is highly sensitive to treatment, which is clearly a good thing, but it doesn't mean that the original genetic or biologic variables that put you into a higher-risk category are not still there.
So we need to distinguish the statistical estimate of risk, and that's all it is—a statistical estimate of outcome, not how you will do, but averages—from disease sensitivity, disease responsiveness, and the durability of that response.
HealthTree • April 9, 2025