VIDEO: Common comorbidities in multiple myeloma

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Comorbidities and myeloma reflect age of patients. I mean, clearly, you know, in the context of understanding the pathobiology of myeloma I think it’s important to just start by appreciating that it’s truly an immunological cancer. So immune deficiency, infection, second cancers — these are part of the landscape of myeloma, unfortunately. The second thing is that with the dysproteinemia, which is such a hallmark of the disease, consequences from that can be myriad, ranging from renal dysfunction, neuropathy, to other end organ injury syndromes, even as broadly speaking as AL amyloid, for example. That can, of course, in its own fashion have cardiac consequences. So, there are a lot of ways to think about the dysproteinemias impacting upon comorbidity. And, of course, the actual direct effects of the disease itself like for example, perhaps the most troublesome from a patient’s perspective is bone pain and bone involvement and lytic bone disease, which could be so debilitating. And then of course we have marrow failure, anemia, leukopenia, thrombocytopenia, and so forth. So there are a lot of issues that could be magnified by virtue of the pathobiology of the myeloma itself. I think, of course, as you just pointed out though, if you’re dealing with a frail or older patient, cardiac, pulmonary, cardiovascular, thromboembolic, all of these issues start to matter. So less toxic approaches that are, you know, tailored to the patient in every sense — be it outpatient, inpatient, adapted to minimize cardiotoxicity, adapted to minimize neuropathy — these are the sorts of factors that play into how we select treatments.

The really exciting news. So, we’ve got the drug classes to meet that, in my opinion. For example, in the proteasome inhibitor space, you know, bortezomib is a mainstay, but neuropathy is its most troubling side effect. Carfilzomib [Kyprolis, Amgen] is a fabulous proteasome inhibitor, but you’ve got to be very careful on the cardiovascular side of things, but it doesn’t cause neuropathy. So, using those two as examples, you can see how you can start to pick and choose what you need to do. The good news about the antibodies, in my opinion, is that they are remarkably well tolerated across most groups of patients, with a caveat of infection being an important one to bear in mind. And then I think perhaps the other mainstay of therapy in myeloma arguably are the immunomodulatory drugs — the so-called IMiDs. And it’s been a privilege to be part of the development of lenalidomide and see the impact it’s had on overall survival globally, let alone in the United States. And at the same time pomalidomide in the same vein. But I would stress to you that we’re learning a lot about that — that immunomodulatory drugs are great in younger patients, great in patients with good robust immunity. Older, frailer patients, who are maybe a little more immune exhausted and have vascular risk, that may be a population in which immunomodulatory drugs are perhaps less effective. Doesn’t mean they don’t help; it just means we recognize their limitations in older patients. And so we need different drugs to meet those different challenges in different age groups.