Case 3: Geriatric Assessment in Myeloma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Ajai Chari, MD:There is information here on both the ISS [International Staging System] and the revised ISS [R-ISS]. Do you use any of these scores—the prognostic scores or staging scores? Is there any difference in your approach for the patient, from a management perspective, based on these scores?

Alfred Garfall, MD:What I like about the revised ISS staging system is that it integrates both laboratory data and the cytogenetic data. Before this system was around, you had these 2 parallel tracks. You didn’t quite know what to make of patients who were high-risk status by 1 and not the other. With the ability to integrate those 2 into the revised ISS staging system, that system is the most useful.

The effect on management, for me, is along the lines that we mentioned with the previous cases. For patients who have an aggressive presentation and are R-ISS stage III, I’d be more likely to use the quadruplet regimen as part of first-line therapy.

Ola Landgren, MD, PhD:The whole idea of staging goes back to 1975, and that’s like 50 years ago. I think the case that was made was published in theJournal of Cancer, and was based on 71 patients. The assumption was that if there’s more disease, that’s worse than if there is less disease. This was in the era of melphalan and prednisone only. And they showed that there was a difference. Then it took another 25 or 30 years to come up with the ISS, which was based on the beta-2-microglobulin and albumin. This is pooled from clinical trial data, so it’s not the real-world data, looking to see if there were blood markers that could be identified that were associated with a poor clinical outcome, intermediate, and less bad outcome. And with all the better therapies, we are sort of seeing that all these numbers are no longer relevant. The whole staging has basically moved toward genomic signatures. Really, the staging has almost kind of gone away, isn’t that right? What do you think, Ajai?

Ajai Chari, MD:One of the main uses of staging is to show that studies have relatively comparable populations. It’s that interstudy comparison. But at the bedside…

Ola Landgren, MD, PhD:From a clinical point of view, I should probably clarify.

Ajai Chari, MD:This patient is screaming treatment. Whatever the staging is, I would say time is kidney. She has a really impaired clearance, right? And often, I don’t think we appreciate that in older patients. Her creatinine level may be OK, but if it’s a small female, that’s a marked impairment. For me, the clinical features are way more important than the staging.

Ola Landgren, MD, PhD:The volume of disease is not necessarily that important. Would you agree with that?

Nina Shah, MD:Well, yes and no. As you’re saying, is that really reflecting what true risk is? I think what Ajai said before, about how people behave, is actually the most important risk factor. You may find that within 4 weeks. You may find out that answer within 4 weeks—that this person is or isn’t responding. Ultimately, I’d like to have that as part of the staging. You can’t do it initially.

Ajai Chari, MD:Right. I think the other point to make is that we shouldn’t disregard bulk. This patient’s IgA is 7200 [APL], and she’s confused, right?

Nina Shah, MD:Right.

Ajai Chari, MD:We don’t want to just say, “Oh, it doesn’t matter how much myeloma you have.” This could be hyperviscosity. It may require plasmapheresis, given the severity of the symptoms. Obviously we have very effective therapies. I think even though it’s an older patient, it emphasizes, again, that risk-benefit optimization.

Ola Landgren, MD, PhD:I agree with that. I try to be a little provocative here. I was thinking, if we look in our clinics, where we have larger programs, we see a lot of patients. My clinical experience is that in the older category, there is more hyperdiploid disease. This patient does not have evidence of that, but my clinical experience is that there is an enrichment for hyperdiploidy in older patients. I don’t know if you share that perspective with me.

Nina Shah, MD:I haven’t noticed that, but I haven’t been looking for it.

Ajai Chari, MD:Maybe it’s just on the Upper East Side.

Nina Shah, MD:Just in New York. Anyway, if that’s true or not, in hyperdiploid cases the disease can grow slowly, and my clinical experience is that there can be a higher burden of disease until the patient comes to the doctor because the disease has been growing very slowly. But when you give them therapy, the disease could then go away quite quickly with a modern therapy. I’m just sharing perspective that the volume of disease, I think, used to be very, very important when there was only 1 inferior drug. But with newer drugs, I think it’s changing. The genomic markers are probably more important.

Nina Shah, MD:Yeah, we all have patients like that who have 90% infiltration of the bone marrow, and it turns out they were just a marathon runner and they didn’t notice it until then.

Alfred Garfall, MD:Yeah, there’s the volume of the disease and the problems it’s causing. Then we have the patients who are 100% plasma cells and might have very severe anemia but no other problems. In this patient, we have hypercalcaemia, confusion, renal insufficiency, bone lesions.

Ola Landgren, MD, PhD:These are the biggest problems. I agree with that. So what about the whole literature on geriatric patients? Is there an age cutoff for that? When do you call a patient a geriatric patient? When do you need to think about adjusting factors? Is age really the major determinant, or are there other factors?

Nina Shah, MD:Well, I think we always say that age is just a number. I think age gives us a time to start thinking about things. We all have a 52-year-old patient who looks as if they’re age 74; and a 74-year-old patient who looks as if they’re age 40. Age is a guide to start thinking, but it is not a cutoff. We traditionally think about age 70, to be age 65, and in Europe it is. But we’ve all transplanted patients older than age 70. We’ve all been aggressive on patients older than age 70.

And so these newer myeloma-based geriatric risk tools that are used should be employed more. I know I am actually guilty of not doing it enough, because we all get confident. We look at a patient and we think, “Oh no, no, no,” or, “Yes.” But we really should be more regimented about applying these tools, myself included. There are patients who really need to get treatment, but some who may not tolerate it. Our first rule is to do no harm. So I think these tools are very important.

Transcript edited for clarity.