How do comorbidities impact treatment decisions? What comorbidities are most prevalent in newly diagnosed myeloma patients

What is a comorbidity?

How do comorbidities impact treatment decisions?

Comorbidities are other health conditions, such as, more commonly, high blood pressure, high cholesterol, diabetes, heart disease that patients have, along with, you know, dealing with their cancer diagnosis, in this case, multiple myeloma.

The average age of diagnosis is in the mid 60s to late 60s, right? And so by that time, high blood pressure is very common. Diabetes is very prevalent.

And because of the multiple myeloma, many patients end up having renal dysfunction. So renal, kidney disease, is a comorbidity that we encounter often. I would say these are the three big ones that we see.

How does diabetes impact myeloma treatments?

Because of their diabetes, we have to be mindful about if patients have longstanding diabetes, that’s not so well controlled. We have to be mindful about peripheral neuropathy because it impacts the choice of therapy we actually give patients. So, you know, diabetes we have to be mindful when it comes to peripheral neuropathy.

But we also have to be mindful about how we dose steroids. Oftentimes in a newly diagnosed multiple myeloma patient when the disease burden is very high, that means there’s a high plasma cell percentage in the bone marrow. Their light chains are very high or the M spike is very high. We want to hit it very hard, go aggressive. And if usually you’re under 70 years of age, I utilize, at least in the first cycle, 40mg weekly of dexamethasone, which is a hefty dose. And if you have a concurrent diabetes diagnosis, then you’re going to have issues with blood sugars, essentially.

And, if I have time, that means I’m not in an urgent setting to start treatment right away. Oftentimes, we utilize the help of our diabetes specialists within the cancer center. So we have a dedicated nurse practitioner who helps us manage mostly diabetes in our patients. Or I will have them go to their primary endocrinologist or primary care in terms of guidance on or before or the days after their dexamethasone dosing, on how to take their insulin or how to increase their hypoglycemic, what sort of diet they should be taking around that time.

So we’re very, very mindful often over the age of 70 because, you know, steroids are sometimes very, very hard to tolerate. I drop the dose down to 20mg and, so it’s at least half and but even with that, I’m very mindful about the sugar.

How does heart disease impact myeloma management?

Heart disease can have a significant impact in the management of multiple myeloma patients. Many of the drugs that we give can or are associated with cardiac toxicity. In the case of carfilzomib, it’s associated with the raising of blood pressure. So hypertension, it can also cause systolic heart failure, or raise the pressure between your pulmonary vasculature that communicates with the heart, called pulmonary hypertension.

So if there’s already preexisting conditions such as this, then we want to minimize further exposure to agents that will cause further damage. We at UT Southwestern are very lucky because we have a very comprehensive cardiology program and we have a cardio oncology team and the CHF team that helps manage our amyloidosis patients.

Cardio oncology, especially when we have patients where we have difficulty to control high blood pressure or they have a preexisting CAD, they’ve had a stent placed, and we want to take them to stem cell transplant. Our cardio oncology colleagues will see them right away. And these sort of will help us, put them on goal directed, medical therapy for heart failure to have their heart function improve if they have low.

And they sort of just guide us along on how we treat. So I’ve actually utilized their help multiple times.

How does renal dysfunction impact myeloma management?

So renal dysfunction. Well, first thing you have to know is what is causing the renal dysfunction. Is it another comorbidity like let’s say they have diabetes inducer hypertension and do you know CKD in the older patients? Or is it actually because they have the light chains that are so high that are sort of clogging up the renal tubules called light chain cast nephropathy.

So you have to understand the etiology, because if it’s light chain cast nephropathy, you’re going to be very aggressive because reducing the light chain burden is actually going to help them recover their renal function faster. But once you sort out this initial first one month or so of treatment, when patients do have light chain cast nephropathy, what is, you know, daratumumab is used up front many times nowadays. That isn't really required.

Renal adjustment would renal function. Even Valcade does not. Dexamethasone does not, however revlimid does. So, you have to adjust the dose based on the creatinine clearance, because the higher dose means that revlimid will hang around longer. And then hence you can have more side opinions. So you worry about toxicity when you're giving them a higher dose. And they need with based on their kidney function actually.

So, we have, you know, I often calculate that myself or I will utilize the help of my pharmacist, in reducing the dose. And as and that's what we do.

Do comorbidities influence fitness/frailty scoring? When we make a decision on who's fit or frail, it's, although we don't always outline it psychologically in our heads. You know, where there's, like, a running list, what the patient has, how is your heart looking? Number one thing we look at, right. Can they if they want to go to transplant especially do they have good heart function? And if they don't, well then I'm going to get them to see their cardiologist. And maybe I'm not going to have I'm not going to be as aggressive about pursuing stem cell transplant right away. So comorbidities do impact our initial decision making and whether a person is fit or frail.

And I think we have to take a step back and delineate is the frailty because of their disease? Because they're you want to be aggressive or is they were frail to begin with. So during my encounters with my newly diagnosed patients, I sit with them and I ask them, what was your, how were you doing before everything went south? What was your quality of life like? Where you walking? Where you active? Where you doing those? I think that gives me a big insight into their fitness.

Many of the comorbidities, with the help of the consultants we have, we can actually manage. I have, with the help of our cardio team or infectious disease specialist or, you know, endocrinologist, we can get them through, a lot of the comorbidities in and get them to the more aggressive therapies.

However, fitness and rehabilitation is actually. I consider that a very important part. So if I see that, there's frailty because of disease, well, then you have to address the disease. And patients who have broken, they were not active because, you know, they have a pain in their hip because there's a lesion there, or they have a pain in their spine and they're afraid to move. As the myeloma heals, they get, they get better, they feel better. Their mobility automatic improves, actually.

So they go from that frail from their disease to actually becoming fit. And I know that, you know, I believe Tanya Wildes has done a lot of work in geriatric oncology, particularly relating to myeloma, about that. And I'm very big on cancer rehab. So we have a cancer rehab program over here.

So my frail patients, which I, you know, whether it's disease or underlying, I send them to our cancer rehab program for evaluation and then get them to physical therapy. And we set small goals. And I encourage walking and the steroids have a, you know, side effect as well because they cause proximal muscle weakness. So I tell my patients to be active so that, you know, physical fitness plays a big role. I believe.

What comorbidities are most prevalent in newly diagnosed myeloma? Comorbidity is a chronic disease that is not myeloma, that you have besides your myeloma. You can say that it could be chronic pulmonary lung disease. It can be congestive heart failure or diabetes, and other cancers as well. So this is competitive.

Yeah, I can tell you a little bit about what it is in Denmark because I think that comorbidities varies from culture to culture. But what we do have, and we did a study again on the Danish Quality Database, where we looked at newly diagnosed myeloma patients and comorbidity. And what was interesting was that, one year preceding the diagnosis, there was an increase in comorbidities. And there is comorbidities like kidney failure, which is part of the myeloma disease, but also congestive heart failures, chronic pulmonary lung diseases, diabetes.

Was there, and in total, 40% of the patients had comorbidities at diagnosis. So that's a lot of patients with comorbidities as early in their myeloma history, because it also develops throughout their history due to treatment.

How do comorbidities impact treatment decisions? You do modify treatment because you don't choose a drug that will give you neuropathy. If you have neuropathy. And if you, for example, also have had a previous pulmonary embolism, then you are reluctant with the, you may say it can be done, but you have to be very careful.

And I think that today where you have so many treatment options, I mean, it's the patients do better, patients that have comorbidities, for example, chronic pulmonary diseases and heart diseases that are severe. They cannot go to a transplant. And a transplant is still the first option for younger patients in Scandinavia. I know it's changing in U.S. but it's still what we do here.

And then you have to treat them otherwise. And with the standard treatments that I available for us and modifying the treatment.