Please explain what comorbidities are and how common comorbidities seen in older MDS patients can affect treatment decisions?
Comorbid conditions or comorbidities are other medical problems besides MDS that can influence both how functional a patient is and also what therapies for MDS can be safely administered. For example, for someone who has advanced kidney failure and is on dialysis, it’s very difficult to know what dose of lenalidomide (Revlimid®) to give them because this drug is eliminated via the kidneys. If the patient has kidney failure, the drug levels might be higher than anticipated.
Other types of organ failure also put patients at increased risk of complications from MDS treatment. For instance, if a patient has emphysema and then gets a pneumonia resulting from the low blood counts that often occur when treatment with azacitidine (Vidaza®) is started, there could be serious complications, and the patient might even die when someone with normal lungs might have survived. In general, comorbid conditions make treating MDS more difficult, worsen the overall prognosis, and can limit the treatment options wehave.
Does the degree or severity of a comorbid condition and the type of treatment given affect MDS treatment decisions?
It certainly does. To go back to the kidney example – there are patients with very mild kidney dysfunction where the abnormality is not much more than a laboratory test result that is slightly out of the normal range, and this type of mild problem has minimal, if any, consequences for MDS treatment. In fact, in some cases this particular comorbid condition can even help: red cell growth factors like darbepoetin (Aranesp®) or epoetin (Procrit®) can improve hemoglobin levels in MDS, but these drugs are not specifically FDA-approved for MDS and so sometimes Medicare or insurance companies balk at paying for them.
However, these red cell growth factors are approved for people with kidney disease, and they are easier to prescribe in that setting. But there are other patients with severely impaired kidneys or end-stage kidney dysfunction. The way that medication would be cleared by the bodies of those patients would be very different.
The severity of comorbid conditions is also relevant to clinical trials. Most trials of new drugs are trying to enroll a healthier subgroup of patients because if one of the study participants has a bad event while on the trial due to a comorbid condition, it could be erroneously blamed on the drug being studied and lead to problems with that drug’s application with the FDA. For other drugs, the way that they are metabolized is different in patients with comorbid conditions, especially liver or kidney disease.
So in many cases, patients with serious comorbidities aren’t eligible to participate in clinical trials. But that restrictive clinical trial eligibility has a downside: it means that when a drug is approved, it has been tested only in patients without comorbid conditions. So if we’re using an approved drug in a patient with a comorbidity, in what is sometimes called the “real world” off-study setting, then we have less of an idea how the treatment will progress since clinical trial results are only partially informative.
Do compound comorbidities necessarily complicate an MDS treatment plan?
Not necessarily; it depends to a large degree on how serious the individual comorbid conditions are and their cumulative effect. In the case of patients with more than one significant comorbidity, it can make patients ineligible for a stem cell transplant or for a clinical trial, and it can make their condition even more difficult to treat with standard therapies such as azacitidine (Vidaza®) or lenalidomide (Revlimid®). The more things that are wrong with a patient, the fewer options there may be. In extreme cases, the prognosis is dictated by the comorbid conditions rather than the MDS.
As an MDS specialist, how do you work with other physicians to coordinate care for patients having other diagnoses, resulting in comorbid conditions?
Communicating with other physicians is a major part of what I do and can sometimes be time-consuming. For example, last month I was attending on a hospital service, and a man from Saudi Arabia flew in by air ambulance and was admitted to my team. He had MDS, but it was the least of his problems, and every day our hematology-oncology health care team spent many hours talking with experts from cardiology, pulmonary disease, infectious disease, intensive care, nephrology, endocrinology, gastroenterology, speech therapy, respiratory therapy, physical therapy, and dietary and nutrition services.
If a patient with MDS needs some kind of elective surgery like a cataract operation, hernia repair, or hip replacement, we try to coordinate that procedure with treatment cycles or with transfusion support in our infusion unit. Or, if it is a non-essential elective procedure, we may delay the procedure until the MDS improves.
Patients with cardiovascular disease or a history of blood clots may be on anticoagulants (blood thinners), and if their platelet count is dropping due to MDS or MDS therapy, they’re at increased risk of bleeding. If that happens, we need to get it touch with the cardiology treatment team and let them know the situation and discuss some medication changes. So it takes time to coordinate with doctors treating comorbid conditions, but it is absolutely necessary to do the best thing for our patients.
If any comorbid conditions improve through treatment, would that allow MDS treatment to change to a plan previously ruled out?
Potentially, if a comorbid condition improves, the plan could change. For instance, I am currently caring for a patient who was found earlier this year to have a weakened heart, and so the patient was not able to be enrolled in a clinical trial for which he might otherwise have been eligible. But after excellent treatment by a cardiologist, including some medication adjustments, his heart function improved enough to meet the study’s eligibility criteria. He was later able to be enrolled on the trial because the study was still open and had not yet met its enrollment goal. So yes -- if comorbid conditions improve, that can open new doors for patients that previously seemed closed, such as a drug therapy or stem cell transplant.
What is most important for MDS patients and family members to know about comorbidities and MDS?
The doctor and treatment team helping care for the patient with MDS should know about any other medical problems the patients has and what medications and their dosages the patient is taking. This information can influence the overall care and treatment. If a patient with MDS also has serious conditions affecting the heart, lungs, or kidneys, these types of comorbidities will have certainly have an effect on what treatments are available and what the prognosis is. We are starting to recognize this influence on prognosis better than we have in the past and are incorporating tools into the clinic that measure comorbidities as well as MDS specific characteristics, like chromosome results or marrow blast counts.
Because most MDS patients are older than age 60, many will have other health problems of the sort that often trouble older persons. The bottom line remains that doctors treating MDS must be aware of all other major health conditions patients have and know who the treating physician is for these conditions.
The patient should not be seen just as someone with an isolated disease – as an “MDS patient.” My patients are all people with rich lives outside the clinic and many aspects to who they are—socially and emotionally, as well as physically. Having a full picture of the patient (which of course includes medical comorbidities) will help us deliver the best care to help them enjoy their lives as much as possible.
David Steensma, MD, FACP is an associate professor at Harvard Medical School and faculty member in the leukemia program at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts. He treats patients with myelodysplastic syndromes (MDS), leukemia, and other bone marrow failure diseases. His research focuses on clinical trials and new drug development and collaborative efforts related to MDS molecular genetics.