In my view, supportive care for MDS patients involves all the things we do as doctors that are not directly related to giving a specific drug or agent that treats the disease. Blood transfusions are the backbone of supportive care for patients with MDS, but supportive care may also include other procedures like giving antibiotics in case of an infection resulting from low white blood cell
How are decisions made about using these two different approaches?
The decision to go with supportive care or active treatment – or doing both – is really based on an individualized approach to the disease. We look at the patient’s MDS characteristics and how these may affect our decision. We look at the other problems or diseases the patient may have (often called co-morbidities) and determine if the patient is suited for a supportive care or active treatment approach. With regard to MDS, we do have a way of stratifying a patient’s risk and this can predict how the disease may behave over time. For those patients who are considered to have higher-risk MDS, it is usually important to try to get them to go on active treatment as long as we think they will tolerate the drugs that we commonly use.
Patients should not think of supportive care and active treatment as completely independent approaches that never happen concurrently – often, they are used at the same time. Several of the drugs used in MDS treatment are ones that will initially make blood counts decrease before they start to increase. So while patients are receiving active treatment, we also support them with transfusions to counteract this initial effect of treatment. This is an example of why supportive care and active treatment might be used concurrently. So you can say that supportive care helps the symptoms of the disease, and active treatment is used to treat the disease itself.
To start with supportive care, a large part of this category is blood transfusions. Active treatment can be categorized as those that are directed towards improving blood counts. One group of agents used is growth factors. This includes red blood cell
growth factors like erythropoietin
(Procrit®) or darbepoeitin (Aranesp®), which is a longer-acting form. There are also growth factors that stimulate white blood cell production. Granulocyte
colony-stimulating factor (G-CSF), also known as filgrastim
, or Neupogen®, is the most common. PEG-fi lgrastim or Neulasta®, is a longer acting growth factor
for white blood cells. These growth factors can sometimes be considered to be part of a supportive care approach. If a patient has a serious infection because their white blood cell count is low, they may receive these white blood cell growth factors to help get over the infection even if they are not regularly getting these drugs as part of an ongoing treatment regimen.
There are also hypomethylating agents, which are the two FDA-approved drugs azacitidine
(Vidaza®) anddecitabine (Dacogen®). These are the primary treatment for the majority of MDS patients who require active treatment. Another FDA-approved agent in this group that also improves blood counts is lenalidomide
(Revlimid®), but it has a different mechanism of action from hypomethylating agents and is categorized as an immunomodulatory agent. Lenalidomide has been shown to be best suited for a subset of MDS patients whose disease is associated with the chromosomal abnormality known as ‘deletion 5q’.
The other active treatment for MDS, one that is potentially curative, is an allogeneic stem cell transplant
, but not all patients are suited for or otherwise eligible for this treatment.
What factors infl uence a decision to move from supportive care to active treatment and does active treatment ever go back to supportive care?
It certainly can go both ways. Patients who are started on supportive care alone are generally those whose treatment team assesses their overall characteristics and determine that the patient may not tolerate active treatment therapy very well. This often can be due to co-morbid conditions that would make active treatment for MDS unsafe.
By the time an MDS patient needs regular and frequent blood transfusions, the disease is declaring itself that active treatment is needed. In MDS patients considered to have lower-risk disease by contemporary prognostic scoring systems, growth factors are often tried initially. If these do not generate satisfactory results, then we would next consider a hypomethylating agent. If the counts improve, we keep these therapies going, with transfusion support as required especially in the initial phase of treatment.
There could diff erent views on this. I view MDS treatment as all-encompassing. If I have a patient on a particular MDS drug, that’s a specifi c treatment for the disease, but everything else I may be doing in association with that, including transfusion support, is still part of the overall therapeutic approach.
How are supportive care and active treatment aligned with MDS subtypes and the several prognostic scoring systems that are used?
The International Prognostic Scoring System
(IPSS) and others have various parameters they use – including blood counts, bone marrow
blast percentage, and bone marrow chromosome (cytogenetic) analysis. With these, we can come up with an assessment of whether the MDS falls into a lower-risk category or higher-risk category. Lower-risk patients are often treated initially with growth factors. Higher-risk patients are often treated with hypomethylating agents. Patients whose disease harbors a 5q deletion on chromosome analysis are usually treated with lenalidomide.
What is most important for patients to remember about supportive and active treatment for MDS?
Patients should recognize that these often go hand-in-hand and that doing one does not preclude doing the other. Patients can transition from one to the other, or have both happening concurrently. With regard to an initial approach for a new patient, it is important to recognize it is an individualized approach – it is not a one-size-fits-all scenario for any one patient. Several factors are generally considered – not only the disease related factors, but also ones specifi c to the patient – their overall fitness and suitability for active treatment. I would also like to emphasize that we are still learning more about this disease – the gene mutations and other factors that contribute to the development of the disease, and how to find better treatment options. Clinical trials are an important aspect of our quest for more eff ective treatment approaches for our patients. New and innovative approaches to MDS are being studied at many centers.