One of the most common concerns among CML patients is also the hardest to explain
For many people living with chronic myeloid leukemia (CML), fatigue is the most persistent challenge they face. Part of the frustration lies in the fact that the source of the issue is hard to pin down: Does it come from the disease, the therapy or are there other factors at play?
According to Dr. Andreas Hochhaus, fatigue is best understood as a syndrome rather than a symptom because it can have many causes. It is also likely underreported because screening for it isn’t routine. “We don’t do quality of life assessments in all patients,” says Dr. Hochhaus, Director of the Department of Hematology and Internal Oncology and Director of the University Tumor Center, Universitätsklinikum Jena, Germany. “It should be done, but it’s not standardized. The more you ask patients about fatigue, the more you will find it.”
Here’s what Dr. Hochhaus had to say on the causes of fatigue, how doctors assess it and what patients can do to manage it.
How common is fatigue among CML patients?
It’s difficult to give a percentage because fatigue depends on several factors. Some patients have fatigue at diagnosis, before any treatment, which means it’s related to the disease itself (through blood levels, anemia and the spleen, for example). The more aggressive the disease, the more relevant fatigue becomes. During treatment, fatigue often depends on the action of the drugs. Some tyrosine kinase inhibitors (TKIs) are associated with more fatigue than others, based on their off-target activity. But there can also be a psychological component related to how patients deal with learning they have an aggressive leukemia. Over time, that should decrease as they learn the disease can be treated well. So, fatigue really depends on disease activity, psychology and treatment.
How does CML fatigue differ from ordinary tiredness?
It’s quite easy to tell the difference. If you’re tired, when you sleep, the tiredness goes away. If you have fatigue, sleeping doesn’t help — it’s still there when you wake up. Sometimes there are somatic causes, meaning they can be discovered and eliminated. For instance, when you have a low level of cortisol in your body, you have fatigue, and this can be related to a drug or to CML itself. When you have a low level of thyroid hormones, you also have fatigue. When you find a cause, you can substitute what is missing. When you cannot, it’s more difficult for doctors to address. In most cases, you cannot find a specific reason.
Are certain TKIs associated with more fatigue than others?
Of course. When you look at the biochemistry, you have different mechanisms and different off-target activities. I’ve had good experience with dasatinib, for instance, which causes less fatigue than other medications because of the short half-life of the drug. You can also use lower doses with dasatinib. Now, most recently with asciminib, you have the most specific drug available, which theoretically should not cause fatigue, based on how it works. But fatigue still shows up, just not as much as with other drugs. That’s why it’s important to highlight that fatigue in CML is not always drug related. You can have fatigue without a specific reason.
Does the fatigue ever go away on its own? What about in patients who have had success with treatment-free remission (TFR)?
If the fatigue is CML-related, it can go away once the disease is in remission. If the fatigue is drug related and causes specific metabolic changes, then it can be difficult. The drug imatinib is a good example of this, because it creates an imbalance between intracellular fluid and extracellular fluid. This can lead to fatigue because the body gets heavier when it holds more water. Patients realize they get tired from this, but it cannot be changed without changing the drug. We accepted this when we only had imatinib, but now we have six drugs available in most countries. That means we can easily change the medication a patient is on. But even after you discontinue a particular drug through TFR, fatigue can still be present. If we assume psychological reasons are the cause, then of course that would still be the case.
When should patients talk to their doctor about fatigue?
They should talk to their doctor right away. In some patients, fatigue is easy to address. If you have low levels of vitamins or cortisol, for example, it’s easy to substitute what’s missing. These issues often depend on how well the doctor and patient communicate. If they have a good relationship and know each other very well, it should be easy to talk about these things. Fatigue is part of the treatment and the disease, but it should not be taken as a final symptom. It can be addressed.
How do you go about assessing fatigue in CML patients?
The first step is to check whether anything is disrupted in the body’s metabolism. We look for somatic causes, things that can be discovered and eliminated, such as low levels of cortisol or thyroid hormones. Anemia is also quite easy to address. If nothing is found, we check the psychology by exploring how the patient has processed their diagnosis. If we still find nothing, we may involve psychological oncologists. We know how common fatigue is from clinical studies, but not from everyday practice because quality of life assessments aren’t always done. There may be a proportion of patients in which it’s not assessed or discovered
What can patients do to manage fatigue?
Physical activity is important, as is a good lifestyle in general. Diet, smoking, all of this matters. If patients were active before CML and then they develop a reason for fatigue, such as anemia, they may reduce their physical activity. This becomes a cycle that leads to more fatigue. That cycle should be changed to a more active lifestyle, and we motivate patients to go out and start physical activity again. We advise them to live a healthy life without placing too many restrictions on themselves. Sometimes, patients just need to hear that they can do it. If your blood levels are fine, just go out and do it.
With more treatment options available now, is fatigue becoming less of a concern?
This is a 25-year-old issue that we first encountered with imatinib. But since we can now address most of the imatinib side effects by changing drugs, it’s not as relevant anymore. We can change the doses, we can change the drugs, we can substitute what should be substituted. If we do all this, fatigue should be less of a problem.