We are fortunate that there are now several highly effective treatment options for CML. The goal of CML treatment is to not only improve rates of remission but also to ensure a good quality of life (QOL). The majority of patients who are adherent to treatment with TKIs have excellent outcomes. For these individuals, the focus in my clinic quickly shifts to trying to preserve QOL and reduce those bothersome toxicities. Side effects in some patients could be possibly ameliorated or substantially mitigated by dose reduction. There is a substantial amount of collective experience among CML experts to suggest that dose reductions are relatively safe in many cases, as long as the patient’s CML is being monitored and the patient is being assessed regularly for improvements in QOL. In the future, we will likely see dose modifications with CML therapies occurring more frequently to support the QOL end points that are most important to patients. Ideally, we will investigate the effect of dose modifications on treatment success through clinical trials.

The monitoring of treatment response has improved with the development of polymerase chain reaction–based molecular monitoring. Despite the usefulness of contemporary guidelines, there is some variability among clinicians in the optimal frequency of response monitoring. Following treatment initiation, I believe that an initial monitoring interval of every 3 months is appropriate. On the one hand, one does not want to be too relaxed about monitoring; on the other hand, monitoring more frequently may lead to micromanagement and unnecessary concern and alarm, as random fluctuations can occur. Ultimately, I think that following available guidelines makes good sense.

It is very important to monitor treatment adherence and treatment response, given the transformative nature of available therapies. Some patients who go into remission stop taking their medications and ultimately develop splenomegaly and leukocytosis. It is often difficult to recapture that same level of the initial response, and these patients become at risk for the development of secondary resistance and progression to advanced-phase CML, which can be difficult to manage medically.

Having lived through a time when CML was not as easily managed as it is today, including a period when patients were expected to eventually die from the disease unless they received a bone marrow transplant, I find that some clinicians have swung a little too far the other way in communicating risk, due to the effective treatment options that are now available (ie, the TKIs).

In my opinion, the big issue relates to medication adherence. When I first meet with a newly diagnosed patient, I make sure that they understand the alarming risks associated with CML, including early death. I then stress the importance of medication adherence. I do this because I have seen so much tragedy when patients are not adherent because they do not understand how serious the disease can be.

Side effects are a major contributor to nonadherence. When we are dealing with side effects, dose adjustment may be necessary. If the clinician has a “handle” on the molecular response, the dose can often be adjusted with confidence, as long as the patient is being monitored per the recommendations. In the future, I look forward to seeing emerging data on the long-term side effects of TKIs. It will be interesting to see how these data will influence practice recommendations moving forward.

We are fortunate in that 4 drugs are currently approved for first-line use in CML, and they are all excellent in helping patients achieve remission. Although TKIs are the standard of care, initially choosing the right TKI for each patient requires careful consideration. The choice of TKI should be based on the patient’s comorbidities, other medical issues, risk score at diagnosis, and insurance coverage.  

Following treatment initiation, monitoring is important. Fortunately, there are excellent CML guidelines available, including those from the National Comprehensive Cancer Network and the European LeukemiaNet, that can help providers make sure that a patient is being well monitored and treated. Although patients with CML may not always look ill, monitoring is essential to assess for early molecular remissions. Importantly, when individuals with CML are intermixed in a clinic of patients receiving active chemotherapy, one may be “fooled” into thinking that they are the healthiest. This, on top of a lack of resources or the busyness of a clinic, can result in guidelines not being followed as closely as they should.