Advances in Treatment of Previously Treated Ph+ Chronic Myeloid Leukemia - Episode 5

Selecting Second-Line Therapy for Chronic Myeloid Leukemia

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Considerations for selecting optimal second-line therapy for chronic myeloid leukemia when a patient progresses.


Moshe Talpaz, MD: Obviously, we have multiple available approved drugs for the management of chronic myeloid leukemia [CML], and the vast majority of patients do fairly well on these therapies. Nevertheless, we do confront some issues that pertain to therapy, especially issues of resistance or some loss of response. Those may be affected by several factors. Primary resistance may have to do with a very long-standing disease that was not diagnosed on time. These patients may or may not have additional mutations within BCR-ABL, and some of those render resistance to some of the therapies. There are also issues of patient compliance, and I can understand that issue. Patients are supposed to get this treatment on a chronic basis for multiple years. And low-level adverse effects are sufficient to sometimes cause the patient to reduce the dose or skip doses, which may reduce the effectiveness of the therapy. It’s also important to emphasize that the patient does not always communicate those issues with the physician, and the physician has to be aware of that possibility. So disease progression in the context of not being able to maintain a major molecular response may be a factor in the development of resistance mutations, or a patient with primary resistance may never achieve this level of response. Those are uncommon but can happen as well, or there may be compliance issues where the patient is not taking an adequate dose and the result is a loss of some of the response.

Several drugs have been approved for the treatment of second-line CML. In the second-line, we mean patients who were treated initially with a different drug, and that drug was not capable of maintaining the quality of remission that we would like to obtain. The choice of a second-line drug is based, one, on the mechanism of resistance that rendered the first-line choice inadequate to obtain remission. And a great deal of effort has been made in identifying the various mutations in the BCR-ABL gene that render resistance to first-line treatment. Second-line drugs can overcome many of those, however, some mutations are more susceptible to treatment with one drug rather than another. There are mutations that are most susceptible to treatment with nilotinib, whereas others are more susceptible to treatment with dasatinib, as well as bosutinib, which is also approved as a second-line treatment and tends to follow very much dasatinib in identifying disease that is sensitive to this treatment.

For me, a major consideration in the choice of second-line drugs has to do with the patient’s general condition. I’m referring to the medical condition. I would prefer one type of treatment if the patient has a history of heart disease, diabetes, or hyperlipidemia. In such a situation, I would prefer the use of dasatinib and bosutinib. Whereas patients who have a pulmonary history or lung disease, in such cases, I would choose nilotinib as the preferred drug. There are more considerations, such as drugs that have to be given twice a day, whereas other drugs are given once a day, the safety profile, and so forth, which affect my thoughts. In other words, the decision on a second-line treatment is based on, at least in my clinic, the reason for the need to move to a second line, the patient’s overall condition, medical issues, and other considerations of compliance, which will affect my choice.

Transcript edited for clarity.