Exploring Current Therapeutic Options and Treatment Selection in CML

Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University, discusses the current therapies available to treat patients with chronic myeloid leukemia (CML) and how to choose between them when there is similar efficacy.

Multiple tyrosine kinase inhibitors (TKIs) are available in this setting, as well as other types of drugs that have been approved recently. Cortes feels that when deciding between 2 drugs that had comparable results for patients with CML, going by the individuals’ comorbidities and other unique factors can help find the best option for that patient.

Transcription:

0:08 | We currently have a good number of drugs. This is where there are so many good options. We have 5 TKIs, and then of course, we have omacetaxine (Synribo), that's approved. But there are still some patients that are not having the outcomes that we want. There are still some issues with toxicity with some of the existing drugs. So as much as we would like to think that all patients do well, actually, if you look at some of the statistics from the frontline studies, by 5 years, 40% of patients are required to change therapy. So clearly, there is still a need for other treatment options. There are some scenarios where it's particularly relevant. For example, patients who've already gone to 2 or 3 TKIs, you start getting into not very effective therapies. Patients with a T315I mutation, we have 1 drug approved for that indication, and so on.

1:21 | A lot of the drug approvals have been with phase 2 data. We do have comparisons in the frontline setting. We've had trials comparing second generation (TKIs) to imatinib (Gleevec) and they do show benefit. So that that allows you to make those decisions. However, between the different second generation TKIs, only very recently, last year at ASH (American Society of Hematology), there was 1 study comparing dasatinib (Sprycel) to erlotinib (Tarceva). It was the first time ever that a second generation is compared to a second generation (TKI). It showed that efficacy-wise, it's completely identical.

1:58 | In the more advanced settings, we haven't had a randomized trial comparing 1 option versus another until asciminib. There is a randomized study of asciminib versus bosutinib (Bosulif) and it showed benefit. Bosutinib was a good control, they had no problem with the design of the study. However, a question that many of us are asking now is, if asciminib is approved, how do we decide between asciminib and ponatinib (Iclusig), which is the drug that we consider in that setting most of the time.

2:31 | So that leads me to the question, how do you make those decisions then, when you're facing these scenarios? I think what we what we tend to end up doing is matching patients according to their comorbidities, the safety profile of the drugs, and trying to use the drug that has the least effects on areas where the patient may be having problems. For example, if you have a patient with pulmonary problems, you may not want to use the dasatinib because there's more of a risk of pleural effusions, and so on. The schedule, sometimes that becomes important. There are drugs that are given once a day with or without food, and others that are twice a day and no food 2 hours prior and 1 hour after and it's a little more complicated, particularly for some patients, depending on their lifestyle, etc. So you use these kind of features to make those decisions when the efficacy either looks the same, or there's no direct comparison.