An Overview of CML Treatment Toxicities

Transcript:

Jorge E. Cortes, MD: I always talk to my patients about toxicities that are common and inconvenient but not life-threatening or severe. The life-threatening ones may be silent sometimes, but they could be there. Myelosuppression is common to all the TKIs [tyrosine kinase inhibitors], and that’s where you need to monitor your patients for neutrophils, platelets, hemoglobin, etc. If they get to be grade 3, then it’s usually recommended to stop therapy, monitor the patient closely, and resume therapy when they recover. They usually recover quickly—within 2 weeks you can resume at the same dose. If not, then they may require a dose adjustment.

You do see some level of other toxicities, some more common with 1 TKI than another. Diarrhea is something that happens with some frequency, particularly with bosutinib and to some extent asciminib but not usually. Patients respond easily to antidiarrhea medications. It’s the same thing with nausea and vomiting; usually that’s manageable. These toxicities tend to improve over time. You need to monitor the glucose of patients taking erlotinib. For many of these drugs, it’s important to monitor the lipase. We talked about lipase elevation, and this has been reported with erlotinib, ponatinib, and to some extent bosutinib. It’s important to keep monitoring the lipase in patients.

Fluid retention can be seen in some patients. Peripherally in imatinib patients. More central pleural effusions, pericardial effusions [can be seen] in patients with dasatinib, 25% to 30% of patients. It’s important to keep an eye on any symptoms that may suggest this. Some of the silent and more serious [toxicities] are arterial occlusive events. We didn’t recognize that these events could happen in patients receiving TKIs, but now we understand that they happen, certainly with ponatinib but also with some of the others—nilotinib and dasatinib for sure, bosutinib a little less, and probably not so much with imatinib. It’s a class effect, and you need to make sure that you monitor all the comorbidities and all the risk factors that the patient has that may predispose them to these entities. This isn’t an adverse event that you want to manage when it occurs. You want to prevent it as much as you can. Certainly, some drugs have a higher risk than others, and that’s important when you’re making your selection, particularly for patients who have high-risk features.

When you’re deciding on your treatment option, you have to keep in mind 2 important elements. No. 1, what gives your patient the best chance of response? After all, we’re treating a leukemia. We’re treating a cancer. You want to make sure you’re offering the best treatment to your patients in terms of efficacy. On the other hand, what is the safety profile? What are the concerns about the safety of each TKI that you have available? Depending on what stage the patient is at, that may make a TKI a good fit for a given patient. In the frontline setting, for example, you have 4 TKIs available: imatinib, dasatinib, erlotinib, and bosutinib. The risk of arterial occlusive events and other things have to be considered together with the goals of the patient. With second-generation TKIs, you have a better chance of getting to the deep molecular responses and, therefore, considerations of treatment discontinuation.

As you move to the second- and certainly to the third-line therapy, you’re moving into more difficult scenarios. It’s not just a matter of giving another second-generation TKI. The risk of mortality goes up and the survival probability goes down when the patient has been resistant to, for example, 2 TKIs. You need to pick the best drug available that will give you the best chance of a good response; that usually will be asciminib or ponatinib. And then, does the patient have comorbidities and risk factors for arterial occlusive events? We talked about the risks with ponatinib. So far, the safety profile is very good with asciminib, so you need to put all these features into consideration. But always keep in mind both sides of the coin: the efficacy, addressing the leukemia, selecting the best treatment for your patient, and the safety profile and the characteristics of the patient, including comorbidities, to give you the best risk-benefit ratio for your patient.

Transcript edited for clarity.