Managing Toxicities from BCR-ABL TKIs in CML

Transcript:Kendra Sweet, MD: When managing toxicities related to TKIs, I think one of the most important things to remember and to point out to your patients is that in a lot of cases, the worst side effects occur very early on and, over time, those start to ease up and they start to become much more tolerable. So, if we are able to support a patient through that early time point, whether it’s steroids for a rash, a diuretic for fluid retention, or nausea medications, the supportive care early on is crucial. It’s not always necessary to change treatment because of toxicities because they can get better over time. In some cases, we may need to dose-reduce. In some cases, we may need to temporarily hold the drug. But in most cases, we can support people through that tough time in the beginning and they can end up doing quite well as time goes on.

In regard to the cardiovascular complications from TKIs, those data are still coming out. The 2 TKIs that have been most closely associated with cardiovascular toxicity, of course, are nilotinib and ponatinib. And the mechanisms by which either of those drugs cause cardiovascular toxicity has not really been clearly defined. But, in a lot of cases, it looks like it may actually be a different mechanism from each drug.

The comprehension in regard to cardiovascular toxicity, people know that it exists. Most people don’t really have great data to tell us what to do to try to mitigate that. So, getting a cardiologist involved and doing what we can do to decrease risks in the same way that we would with someone who is not on a TKI, I think is absolutely essentially. But at the end of the day, we have a lot more research to do to really fully understand the mechanism by which these drugs cause cardiovascular complications and then what we can do about it to decrease that risk.

Naval Daver, MD: In general, we try to have good communication with the community physicians. So, we, at MD Anderson, receive a number of referrals from outside of Houston for patients with chronic phase, especially grade patients with last blast phase, x-rated phase, chronic myeloid leukemia. In general, our policy has been, when we see the patients initially and we start them usually on one of frontline protocols for CML, we will call or e-mail the community physician and let him know that the patient is enrolled on a protocol. And we actually, since we treat about 80% to 85% of our patients on clinical trial, have standardized clinical trial paperwork that we would send to the local physician that usually includes what kind of trial the patient is on, the abstract of the trial, and then what labs are needed on that patient and at what frequency. Usually, those are requested to be faxed to us so that we can keep it in our FDA binder.

And so, in general, especially on the protocols, the communication has been very good. In my practice, I usually give my e-mail or phone number to the community physicians as well so that if they have a question, they can reach me quickly. But especially in chronic diseases, such as CML, or other diseases, like myelofibrosis and polycythemia vera, that we see a lot, I think it’s very important to make that initial communication with the community physician, either on or off trial, and also to let the community physician know that we are really the consultants. We will be helping to monitor the patient from a distance, but really they are still going to be the primary doctor who the patient will be going back to, who will be the frontline to deal with any emerging toxicities. They can reach us, but they really have ownership of the patient. And I think that works beneficially in 2 ways. It makes the community physicians also feel comfortable that these patients are not going to be staying or taken over by MD Anderson or any other major institution. We’re just being the consultants, so they will continue to follow the patients.

And I think it also makes it easier for us because we see a lot of referrals. So we do not have the bandwidth to become the primary for these patients. I think in chronic diseases, even more than in the acute leukemias, it’s very important to have a very good communication with these physicians.

Transcript Edited For Clarity