Chronic myeloid leukemia (CML) accounts for 15% of all adult leukemias and is characterized by heterogenous clinical manifestations. In recent years outcomes for patients with CML have greatly improved, in part due to the advent of tyrosine kinase inhibitor (TKI) therapy. At the Oncology Nursing Society 43rd Annual Congress in Washington, DC, i3 Health spoke with Sara Tinsley, PhD, ARNP, AOCN, from Moffitt Cancer Center, about therapeutic advances in CML and the importance of ensuring patient adherence to TKI therapy.
What was your research about?
Sara Tinsley, PhD, ARNP, AOCN: Our research looked at the role of nurses, nurse practitioners, and physician's assistants in managing the care of patients with CML. CML is a myeloproliferative neoplasm where the bone marrow puts out an overproduction of cells driven by the translocation of chromosomes 9 and 22, which creates the oncogene BCR-ABL. The beauty of that is you can monitor BCR-ABL by PCR testing on the peripheral blood and the bone marrow.
When a person with CML is diagnosed, they usually present with a high white blood cell count or a high platelet count. They may have anemia or a normal hemoglobin level. In the white blood cell differential, you have myeloids, meta myeloids, a lot of immature cells, and sometimes you have a small percentage of blasts. That leads them to get referred to a hematologist where they get the diagnosis and you get a baseline PCR for BCR-ABL. Using an international scale, at this point they are usually prescribed a tyrosine kinase inhibitor (TKI), which is oral chemotherapy that targets the intracellular pathway where the translocation is occurring.
TKIs block the translocation of chromosomes 9 and 22. You can measure that in the blood very precisely. The NCCN guidelines have milestones that patients are supposed to meet. Usually, you monitor every three months and then you take the baseline and compare it. The goal is to get them into a major molecular response and beyond.
What do you do when there is an increase in PCR?
Dr. Tinsley: The first thing you do when you see an increase in the PCR is ask the patient if they're taking their medication as prescribed. If they're not, then you need to look at the reasons they're not taking their medication. Then if they really say they've not missed any doses, you need to dig deeper. Usually, you would repeat the PCR as soon as you see that it's increased significantly and check for any mutations in BCR-ABL with kinase domain mutation analysis.
With oral therapy, there are issues of adherence. What is the role of advanced practice providers and nurses in making sure that patients take their oral therapy?
Dr. Tinsley:Lisa A. Nodzon, PhD, ARNP, AOCNP, who co-authored the abstract, sees patients all the time at Moffitt Cancer Center. She develops relationships with them so they come to see her. They see the doctor less frequently. The nurses help monitor the PCR. We call the patients back and tell them what their PCR was and go over the next steps. If it goes up, they have to come back in and get it redrawn.
We do a lot of the behind-the-scenes work as far as monitoring the patients, contacting them to make sure they're coming in when they're supposed to, and checking in if they miss an appointment. We try to be their coaches and cheerleaders to keep them on their treatments.
What are some of the significant adverse events of TKIs, and how do you manage patient concerns about the safety of these agents?
Dr. Tinsley: The most common symptom that we usually hear has been reported or published is fatigue, but also myalgias and some cardiac effects. One of the TKIs is known for its potential to prolong the QT interval.
Before starting therapy, we go over the education and discuss the most common side effects they may or may not get. If they are having symptoms similar to what the package insert says, we ask them to call us instead of stopping the medicine because there are things we can do to help ease them through the symptoms. Some of the adverse events are pretty scary. We make sure that they have the phone numbers to reach nurse triages who answer the phones. I always tell the triage nurse or nurse navigator to send me an email when my patients call because I want to know why they are calling.
If you're checking on them, then you will see what symptoms they're having. We usually address fatigue, but with time, some adapt to their level of fatigue or it gets less intense once their disease is better controlled. Some TKIs are associated with edema. Sometimes you have to give a little diuretic if that's causing them issues.
For whichever symptom they have, we try to make sure it's manageable. If it's not, maybe they need to switch to one of the other TKIs since there are five, but you don't want to go through them too quickly.
I had a gentleman on imatinib and his PCR kept going up. He didn't have any mutations so we switched him to a different TKI. He had Barrett's esophagus and he was having severe reflux because he couldn't take his proton pump inhibitor, so he was distressed over it and wanted to just stop taking the medication and take his chances. We referred him to GI and the gastroenterologist said that he really needed to take his proton pump inhibitor. We had to look at this particular medicine's instructions and work with it. He couldn't eat for two hours before and one hour after the medicine, twice a day. He had a calendar that would say what time to take the medicine based on when he woke up. We had to schedule that proton pump inhibitor for the middle of the day so that it had less chance for interaction with the TKI.
We are monitoring him more closely, but he was going to stop therapy. He asked, "How long would I have to live if I just quit this stuff?" I said, "You don't want to do that. We can work with this." You really want them to stay on their treatment if they're responding.
How have TKIs changed the CML treatment landscape?
Dr. Tinsley: That's one of the miracles of my lifetime. I'm glad that I lived through it because I used to take care of patients with CML when I worked in transplant. That was what you did for CML patients. They underwent bone marrow transplant. Many of them died, but if they didn't die, they were cured.
Now we have oral therapy. Most patients who have CML don't go to transplant now. As long as they take their medication, have a response, and meet these milestones, they should be able to live a normal life expectancy.
About Dr. Tinsley
Sara Tinsley, PhD, ARNP, AOCN, is an oncology nurse in the Department of Malignant Hematology at Moffitt Cancer Center. Dr. Tinsley has been the recipient of numerous educational and professional awards, including the American Cancer Society Doctoral Degree Scholarship in Cancer Nursing in 2012. In addition, she has published extensively in journals such as American Journal of Hematology and Supportive Care in Cancer.
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