Sandra Allen-Bard, BSN, MSN, NPC, ANCC, AOCNP: Hello and welcome to this Medscape Education CE program titled "The Nurse View: Common Clinical Challenges and Best Practices in Chronic Myeloid Leukemia." My name is Sandy Allen-Bard. I am a leukemia nurse practitioner at Weill Cornell Medical College in New York City.

I am pleased to be joined today by Patricia Ault, family nurse practitioner at MD Anderson Cancer Center in Houston, Texas; Stephanie Bauer, a nurse practitioner at Washington University School of Medicine in St Louis, Missouri; and Mary Beth Rios, research nurse manager in the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas. Welcome.

Before we begin, let me note that this program includes discussion of investigational agents not approved by the US Food and Drug Administration (FDA), as well as off-label uses of agents approved for use in the United States.

The goal of this program is to discuss the optimal approaches for treating patients with chronic myeloid leukemia (CML), including strategies for choosing treatment, monitoring responses, and optimizing adherence.

CML treatment has really evolved, with 3 drugs approved for frontline therapy and the recent approvals of bosutinib, ponatinib, and omacetaxine for resistant disease. For the oncology nurse, critical management issues include understanding treatment choices, monitoring for response, and ensuring adherence. We have gathered to discuss these issues and the challenges involved in providing optimal care for patients with CML.

Mary Beth, can you talk about the options for newly diagnosed CML patients?

Mary Beth Rios, RN: These are exciting times in the world of CML. We have moved from an era of interferon or stem cell therapy being the only options for patients with CML to there being 6 drugs approved by the FDA for treatment.

Three drugs are approved for frontline therapy: imatinib, dasatinib, and nilotinib. Imatinib was approved earliest, in May of 2001, at a dose of 400 mg daily. We now have 10-plus years of data with imatinib, and we know that it is safe and effective.^[1,2] Many people are still being treated with imatinib today. There have been some studies that have looked at imatinib 800 mg, and suggested that there is an improved response rate with 800 mg.^[3,4] However, 800 mg is not an approved dose, and it is not a recommended dose outside of a clinical trial.

Dasatinib was the next drug approved by the FDA, at a dose of 100 mg daily for patients in chronic-phase CML.^[5,6] Dasatinib has a slightly different toxicity profile than imatinib, and it is important to note 2 very rare but serious adverse events that may occur with dasatinib. The first one is pulmonary arterial hypertension. This is something that providers need to consider when they are thinking about what strategy to use for patients with CML. It is a very rare, but very serious, side effect. The other side effect that we commonly associate with dasatinib is pleural effusions. They do occur and they can occur anytime during therapy, including in patients who are on long-term dasatinib therapy. These adverse events are not contraindications for therapy, but they do need to be considered in patients who are going to undergo this therapy.

The third drug approved for frontline therapy is nilotinib. It has a black-box warning from the FDA. This means that there are special precautions that providers need to take when considering nilotinib therapy. The black-box warning is for QT prolongation or cardiac arrhythmias. This needs to be considered for patients known to have cardiac arrhythmias. The FDA recommends an electrocardiogram to check QT prior to starting therapy with nilotinib and approximately 1 week into nilotinib therapy, and also optimization of magnesium and potassium levels prior to starting therapy with nilotinib and during therapy.

Nilotinib is approved at a dose of 300 mg, and it is taken twice a day. The issue with nilotinib is it must be taken on an empty stomach, which means 2 hours before or 1 hour after a meal. This can be problematic for some people. That, again, needs to be part of a discussion with a patient when considering treatment. Both imatinib and dasatinib can be taken with meals.

The other 3 drugs currently approved by the FDA are not for frontline use. The first is bosutinib. That is approved for use in patients whose disease has failed to respond to at least 1 prior tyrosine kinase inhibitor. Ponatinib, which received the most recent approval, also is approved by the FDA to treat CML that has failed to respond to at least 1 tyrosine kinase inhibitor. Finally, omacetaxine is approved by the FDA for patients with CML that has failed to respond to at least 2 prior tyrosine kinase inhibitors.

Ms Allen-Bard: How do you decide which frontline therapy to start with, now that there are 3 approved?

Ms Rios: I forgot to mention that because imatinib is the oldest drug out there, it will be the first one to come off patent, and once it does financial issues may come up regarding initial choice. However, right now, according to the National Comprehensive Cancer Network, or NCCN, guidelines, all 3 therapies -- imatinib, dasatinib, and nilotinib -- are recommended as frontline therapy.^[7] The practitioner would really have to look at the patient's clinical history when deciding what therapy to use. In addition to clinical history, also look at lifestyle.

Patricia S. Ault, FNP-BC, DNP: Mary Beth, could I ask you a question about cost? Is the insurance going to take up some of the cost? I know the other drugs are very expensive, so it seems as though it is going to be a big issue. Are they going to order one drug over the other because of the cost, in your opinion?

Ms Rios: That is a very good point and we just do not know what is going to happen with the price of these drugs and copayments. As you know, every insurance has different copays. I have seen patients with a copay of $30 per month up to $1000 per month.

Dr Ault: It is for a lifetime of treatment.

Ms Rios: Right, these are lifetime therapies, so cost is definitely an issue.

Ms Allen-Bard: Does bone marrow transplant or stem cell transplant play a role in CML now that we have these other drugs?

Ms Rios: Yes, it certainly does, but not for frontline therapy. Imatinib, dasatinib, and nilotinib are highly effective, safe drugs, and the risk-to-benefit ratio for performing a stem cell transplant upfront is too high -- it should not be done. The patients should be given the opportunity for disease control initially with a tyrosine kinase inhibitor.

Dr Ault: What about the younger patient with a family?

Ms Allen-Bard: I was just going to ask what happens with a 20-year-old? I have a few 20-year-old patients in my practice who are in college and are not as compliant with their oral drugs. Do you offer transplant to those types of patients?

Stephanie Bauer, BSN, MSN, FNP: I still think the risk outweighs the benefit. The toxicity of a transplant is life altering; it can lead to secondary complications, a high risk of infection, graft-vs-host disease. Optimizing the oral therapies first would be more beneficial to the patients, even if they are 20 years old. We have 10 years of imatinib data, and if we keep going as we are going, these patients should remain in good condition with chronic, stable disease. We should have a future with oral therapies. Still, we do not know the answer completely, because we are still early on with these new tyrosine kinase inhibitors.

Dr Ault: It is quite a controversial topic among practitioners.

Ms Rios: It certainly is, but I think this is where proper education comes in. It is easy for patients to say, "I do not want to take a pill every day for the rest of my life; I'm just going to opt for the transplant, and I will be done in a month." And that is simply not the case with stem cell therapy.

Ms Bauer: Monitoring has changed quite a bit in the last 10 years as well. Before, we had either chemotherapy or transplant as our option for therapy and now we have oral therapy. So you approach the patients as if they have a chronic disease, like diabetes or hypertension. The goal is to first decrease the leukemic burden of the disease, and then to prevent the disease from progressing to more accelerated or blast phase. Once patients progress to that point, your treatment options are limited. You are more likely to have to do a transplant in that patient population.

In the NCCN guidelines there are milestones for patients' progress, and those milestones are used as tools.^[7] The provider should look at these tools and then decide whether the patient is hitting those milestones appropriately and, based on that, make a decision on when to switch or to continue therapy.

One of the main things you want to look at is a complete hematologic response. When the patient's blood cell count is normalized, that would be the first response, the first milestone that you hit.

Ms Allen-Bard: When would you want to see that milestone?

Ms Bauer: You would want to see that at 3 months after starting therapy. If you do not see that milestone reached, then you need to investigate a little bit. Is the patient taking his or her medication? Is there a drug-to-drug interaction? Not reaching the milestone does not necessarily mean you need to switch therapy immediately, but it definitely puts a red flag up that the patient may not be responding to the medication.

The next milestone in the guidelines is cytogenetic response. Most studies, including the IRIS study with imatinib,^[1] the ENESTnd with nilotinib,^[8] and the DASISION trials with dasatinib,^[5] have looked at cytogenetic response. What they have found is that if patients have a cytogenetic response in the first 12 months, they have a better chance of their disease progression decreasing in the future months or years. So cytogenetic response is one of the main milestones that you want to achieve.

At baseline, patients should undergo a bone marrow biopsy with cytogenetics by karyotype, which is standard. A fluorescence in situ hybridization (FISH) test, which is a peripheral blood cytogenetic test that looks for the abnormal chromosome that causes the disease, the Philadelphia chromosome, may also be considered. This abnormality causes an abnormal fusion gene called BCR-ABL.

The next test is a molecular study, which looks for the abnormal fusion gene. A molecular study can be done 2 ways. One is qualitative, which only gives you a false-positive or negative result so is generally not preferred, and the other is quantitative. That test is called real-time polymerase chain reaction (RT-PCR) and should be performed at baseline and then throughout the progression of the disease. The NCCN guidelines recommend testing at 3 months, 6 months, 12 months, and 18 months.

Ms Allen-Bard: Are the PCR tests done with bone marrow or with blood?

Ms Bauer: The original test should be done with the bone marrow. When you are definitely checking cytogenetics, you want to see the abnormal chromosomes. There is some controversy among experts over using FISH vs straight bone marrow karyotype. The guidelines still recommend standard karyotype use. However, you also could use peripheral blood FISH if you are unable to use the bone marrow. Some patients have a dry tap when you try to use the bone marrow and you cannot get enough dividing cells to do the cytogenetics testing, in which case FISH may be an alternate way of monitoring.

Ms Allen-Bard: In my practice, we do not use FISH with peripheral blood for monitoring. Do you use it in your practice?

Dr Ault: We do. We use FISH quite a bit, but I have often thought it is because we are an academic center. We want to gather more information. We want to see the characteristics of this disease.

Stephanie, I had a question: You mentioned how often you do the PCR test. I do not know whether you have seen this, but in the community they are beginning to use PCR monitoring without benefit of a bone marrow sample, and we are beginning to see that in some of the practices. Have you seen that happening?

Ms Bauer: Yes, I have seen that a couple of times, particularly in patients who have been referred to us. Nowadays, the primary oncologists tend to start the therapies, and then patients are sent to the academic centers if there are complications or they do not get a response. In the rural areas, I have seen cytogenetics missed in the middle of that first year, which is really troubling, because the guidelines are based strictly on what the cytogenetics are doing in those first 12 months.

Major molecular response (MMR) is important and our knowledge about it is evolving as we speak. We do not have a complete understanding of what it means to hit an MMR, but we know that, based on some of the studies, if you see an MMR at 12 or 18 months then the progression-free survival may increase and those patients' disease will have less time to transform into an accelerated or blast phase.

Dr Ault: The gold standard is still complete cytogenetic remission.

Ms Bauer: By the NCCN guidelines, yes.

Ms Allen-Bard: That is assessed by bone marrow cytogenetics?

Ms Bauer: Yes, bone marrow cytogenetics. You can use FISH, but to confirm that a patient is in cytogenetic remission, you should do a bone marrow test. After that, you can move to just using the MMR or the molecular testing for follow-up, which is also stated in the NCCN guidelines.

Ms Allen-Bard: Molecular testing is the PCR by blood. That is recommended every 3 months?

Ms Bauer: Every 3 months -- every 3 to 6 months up to 3 years. That is looking for minimal residual disease. It is a more sensitive test. If you are looking at cytogenetics, you are looking at 20 metaphases on bone marrow karyotype, so you want to make sure that you have those 20 metaphases seen.

If you cannot get dividing cells then you can do the FISH test, which gives a percentage of that abnormal chromosome. You just want to see that go to 0; that is what your goal would be over the year.

At any time that you see that that is not occurring, then you also go back to asking what is wrong. Is the patient not taking the medicine? Are there interactions? Is a mutation developing? Those are things that you need to think about when you are looking at those patients.

Ms Rios: There are a couple of issues with molecular response or molecular monitoring. It is not well understood by a lot of people, but it is a number that providers and patients are interested in. The number that they want to get to is 0. There are some providers and patients who feel that if their number is not 0, despite the fact that they have a complete cytogenetic remission, they are somehow failing therapy. This is simply not the case, and it is one of the most important points we need to bring to people's attention: that survival does not simply mean chasing that 0 PCR response rate or PCR level, that patients can have long-term survival with some disease apparent by molecular response when they maintain a complete cytogenetic remission. There is a lot of education needed for patients and providers about exactly what is the significance of the molecular test.

We see patients coming from local physicians who have PCR tests run once a month, and that is too often. There is too much variation in the PCR. In our lab at MD Anderson, PCR results can vary up to 1 log without clinical significance. This is a very important point.

Dr Ault: I had been noticing that a lot of physicians are monitoring only by molecular responses and not understanding that fluctuation of this is normal. In practice, what do you recommend? We watch the trend over a certain amount of time rather than the actual numbers.

Ms Bauer: I agree with that, because you may not see the numbers go to 0. You need to look at what the patient's baseline number was and how many log reductions that you see. Your goal is to get to a 3- to 4-log reduction. You may still have a slightly positive number, and as long as it is stable, the patient may not progress and may not even need to switch therapy at that point.

Ms Allen-Bard: You do not make clinical judgment or clinical decisions based on PCR fluctuations.

Ms Rios: According to the NCCN guidelines, there are no guidelines for what to do for patients with a rising PCR level other than to monitor the rising level.

Dr Ault: I just do not think we are there yet. We have more research to do to find out the real answers. We speculate a lot, but we cannot base our care on speculation. We have lots of drugs, but does that mean that we have to use them within 3 months? No, I think we have to be more conservative and watch the patients by monitoring them.

Ms Rios: You raise a very good point. Because we have so many drugs, I worry that clinicians are going to be quick to change, because they have so many other options.

Dr Ault: What if it is the patient who is going to be quick to want to change? Remember, in the beginning, they wanted the magic bullet. Now they want the other magic bullet because this drug seems to be better than that one, and they are not as tolerant with the toxicity or the side effects anymore.

Ms Bauer: I think you have to remind patients that there still are only 6 drugs and you have a lifetime of taking medication (at least until we get further data on whether we can ever stop using the medications). Approximately 5% to 20% of patients may develop mutations or develop resistance to these drugs, so we need to explain to patients that if they have a good, stable, chronic condition and they tolerate the medication, then they should really stay with it, whichever one it may be.

Ms Allen-Bard: If you find resistance or increasing PCR levels, do you do another bone marrow test? Do you send for mutation analysis? How does that work in your practice?

Ms Bauer: Definitely, if you see a trend. I do not think you should jump on doing all this investigational work if you have normal blood cell counts and you have a mild increase in your MMR, or if your cytogenetic results were already negative. In those cases, you need to wait it out and repeat the test. But if you start to see a trend, or a change in the blood counts, then that would merit more investigation. If you get a 2- to 3-log increase on your MMR, or even any evidence of cytogenetics positivity, then you should look for mutation analysis and see whether there is any particular mutation that might be new. You might need to change therapy based on what mutation you find.

There is one mutation, T315I, that is known to be resistant to nilotinib, imatinib, and dasatinib. Ponatinib is the only drug that is supposed to have some response to T315I mutation. A patient with that mutation may also need to be considered for a clinical trial or a stem cell transplant. Those are the patients you have to worry about, whose disease will progress fast and who may need a transplant.

Dr Ault: I agree with all of that, but in the beginning, the obligation is to counsel the patient, because they may have stopped taking their drug on purpose, or reduced their dose because of toxicities.

Ms Allen-Bard: If we see continued rises in PCR levels, do we address the patient and how do we address the patient? Is the first question always "Are you taking your medication?"?

Dr Ault: Yes, this is important because adherence is a determinant of treatment success. With poor adherence comes a decrease in clinical benefits. There are a lot of drugs coming on the market, with many planned as oral agents. So communication and the relationship with the patient will be even more important.

The nurse used to be the one at the patient's bedside giving the intravenous formulation. You knew their family, their dogs, everything about them. That is no longer the case. We are not seeing patients as much. So the relationship has to be set up very early along with the discussion of the importance of being adherent with these medications.

What is nonadherence? There are not a lot of studies, but 3 very important papers have given us a benchmark.^[9-11] They suggest that only taking about 85% to 90% of your medication correlates with a loss of response or no response and a complete acceleration of the disease.

Ms Allen-Bard: So, missing 1 or 2 pills a week or a month?

Dr Ault: If you calculate that if you are supposed to be taking the drug, let us say once a day for 30 days in a month, and if you go by the 10% to 15% rate of nonadherence, that means if you miss 3 of those medication doses (or if it is twice daily dosing, 6 of those), then there seems to be an increased risk of progression of disease and, of course, then shorter survival. So adherence is very important.

Ms Allen-Bard: Do you find that nonadherence to the drugs is because of toxicity, or side effects? Or are there more-involved issues, such as the patient not having a relationship with the healthcare provider so they do not call if they have diarrhea or are not feeling well, or they just decide on their own to stop taking their medication, perhaps because of financial burden?

Dr Ault: There are a lot of things involved -- it is multifactorial. There are patient-related issues, disease-related issues, treatment-related issues, and socioeconomics. Mary Beth has already mentioned the cost of these medicines. It is tremendous. A lot of people are out of work. They do not have money. The copays are very, very high.

Then there is the whole health system. Maybe there is no convenient clinic. Things may be set up so patients cannot get there; they may not have transportation. There are a lot of issues that focus around nonadherence, more than just not taking the pill.

Ms Rios: One thing that is very important to be aware of is patient response when they are doing well. We monitor patients every 3 to 6 months, and with these highly active agents they do very well. We have them on therapy for 2, 3, 4, 5 years, and every time they come in to the office, thankfully, we say: "You are doing great; everything is fine; you are in cytogenetic complete remission [either a complete molecular remission or a major molecular remission]. You are doing great; stay on your therapy; we will see you in 6 months." So some patients think, "Hey, I am doing great; I can stop taking my drug." I discover this phenomenon particularly when the PCR levels, the molecular test results start to rise. A lot of patients then admit they stopped taking their drug. They thought they were cured and did not need it anymore.

Dr Ault: One of the major causes of nonadherence of course is the treatment side effects. There are a lot of clinicians that manage the side effects and the patient very well. They encourage the patients, they meet their needs, and then the patient is more likely to stay on treatment. But what about the patient with horrendous side effects? If they do not feel comfortable calling their clinician, they are more likely just to stop taking it.

Ms Allen-Bard: Right, patients often get worried. They think the clinician is too busy and they do not want to disturb her or him.

Dr Ault: It is really important to let our patients know these things up front: patient-related factors like the lack of information out there; what will happen if the patient misses 2 or 3 drugs?; what if the patient is a woman who wants to get pregnant? Our duty to our patients is to educate them and to manage the side effects.

Ms Bauer: I agree. Educating our patients so they understand their own disease and what you are looking for empowers them to stay on track. A lot of my patients are very savvy about their disease and they want to take control. To them, it plays a part in the disease itself, like they can manage it.

Ms Allen-Bard: Do we discuss that if they do not take their medicine then the disease will get worse?

Dr Ault: Yes, you have to talk to them. This is a predictive thing. This may not be entirely correctly, but I always compare their CML experience to AIDS; with AIDS, if you do not take your medicine, the disease comes back and you are going to die.

Ms Bauer: They have documented that in chronic phase, if patients take no therapy they could progress to blast phase within 3 to 5 years. If you end up in blast phase, then you have acute leukemia, and you might have to go to transplant, which is something you want to try to avoid if you can.

Dr Ault: That is why the strategy should be right up front to open the lines of communication. You explain it to patients right front up. If they are coming to you but they live far away, in a rural community, for example, you make sure that they are educated.

There are very informative websites now that you can recommend to patients. There are other things. You can give them a calendar.

Ms Bauer: Yes, particularly for patients who I feel may not be on target in taking their medicines. You can usually tell: sometimes they are younger and they are in school. They try, but it is just that they are young and they are busy. So giving them a calendar that shows when they need to take their medicines can really help them. Anything -- iPhones and iPads now have alarms – anything you can give to people to help remind them to take their medication can help.

Dr Ault: Also, to go back to what Mary Beth said, a lot of patients get in a mindset of, "I am cured, I have no disease," and they falsely believe that they no longer need their therapy. So you have to investigate their mindset and help them understand that, for right now, therapy is lifelong. This is all we have. You may or may not be able to stop using the medicine.

Ms Rios: This is where I think the impact of imatinib becoming generic is going to have a significant effect, even though both dasatinib and nilotinib were superior to imatinib in randomized, clinical trials of dasatinib vs imatinib 400 mg^[6] and nilotinib vs imatinib 400 mg.^[12] I think that when imatinib becomes more reasonably priced through generic versions, we will see more use of imatinib. Of course, I do not know that -- this is my speculation.

Ms Allen-Bard: Of course, we were very happy with imatinib several years ago. It was the wonder drug. Now there are super wonder drugs.

Dr Ault: They want that other one.

Ms Allen-Bard: Are we spoiled by the super wonder drugs? Will we be OK with prescribing generic imatinib when it becomes available?

Ms Rios: We have to treat the patient with the best available option for the patient.

Dr Ault: Mary Beth, you had said that dasatinib and nilotinib were the superior drugs.^[6,12] But have you seen or read in the literature that being superior, meaning achieving the first milestone, has increased survival? I think the end result of all this is long-term survival.

Ms Rios: That is of course the key. These were milestones as defined in a clinical trial: complete response rate and MMR rate at a certain time point. More patients achieved that with dasatinib than with imatinib; more patients achieved that with nilotinib than with imatinib. However, there was no survival benefit.

Ms Allen-Bard: They had deeper responses, or quicker, deeper responses. And those patients did not progress to advanced disease.

Dr Ault: Correct. There was less progression. But how will all of this translate? There were patients taking imatinib who did not progress, and they are still taking the drug and they are long-term survivors.

Are the insurance companies going to say you need to take imatinib, because it is our formulary and it is cheaper? Insurance is going to have a big impact on these decisions. These patients are going to run out of money.

Ms Allen-Bard: This brings me to the study over in Europe looking at patients who have been "disease-free" or whose disease has been undetectable for more than 2 years.^[13] Do we stop using the drug and observe and see what happens? That trial is running and has shown us about a 60:40 split, with about 60% of patients relapsing.

Ms Bauer: It is too early to say whether we can stop. I think we just have to wait it out and see. We do not have the longevity of imatinib yet or the other drugs either. We do not even have 10 years of experience with nilotinib or dasatinib yet. It has only been really 10, 11 years since these medications have been developed, so it is still very early.

Ms Rios: I find the data on stopping therapy very intriguing because, of course, I project my own feelings onto all my patients and say I do not want to take a drug every single day of my life; of course I want to stop the therapy. But it is highly individualized.

We have physicians in our hospital who believe you can stop therapy, and we do stop it. Eligible patients have to be in a complete molecular remission for at least 2 years. Many of them are in complete molecular remission for much longer than that. We monitor the molecular response by peripheral blood PCR at least every 2 months when they come off therapy.

Ms Allen-Bard: We also have been offering patients the option to stop, but only a very small number of patients, a select few. We have been monitoring their PCRs monthly just to keep an eye on them.

Ms Bauer: This approach relies on individual institutions' guidelines.

Ms Rios: Right, it should never take place outside of a clinical trial. That is how we are doing ours.

Dr Ault: At the least with very, very close monitoring.

Ms Bauer: It would be better in a clinical trial setting, because then you can record all the data and put it out there.

Ms Allen-Bard: Are there any predictors of poor adherence?

Dr Ault: There are not a lot of studies out there, but we are finding some trends.^[14] We found that the single male who is unemployed is less likely to be adherent. On the other hand, a working, married person, whether male or female, is more adherent. Patients need their support system. If they have a good relationship with their clinicians, they are more apt to call. And as I said earlier, their belief system is important: "Do I believe that this is beneficial for me to take the rest of my life?"

Let us say your patient is 20 years old -- and it seems to me that CML is no longer an "old man" disease. We see a lot of young people coming in. And they want to start a family, they want to go party -- there are all aspects of life for them, and we need to look into all of these big issues.

Ms Bauer: Yes, but you have the same issues with patients with diabetes and hypertension.

Dr Ault: Except that cancer is a little more persuasive. We have tried to compare adherence in cancer to that in hypertension and diabetes, but I do not think they can be compared that way. If you miss 4 pills of your hypertension medication, are you going to have a stroke? You do not know. So nowadays, I am putting more importance on educating the patient for long-term survival. It is a chronic disease now, and we have to manage it as a chronic disease. When it no longer is chronic, you are into a very acute stage of disease with a rapid death.

Ms Allen-Bard: On the other hand, I have had patients who stop taking their CML medicine but not their hypertension or diabetes medicine. They say they do not want to have a stroke. They do not seem to be as worried about CML evolving into acute phase that does not respond to any treatments. So it is interesting how different people choose which medications to continue to take.

Dr Ault: I still see them taking their CML medication first. The main theme among our patients in one study that we just finished was, why would anybody miss their medication? It is a death sentence. So I think we are doing the right thing. We are educating our patients.

Ms Bauer: As you said, there are plenty of tools out there on websites.

Dr Ault: All kinds of things.

Ms Allen-Bard: You improve adherence by education.

Dr Ault: Education was our main goal. We put it online, and we can recommend the sites our patients can go to for more education. They also have great networks. They are always talking to each other, so they are always discussing that. I think that is a good thing.

Ms Allen-Bard: Yes, websites are big; the blogs and CML Earth and all these support systems that are on the Internet are quite useful.

Dr Ault: Plus there is this kind of programming, peer education. I think there are a lot of people who do not know everything in depth, and if we continue with the peer education, then pretty soon it is in the literature and in the publications; it is very important.

Ms Bauer: We also should note the importance of caregivers. We should educate them as well, so they can help patients.

Dr Ault: Yes, people with smaller support systems, not as much caregiver help, are also prone to less adherence. You are right; the caregiver is very important.

Ms Bauer: We always forget about the caregivers.

Ms Allen-Bard: Support systems are very important, especially for side effects management and calling clinicians, and even just as a kind of cheerleader behind the patient.

Thank you very much, panel. I think it was a great discussion. In summary, we have covered several things: that we want to have patients adhere to the correct medication; that we, as healthcare providers, need to choose the correct medication for patients that best suits their lifestyle and their needs; and that it is necessary for our patients to then be able to stay on the medication, because the need for adherence is the most important thing for these patients to understand.

We also learned how to monitor patients correctly according to the NCCN guidelines, and we want to keep these patients reaching the milestones.

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