 program titled, “Considering Chemotherapy-Free Treatment Options in CLL.” Evolutions in care have led to improved outcomes and more tolerable treatment options for patients with chronic lymphocytic leukemia [CLL]. And now, there is even the opportunity to forego chemotherapy altogether.

I am Dr. Harry Erba, professor in the department of medicine at the Duke University School of Medicine and member of the Duke Cancer Institute in Durham, North Carolina. I am joined today by Nathan Ferguson, who is going to share the details of his journey with chronic lymphocytic leukemia and subsequent treatment with novel therapy. We are also joined by Dr. Ian Flinn, Nathan’s care provider and director of the Lymphoma Research Program at Sarah Cannon Research Institute and Tennessee Oncology in Nashville, Tennessee; Lisa Ferguson, Nathan’s wife and caregiver; Camille Ballance, hematology nurse practitioner for Tennessee Oncology in Nashville, Tennessee; and Doreen Zetterlund, patient/advocate representative from the CLL Society. Thank you so much for joining us. Let’s begin.

I’d like to start with you, Ian. Can you tell us a little bit about CLL, how it fits into B-cell lymphomas, and just how prevalent it is?

 First of all, CLL is a malignancy, one of our white blood cells, a B-cell malignancy. It’s a chronic disorder, as the name points out, meaning it’s a slow growing disorder, it does not generally grow very quickly. It’s very different from say acute leukemias, where they are often medical emergencies.

CLL is a cousin or closely related to lymphomas. Lymphomas are other malignancies of lymphocytes. Generally, they present with large lymph nodes, they’re swollen, whereas patients with chronic lymphocytic leukemia tend to have an elevated white blood count or anemia or low platelets. Now, clinical lymphocytic leukemia is the most common leukemia in the United States, although it’s still relatively rare compared to other cancers. There are somewhere around 15,000 new patients who are diagnosed with CLL every year in the United States.

Because it is a chronic illness, I imagine that more people than that are living with it in the United States.

 Exactly. If you think about the prevalence of the disease, how many people are living with it, it’s huge. Because, thankfully, it does grow very slowly and there are many options for treatment these days.

And now we do have some more options that we’re going to be talking about, but they all were developed based on a deeper understanding of the biology of the disease. Can you share some of that information with us?

 The biology of the disease, as I mentioned, is that these cells are slow growing, and in fact, unlike acute leukemias where the cells grow rapidly, this is a disease of what we call lymph accumulation. Meaning it’s not so much that the cells, at least in the beginning, these malignant lymphocytes are growing quickly, but that they fail to die. Most cells in our body—hair, your gastrointestinal tract&mdash;live through a normal lifecycle, where the cells are supposed to begin as a young cell, then go through a maturation and die off. The problem in CLL is that these cells don’t die off. Now there are some new advances in the biology understanding of how the signaling events prevent these cells from dying off. And there’s a whole class of drugs that have been developed, a whole family of drugs that have been developed, that take away some of these survival signals, block the signals that are driving this slow and perennial growth of malignant cells.

In this case, we’re talking predominantly about a class of drugs called Bruton tyrosine kinase [BTK] inhibitors. And they were a major breakthrough in the development of therapies for patients with CLL. The history dates back to Ogden Bruton, M.D., who was a pediatrician at Walter Reed National Military Medical Center. He noticed that these children who came into his practice had problems with recurrent sinopulmonary infections, lung and sinus infections. And that seminal clinical observation in the 1950s ultimately led to the discovery of what was causing this defect. And it was this Bruton tyrosine kinase, as we now call it, that was missing in these children.

Well we’ve taken that disease and turned it into a therapy. We now pharmacologically, through medications, can block that same pathway using these Bruton tyrosine kinase inhibitors and turn to very effective, low side effect treatments for patients.

We’re also targeting the signals that keep the cells from dying, is that right?

 Exactly. There’s a signaling that occurs that is turned on in CLL cells that shouldn’t be turned on. And so by inhibiting that signaling event, we’re able to block that signal and allow the cells basically to go through a natural death that they should have undergone if they weren’t transformed and didn’t have malignant transformation.

Background on Chronic Lymphocytic Leukemia and Treatment

When I see patients in clinic one of the most common questions I get is, “Why me? Why did I get it?” Are there any risk factors that are associated with developing CLL [chronic lymphocytic leukemia]?

 I get that question too. “Why did I get it? Why didn’t my neighbor get it?” It’s amazing how little we know about this. We do know that CLL is much more prevalent in Western countries than it is in say Asian countries. It’s a rare disorder in Japan. Lymphomas in general tend to occur in a belt in the United States, where they’re more common. For instance, it tends to be around agricultural areas that this is more common. It’s more common in white males than it is in other groups. But exactly why that occurs, we don’t know. It does look like people who immigrate to this country ultimately are low risk. If they are from Asia and they immigrate to the United States, within a few generations their risk becomes pretty similar to the rest of the population. So that led people to think that there has to be some environmental exposure.

And finally, there is a rare form of CLL that is a familial form. And so we know that family members of patients with CLL are at increased risk of getting CLL. That said, you can still take comfort in that the absolute risk of family members getting CLL is small compared to, unfortunately, all the other things that we face.

That’s a really important point. Often, we talk to our patients about some of the genetic changes that we can now identify in the leukemia cells that help with risk stratification. And the first question I get is, “Are those genetic changes things that I can pass on?” And it’s really important to explain that, no, those genetic changes are in the cancer itself.

 Exactly. It’s not what we call a germline mutation. It’s not an inherited thing. For instance, you often hear about how in breast cancer, there are these genes that can be passed on to family members. That’s not what we’re seeing here, and we can’t identify the gene that’s causing CLL. And it looks like there’s not one. When we do molecular profiling of CLL cells, there are many different changes that occur. It’s not just one problem. In lymphomas, there are often these genetic changes that occur where two chromosomes within the lymphoma cells—again, not within the rest of the patient&mdash;break off and often change partners and drive it. We just don’t have that in CLL.

So these cells accumulate. What are the complications that arise from that for our patients?

 You can think of different groups of issues that can occur. I think one of the issues is that as the cells proliferate and grow, you can have problems where they crowd out and cause marrow dysfunction. They don’t allow normal cells—red cells, platelets, other white blood cells&mdash;to grow in the bone marrow. And that means someone can become anemic. Their hemoglobin drops, their energy is going to go down, they’re going to be tired. Their ability to exercise will go down. They can have problems with platelets. Platelets are the cells in our blood that help us clot blood. And so, there can be a bleeding risk if those drop down.

I think one of the harder to quantify but real issues is problems with their immune system. We often talk about what the good white blood cells are, the neutrophils that help us fight off bacterial infections. But even when patients have normal neutrophil numbers, because of these interactions between the different parts of our immune system, even in patients who aren’t actively being treated, there are some defects in the immune system that occur. And unfortunately, this tends to accumulate over time. Patients who are early on in the course of the disease, they may have pretty close to a normal immune system. But as time goes on, whether it’s with or without therapy, there can be other defects that occur and make people more susceptible to infection. Infection is one of the biggest issues that patients with CLL face.

This defect in the immune system not only may lead to infection but some have hypothesized that this might be why CLL patents may have a higher risk of other cancers too.

 Yes, that’s a great point too. There does seem to be a family of secondary disease: most commonly skin cancers, honestly, but there are other malignancies that occur as well. This defect in the immune system may allow other malignancies to grow. We know that no cancer should exist in our body. Our immune system should be able to surveil and take care of that and get rid of and eliminate other cancers. But when your immune system doesn’t work correctly, then it’s an opportunity for cancers to grow, and there is an increased incidence of secondary malignancies in patients who have CLL.

Chronic Lymphocytic Leukemia: Risks and Complications

Doreen, in speaking with patients, do they consider their illness a chronic one that they’re going to have for a while?

 Yes, I think inherent in the name is that this is going to be a lifetime condition. Long remissions are hoped for, and that’s what we’re all striving for. But it is something that you have to adjust to in your life, to make accommodations for that in your life for treatment, for checkups, and for regular medical intervention.

Nathan, how did that information, that’s a chronic illness, affect your lifestyle?

 The chronic portion came probably about a month after I was diagnosed. The first month it was hard dealing with that. And as I got more knowledge and understood the chronic nature of it, it became easier to tolerate. And with the knowledge and these new treatments that have come out, I went from feeling that it was going to be a short-term issue to whatever my options were treatment-wise. And with the new treatments, things are getting pushed out farther and farther. Because of my age at diagnosis, 45 years old, I tend to be on the lower end of the diagnosis range. I have a longer time to deal with it. Knowing that there are more treatments out there, it has switched I believe to a chronic illness, I’m more at peace with it.

It’s a very common reaction, by the way. And just yesterday I was sitting with one of my own patients with a different chronic leukemia, and six months into her chronic therapy for that she said, “When I was diagnosed I was in the go-go-go mode: I’m going to tackle this, I’m going to learn about it.” And now it’s six months later, and that might affect how you feel over time. Has that affected you, your relationship with Lisa, or family?

 It has. I look at my initial diagnosis in two stages. The first was the devastating news. I was 45 years old, I had two kids in elementary school, and at that time as I started researching, I came in right as these novel therapies were starting to come online outside of clinical trials. And that was back when you would type in “CLL” on the internet and it would say, “You’re dead in 7 years.” Misinformation was out there. So the first three weeks were really rough on me. I got the knowledge and the current data as things progressed, but it was definitely a trying time initially. And like I said, the knowledge and getting the provider that I needed, that helped.

 I didn’t understand the chronic portion of it in the beginning. The first provider that Nathan saw, she very much made it seem like we’re going to do chemotherapy and then you’re good to go. As he was seeing his second provider—he had a second provider, and then we went for a third opinion with Dr. Flinn&mdash;the reality of it sunk in for me. And I certainly was grateful that Dr. Flinn could explain that this is becoming more of a disease that you have to manage for the rest of your life. Because of course, I feel like we’re young in the sense that he was 45 years old, I was 35, and our children are young. So initially it was very difficult for me to imagine if the worst were to happen. And we had also just moved to a new state, I’d started a new job. It was a very challenging time for us in general.

But I think as time went on we understood that it is unlikely for him to die any time soon. And I think when you’re constantly dealing with something every day, it just becomes your new normal. It’s not like you feel this shock or overwhelming grief forever. Initially you do. I think, too, we have children who are young, so it forced us to not focus too heavily on it. The kids still needed us, still had their own problems and things that we had to deal with, and that was helpful. But yes, initially it was a very shocking thing to deal with and it was rough.

We’re going to come back to talking about your children. Ian, I want to come back to you though. It sounds like Nathan went into therapy quite quickly, and we’ll talk about why that might be, but does everyone need therapy immediately?

 No, thankfully not. Many patients are diagnosed these days through a health maintenance examination. They get a CBC [complete blood count] drawn. Their physician realizes they have a mildly elevated white blood cell count. They’re completely asymptomatic and really have no need for therapy at that time.

We know through decades of clinical trials that we do not need to start therapy at the time of diagnosis. This is one of the hardest concepts to get across to patients to begin with. They say, “You just diagnosed me with a cancer, and you want to do nothing? You must be crazy.” Everything anyone has ever learned about treatment of cancer is that early therapy is the key to long-term success. Diagnosis early and then treatment. But this one of the exceptions. And we know that our therapies today are excellent. They are really good. They’re so much better than they were a decade ago.

But people aren’t necessarily better off being treated early in the course of the disease than waiting till they start to show signs or symptoms of it. I tell patients that if you come in to me and the first thing I ask you is, “Can you tell that there’s anything wrong?” and they say, “No, I can’t,” then there’s no medicine that I can give you that’s going to make you feel better than that. And so, we’re oftentimes better off waiting until there are other clinical manifestations; they start to develop problems from the disease, and then we start therapy at that time.

Ian used some of those words, “watch” and “wait.” Camille, what do patients tell you about this watch and wait approach?

 What’s interesting is that we’ve had some patients come to see us who actually want to watch and wait, where they’ve been to other providers and they know enough about the disease or they want to push treatment off. I just try to tell patients that, like Dr. Flinn said, as long as they’re feeling good and there are no obvious reasons to start treatment, then it’s not going to harm them in the long term. Because I think that’s a question they have, right? What kind of damage is this going do to me if we don’t do anything right now? And so, you just have to reassure them that there are not going to be any long-term issues with survival or organ damage if we don’t do anything.

But Doreen, some patients say it’s not watch and wait, it’s watch and worry.

 I think the most important thing is to educate yourself. And with chronic lymphocytic leukemia [CLL], we usually have time before we need treatment. It’s so important to educate yourself and make sure that you’re getting accurate information. The CLL Society was formed by a group of patients, led by a doctor who was a patient with CLL himself, and knew the importance of trying to get accurate information out there because there is so much on the internet that will increase that worry.

If you educate yourself before you need treatment, I call it frontloading your education before you need it. Learn the options out there. Learn your markers and what the best options are for your CLL. And then you can sit back and wait and know what to look for. Of course, your care provider will be watching you closely. And then when it’s time to start treating, you have whatever treatment is suggested. You have an idea of, what are the side effects of that treatment? What are the benefits of combination treatments? I think education is the most important thing in that watch and wait period.

 I would add to that because I completely agree, but I also think it’s important to be careful of where you are going for your education. As you were saying, there is so much information, but not any wisdom behind it or context. The people can get really afraid.

 And cllsociety.org is the organization: there are all sorts of resources, videos, a glossary of terms, treatments, and doctors who specialize in CLL. There’s so much information there, and that group has culled the information to make it current and accurate.

The Indolent Nature of Chronic Lymphocytic Leukemia

Let’s move on now and let’s get to why we—the four of us on the ends&mdash;do what we do every day. It’s for Nathan and Lisa. Why don’t you bring us through your story? How did you present? What did doctors do for you in terms of evaluating you? How was that?

 I had a little bit of a different diagnosis journey. As Lisa had said earlier, we moved in early 2016. Looking back on it, I hadn’t been feeling very well. I was working in the ER [emergency department] during the night shift, so I was moving back and forth from days to nights, and I was feeling down from that. So there was general fatigue, but I blew it off as just getting older and working the night shift. And earlier in the year, I started to developing hives, and I’d never been allergic to anything in my life. I started trying to figure out what was going on with that. Lisa was hired for her job, so then the move was the focus. The hives started getting worse and worse. I could never really figure them out. Finally, I decided that when we get through this move, I need to go see my primary care doctor and see what’s going on. I also had had a touch of a lung issue.

We did the move and the physical portion of the move really destroyed me, more so such that I realized, something is going on. So I saw my PCM [primary care manager] about two weeks after that. I just thought I would go for an allergy referral. He gave me an albuterol inhaler for my lungs. He talked about doing an X-ray of my chest, and I said, “I don’t really think that will do it.” So he agreed to do a CT [computed tomography] scan of my lungs.

I got my allergy referral, set up that appointment. I went and had my CT scan done and I got a call the next day and he said, “Your spleen and a couple of your lymph nodes are looking a little enlarged, so we want to redo the scan with IV [intravenous] dye to get a better look at them.” I asked, “Well, what are they concerned with?” He said, “Well, let’s repeat this and give me a call a week after and we’ll figure it out.” At that point, he didn’t want to do any laboratory work. I quickly booked the CT scan because I was concerned, they called me back and asked about doing some laboratory work to make sure I was OK with the IV dye, and I asked them to do a CBC [complete blood count] on me as well. I went to the CT scan that day and had the IV dye. They drew my laboratory tests earlier. When they finished the CT scan, I asked the technician if he wouldn’t mind pulling up by CBC. So he pulled it up and my white cell count was 80,000 per µL, and as a nurse I knew that was beyond bad. I said thanks and I started heading down to see my primary care doctor, who was in the hospital.

As I was leaving he said, “Mr. Ferguson, they need you down in primary care.” I said, “Yes, I know.” I went down there. The provider I saw said, “We’ve booked you a quick visit to the oncologist today,” and that was the first step. I went and saw that doctor. She felt pretty sure that I had CLL [chronic lymphocytic leukemia]. She was a general oncologist. I hate to say nonchalant, but she said, “We’ll do some chemotherapy and you’ll be OK.” And of course, I was devastated. So that was off-putting a little bit. She handed me a script to go get a port in place and said I’d probably be doing chemotherapy in the next three months. I had a bone marrow biopsy the next day, and that started the first portion of my journey.

 That was in May of 2016. As I said, I was pretty much devastated. I had lost about 14 pounds in three weeks. I’m a stress non-eater. I just had zero appetite, and the key to getting better was getting accurate knowledge and then moving on.

After about three weeks of figuring out that chemotherapy wasn’t really the route I wanted to go, I learned about the new novel therapies. I booked a second opinion in Louisville, Kentucky, at a cancer center there. I went up there, and I liked my doctor there and I told him, “Chemotherapy and ports,” and he said, “No, no, no, let’s get a few months of laboratory work and we’ll start going from there.”

I had found the CLL Society by then, and one of their big caveats is you need to have a CLL specialist in your corner so that you’re assured that you’re getting the best care. I went to my insurance and asked for the third opinion, which I got, and I’m fortunate that I have Dr. Flinn fairly close by for me. I drove down and saw Dr. Flinn and he pretty much agreed with the second doctor, that we’ll watch and see how it goes. And I’d say it was about August of 2016 that I saw Dr. Flinn for the first time. And the goal at that point was maybe to see him every year until something changed.

Mine progressed fairly quickly. I think it was probably due to the stress. I went from an 80,000 per µL white cell count, and I think by December-January, I was 180,000 per µL. And so, after I saw Dr. Flinn, I went back to the James Graham Brown Cancer Center. I saw him a few times and as my count was going up, my red cells were going down and my hemoglobin was going down, so I knew that I was going to need treatment fairly soon.

Nathan's Story: Receiving a Diagnosis of CLL

Ian, is there any other information that you needed about how the diagnosis was made or work-up? It’s leukemia, did he need a bone marrow biopsy to be done? Was there a CT [computed tomography] scan of his belly? All those things, including lymph node biopsies.

 In general, no. There was an era when we did bone marrow biopsies on everybody. Nowadays I don’t really think that’s necessary for most patients. We can make the diagnosis from the peripheral blood. There are sophisticated techniques, flow cytometry, to characterize the cells. There are a bunch of prognostic factors that we now obtain to help us understand what an individual’s risk of progression is, sooner or slower than others. They can be done from the peripheral blood. That’s using FISH [fluorescence in situ hybridization], looking at mutational status of the hemoglobin heavy chain. Now we’re doing next-generation sequencing, where we’re looking at individual genes within the cells to individualize therapy and to understand a patient’s risk. And that can all be done from the peripheral blood.

In general, outside of clinical trials, it’s not really necessary to do CT scans unless someone’s having symptoms or you’re worried about a large lymph node or there’s pain someplace, and you’re trying to evaluate that. That probably doesn’t need to be done very often. And I really don’t do biopsies of lymph nodes either, because all the information you’re going to get from that lymph node biopsy really can be obtained from the peripheral blood. So, unless there’s a specific reason, a symptom that someone is having that’s different in one group of lymph nodes versus the other, then it’s generally not very productive to biopsy.

One of the questions that you’ll see listed in the American Cancer Society for our patients with cancer to ask their physician is, what stage do I have? And I always point out to my patients that staging in leukemias is quite different, because if we use the lung cancer or breast cancer staging, everyone would have stage 4 because it’s throughout the blood and marrow. But we use different staging here. How do patients typically present and what are the stages?

 In the United States we generally use the Rai staging system, it has some very easy clinical parameters. As you mentioned, unlike solid tumors where it makes a difference where the malignancy is, this is a blood cancer. It’s throughout out body, and so that kind of staging system doesn’t work. But we’re looking at whether someone has lymph nodes that are enlarged; whether someone’s spleen is enlarged; whether someone’s anemic; or whether someone’s thrombocytopenic, meaning a low platelet count; or whether they just have an elevated white blood cell count. Those are basically the five stages of chronic lymphocytic leukemia. Of course, the platelets being the more advanced and patients without any lymph node involvement—just an elevated white blood cell count&mdash;is the lowest stage.

I think most patients present with early stage disease. They’re going to present with stage 0 or 1 disease, meaning they have just an elevated white blood cell count or maybe some lymph node involvement. And I think the other thing to point out is that the staging system is really important, but nowadays what’s more important are some of these other prognostic factors. Within the malignant cells, we’re looking at what’s happened to the chromosomes or what’s happened to some of the genes. That turns out to be in the long run probably more important prognostically than even the clinical stages.

Lisa, how was it for you, Nathan going through these evaluations, doctor after doctor after doctor; three doctors, right?

 Yes, three doctors. It was very emotional for me. When he saw his white blood cell count and he called me, I was at work. I work almost an hour away. We had been talking about this before that appointment, so I knew something was going on. I certainly didn’t think it was cancer. So it was devastating for me emotionally because initially, I thought, “OK, are you going to die? Am I going to have raise our children myself?” And so, I wasn’t a fan of the first provider. I liked both the second provider and Dr. Flinn. I thought that they presented everything in a way that was understandable, such that I got it. I’m not a medical professional and Nathan is. I appreciated that, and I think that both of them have very calm natures, which was helpful to me because I was feeling very chaotic inside.

It was just a very emotional time. I was trying to keep it together on the outside and be productive at work, and still make sure our kids had everything that they needed. By the time we saw Dr. Flinn, that was three months into his diagnosis. We had calmed down a little bit. We had a little better handle on what was going on. But yes, it was emotionally very difficult.

What's Included in the Diagnosis and Staging of CLL?

Let’s pick up on Nathan’s story. You were about to get into treatment choices. Let’s first look at the history here and until recently, it was chemotherapy. Do you want to walk us through that, Ian?

 We first started with some of these newer targeted agents about a decade ago, and frankly when we saw such amazing results in patients who had relapsed disease and were no longer responding to chemotherapy, it never occurred to me that we would still be using chemotherapy or chemoimmunotherapy 10 years later.

But relatively recently, we have very good evidence showing that no matter what chemotherapy you used, depending on whether you were old or young, and whatever the underlying risk factors are, in large randomized trials where half the patients get chemotherapy and half the patients get ibrutinib or an ibrutinib combination, ibrutinib—the small molecule, the targeted agent, the non-chemotherapy drug&mdash;is superior, or at least as good as any chemotherapy regimen, no matter what group you’re in. And so, it’s amazing to me that it’s taken this long to get where we are, but these days I think that for the vast majority of people, they’re going to get one of the BTK [Bruton tyrosine kinase] inhibitors or another small molecule targeted agent and not chemotherapy frontline.

You brought up a very important point right at the beginning. How we know these new therapies in the upfront, previously untreated patients are important are from clinical trials. And it’s only through the courage of our patients to join well designed clinical trials, where we’re trying to figure out what is the best approach, that we’re going to actually solve some of these questions. But that takes time. It might be obvious but we have to prove that that the toxicities and the efficacy, the effect of it, are in favor of the new therapy over the old therapy.

 And it seemed obvious to me that this was going to be better. But in reality, that’s not true. I have my own biases, right? I work with these drugs. I see it happen. But it’s not until you test it in much larger patient populations that have people who are young, people who are older, people who have illnesses, and people who are otherwise in good health that you can really tease out some of these subtle differences. And even though my bias was that these drugs were going to be better, we did learn that unfortunately there are side effects associated with some of these medications in the long term, and they have to be taken into account as well.

Camille, this is something that actually oncology nursing as a practice has had to deal with in general in all of oncology, moving from infusional, cytotoxic, tough chemotherapy to oral regimens. What’s that been like? What have you seen with patients in terms of when you were an infusion nurse as opposed to now?

 Well, not for CLL [chronic lymphocytic leukemia], but we still do quite a bit of infusion nursing for some of the other lymphomas. But typically, the oral drugs are much more well tolerated, and the patients are not going to lose their hair, which is big for everybody, but especially for women. That’s a big question that we get. Also, I feel like the GI [gastrointestinal] toxicities are not as bad. You can certainly have GI toxicities, especially when you’re taking more than one oral chemotherapy. But they’re not nearly as bad as with some of the IV [intravenous] chemotherapies that we give.

When we’re preparing patients to go on treatment, I try to tell them they’re not going to have every single side effect, right? You’re not going to have every single one, let’s just start with that. Because it’s just so overwhelming. And especially if it’s someone who we’re having to start therapy for sooner rather than later and they haven’t had time to absorb what’s going on, they are very overwhelmed. Especially when you have patients who are newly diagnosed, they can’t believe that they have cancer to begin with, and now we’re putting them on therapy. It’s important to try to walk them through and let them know that they’re not going to get everything, and that it’s OK to not absorb all of this right now. They can ask questions later. We’re here to help them through it.

Doreen, what are some of the challenges for our patients going from time-limited infusional chemotherapy that’s given in a doctor’s office to getting pills as an outpatient that are quite expensive and are charged to our patients in a different way?

 I’m in a clinical trial so the drugs are provided, which is a huge benefit. And it’s a concern for everybody. We see these drugs having such a great impact on survival and progression-free survival and with limited toxicities. We all want them. And then the question is, how do you get them?

A clinical trial is great. It adds to the science. It provides the drug for a greater number of people. It’s important to know if your insurance company will cover these drugs. And there are grants and other co-pay assistance programs that usually the cancer center nurse practitioners can help you find, or financial folks at your treatment institution. The CLL Society lists these organizations. LLS [Leukemia & Lymphoma Society] has co-pay assistance grants. There are patient access network grants, and it’s good to find the broad range of these organizations that provide these grants. And you can do that as an individual, you can do it through your cancer institution. The CLL Society lists them. Find all of your options, and it’s different for everybody: if you’re on Medicare, if you’re not on Medicare. So you really have to find out what your particular situation is. And I found that it’s difficult to project that. Until you’re there it’s hard to find out what you have access to. You think maybe your income limitations will stop you from qualifying for a particular grant, but that’s not always the case. It’s nice to plan ahead and be aware, but you won’t know what applies to you until you get there.

Ian, I’ll put you on the spot then. We used to call it immunochemotherapy, right? Antibodies against the cells and chemotherapy. Is that out, for first-line therapy?

 I think for the vast majority of patients, it’s out. There are some very niche populations of patients who have very unusual characteristics such that people still argue about it. But I have to say, when I talk to patients and you say, “Would you rather get chemotherapy, or would you rather get a pill?” There isn’t a lot of discussion. It doesn’t go on very long until people say, “I don’t want the chemoimmunotherapy.” The only advantage of chemoimmunotherapy is that it’s an episode of care. It’s six months of treatment and you’re done, for a while at any rate. And so, there’s a rare patient for whom that might be an important characteristic.

However, in our current generation of clinical trials, we’re now looking at ways of using combinations of these oral medications, these targeted therapies, to once again go back to that time-limited therapy, so it’s not so daunting to say, “You’re going to take this pill for the rest of your life.” Being able to say, “You’re going to take it for a year,” is much more palatable, much more attractive.

This is a really important discussion about how chronic the therapy is because I’m an acute leukemia doctor, and I always laugh at the papers that are written saying that some new therapy was relatively well tolerated. Well, it’s relative to what intensive chemotherapy is like for patients. But there are still side effects and they can be chronic. And so, as you point out, this move to making it a time-limited therapy by combining agents is really critical for our patients with CLL.

The Treatment Landscape of Chronic Lymphocytic Leukemia

We’ll move back now to your journey. There you are with Dr. Flinn, and what did you hear him say? It sounded like you already had a very strong opinion, but how did you think about it?

 I did. I was leaning definitely to not do any chemotherapy, I was IGHV [immunoglobulin heavy chain gene] unmutated. I knew that chemotherapy, while it potentially could work, had around a 50% failure rate at five years. I want to say the five-year data had just come out on the initial ibrutinib trials. And while it was a small study for non-previously treated patients, of the 31, 90% of them were still progression-free at five years. So just looking at that I thought it was obviously a better deal, and the curve was pretty much a straight line. And then the group that was in that trial that was previously treated with however many treatments, their curve was steadily heading down.

The doctor who I liked in Louisville, Kentucky, thought at that point I should maybe go through FCR [fludarabine, cyclophosphamide, rituximab] chemotherapy and save ibrutinib for down the road. And I’m looking at these data thinking, I want to be in the top group, not this previously treated group. So I went back to see Dr. Flinn. As I said, at the time it was a gray area in what the choices were. And he brought up that he was about have an ibrutinib and venetoclax trial start. And I had already read up on venetoclax and I thought, that’s what I want to do, immediately. It took a couple of months for Tennessee Oncology to get that spun up and get all their paperwork done, and I pretty much had all my stuff ready to go. I believe I’m his first patient in that trial with his group. The trial in other sites started earlier.

Is that standard treatment now, that combination?

 I wouldn’t call it standard. I think it’s an incredibly exciting concept in trial, and we’re still following patients like Nathan on it to understand the long-term outcomes. But it is a good therapy. I still think the single agent ibrutinib is probably the most common and the most standard frontline therapy. There are other frontline therapies with venetoclax that don’t use chemoimmunotherapy. But regarding the combination of venetoclax and ibrutinib, I don’t use it outside of a clinical trial. I believe in it and I’m hoping that this ultimately will be proven to be the best therapy, but there are a lot of questions that we don’t know the answers to.

As we talked about earlier, it’s also quite expensive if you’re not part of a clinical trial. And I think there’s real debate, or as we say “equipoise,” in the field. And we don’t know the answer about whether you’re better off sequentially using these therapies or using them together at once. And so I don’t do it outside of a clinical trial for most patients.

As long as you brought up clinical trials, I want to put a plug in for our audience that the studies that showed the benefit of these targeted therapies over chemotherapy were sponsored by your tax dollars, our tax dollars. They were sponsored by the National Cancer Institute, and it was Americans with CLL [chronic lymphocytic leukemia] who agreed to be on these studies to answer that very question that was facing you, Nathan, at the time. Lisa, what did you think about his choice?

 I honestly did not have a strong opinion one way or the other. Nathan did a lot of research. Sometimes I felt like he over researched because of where we were in our lives. Our kids are in school and since we had just moved, and he was diagnosed within a couple of weeks of us moving, he didn’t go to work. So he had a lot of time all day long to research. And it was all we talked about for a long time.

Given everything that he understood and knew, and as a nurse himself, he understood things in a way that I didn’t. So I didn’t have a strong opinion one way or the other. There was some fear in feeling like he was a guinea pig. And at 45 years old, with young children, I didn’t necessarily want my husband to be a guinea pig. But I think that’s where the providers were really good about explaining the benefit and how this is one of Nathan’s best chances for a long remission. I trusted Nathan that he understood it more, and I felt that ultimately it was his decision because this is happening to his body. And yes, it’s our lives, but he had to be comfortable, and so I really put my trust in whatever he felt was best for him.

Nathan's Story: Choosing Chemotherapy-Free Therapy for CLL

Nathan, let’s move on to what you’ve experienced taking actually two of the most common drugs we use now in CLL [chronic lymphocytic leukemia], in your case in combination: ibrutinib, which targets BTK, the Bruton tyrosine kinase; and the other pathway, BCL2 [B-cell lymphoma 2], the protein that blocks the cells from dying, that’s where venetoclax works. You’re taking both of them. What have you experienced taking those medications? You got the drugs on a clinical trial, so cost was not an issue.

 I started ibrutinib around January of 2017. My white cell count was about 170,000 per μL. I actually tolerated it very well initially. I had some GI [gastrointestinal] difficulty. Other than that, I tolerated it very well.

Let me ask you, what happened to your white cell count immediately after you started? Did you notice any change? Did it get better right away?

 Mine actually went down, which I think about a third of the patients experience. I didn’t have bulky disease, so my spleen, while enlarged, wasn’t terribly enlarged, and my lymph nodes were enlarged, again, but not terribly enlarged.

So you didn’t have it go up like some patients do.

No. I was having the terrible hives before; I couldn’t go anywhere without bringing Benadryl with me every day. I started ibrutinib, and I think I had a mild case of the hives the second day, and by the third day the hives were gone completely, and they have not returned since. I received ibrutinib for I think three or four months, and then my white cell count went from 180,000 per μL to 40,000 per μL the next month and then down to the 20,000 per μL range. It rapidly declined, so when I started the venetoclax on month four, I was in the 14,000 to 20,000 per μL range. I started venetoclax, and I didn’t notice any real overt side effects from adding the venetoclax.

Did you just start taking it at home, the venetoclax?

 No, I had to come in at that point. They were still working out the tumor lysis syndrome issues.

Let me stop you there. Ian, can you tell us a little bit more about that?

 Sure. Venetoclax is a fantastic drug but it has a side effect such that, in some patients, it causes sudden killing of all the lymphocytes at once. While this may sound like an attractive thing, killing leukemia, the side effect is that it can release potassium, uric acid, and other electrolytes, and there can be damage to the kidneys or arrhythmias. And so that can be a dangerous side effect. But we’ve learned how to give this drug very safely by not giving it all at once but marching up on the dose weekly until we get to the targeted dose. And through this and with careful monitoring of the blood, it can be safely given to patients, and the vast majority of patients can be treated on an outpatient basis.

 I went in, I started the venetoclax. They checked my blood I believe around eight hours later, and unfortunately my disease was a little bit weirder or atypical or non-typical. Usually you’ll have problems with potassium, and actually my phosphorous went up, so I spent the night in the hospital to take care of that. And after that, I had no issues at all with the ramp up of venetoclax. I took both for eight or nine months. They rechecked everything. They did a bone marrow biopsy for MRD [minimal residual disease] negativity, and that was the Y in the trial I was in. I came back MRD-negative, so I was removed from venetoclax, and then I was either put in a placebo group or a group that continued the ibrutinib. It’s blind, so I’m not officially aware of what I’m taking now.

 I personally believe I’m still on it because I still have a little bit of bleeding issues, nothing horrible.

Interesting. Yes, sometimes the side effects can tell you. But let me ask you an important question. I remember this all started during your move. You felt wiped out, and a lot of times my patients who are taking even these chronic medications that target different things still feel fatigue. What happened to yours?

 I would say my fatigue is better. However, fatigue is also a side effect of ibrutinib. I feel better than I did pre-treatment, but honestly for normal everyday life I didn’t feel horrible. It was more if I had to pick up and move something heavy, that is where it really was affecting me pre-treatment. But now I feel fine and I can work out and not feel overly tired.

CLL: Experience With Chemotherapy-Free Treatment

Ian, I struggle with this with my patients. They tell me they’re fatigued, yet they’re going to work, they’re doing all these things. I look at them and I say, “Gee, I feel kind of tired today, too.” What is this cancer or chemotherapy pill, or targeted pill fatigue, that we’re talking about?

 I struggle with the same questions, but it’s real. Quantitatively, there is a fatigue associated with it. I think ultimately that’s why it’s attractive that some of these studies are trying to get people off of treatment because that goes away. And it is often difficult to tease out from the underlying leukemia. We know that CLL [chronic lymphocytic leukemia] causes a lot of fatigue. It can be overwhelming fatigue in some patients, where they can’t even get out of bed. In our world that we live in these days, everyone has some degree of fatigue, but it’s definitely different and more prevalent in patients on these therapies.

Doreen, what do you hear about the fatigue?

 I deal quite a lot with fatigue, and I had it pretreatment. I also have it on continuing treatment. So I continue to deal with fatigue, but what I would say is improved, is the emotional fatigue that came from that watch and wait period. When will I be treated, and what will I be treated with? That worry has dissipated. I know I’m doing well. I’m responding well to treatment, and that degree of fatigue is relieved. But it is ongoing, and what choice do we have? We have to take care of our lives. We have to take care of our families and work if we can, and so you push through.

It is one of the things I discuss with my patients. It may be the pill, and we know these agents do that, but every person who’s touched by cancer is a different person after that. Is it the emotion of dealing with the cancer? It may be very similar to this chemotherapy brain that we hear about. How much of it is the drug and how much of it is our humanity and how we’re dealing with the stress of that? The science has actually had a very difficult time trying to sort that out. Lisa, what do you think? How is he doing?

 I know that Nathan’s personality is such that he doesn’t necessarily minimize things, but I think he realizes there are people who probably have worse situations and feel worse. His personality is such that he said, “Well, yes, I’m tired but it’s not preventing me from taking care of the kids and getting them to their appointments, or going to work.” He’s somewhat minimizing the other side effects as well. He had, and sometimes still occasionally has, GI [gastrointestinal] issues associated with it. And I think he didn’t even mention the joint pain or joint fatigue that he feels; and I know he feels those, he’s just not a complainer. I think for him it wasn’t apparent to anybody that he had cancer, and it wasn’t apparent to other people that he was tired. I think that you made a good point about the emotional fatigue. Certainly with Nathan, I’ve never seen him depressed until he was diagnosed, and that was a very depressing time for us. I think finally starting treatment and moving past it and just increasing your knowledge, it does help to not have that emotional fatigue on top of your physical fatigue. Because I think that people don’t think about the toll it takes on you. I felt fatigued and I didn’t have cancer. It’s just emotionally very difficult.

Actually, as long as you brought that up, let me jump to that. Is there any support for the supporters, any support for the caregivers out there?

 I’m not a group-joining person, but I know that there are support groups for caregivers. I know that there are groups in Louisville, Kentucky. That’s about an hour from our house, so I wasn’t necessarily interested in going all the way there for that specific one. I think you have to find what works for you. I chose to go to see a therapist one-on-one because of his diagnosis and the huge change in our lives, because we had just moved and I just had gone back to work. It caused some depression and anxiety. For me anxiety was a big problem. Yes, there are support groups, but I think it’s about finding what works for you. What worked for me was going to see a therapist to get all of this out and not burden him with it. I was burdening an objective person who could see where I was at and give me tools to work through the depression and anxiety.

Addressing Physical and Emotional Fatigue in CLL

Camille, when you talk to patients and see patients in clinic with CLL [chronic lymphocytic leukemia] on ibrutinib, what side effects are you looking for particularly in terms of how they’re tolerating the drug? What do you ask them about?

 Once they get the drug, we always see them about two weeks after to see where things are. Sometimes the fatigue will get worse before it gets better, depending on what’s going on with the patient, and so I let them know that ahead of time, that it will get better. Those first few weeks can be rough. There can be increased joint pain. There can be rashes. I feel as though we see a lot of rashes, and so that’s something to watch for. Obviously, there are bleeding risks. There are also issues with the heart, so I’m always asking, “Are you having dizziness, shortness of breath,” all of those things, “Is your heart racing?” We have to watch for that. But the first few weeks you really have to encourage them that it will get better because some patients have a hard time.

Yes, we have to be really careful about how we educate them about things that they were doing up until ibrutinib. For example, with the bleeding risk, maybe no aspirin or other drugs that might increase the bleeding risk.

 I think Nathan was told not to use a table saw, just in case.

 Yes, absolutely. Right now, it’s no heavy machinery. We’re not cutting down trees.

 Did we tell him that or did you tell him that?

 I think I probably told him that. I tell all of our patients that.

Camille, sticking with you, how do you ask them about adherence? The drug doesn’t work unless it passes the lips.

 A lot of times I just start with, “Are you having any trouble getting your refills? Are you getting them on time?” I ask about that a lot to be sure that they’re getting them.

Why? Don’t you just go to Walgreens and pick it up?

 They have to come from a specialty pharmacy. We’re very fortunate that we have a specialty pharmacy with the practice that is amazing, and it calls the patient, they do education, and they ensure adherence. But still with insurance and assistance and with the turn of the year and all of that—people’s insurance changes&mdash;I always start with that. And it opens the conversation.

Doreen, how about other ways, forgetting to take your pill?

 I think adherence is so important. You set yourself a timer on your phone if you need to. I’m keeping a diary with the clinical trial, so that helps me to remember because I have to check off that I’ve taken the medication. We’re so lucky to be alive, we have to do our part and adhere to the dosing requirements and our schedules.

Nathan, are there any restrictions on what else you can take around the time you take that pill, any food restrictions or other drugs?

 The main one with ibrutinib is grapefruit, and some certain type of orange.

 It’s in marmalade, so I avoid marmalade. Other than that, for me it’s hard because I was otherwise healthy, so I went through periods where I took a multivitamin, but I was on zero prescription medications prior to this. I do my best to stick to my daily routine of taking it.

 One point I would like to make is that it’s also important for patients on these drugs, ibrutinib or other drugs, to let their doctors or their providers know if some other doctor prescribes another medication. Because there are now very complicated drug-drug interactions, and we always do a computer search and look at someone’s new medications because it can dramatically change how the drug is metabolized in the body and either make the dose much higher than intended or much lower. And so, it’s important that they discuss that with their physicians.

That’s critically important to do, and with their oncologist. Don’t ask the doctor who’s prescribing the other drug, ask the oncologist who’s prescribing the chemotherapy pill. And along those lines, the other group of people who have kept us and our patients out of harm’s way are the pharmacists. But they have a challenge here because, as Camille pointed out, these drugs are coming from specialty pharmacies, and they may not know that our patients who are being prescribed one thing by their PCP [primary care physician] or some specialist are getting that drug. So again, let the pharmacist know but especially let your oncologist know. Yes?

 To back up what Ian was saying, there are herbal supplements. We really have to be careful with herbal supplements, too, because we don’t know how some of these things react with these oral drugs. The patients really have to make sure to let us know if they’re thinking about starting even a diet pill or anything that may seem safe over the counter.

Chemotherapy-Free Therapy for CLL: Communication and Adherence

Life is going on, and you are taking these drugs. You think you’re still on them, not a placebo. Are there any special challenges in terms of chronically being on therapy now?

 No, I’ve pretty much been on it now for three years, a little over that, so it’s routine now. It’s really the only daily reminder I have that I’m on a medication at all.

You said that you’ve been evaluated and you’re MRD [minimal residual disease]-negative. Ian, do you want to tell us what that means?

 MRD or minimal residual disease is a way of looking at the very rare leukemia cells still left in the body. We are looking for the needle in the haystack, the one in a million cell that might still be there. Believe it or not, our definitions of complete remission until very recently would allow someone to still have 30% of their bone marrow involved with CLL [chronic lymphocytic leukemia] cells, and that could be considered a complete remission. And clearly, if you can still see the disease, then you’re not in a complete remission. So now we’re looking at ways of getting to levels that we can no longer find when we use very sophisticated techniques.

There are a variety of different approaches. The most common is through something called flow cytometry, which can either be done on the blood or bone marrow or both. But with these techniques, these new drugs and combinations, we’re able to get patients to unprecedented levels of depth of remission, meaning beyond our ability to detect it. And I think it’s undetectable minimal residual disease that’s going to allow us to get patients off of treatment again. We can go back to these time-limited therapies instead of having someone on continuously. If you can still find the leukemia cells in someone, it’s not surprising that if you take someone off one of these medications, sooner or later the disease is going to come back. And so, this is where this next generation of clinical trials is going in trying to change how we approach the disease.

It sounds like that’s the kind of trial that Nathan is on, where he’s either continuing or not continuing therapy. I think one of the challenges we have obviously is that, yes, the disease can come back, but as you had mentioned, we can sequence these drugs. And as Nathan said, these drugs have side effects. It’s a really important question. Nathan, how do you rationalize the fact that he just told you that he cannot find the CLL in your body, and you’re still feeling tired, achy, and a little bit of GI [gastrointestinal] discomfort from taking a pill? Does it make you want to stop, or maybe forget it some days? You’re going on vacation with your wife, you don’t want to take it. Do you feel any of those things?

 No, I pretty much have it in my mind that I need to take it. It is challenging during vacations. It’s when I get out of my routine that I may miss a dose for that day. Knowing that I am MRD-negative and the chronic nature of taking these pills, I believe that missing a day, while not ideal, isn’t going to really overtly affect my long-term prognosis. But for me, I’m fortunate that my symptoms aren’t causing me undue hardship during the day. Yes, I have some aches and pains, but I had them before I had the CLL. It’s just part of life.

 Doreen, are there any other facilities or referrals out there that can help people with the long-term psychosocial consequence of therapy?

 I think your oncology team is probably best and can refer you to social workers within your treatment center. The CLL Society has different resources, not necessarily psychosocial resources, but there are a lot of places you can start with by accessing those resources. I think your oncology treatment center is probably the best place to go for that. There is a support element to the CLL Society. We started with one group in Orange County in California, and now we’ve spread across the country. We have 38 different groups. You do get a lot of support from being with others who are in your situation and bouncing ideas off of them, symptoms, treatments. I think that sense of community is important, and that can help you ride the waves that come and go in this diagnosis and the chronic nature of the disease.

A discipline that’s growing in many cancers is palliative care teams. Ian, Camille, do you refer your patients to palliative care teams? I’ll start with you Camille. How does that go over?

 Especially for patients who are in a lot of pain or just having a hard time, palliative care teams are wonderful. It really helps when maybe we’ve been trying to manage certain side effects and are having a harder time. That’s what they’re there for. But I would say especially for patients who have a lot of issues with pain, it helps a lot.

 Thankfully that’s not a very common event with CLL. But we use it more commonly in other diseases or sometimes when things aren’t going right in CLL, it can be a great help. But gratefully, it’s not common in CLL.

Considerations for CLL as an Enduring Disease

What is his future like, Ian? What is Nathan’s future in terms of what’s next? Is he waiting for the other shoe to drop? And if so, do you have any tricks up your sleeve?

 I hope we’re not waiting for the other shoe to drop. I’m looking at this as a tremendous opportunity here to not have that happen. But certainly, ultimately, for most patients with CLL [chronic lymphocytic leukemia] the disease comes back, even on these exciting new drugs and exciting new therapies. But there are still opportunities here. I think he was on venetoclax for a short period. It might be that it gets repurposed and back in therapy. We’re now developing next-generation BTK [Bruton tyrosine kinase] inhibitors that overcome resistance. If someone becomes resistant to ibrutinib or to acalabrutinib, there are common mutations that occur, and there are now next-generation molecules and drugs that get around that side effect. So we’re trying to stay one step ahead all the time, and there clearly are other options.

And same thing is happening in acute leukemia, where we have these targeted therapies, and then the disease learns how to be resistant to them. And we’re learning how to target that. So there is a lot of reason for hope, but there’s not going to be one cure for every person. Nathan, how is it living with that knowledge that you’re on therapy and it might come back? How do you deal with that?

 For me and my personality, I look at it more as right now I’m MRD [minimal residual disease]-negative. If I went to some doctor and they told me to get a full checkup, they could look and they wouldn’t find any trace of cancer in me, at least not CLL. I see that as even if it does come back, it’s not like it comes back and I will need treatment tomorrow. It could come back in 15 years and it might slowly progress at that point, and I will have another 10 years. Who knows what will be out there in that amount of time? The new treatment options that are coming down the pipeline right now are pretty amazing, and hopefully the kinks will be worked out of them if down the road, I need them.

Has this affected your interest in other health maintenance? Is it more or less prevalent?

 I think like most people who are diagnosed with cancer, you get spun up and think, “All right, I’m going to go vegan and I’m going to work out every day,” and then life happens. Especially with this, once I had treatment, I’m back to my normal life prior to being diagnosed, for the most part.

 Life is normal. We have our new normal. I would say it’s pretty close to what it was before. For me, I’m a pessimist, I’ll be honest. I’m waiting for the other shoe to drop. As ready as I was for him to get treatment, there was a part of me that felt the opposite, that once he’s in remission, once he’s MRD-negative, then we’re on a timeline, and we don’t know what that timeline is.

And I’m a planner. I do very well with routine, so when Nathan was active duty Air Force and he would deploy, the way I coped with it was that I had a routine. I became, very much, a planner—here’s what we’re doing for the next whatever&mdash;so it is a struggle for me personally because I don’t know what’s going to happen. And I don’t like not knowing what will happen, but I will also say that this has forced me to be more appreciative of our lives right now and focus on how he’s healthy, he’s good, our kids are doing very well, and we are doing very well in our relationship. It’s difficult. It forces you to look at things differently.

Chronic Lymphocytic Leukemia: What Happens at Progression?

I’m going to turn to both Doreen and Nathan for this next question. What are the good sides of support groups for our patients? What are the maybe not so good sides for our patients? My patients come back from support groups, and I hear different kinds of stories. Doreen, what do you think?

 I think it can be mixed. Overall, I think it’s beneficial, but you don’t have to be committed such that you go every single time they meet. You can go as you need it. I think you hear about side effects from other people that may not pertain to you, and that can cause worry, but then you can also hear good stories. You have to just modulate it to your own mood and your own needs. I actually belong to two support groups. One is CLL [chronic lymphocytic leukemia] specific with the CLL Society that really helps me with the education part of it. The other is a general cancer support group, and there are people there with all different kinds of cancers, and sometimes their outcomes are not as good. And so, it can be sad to lose people who you’ve become close to. But I think you have to know when to dip in and when to pull back, and that’s a personal decision.

I actually help run the Nashville CLL Society group, and she’s right, different people can take different things from it. We try to push their website. It’s run by a doctor. It has a board of other CLL specialists, doctors who review content. And of course, the LLS [Leukemia & Lymphoma Society] site has great resources as well. What I try to tell people one-on-one is that while many people have this disease, we’re all different. I can hope that I’m in a certain demographic in the data, but there are always outliers. And some people are very upbeat, some people have issues with depression. If you have an issue with depression, this is going to take more of a toll on you than someone who’s more upbeat. And it’s hard to see how I’m 45 years old, I was diagnosed and treated within seven months, and then you meet someone who’s had it for 20 years and hasn’t had to have any treatment. We’re all different. You try to offer what support you can.

I think the skill of the leader of those groups is really important in guiding the conversation so it’s not all negative or all positive but allows people to speak. And so find the group that you feel comfortable with.

 And we always try to push having a CLL specialist in your corner. You may not necessarily need to see them for every visit, but they need to be part of your treatment plan, so that they’re making sure that you’re going to go down the right treatment path for you or that you’re given the options. And if you choose to go a different route, you’ve at least been informed and know the risks of each option.

 Lisa, are you ready? I’ve been saving this question for you.

One of the most common questions from my patients is, what do I tell my kids? Take a moment. Walk us through that. Nathan is diagnosed. How do you tell your kids, when do you tell your kids, how much do you tell your kids?

 We have always been very open, especially with medical things or body things, health things. Because Nathan is a nurse, we’ve always talked about it in age appropriate clinical terms. So, when Nathan was diagnosed, we actually found out right before our oldest daughter went to a week of space camp down in Alabama, and I did not want to tell her before she went away for five days and had to worry about her dad. At the same time, our younger daughter was staying with my mother in Alabama while my older daughter was at space camp. So Nathan and I actually had a week where we could talk about how we’re going to tell our oldest. Our youngest was 5 years old, so she was pretty young, and I didn’t really think she was going to be as affected by it.

When we got our older daughter home, we were sitting outside on the back porch and we just said—not bluntly, but there’s no other way to say it&mdash;“Daddy has cancer.” And then we talked a little bit about what we knew at the time, which was not a lot, but I think by that time we knew it wasn’t as if he was going to die tomorrow. We told her, we said that there are a lot of treatments, there’s a lot of hope here, and she didn’t want to talk about it for a while. She went into her room, she cried, and then it just became normal. It started as a normal conversation. We talked about it at dinner time. Whatever our previous topics were, this became something that we discussed. And as Nathan learned new things, we would discuss it.

One of the things we do at dinner time is we talk about two good things and one bad thing from our day, so that our kids can focus on how there are more good things that are happening than bad. And it came to this point where every bad thing was, "Daddy has cancer.” After a few weeks of this, I said, “OK, the bad thing cannot be that Daddy has cancer. What else is going on? Let’s try to bring this back to how you still have to live your lives.” I think you have to figure out what works for each of your kids. When we told my oldest, my personality is that I want to talk about everything. Hers isn’t, and you shouldn’t force them to go against their personality. Eventually they’ll open up. They did start a father-daughter diary, where if she wasn’t comfortable verbally asking a question, she could write it in the diary and give it to him and he could respond to her in writing. They did that for a little bit.

With our youngest one, she just thought, “OK, Daddy has cancer.” He took her to the library and she’s very extroverted, so she met this little girl and her mom, and she said, “Oh, we just moved here and my mom works in Louisville and my dad just found out he has cancer.” She was young enough where she could talk about it without realizing the impact. You have to allow for that, too. And I’m grateful that my kids have very different personalities, so it allowed us to tailor it to each of them.

 As I discussed earlier, this was all based off information from my first local oncologist, so it was, “You’re going to get a port and get chemotherapy in three months.” And we just moved there, so I was expecting to be sick a few times a month, and that was what drove that reaction. If I had to give personal advice for people going through this, it would be to see your specialist and get an idea of what treatment is going to look like and when, if you have a few months of lapse, so that you do not have to go through that very quickly like we did. Because we thought we were in a rush when we weren’t at all, and then this comes up quite frequently in forums and with people. They would ask for advice about how to tell your kid, and I always say, “You know your child, I don’t. You should know what your child can handle.” For me personally, use advice off the internet for that. You might say, “My kid is very outgoing and this is how we told her,” but I would leave that choice up to that parent.

 That’s great advice. I don’t know that you can have one way of having this conversation. Every family, every dynamic is different. You also have a very young family. Most patients with CLL are older and their children are either teenagers or adults, and so it’s a very different conversation.

 I think you have to be careful about what you share professionally, depending on what age you are. Once it’s out, it’s out, so you might want to just share that with your closest immediate friends and your supervisor if need be, based on your treatment and the medical follow-up appointments that you have. I think it’s good personally for your soul to share it with people, but you also have to be aware that there are ramifications professionally and socially as well. Share on an as-needed basis.

Chronic Lymphocytic Leukemia: Patient Support and Communication

We’ve touched on this before, but we’re coming to the end of the program. I think we clearly couldn’t cover everything in this short amount of time, and there’s a lot of information out there and there’s a lot of misinformation. I’d like each of you to tell me and tell our audience, what sources are out there for information that is reliable? I’ll start with you, Ian. What do you tell your patients?

Where to go to get information, or not to go maybe.

 I think some of the more mainstream venues such as the LLS, the Leukemia & Lymphoma Society, or the CLL Society, which is a dedicated group toward CLL [chronic lymphocytic leukemia]. You’re going to get very accurate information there. I think those are probably the two places that I tell people to go.

 I would echo that. CLL Society is specific to CLL; LLS in general. But it’s so important to educate yourself and we usually have time, so don’t feel rushed. Take time to educate yourself and make the right decisions for you.

I always like coming back to the point that doctor means teacher, and the most important thing that we can do as physicians is teach our patients what we know about the disease, what to expect, and the treatments. Every cancer patient deserves the time from their physician and the physician’s team to get that. So often, the physician’s team will have nurse practitioners, nurses, and pharmacists who can help. Pharmacists are a great ally in the clinic who can give you real information about the medication that you might be prescribed. But advocate for yourself.

The patient should advocate for themselves, and if you’re not comfortable with the first or the second doctor who’s not giving you that time, find someone who can give you that time because you deserve it. Come with your list of questions. Make your doctor sit down and answer them. But that takes a lot, and patients have to advocate for themselves. You were lucky, Nathan. You’re a nurse. You asked for that CBC [complete blood count] because you knew, and most of our patients don’t have that education. It can be a challenge, but our patients should feel free to advocate for themselves as well when they see their physician. Well, this has been extremely informative. Before we end this discussion, I’d like to open up the floor and ask each of you to provide some final thoughts. I’ll start with you, Ian.

 My final thoughts are that our therapies today are radically different than they were a decade ago, and frankly they’re different than they were a year ago. We’re now looking into new combinations, new regimens, and I think tomorrow they’re going to be even better than they are today. And so I think the thing I’d like to leave people with is that there’s tremendous hope in therapies for this disease.

As Dr Flinn said, it may sound bad, but I tell people that if you’re going to have CLL, there’s never been a better time. And 10 years from now, it’s going to be even better. The person who was diagnosed 20 or 30 years ago had hardly any of the options that we have today.

 I want to just for a second focus on the caregiver. It is important to support the patient and be there for them. But it’s also important to remember that you have feelings about this, too, so finding your outlet and your coping mechanism is really important. I know self-care is a really big buzz word, but it is really important to make sure that you’re emotionally and mentally able to be the best person you can be so that you can support your spouse or whoever the patient is.

 I completely agree with what everybody just said, but also do not be afraid to reach out to the care team, the providers, or the nurses if you need them. Write the questions down and make sure that you’re with a team that will take time with you if you need it.

 I would say educate yourself, and this is not a death sentence. We’re so fortunate to live in this time with these advances in medication. Live your life. Don’t forget to live your life.

I’ll add one final comment, and it piggybacks on what I was saying before. Your physician, your oncologist, and your team are there to educate you about the disease. And you are sitting in a room where you’ve just been told you have cancer, and then you hear what the teacher sounds like on Charlie Brown. That’s what you’re hearing, “Wah, wah, wah,” and that’s all you’ll hear. Bring someone with you. But in my opinion, don’t be afraid to record it. Obviously, ask your physician, but record it. Play it back later. It’s there as a reference for you. Some doctors feel very strongly about that.

 I used to have it happen much more often with people, and I would encourage them to do it for the reasons that you’ve outlined, but less so recently.

Well, thank you for your contributions to this discussion. On behalf of us all, we thank you for joining us. We hope you found this 

 discussion to be useful and informative.

Considering Chemotherapy-Free Treatment Options in CLL