CLL Treatments and Clinical Trials Archives

When it comes to treatment, CLL patients and their care partners have much to consider. There are often many options available, each with advantages and disadvantages. Some people may seek clinical trials, others may have few feasible options. Understanding treatment options, goals, and what to expect are vital to achieving the best possible outcome for you.

More resources for Chronic Lymphocytic Leukemia (CLL) Treatments and Clinical Trials from Patient Empowerment Network.

Confused About Immunotherapy and Its Side Effects? You Aren’t Alone

“You don’t look like you have cancer.”

More than one patient undergoing immunotherapy to treat cancer has reported hearing statements like that. Immunotherapy is one of the recent advances in cancer treatment that belie the stereotypes about the effects of cancer treatment. 

The side effects of immunotherapy are different from those associated with chemotherapy and radiation. However, that does not mean immunotherapy does not have side effects. Patients and care partners need to be aware of these potential side effects and to be vigilant in addressing them with their oncologists because they can signal more serious complications if left untreated.

What is Immunotherapy?

Despite the increase of immunotherapy treatment options in recent years and considerble media attention paid to advancements in this field, there remains confusion about immunotherapy and its side effects. Many cancer patients are unaware of whether immunotherapy treatments are available for their specific diagnosis. Others don’t know that genetic profiling of their tumors is usually required to determine if immunotherapy is an option and not all treatment centers routinely conduct genetic profiles of tumors. A  survey by The Cancer Support Community found that the majority of patients who received immunotherapy knew little to nothing about it prior to treatment and were unfamiliar with what to expect.

Immunotherapy works by manipulating the patient’s immune system to attack cancer cells. It is perceived as gentler and more natural than chemotherapy and radiation, without the same destructive effect on the body’s healthy tissues.  This, combined with a lack of prior understanding of immunotherapy, can lead patients and care partners ill-prepared for possible side effects.

Furthermore, immunotherapy is a category of therapies, not a single type of treatment. There are a variety of immunotherapy drugs, most of which are administered via infusion.  Side effects will vary by drug, the cancer and its location, treatment dose, and the patient’s overall health.

The following are the most common types of immunotherapy.

  • Checkpoint inhibitors use drugs to block proteins in the patient’s immune system that would otherwise restrain the immune system, often referred to as taking the “brakes” off the immune system.
  • CAR-T therapy modifies the patient’s T-cells in a lab to enhance their ability to bind to cancer cells and attack and kill them.
  • Oncolytic virus therapy uses genetically modified viruses to kill cancer cells.
  • Another therapy uses cytokines (small proteins that carry messages between cells) to stimulate the immune cells to attack cancer.

Immunotherapy can be part of combination therapy. It might be combined with chemotherapy. It might be used to shrink a tumor that is then surgically removed.  Or multiple immunotherapy drugs might be used simultaneously.

What Are The Side Effects?

With immunotherapies, side effects typically occur when the immune system gets too revved up from the treatment. The most common side effects for immunotherapy treatments are fatigue, headache, and fever with flu-like symptoms. Some people also experience general inflammation often in the form of a rash. Many melanoma patients report blotchy skin discoloration, called vitiligo, during treatment. These milder side effects can usually be managed with over-the-counter remedies and adjustments to daily activities.

For checkpoint inhibitors, the fastest growing segment of immunotherapy treatments, mild side effects occur in 30% – 50% of patients. Serious side effects typically occur in less than 5% of patients. (See “Understanding Immunotherapy Side Effects” from the National Comprehensive Cancer Network and the American Society of Clinical Oncology.)

Less common side effects are blisters, joint pain, thyroid inflammation, and colitis (inflamed colon resulting in diarrhea with cramping). Some patients who receive CAR T-cell therapy develop a condition known as cytokine release syndrome, which causes fever, elevated heart rate, low blood pressure, and rash. 

In rare cases, immunotherapy has resulted in lung inflammation, hepatitis, inflammation of the pituitary, and detrimental effects on the nervous and endocrine systems. In most cases, the conditions clear up when treatment ends.  However, there have been outcomes in which immunotherapy caused diabetes or tuberculosis.

“Overall there are fewer side effects [with immunotherapy],” explained Dr. Justin Gainor, a lung and esophageal cancer specialist at Mass General during an Immunotherapy Patient Summit hosted by the Cancer Research Institute. “But the immune system can affect anything from the top of the head down to the toes. Any organ has the potential to be affected.”

As the application of immunotherapy has expanded, so has our understanding of the potential side effects. Like most medical treatments, how one person responds to immunotherapy can be different from another even when the cancer diagnosis and drug therapy are the same.

The essential thing patients and care partners need to know about side effects is they should always be reported to their oncologist or nurse oncologist.

Why Patients Should Talk to Their Provider About Immunotherapy Side Effects

Because immunotherapy has created newer therapy options, there isn’t the volume of experiences as with older treatments. The infinite number of variables that patients provide once a treatment moves beyond clinical trials and into the general patient population generate more diverse outcomes.  And, as most therapies are less than 10 years old, there hasn’t been an opportunity to study the long-term effect of these therapies. This is why oncologists advise patients and their caregivers to be extra vigilant in noting any changes experienced during and after treatment.

Many side effects are easy to treat but medical providers want patients to be forthcoming in discussing any and all side effects. This is in part to improve understanding of side effects, but also because a mild cough or a case of diarrhea might be harbingers of a more systemic issue that will grow worse if left untreated.

Patients should not be hesitant to discuss side effects because they fear they will be taken off immunotherapy.  Sometimes a pause in treatment might be necessary, but the earlier the oncologist is made aware of a side effect, the less likely that will be necessary.

In addition, patients undergoing immunotherapy should always take the name(s) of their immunotherapy drugs and the name of their oncologist when seeing medical professionals outside of their cancer treatment team. This is especially important when visiting the ER.  Because immunotherapy drugs are newer and highly targeted to certain cancers, many medical professionals remain unfamiliar with drug interactions and treating related side effects.

Immunotherapy On The Rise

Immunotherapy treatments have resulted in reports of remission in cases that would’ve been deemed hopeless just five or 10 years ago.  The Federal Drug Administration (FDA) has approved various immunotherapy treatments for melanoma, lung cancer, head and neck cancer, bladder cancer, cervical cancer, liver cancer, stomach cancer, lymphoma, breast cancer, and most recently bladder cancer.  (Here is a list of  immunotherapies by cancer type from the Cancer Research Institute.)

“It’s revolutionized how we treat our patients,” says Dr. Gainor of Mass General about immunotherapy’s impact on lung and esophageal cancer.

Advances in immunotherapy research and trials continue to generate optimism and excitement. A clinical study in Houston is looking at using immunotherapy to prevent a recurrence. Researchers in Britain recently announced a discovery that might lead to advances in immunotherapy treatments to a much broader array of cancers.

While there is excitement around the field of immunotherapy and it has resulted in unprecedented success in treating some previously hard-to-treat cancers, it remains an option for a minority of cancer diagnoses.  It works best on solid tumors with more mutations, often referred to as having a high-mutational load or microsatellite instability (MSI) high. And it is not universally successful for every patient.

With hundreds of clinical trials involving immunotherapy alone or in combination with other therapies, it is certain more treatment options are on the horizon. As more therapies are developed and more patients with a greater variety of conditions undergo immunotherapy, we will also increase our understanding of potential side effects.

Side effects should not dissuade patients and care partners from considering immunotherapy if it is available or from advocating for genetic tests to deteimine if it is an option. Many patients undergoing immunotherapy have previously undergone chemotherapy and report that the side effects are fewer and milder by comparison.  The important thing is that patients and their partners know what to expect and communicate with their treatment team.

If the next 10 years in immunotherapy research and development are anything link eth elast 10, we can expect more exciting advancements in the battle against cancer. For more perspective on what’s ahead for immunotherapy see the Cancer Research Institute’s article: Cancer Immunotherapy in 2020 and Beyond.

Understanding Clinical Trials: A Jargon Buster Guide

When it comes to cancer treatment you or a loved one may be considering participating in a clinical trial as a treatment option.  Clinical trials are designed to evaluate the safety and effectiveness of a treatment. They may involve researchers administering drugs, taking blood or tissue samples, or checking the progress of patients as they take a treatment according to a study’s protocol.

Learning about clinical trials can be a steep learning curve – not least because the process comes with a lot of new terms, acronyms and jargon.  To help you, I’ve put together this list of the most common terms you will find when you are researching clinical trial information. This is not an exhaustive list but it is a helpful starting point. At the end of this article you will see links to find more information.

Adverse Effects (AE)   

Also called Adverse Events, or Adverse Drug Reaction, AEs are any harmful event experienced by a person while they are having a drug or any other treatment or intervention. In clinical trials, researchers must always report adverse events, regardless of whether or not the event is suspected to be related to or caused by the drug, treatment or intervention.

Arm 

Subsection of people within a study who have a particular intervention.

Bias

Bias is an error that distorts the objectivity of a study. It can arise if a researcher doesn’t adhere to rigorous standards in designing the study, selecting the subjects, administering the treatments, analysing the data, or reporting and interpreting the study results. It can also result from circumstances beyond a researcher’s control, as when there is an uneven distribution of some characteristic between groups as a result of randomization.

Blinding

Blinding is a method of controlling for bias in a study by ensuring that those involved are unable to tell if they are in an intervention or control group so they cannot influence the results. In a single-blind study, patients do not know whether they are receiving the active drug or a placebo. In a double-blind study, neither the patients nor the persons administering the treatments know which patients are receiving the active drug. In a triple-blind study, the patients, clinicians/researchers and the persons evaluating the results do not know which treatment patients had. Whenever blinding is used, there will always be a method in which the treatment can be unblinded in the event that information is required for safety.

Comparator

When a treatment for a specific medical condition already exists, it would be unethical to do a randomized controlled trial that would require some participants to be given an ineffective substitute. In this case, new treatments are tested against the best existing treatment, (i.e. a comparator). The comparator can also be no intervention (for example, best supportive care).

Completed

A trial is considered completed when trial participants are no longer being examined or treated (i.e. no longer in follow-up); the database has been ‘locked’ and records have been archived.

Control

A group of people in a study who do not have the intervention or test being studied. Instead, they may have the standard intervention (sometimes called ‘usual care’) or a dummy intervention (placebo). The results for the control group are compared with those for a group having the intervention being tested. The aim is to check for any differences. The people in the control group should be as similar as possible to those in the intervention group, to make it as easy as possible to detect any effects due to the intervention.

Efficacy

How beneficial a treatment is under ideal conditions (for example, in a laboratory), compared with doing nothing or opting for another type of care. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed.

Eligibility Criteria/ Inclusion and Exclusion Criteria

Eligibility criteria ensures patients enrolling in a clinical trial share similar characteristics (e.g. gender, age, medications, disease type and status) so that the results of the study are more likely due to the treatment received rather than other factors.

Follow-up

Observation over a period of time of participants enrolled in a trial to observe changes in health status.

Informed Consent

A process (by means of a written informed consent form) by which a participant voluntarily agrees to take part in a trial, having been informed of the possible benefits, risks and side effects associated with participating in the study.

Intervention

The treatment (e.g., a drug, surgical procedure, or diagnostic test) being researched. The intervention group consists of the study participants that have been randomly assigned to receive the treatment.

Investigator

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator (PI).

Multicentre Trial

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.

Number needed to treat (NNT)

The average number of patients who need to receive the treatment or other intervention for one of them to get the positive outcome in the time specified.

Outcome Measures

The impact that a test, treatment, or other intervention has on a person, group or population.

Phase I, II, III and IV Studies

Once the safety of a new drug has been demonstrated in tests on animals, it goes through a multi-phase testing process to determine its safety and efficacy in treating human patients. If a drug shows success in one phase, the evaluation moves to the next phase

  • Phase 1 tests a drug on a very small number of healthy volunteers to establish overall safety, identify side effects, and determine the dose levels that are safe and tolerable for humans.
  • Phase II trials test a drug on a small number of people who have the condition the drug is designed to treat. These trials are done to establish what dose range is most effective, and to observe any safety concerns that might arise.
  • Phase III trials test a drug on a large number of people who have the condition the drug is designed to treat. Successful completion of Phase III is the point where the drug is considered ready to be marketed.
  • Phase IV trials can investigate uses of the drug for other conditions, on a broader patient base or for longer term use.

Placebo

A fake (or dummy) treatment given to patients in the control group of a clinical trial.  Placebos are indistinguishable from the actual treatment and used so that the subjects in the control group are unable to tell who is receiving the active drug or treatment. Using placebos prevents bias in judging the effects of the medical intervention being tested.

Population

A group of people with a common link, such as the same medical condition or living in the same area or sharing the same characteristics. The population for a clinical trial is all the people the test or treatment is designed to help.

Protocol

A plan or set of steps that defines how something will be done. Before carrying out a research study, for example, the research protocol sets out what question is to be answered and how information will be collected and analysed.

Randomized Controlled Trial (RCT)

A study in which a number of similar people are randomly assigned to 2 (or more) groups to test a specific drug, treatment or other intervention. One group has the intervention being tested; the other (the comparison or control group) has an alternative intervention, a placebo, or no intervention at all. Participants are assigned to different groups without taking any similarities or differences between them into account. For example, it could involve using a computer-generated random sequence. RCTs are considered the most unbiased way of assessing the outcome of an intervention because each individual has the same chance of having the intervention.

Reliability

The ability to get the same or similar result each time a study is repeated with a different population or group.

Sample

People in a study recruited from part of the study’s target population. If they are recruited in an unbiased way, the results from the sample can be generalised to the target population as a whole.

Subjects

In clinical trials, the people selected to take part are called subjects. The term applies to both those participants receiving the treatment being investigated and to those receiving a placebo or alternate treatment.

Trial Site

The location where trial-related activities are conducted.


References

The Canadian Institutes of Health Research (CIHR)

TROG Cancer Research

ICH.org

NICE

Further Resources

American Society of Clinical Oncology’s Cancer.Net trials site

National Cancer Institute (NCI) Clinical Trials lists open and closed cancer clinical trials sponsored or supported by NCI. 

ClinicalTrials.gov database of privately and publicly funded clinical studies

CenterWatch Clinical Trials Listing

How Could CLL Treatment Advances Benefit You?

 

How Could CLL Treatment Advances Benefit You? from Patient Empowerment Network on Vimeo.

 Dr. Kerry Rogers reviews recent chronic lymphocytic leukemia (CLL) treatment advances and explains how patients may benefit from evolving research.

Dr. Kerry Rogers is a hematologist-oncologist at The James Cancer Hospital and Solove Research Institute. More about Dr. Rogers here.

See More From The Fact or Fiction? CLL Series


Related Resources

  

Tips for Determining the Best CLL Treatment for You

  

The Truth About CLL Treatment Options

  

What You Need to Know About Developing CLL Research


Transcript:

Patricia:

Excellent. What do you think about the future – how do you feel about the future of CLL treatment? What makes you hopeful?

Dr. Rogers:                 

Oh. Well, I think a couple things. One is for CLL, in many ways, the future is now, and I think it’s only going to get better from here on out.

So, a little less than a year ago, two very large clinical trials were reported that compared our best chemotherapy to oral targeted therapy with an ibrutinib-based regimen for CLL, and the oral targeted therapy was superior in terms of something we call “progression-free survival,” which is how long people were alive without their CLL coming back or causing problems.

So, oral targeted agents, which, in general, not – everyone’s an individual, so until you try a treatment, you don’t know what’s gonna happen, but in general, have fewer side effects than chemotherapy, are better at controlling CLL than chemotherapy, so that’s what I like to put in the category of “the future is now,” and I think it’s only gonna get better. So, we’re improving on our existing oral targeted agents with next-generation drugs that have slightly different side effect profiles.

We are also studying combinations of these drugs, and oral targeted agents, and monoclonal antibodies to try to make treatment shorter, to try to get remissions deeper, to really try to improve the quality of life of people taking these therapies and not just improve how long they live with CLL.

And then, for people that really have the worst of the luck with CLL that have really high-risk findings, that don’t benefit for as long as we’d like from oral targeted therapies, that their CLL comes back after a couple years on those, I think the most exciting thing is really CAR T-cell therapies and those cellular-based therapies that aren’t donor stem cell transplant because I’ve seen people who have really benefited from those who had terrible problems from their CLL before that, and I think that’s gonna improve quality of life for a very specific subset of our CLL patients.

That is still in clinical trials for CLL, but has been in enough of them I can feel very confident that we have an idea about what the side effects are and how well it works. So, that’s really exciting. Can I add just one more thing about this before I…?

Patricia:                      

Absolutely.

Dr. Rogers:

So, I saw a consult recently for a person that was recommended to start treatment for CLL. His questions for me were, “Should I start treatment now, and what treatment should I take?” This person had never had a treatment before. So, I agreed with his oncologist, who said that he should start treatment now, and his oncologist had talked about several options, but I think with some of the changes in what we’re recommending for CLL, his oncologist had also wanted him to come see me to get a recommendation too, so it was like, “Oh, that’s great. Why don’t you go see Dr. Rogers at Ohio State and see what you should do?”

And so, one of the things he had discussed with the two oncologists in his office closer to his home were, “Oh, we have these – we have ibrutinib, it’s a really outstanding oral targeted agent, but you’ve gotta take it for a really long time, so why don’t you just take chemotherapy, because I think something better will come along?”

And, I was like, “This something better. Literally, this was demonstrated to be better than the chemotherapy. Something better did come along, and it’s this.” So, ibrutinib is better than chemotherapy. I think the idea of “Why don’t we do a less effective treatment because something better might come along?” is not true anymore. We have something better. And, he actually decided to enroll in a randomized phase 3 trial that’s gonna set the new standard of care in CLL, so he was very excited to get treatment as part of a research study. I think he decided that was actually really important to him, and he really liked what the study was.

But, it was just – it was kind of like, “Maybe something better will come along.” I’m like, “Something did.” So, that’s kind of the nice position that many people with CLL are in now. There’s still a lot of work to be done in CLL, but I just get increasingly hopeful as therapies get easier to take and more effective.

The Truth About CLL Symptoms

 

The Truth About CLL Symptoms from Patient Empowerment Network on Vimeo.

When it comes to CLL symptoms, what’s fact and what’s fiction? Dr. Kerry Rogers reviews chronic lymphocytic leukemia (CLL) symptoms and discredits common myths. Want more information? Download the Program Resource Guide here

Dr. Kerry Rogers is a hematologist-oncologist at The James Cancer Hospital and Solove Research Institute. More about Dr. Rogers here.

See More From The Fact or Fiction? CLL Series


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Transcript:

Patricia:

Sure. Let’s talk about symptoms a little bit more. Here are a few things that we’ve heard from CLL patients. Are these fact or fiction? “I shouldn’t travel if I have CLL, since I may get an infection.”’

Dr. Rogers:

I think that is fiction. So, I’ve heard this, too, and the way I like to think about it is if you’re expected to live with CLL for a very long time, you had better go out and do the things you want to do. This is not supposed to keep you a prisoner in your house. Now, if you’re in the middle of starting some sort of more intensive treatment for it, or less intensive treatment, but you started last week, that is not a good time to go somewhere where there are no hospitals – in the middle of the Pacific Ocean or to rural Africa. So, you’ve gotta be smart about those things, but you wouldn’t go to rural Africa the week after you had a heart attack, either.

So, I think for people who are doing well, living with CLL, but aren’t needing some sort of – in situation where they need a lot of medical visits and care right now, definitely travel. And then, yes, you can get infections when you travel, but you can get infections in your own neighborhood, and I don’t think that keeping yourself only in your neighborhood or where you live is really gonna help you live any better.

You do have to be kind of smart about it. So, if you’re gonna go somewhere where there’s malaria, go to a travel clinic. Make sure that you take the advice of the travel clinic. If you’re going to Houston, you probably don’t need to do anything special. If you’re going to Central America, then you might wanna go to a travel clinic. And, as you know, most people with CLL are instructed to avoid live vaccines, so you have to tell the travel clinic, “I’m going X place. What are the recommendations? I’m not supposed to get live vaccines.” Sometimes, they can recommend low doses of antibiotics to avoid this. They have practical ways to avoid it – for ticks, if you tuck your pants into your socks.

So, being cautious and taking care not to get infections is good advice, but I don’t think it really helps people to limit their travel. Does that make sense? If someone got a stem cell transplant or something, that’s a different category. I’m talking about most people with CLL.

Patricia:                      

Sure. Well, you mentioned the problem with live vaccines and patients with CLL. Should patients with CLL get a flu shot or vaccines? Because we hear from some patients – they say they shouldn’t.

Dr. Rogers:                 

Yeah. So, because CLL is a cancer of the immune system cells – B lymphocytes – it makes the rest of the immune system function differently than in healthy individuals. So, the benefit that people get from vaccines if they have CLL is actually less, so the – if you get a flu shot, it doesn’t decrease your risk of getting the flu the same way it would for a healthy adult.

However, it’s still a good idea to do because people with CLL live at a higher risk of infection, and the way I view it is you should take every opportunity to decrease your risk for infection because influenza is curable, and if you can decrease your risk even a little bit, I would do it. Now, live vaccines are a bit of a debate because people who are immunocompromised don’t get them. So, live vaccines are a live virus similar to the on that you’re being vaccinated against.

So, examples of live vaccine are the oral typhoid vaccine, the MMR vaccine – I know we’re having measles outbreaks in some parts of the country, so MMR is kind of off the table. There is an intranasal flu vaccine that’s live. It’s very hard to get these days and uncommon to be offered. So, I recommend people get all the vaccines they’re due as long as they’re killed vaccines.

There is now a new shingles vaccine called Shingrix, which is a killed vaccine. I’ve had many patients get that. We’re not sure how well it works in CLL; probably not as well as in healthy adults, but it is safe, so if you get your hands on it – it’s been on shortage – there’s no reason not to get these things. I do think for people that have had really severe vaccine reactions that’s always an individual conversation with your doctor.

Patricia:

Yeah, it sounds like it. How about this one? “I’m not experiencing symptoms, so I don’t need treatment.”

Dr. Rogers:

That may or may not be true. So, in some cases, especially if people are in monitoring or observation for their CLL, the goal is to start treatment before you get horribly sick, right?

So, in some cases, you’ll see that the changes in the blood really predict that someone’s going to start to be really sick from CLL in the next few months. You might see their platelet count is going down, or their hemoglobin is going down a lot, and so, there’s kind of a level – so, a platelet of 100 and hemoglobin of 10-11 where you think about treatment. It’s not like, “Oh, you hit this level, you need to do treatment tomorrow,” but it’s time to plan a treatment.

Also, that is the one group of CLL patients where a bone marrow biopsy is really needed to make sure that the decrease in blood counts is CLL and not something else. Most of those people feel fine, but if your platelet count is headed down, it’s probably best to start treatment before your platelet count is below 10 and you start having bleeding symptoms. So, there are some people who are recommended to take treatment for CLL because their doctor has noticed that they’re gonna be at risk for developing problems or symptoms that might make them feel much less well.

And so, you wanna start the treatment when you’re still feeling good and before you’re having a lot of bleeding and issues. However, the majority of people who don’t have symptoms don’t need treatment for it. Quite a while ago, they did randomize people with intermediate- or high-risk CLL to either chemotherapy at diagnosis or delayed until they had one of those treatment indications I’ve been talking about, and treating it with chemotherapy just because you’ve diagnosed it did not help people live longer or better. So, if people are not having symptoms and their doctor doesn’t notice a problem, there’s no reason to treat it.

Patricia:                      

We talked a little bit how diet and exercise can help with symptoms, but can they control symptoms? Tricky question.

Dr. Rogers:                 

I’m not sure. I think that’s really individual. The thing I get asked all the time is, “What diet do I go on to make my CLL go away, or so I never need treatment?” And, there are no evidence-based diets to make your CLL go away. The coffee enema thing doesn’t work. The no-sugar thing – I’m not sure that works.

I do tell my patients to try to eat and behave as if they’re gonna be around a long time because people with CLL usually expect to live many, many years, and heart disease is still killing people in this country, so you can’t stop managing your diabetes, you can’t start eating hamburgers when you have horrible heart disease, so I think you still have to follow a regular, healthy adult diet.

Most people feel better if they eat fruits and vegetables and try to eat a well-balanced adult diet, so I think that helps pretty much everyone, even healthy adults, but I don’t have any specific diet to control CLL symptoms, although I did have one guy that said ever since he’s been eating white toast every morning, all his symptoms are much better. So, if you find something that works for you, it doesn’t matter what it is. If it’s working out for you, you should do it.

How to Take Control of Your CLL Symptoms

How To Take Control of Your CLL Symptoms from Patient Empowerment Network on Vimeo.

 From fatigue to swollen lymph nodes, Dr. Kerry Rogers discusses her approach to managing common chronic lymphocytic leukemia (CLL) symptoms.

Dr. Kerry Rogers is a hematologist-oncologist at The James Cancer Hospital and Solove Research Institute. More about Dr. Rogers here.

See More From The Fact or Fiction? CLL Series


Related Resources

  

The Truth About CLL Symptoms

  

Fact or Fiction? CLL Treatment & Side Effects

  

Overwhelmed By a CLL Diagnosis? Key Steps to Take


Transcript:

Patricia:

Dr. Rogers, we’ve talked a little bit about symptoms – fatigue, night sweats, swollen lymph nodes. How do you manage the symptoms of CLL?

Dr. Rogers:

That’s a good question. So, if people have enough symptoms from CLL that’s really impacting their life significantly, then I suggest they take a CLL treatment.

So, if people have big lymph nodes that are interfering with what they’re doing – like I said, that nice man that was too fatigued to get his mail off his porch – that’s a reason to do a CLL therapy, treat the CLL, and make those symptoms go away. The really difficult ones are when you’re not sure if someone’s fatigue is related to CLL.

So, there’s many people I take care of that are living with chronic levels of fatigue that are not enough to impair their daily activities much, and you’re not sure what it could be related to, so one thing I like to do for things that aren’t clearly severe CLL symptoms is try to figure out what else could be causing it. So, I know myself and many other physicians I work with closely that treat CLL – we think we might diagnose more people with sleep apnea than fatigue related to CLL, and getting your sleep apnea treated is very important. So, it’s always important to do a very thorough look to make sure that these symptoms are from CLL.

And then, in terms of milder fatigue, treating CLL won’t always make that better because people usually live with some chronic side effects from the treatment, and it’s really hard to improve on feeling really good. So, if people have some mild fatigue but feel pretty good in general, it can really only make that worse at some point. And, I find that people themselves find ways to manage. Some people who might be in the actually elderly category like to nap, especially if they can and they’re retired.

Younger people actually shockingly sometimes find moderate exercise helpful. And, I know a lot of people find moderate exercise helpful for other forms of fatigue. So, for people living with mild levels of fatigue, that is definitely – people have those strategies to exercise. A couple people really improved their nutrition and found it helpful. So, sleeping better, focusing on maximizing benefit from things you can do, is good.

In terms of night sweats that people get sometimes that aren’t too severe, usually, they find ways to manage with fans or things like that in the bedroom.

Patricia:

These sound like important quality-of-life conversations with your physician.

Dr. Rogers:

Definitely. And, I think any time people have symptoms, it’s always good to talk to definitely your hematologist, especially if you have CLL and you don’t know if it’s CLL-related or it could be, and then, also, your primary care doctor or your general doctor, because sometimes, they’re really good at thinking of what else could be contributing, and occasionally, it’s a back-and-forth before you really determine what’s causing this and if it’s CLL-related, but either way, feeling better is really important.

The Truth About the Causes of CLL

The Truth About the Causes of CLL from Patient Empowerment Network on Vimeo.

 What causes chronic lymphocytic leukemia (CLL)? Dr. Kerry Rogers shares facts and addresses common misconceptions about the causes of CLL.

Dr. Kerry Rogers is a hematologist-oncologist at The James Cancer Hospital and Solove Research Institute. More about Dr. Rogers here.

See More From The Fact or Fiction? CLL Series


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The Truth About CLL Symptoms

  

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Transcript:

Patricia:                      

Here we go. Dr. Rogers, let’s talk about facts and fiction around CLL. Here’s what we’ve heard from CLL patients. Are these fact or fiction? “Exposure to pesticides caused my CLL.”

Dr. Rogers:                 

So, this is a very difficult one, and I will preface this by saying I’m not actually an expert in environmental exposures. I am more an expert in CLL management. But, there is some evidence that exposure to pesticides, including Roundup, increases the risk for developing non-Hodgkin’s lymphoma, and there’s a class-action lawsuit against Roundup that my patients keep asking me about.

I think it’s really hard to say for any one person whether or not their cancer is caused by pesticide exposure. If it’s someone that sprayed Roundup in their garden a couple times, then no, I wouldn’t think so. If it’s someone that was bathing in it regularly, exposed to it on the farm all the time, then it might have contributed, but there’s usually more than one thing that goes into someone getting CLL, so I would never plant the entire blame for something on one particular exposure, but I do think it’s quite possible that pesticide exposure can increase a person’s risk for developing CLL and non-Hodgkin’s lymphoma.

Patricia:                      

This is probably applicable just to veterans. “I was exposed to Agent Orange, and it caused my CLL.”

Dr. Rogers:                 

So, the same stuff I said about pesticides applies to Agent Orange, but Agent Orange can be a factor in developing CLL. It is in the VA list of diseases associated with Agent Orange exposure. So, for anyone that was exposed to Agent Orange that developed CLL, I would really encourage them to go to the VA and get their Agent Orange intake interview because they are likely entitled to VA benefits because they have CLL and were exposed to Agent Orange.

Patricia:                      

Do you hear that often from your patients who were exposed to Agent Orange?

Dr. Rogers:                 

That they’ve gone to the VA? Yes. Actually, I have a couple people that – many of these people get care at the VA, which is also great, but I do take care of a couple of people who have VA benefits due to Agent Orange exposure who have CLL for sure.

I also have a couple people that, despite the fact that they were exposed to Agent Orange, didn’t feel like going to the VA and seeing if they could get benefits, and I think that’s very reasonable, too. Whether or not people wanna do that is an individual decision, but is definitely on the list of Agent Orange exposure-related diseases. And so, the VA could provide care, medications for CLL, and in some cases, other financial benefits, so for anyone who would like, I think contacting the VA if you have CLL and were exposed to Agent Orange is not a bad idea.

Patricia:

How about this one? “CLL is only a disease of the elderly.”

Dr. Rogers:

Oh. Well, that one is definitely not true. So, CLL is not really a disease of children. I’ve never seen someone under 18 with it, and of course, the median age of diagnosis is somewhere between 65 and 70, sort of around 65, so that means that there’s a lot of people less than 65 living with CLL.

I’ve seen people as young as 20, I’ve seen some people in their 30s, I see many people in their 40s and 50s, and also, part of this question is what do you consider elderly? I don’t really know that I consider people in their 60s elderly in many cases. So, people in their 90s are usually willing to accept that they’re elderly, but people in their 60s, often, I wouldn’t call them elderly, and I know you draw these age numbers to say you’re a senior citizen, but there’s more things that contribute to the word “elderly.”

So, I guess what I’d say is this is – CLL is definitely not exclusively a disease of the elderly. There are many people in their 40s living with this, and I’ve seen people as young as their 20s, and then, also, you gotta figure out for yourself where you’re gonna draw the line and say “elderly.”

Patricia:

Sure. How about this one? “CLL is genetic, and my children may inherit it.”

Dr. Rogers:

So, this is a very difficult question. Instead of saying CLL is genetic, I think what I would say is that CLL is heritable, meaning it can run in families.

And, the rough estimate is that 1 in every 10 people that are living with CLL have someone in their family that will also get CLL, so we know that it does run in families – not in every case, but many cases – and I think at least in terms of people I’ve seen with this, people come and see me, and they either say, “Oh yeah, sure, my cousin, my uncle, my parents, my brother – everybody had CLL.” Or, they’ll say, “Really? Someone else in my family could get this?” So, it becomes pretty clear who’s gonna have it in their family and who’s not, but it does increase the risk of your family members getting CLL.

The interesting part of that is as a CLL community, I think we have not done a very – or, we have not been able to pin down a gene that causes it. So, if you think about breast cancer, colon cancer, you can say, “Oh, someone has a BRCA mutation, the family needs to get tested, we can do something to avoid your kids getting breast cancer.”

But really, with CLL, they’ve done a lot of research looking at family cohorts – and, by “they,” I mean not me specifically, but other CLL researchers have done this – and really have not identified anything that’s saying, “Oh, if you have this gene, you’re gonna get CLL, you’re at risk for CLL,” so, we can’t say it’s genetic and there’s one gene it’s pinned on, although it might be genetic based on a constellation of genes or a gene we haven’t identified. So, I think that’s kind of interesting.

The other thing that I’ll say that’s really important when thinking about whether or not your family could be at risk for CLL is that even people that have very what we call unfavorable or high-risk CLL, with something like deletion 17p, other family members that have CLL end up having a pre-CLL condition called monoclonal B lymphocytosis, or 13q CLL, or 11q CLL, so they have a completely different genetic feature for their CLL, even though you can tell they’re in the family as people with CLL.

So, it’s not that the CLL genetic factors we use to predict how you’re gonna do with it are inherited throughout the family, just the risk for getting CLL. I think that’s important to realize.

The other thing is that unlike breast cancer, where you say, “Oh, this is in your family, you should get breast MRIs, you should consider a prophylactic mastectomy,” there’s not a good screening system for CLL, and since when it’s diagnosed, it’s observed, and there’s no known way that we have to prevent it, it’s not like you have to go and get your entire family tested because we don’t have a genetic test, and a screening is not as beneficial as it is in breast cancer where you can get a surgery to prevent yourself from getting the disease. Does that make sense? Okay.

Patricia:

Thank you. What are some of the things that you hear from your patients that we haven’t mentioned?

Dr. Rogers:

About CLL?

Patricia:

About the way they got it.

Dr. Rogers:

Oh, the way they got it. Hmm.

I think the most common things I hear from people that we haven’t mentioned are in either the exposure category, to things that aren’t known to cause CLL, or infections, like, “Oh, I had a really bad bout of influenza,” or “I got pneumonia, and then I got CLL.” I don’t know if these – I don’t know if any infections that are demonstrated to cause CLL.

Sometimes, the white count can go up when people have infections in response to that, because they’re still living immune system cells, so if people get diagnosed when they have an infection because they got their blood drawn or because their white count went up because they were sick, but that’s something common I hear. And so, it’s really hard to say, “Your bout of pneumonia isn’t why you got this,” but it is frequently how people get diagnosed with that, so I hear that sometimes.

Patricia:

What are the actual causes of CLL? What do we know?

Dr. Rogers:

So, CLL, like most blood cancers is – the way I like to think about it is that your blood cells are one of the most rapidly growing and dividing cells in the body.

You know how over the course of your lifespan, your skin sloughs off, your hair grows, you have to cut it? So, your blood cells divide and turn over within your body, and they’re really quite rapidly dividing, and when cells divide, they replicate their genetic material, and just because it happens so many times over the lifespan, they make mistakes and pick up mutations.

So, many of the mutations they pick up either cause that cell to die, which is fine, or cause your immune system to attack it as abnormal, which is fine. But, in some cases, the mistake or mutation they made when the cells were dividing causes the calls to become broken or mutated in a very specific way that makes them CLL. And, it’s probably not just one mutation; it’s probably a series of them that accumulate to cause CLL.

And so, some of these things are those things we test for in a FISH panel, like 17p is an abnormal genetic change that happened as these cells were dividing over the course of the person’s lifespan, but there’s probably more changes than that that go on, and eventually, the cells become CLL, grow out of control, and have the common features of CLL. So, that’s how I like to think about it.

And then, these questions of “Oh, did pesticides contribute? Did this contribute? Did Agent Orange contribute?” is really just about did those agents cause your cells to break or mutate more, or in a specific way that would make them CLL? So, a lot of things that cause cancers in general, and not just CLL or increased risks for cancers in general, are things that alter, break, or change DNA.

CLL Staging: What Does It Mean for You?

 

CLL Staging: What Does It Mean for You? from Patient Empowerment Network on Vimeo.

Dr. Kerry Rogers explains chronic lymphocytic leukemia (CLL) staging and how it can impact a patient’s prognosis, treatment options and overall care.

Dr. Kerry Rogers is a hematologist-oncologist at The James Cancer Hospital and Solove Research Institute. More about Dr. Rogers here.

See More From The Fact or Fiction? CLL Series


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Essential Lab Tests for CLL Patients


Transcript:

Patricia:

Let’s talk a little bit about how CLL is staged, Dr. Rogers.

Dr. Rogers:

So, unlike most cancers, where CLL is staged with CT scans or PET scans, the staging for CLL is actually remarkably simple, and I really like this because it limits the amount of testing you have to do for people, especially the people that might be just monitored for their CLL or observed. You don’t wanna put them through a lot of intensive testing they don’t need. So, the only two things you need to properly stage CLL are a complete blood count and a good physical exam.

So, in the United States, we use something called RAI staging, which is R-A-I staging, and before I launch into what it is, I will just say that even RAI stage 4 CLL is very treatable, and people do well for many years, so this is not the same as when you think about lung cancer or breast cancer staging, where stage 4 is a much worse spot than stage 1. The staging for CLL – all of it is still very treatable.

So, RAI stage 0 is when you only have an increase in lymphocytes, which is the CLL cells in the blood. Stage 1 is when you have increasing lymph nodes in addition to that. Stage 2 is an increased size of the liver or spleen. And then, if someone has anemia from CLL, then it’s stage 3, and stage 4 is if you have low platelets from CLL. So, 3 and 4 are indications that the bone marrow’s not working well due to CLL.

Patricia:

Dr. Rogers, it seems like CLL is a very manageable disease. What are you considering when you’re making a prognosis with a patient?

Dr. Rogers:

So, for many people, CLL is a very manageable disease. Like I said, some people have had CLL longer than I’ve been a doctor and have needed no treatment for it. However, there are people with CLL that go on to have a lot of difficulty from it, including not doing well with more than therapy or needing really new, advanced therapies, like something called CAR T-cell therapy.

So, for any individual person, you can never say how it’s gonna turn out for them, but we do use our experience taking care of lots of people with CLL to make an educated guess as to if this person’s gonna be someone that’s gonna expect to need a lot of treatment in their lifetime, or maybe no treatment in their lifetime.

And, the main things we look at in addition to just the staging or are they having symptoms or problems from CLL yet is molecular testing. So, these are genetic tests just on the cancer cells, so they’re not genetic tests that other people in the family get tested for, it’s just changes in the cancer cells, so that can give us a guess as to how long before people need treatment and how well they’ll respond to treatment.

And, I know a lot of people are probably already familiar with this, but there’s a particular chromosome change you can test for called deletion 17p, and that predicts a shorter time to needing treatment, needing more treatments in your lifetime, maybe going on to needing those advanced treatments like CAR T-cell therapy.

It used to be recommended that people with 17p get regular like-donor stem cell transplants, which, in some cases, is still done. And then, on the other end of the spectrum, there’s a chromosome change called deletion 13q, which predicts that in many cases, people don’t need treatment for many years and do very well. So, there’s a panel of chromosome changes that can predict where people are gonna fall on the spectrum.

The other chromosome change that’s become important is something called complex karyotype – and again, this is just in the CLL cells, but the karyotype is the arrangement of the chromosomes and these – the other tests I was talking about are chromosome changes picked up with a test called FISH. This is just looking at all the chromosomes, what they look like, and if there are three unrelated genetic abnormalities are more, it’s something called a complex karyotype, and it predicts people will fall in this category of needing more treatment or having more things to do with their CLL in their lifetime rather than not.

And then, the third thing that is really important is something called – and, this is gonna sound long – but, it’s immunoglobulin heavy chain gene mutational status, and mutations in the immunoglobulin heavy chain gene occur normally as these B cells mature, so people that are mutated have more mature cells that became CLL, and people that are unmutated have less mature cells, and people who are mutated that have more mature cells tend to have fewer problems from CLL in their lifetime, and there’s a few implications for CLL treatment for that category.

So, I kind of take all those things into consideration, and then, the other thing that I think is important to consider is newer molecular testing, but that’s still in development, so I think I’ll just end there for now in what I take into account.

Patricia:

I did want to ask one follow-up. Dr. Rogers, how often do you like to check in with your patients with CLL?

Dr. Rogers:

Oh, that’s an excellent question, because I think it really depends on how they’re doing.

So, people that have had a lot of changes in their CLL, like the white counts increasing, healthy blood counts going down, lymph nodes changing – then usually, I see them back more often, so I even see someone maybe six or eight weeks later if they have a lot of changes. And then, generally, people who are having changes in their CLL are taking treatment for CLL; I’ll see them at least every three months.

However, like I said, there are people who have had this CLL for decades with no changes in how their disease is, so those people I’ll see every six months, or even sometimes once a year, especially if it’s been 10 years and nothing has changed with the CLL. Even though I like them and enjoy seeing them, I’m sure they have things they’d like to do rather than coming to see me.

Key Signs That It’s Time to Treat Your CLL

Key Signs That It’s Time to Treat Your CLL from Patient Empowerment Network on Vimeo.

 Dr. Kerry Rogers defines chronic lymphocytic leukemia (CLL) and reviews key indicators that could signal it’s time for a patient to begin treatment.

Dr. Kerry Rogers is a hematologist-oncologist at The James Cancer Hospital and Solove Research Institute. More about Dr. Rogers here.

See More From The Fact or Fiction? CLL Series


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Fact or Fiction? CLL Treatment & Side Effects

  

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Transcript:

Patricia:

Dr. Rogers, let’s just get a brief overview of CLL and how it progresses.

Dr. Rogers:

So, I’m sure everyone already knows that chronic lymphocytic leukemia is a chronic blood cancer of a cell called the B lymphocyte, and with the frequency that people are getting blood tests these days in the United States, the most common way that I see people diagnosed with this at this time is actually just having an increased white blood cell count when they went to get routine blood counts.

So, it seems like the majority of people being diagnosed are diagnosed at a time when they’re not actually having symptoms from the disease, and maybe everyone already knows or not, but the way that’s managed is that the disease is actually just monitored until some sort of what I like to call “problem” from it develops.

So, I’ll go over what the problems are that can come along as the CLL progresses, but it’s important to realize that there’s many people alive and living with CLL doing very well and not having any problems from the disease yet, and I’ve seen a couple people that have had this disease longer than I’ve been a doctor, and one person that almost had this longer than I’ve been alive with no problems from it.

So, developing something from CLL that’s gonna need treatment is not universal. So, as the – for the majority of people, though, CLL – over its natural history – will go on to progress to cause what I like to refer to as “problems” from it. Some people call them “treatment indications.”

So, when problems are developing is about the time you consider treatment before you get really sick from it, and there’s a couple main ways that the CLL can cause problems. One is that the CLL can build up in the places where those cells live, which is the lymph nodes, so people can get really big lymph nodes in their neck, in their groin area, sometimes inside the body, causing problems. And, lots of people have small lymph nodes that aren’t causing problems, and that’s okay, but if they become really big or problematic, then it’s time to do something about them.

The cells can also build up in the bone marrow, so the bone marrow produces all your healthy, normal blood cells that go into the blood and have a lifecycle in the blood. So, if your bone marrow fills up with CLL cells, then you can’t produce the regular, healthy blood cells, and it’s time to do something about the CLL.

Sometimes, the white count can get really high, and that’s not always a reason to do something, but most people do see – over the natural history or course of having CLL – their white blood cell count and lymphocyte count increases, and there’s not actually a firm number where you say, “Boy, you hit X number, it’s time to treat this,” but if the count is increasing rapidly, then usually, you want to treat this before it increases so much that you develop an issue from that. And then, the last category of things that happen with CLL that’s a problem from it are what we call constitutional symptoms.

So, this can be fatigue that’s limiting your activities, like I took care of someone that was too tired to get the mail from his porch due to CLL. He’s doing great now, but that would be a problem. Sometimes drenching night sweats or an extreme weight loss – and, I’m not talking about people that do Atkins diet lose weight, I’m talking about people that are eating everything and losing weight just because of the CLL.

And, the reason this happens that – CLL is a cancer of B lymphocytes, which are immune system cells, so they can release some of the same chemical mediators that your immune system releases for an infection, and that’s what causes some of those symptoms. But, the main things that progress over the course of having CLL are increasing lymph nodes, lowering of your healthy blood counts due to increasing CLL in the bone marrow, the white count can go up rapidly, or people can develop really problematic constitutional symptoms from it.

Minimal Residual Disease (MRD): What Does it Mean for You?

Minimal Residual Disease (MRD): What Does it Mean for You? from Patient Empowerment Network on Vimeo

Dr. Matthew Davids defines the term minimal residual disease (MRD) and explains its role in managing chronic lymphocytic leukemia (CLL).

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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Transcript:

Dr. Matthew Davids

So, one term that patients often come across when they’re looking online that they might not know exactly what it means is so-called MRD. This stands for minimal residual disease.

And MRD is increasingly becoming an important endpoint in our trials, meaning that it’s a test that we rely on to try to make decisions about treatment in the trials. And we’re hoping that this will be a strategy that we can eventually use in regular clinical practice.

So, what is MRD? Basically, MRD is a way to look, at a very, very molecular level, at tiny, tiny amounts of the disease. And this a feature of the fact that we have very effective treatments for CLL, and so we can give various treatments, whether it’s chemoimmunotherapy or drugs like venetoclax, for example. And then we can look under the microscope in, for example, the bone marrow tissue, and we might not see any CLL cells. So, we might call that a complete remission.

But often, there’s still evidence of molecular disease left behind that we can’t see under the microscope, but we can use very sophisticated biological techniques to actually detect what we call MRD. And we find that, if there is MRD present, that patients don’t tend to have as durable of a remission compared to when MRD is so-called undetectable.

So, it’s a very important term to understand. When patients get to an undetectable MRD state, that’s a very good thing. It means that they’re likely to have a very long response to whatever therapy they had. But you also have to remember that MRD itself has its limits of what it can detect. And so, just being undetectable for MRD does not mean that you’re necessarily cured of the CLL.

And there are patients who have undetectable MRD who later do have a recurrence of the CLL. But it does help us guide the treatment in terms of knowing that patients are in a good remission, that they may be able to stop the treatment that they’re on and enjoy a long response without the need for ongoing treatment.

But eventually, for most CLL patients, the disease will come back. And we can detect that sometimes with this MRD test as well. And that’s an interesting research question ongoing as to whether we should intervene at that point to restart therapy when we first see the MRD test become positive again. And hopefully, that’s something that we’ll continue to learn about as we further explore that question in clinical trials.

Diagnosed with CLL? An Expert Outlines Key Steps

Diagnosed with CLL? An Expert Outlines Key Steps from Patient Empowerment Network on Vimeo.

You’ve been diagnosed with chronic lymphocytic leukemia (CLL), now what? Dr. Matthew Davids explains key steps to take following a diagnosis. Need help speaking up? Download the Office Visit Planner and bring it to your next appointment here.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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How to Learn More About Your CLL


Transcript:

Dr. Matthew Davids

So, if I were diagnosed with CLL today, we’ve discussed some of the resources that are available in terms of educating one’s self about the disease: CLL Society website, other videos on VJHemOnc, things like this. There are other websites that give more basic information about the disease, for example, Lymphoma Research Foundation, American Cancer Society, American Society of Clinical Oncology.

So, personally, I would want to know a lot about the disease. And I would probably first turn to these particular resources, which I think can be very helpful.

I would certainly partner with a local oncologist hematologist who can help guide the management. But one thing that you should remember is that most general practitioners for oncology may only see a few CLL patients a year, and the field has changed quite a bit over the last few years. And it can be hard to stay completely up to date on all of these developments.

So, one thing that I would think would be very helpful for anyone diagnosed with CLL is that, if you do have access to a major center that has someone who specializes in CLL or at least in lymphomas, that can be a great resource. And so, I do recommend, if patients can do it, to try to seek out a second opinion from a CLL specialist. And this can be very helpful even if the recommendation is still just observation, that they can help educate about the disease, identify other resources for educational purposes, and just become a part of your team, to have them available down the line.

And I see many patients like this who come for a second opinion at diagnosis. And I kind of tell them, “Go back to your local doctor. Stay on observation. It’s likely you’ll do well for many years on this watch and wait strategy. But at the time when they’re recommending that you need treatment, come back and see me then. It’s easier to get in once I know you.”

And at that point, I can help reassess, 1.) Do I agree that treatment is really needed at that point? Sometimes, it’s actually possible to wait even a bit longer; and then, 2.) What would I recommend for the best treatment option at that time? Could be a clinical trial that might only be available at that center. And I think unless you have a CLL specialist on your team, it’s gonna be hard to know about those available resources.

So, it’s not that you necessarily need to follow exclusively with a CLL specialist. But it’s more to just have them involved, have them know about you. And that way, if you need them down the line, they’ll be available to help support you.

I think in terms of education and self-advocacy, this is a very personal issue. And so, for many of my patients, it’s very important that they are educated about the disease and kind of know the ins and outs of the different clinical trials and so forth.

But it’s also important to remember that that’s not gonna be true for every patient. A lot of my CLL patients are also older patients, and they may not want to know all the details of what’s going on. I think it is important to have someone who’s involved with your care know about these details. Ideally, if it’s not you, it might be a spouse or a partner or a child, for example. A lot of my older patients don’t wanna know all the details about the molecular biology and the clinical trials. But often, it’s their son or daughter who is there with them who wants to know this.

And so, I think it’s helpful often to bring a family member with you to the visits. Because as you can see even from today, there’s a lot of information to learn, and it can be hard to remember everything.

So, having someone else, another set of ears and eyes, someone else can maybe take some notes at the visit and review them with you later, I think can be very, very helpful in terms of your own self-awareness about the disease.

So, in general, I love when patients ask me questions. Sometimes, they are very savvy questions. They are familiar with the literature, and they can kind of really push me to explain my opinions and beliefs about certain treatments. And sometimes, they’re just very basic questions that may be seem silly to the patient but are really not silly questions.

Really, this is a brand-new area for most patients. They have no experience with this when they first start out. So, they should never feel like they’re bothering their oncologist with these questions. I think it’s really important for them to understand the basics of what’s going on. That should really be a minimum for every patient.

And then for patients who wanna know more about some of the details from the research and the clinical trials, I think their doctor should also be able to help explain that to them as well. So, they should never feel like they’re bothering their oncologist with their questions.

Could a Clinical Trial Be Your Best Treatment Option?

 

Could a Clinical Trial Be Your Best Treatment Option? from Patient Empowerment Network on Vimeo.

Is participating in a clinical trial a last resort or could it be your best treatment option? Dr. Matthew Davids explains the clinical trial process and what’s involved in patient participation.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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Transcript:

Dr. Matthew Davids

My patients often ask me about clinical trials and whether I think that would be a good fit for them. I think there is, in some cases, a bit of a misconception that clinical trials are a last resort for our patients. And we do have some clinical trials that are exploring brand new mechanisms of a drug that have never been used before.

And in that scenario, I would only recommend a trial like that for a patient who has already exhausted all of the standard options.

But I think that, in my opinion, clinical trials should really be the first best choice for most patients. Because we have many trials in CLL that are using the drugs that are already approved, so we know that they’re gonna be effective. And now, we’re putting them together for the first time in new combinations and in new creative ways that will help to advance the field. And most of the trials we have in CLL are not randomized, placebo-controlled. So, patients know what they’re getting. They’re gonna be getting an effective therapy.

And this is a way that they can really get access to cutting-edge care. I would say when you’re a part of a clinical trial, you have a lot of other eyes watching you. In addition to your oncologist and the infusion nurses, for example, you also have research coordinators, research study nurses. Some centers have additional scheduling staff that helps with the clinical trials. So, it’s really a way to get excellent quality clinical care, often getting access to cutting edge treatments.

And so, here at Dana Farber, for example, we try to have a clinical trial option available for patients at every stage of the disease, so that we have trial options for patients who have never had treatment for their CLL, trial options for patients who have maybe only had one or two prior treatments, and then some of those other more experimental clinical trials for patients maybe who have exhausted some of the other options that are available by the FDA-approved therapies.

So, I’m really a huge advocate for clinical trials. I think that’s how we’ll continue to improve the treatment options for our patients with CLL.

CLL Treatment Advances: What Do You Need to Know?

CLL Treatment Advances: What Do You Need to Know? from Patient Empowerment Network on Vimeo

Dr. Matthew Davids reviews promising chronic lymphocytic leukemia (CLL) research and shares online resources for patients to stay informed as treatments develop.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

See More From The Path to CLL Empowerment

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Transcript:

Dr. Matthew Davids

So, this remains a very exciting time for CLL research. The last several years have witnessed the development of a number of these novel agent-based approaches, these oral drugs that target the different pathways inside the CLL cell that the cell survives with.

And so, we’ve really kind of reached the end of the beginning, as I call it, because the first goal, of course, was developing each one of these novel agent drugs on its own. We had to show first that they were safe and figure out what the dose was for patients, and then figure out that they’re effective on their own. And we’ve kind of checked those boxes at this point and reached a point where we have now several different novel agents that are FDA approved already for CLL patients.

And so, I think the big research challenge now going forward is kind of twofold. One is identifying the best combinations of these drugs to put together. And No. 2, identifying which patients will benefit most from which specific combinations.

And so, there’s a number of different clinical trials going on right now looking at these questions.

And just kind of highlighting some of them, one of them is the study of venetoclax with obinutuzumab that I mentioned before. We just had a pretty early readout from this study. But I think it’s gonna be very important to see how patients do over time after they finish the one year of therapy, and both for this study as well as another study called MURANO, which looked at the patients who had already had prior chemotherapy-based regimens and then received venetoclax, in this case with rituximab.

In both cases, when there’s time-limited therapy, I think a key research question is gonna be, when those patients do have progression of the CLL – hopefully years later – do they respond again to that same treatment? Can you use venetoclax again? And do the patients respond nicely? And if they do, then that could be a very nice intermittent treatment strategy to allow patients to be off therapy for a period of time, and then only to receive additional treatment when they need it.

I think another important and exciting area is the combination approaches. And I’ve talked about both ibrutinib and venetoclax as probably two of our most promising new drugs. And so, there are now a number of different studies exploring the combination of ibrutinib plus venetoclax given at the same time. And some of the initial data that’s been published looks very promising. This is a very well tolerated and highly effective combination in the initial studies. It’s all oral, which is nice. So, it’s just pills without the need for any infusions. And again, it’s designed to, hopefully, be a time-limited regimen, and patients hopefully will have a nice durable response after an initial treatment with these two drugs.

There are certainly a number of other drugs that are very promising as well. There’s a whole class that we haven’t talked about yet called PI3 kinase inhibitor drugs. We have two such drugs currently approved now for CLL patients, idelalisib and duvelisib. These drugs also are very effective for treating CLL but tend to have more side effects when they’re given as the first therapy. So, most patients will start with a different therapy. But then the PI3 kinase drugs can be a great option for patients who are in the relapse setting after they’ve had prior treatments.

And there’s another one in development called umbralisib, which also looks very promising and seems to perhaps be even the safest of these PI3 kinase inhibitor drugs. And that’s not yet FDA approved. But we anticipate it’s likely gonna get an approval relatively soon.

And so, combining these new PI3 kinase drugs also with venetoclax is an area of research interest, and a number of other combinations. As you can imagine, the longer the list grows of drugs, the more different combinations we can explore. And we’re trying to use the science from the laboratory to try to determine ahead of time what we think are the most promising strategies because we can’t do clinical trials of every single combination. But those are some of the sort of novel agent studies that I’m excited about right now.

I think the other area that could prove to be very helpful for our CLL patients is CAR T-cell therapy, which stands for chimeric antigen receptor T-cells. CAR T-cell therapy is a way to harness the body’s own immune system to fight cancer.

So, to do this, we would take cells out from a patient. And these are T lymphocyte cells. So, not the CLL cells, but a normal immune cell called a T lymphocyte. And then the cells get educated outside the body to recognize CLL cells more effectively. And they’re grown up and expanded and then reinfused into a patient, where they can go around and kill CLL cells. This can be a very effective treatment and can lead to complete remissions with durability.

And this approach is now in clinical trials. There are some risks to CAR T-cell based therapy. Something called cytokine release syndrome, where patients can get very sick, almost like they have a severe infection, but they don’t have an infection. There’s some neurologic risks to this as well that can be quite scary if they happen but in almost all cases are reversible. So, I think that this is an interesting area of research right now. It’s certainly not yet approved by the FDA for CLL. But we hope that, over time, as the CAR T-cell therapy becomes more effective and has fewer side effects, that eventually it will become a therapy option for patients who have had prior treatments for their CLL.

So, I think despite the fact that we’ve made a lot of advances in the last few years, we still have a lot of work to do in the research area to try to improve our treatments even further for our CLL patients.

So, in terms of how patients can stay informed about all these developments, it frankly is quite challenging, even for us in the field, to keep up with all of this. But there are some resources that can help. The first thing I would say is that the research tends to come along in fits and spurts, and one of the fits is generally the big research meetings where we all gather together to present our new data.

And probably the biggest highlight of the year is the ASH meeting, American Society of Hematology, which is usually in early December. That’s a good time to start looking on the internet for news about CLL, latest treatments, those sorts of things. Often, it’s kind of early December where we first hear about these breaking stories.

Another meeting that’s become big over the last few years is the European Hematology Association, which usually takes place in mid-June. And that’s, again, another time when we often see new data coming about. And one area where I would say this could be very helpful – or one website that I think is helpful – is the CLL Society website. This is led by Brian Koffman, who himself is a CLL patient.

And he kind of collates a lot of the information from these meetings and puts them in one place on his website. He’ll often interview CLL specialists to get their opinion about some of the newest developments. And so, I think Brian’s webpage, CLLSociety.org, can really be a great resource for getting up to date on the latest data.

There certainly are other websites out there now as well which are helpful. For example, another one that I’m working with closely is called VJHemOnc. And VJHemOnc comes to these big meetings, again, interviews a lot of the experts on their takes on the new data.

And I find that this platform in particular, the video-based platform, can be very engaging. It really forces us, as the investigators, to kind of hone down on what the most important key points are and give little snippets about that. And I would think that would be easier for our patients, in many cases, to digest, compared to some of the original papers themselves, which can be quite dense.

So, those would be my major resources that I’d recommend for CLL patients who are looking for additional information on the latest research.

CLL Treatment Decisions: What Path is Best for YOU?

CLL Treatment Decisions: What Path is Best for YOU? from Patient Empowerment Network on Vimeo.

 Dr. Matthew Davids discusses factors that can impact a chronic lymphocytic leukemia (CLL) patient’s treatment course, including genetic testing results, age and co-existing conditions. Want to Learn More? Download the Find Your Voice Resource Guide here.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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Transcript:

Dr. Matthew Davids

So, there are a number of different factors that go into the decision of which of these regimens to choose for the initial therapy of CLL. One of them is certainly the age and fitness level of the patient and what other medical issues they have. So, as patients get above the age 65, they typically may have other medical issues and may not tolerate more aggressive chemoimmunotherapy-based regimens like FCR. But they could certainly tolerate the novel agent regimens like ibrutinib or venetoclax plus obinutuzumab.

Another consideration that comes into play is the biology of the CLL cells themselves. Some patients with CLL have a higher risk form of the disease. We call this either deletion 17p or TP53 mutation. And those patients typically do not benefit as much from chemoimmunotherapy.

So, even younger patients there, we think about a novel agent-based approach. And we have, again, the longest-term data on ibrutinib for that population, although venetoclax plus obinutuzumab is also a consideration.

And then as we think about debating between these different options, we also think about the specific other medical issues that a patient may have. So, ibrutinib does have some risks in terms of atrial fibrillation, which is an abnormal heart rhythm. It can cause patients to be a bit more prone to bleeding or bruising. And so, for patients who have these existing risks, if they have heart disease already, or if they’ve had issues with bleeding recently, ibrutinib may not be the best option, and venetoclax plus obinutuzumab would be appealing for a patient like that.

Now, with venetoclax and obinutuzumab, it can be such a potent regimen that it can break the tumor cells open too quickly. This is something we call tumor lysis syndrome. It’s not something we’ve seen commonly with this regimen. But we do watch patients very closely when they’re first dosing.And so, for example, patients who have poor kidney function might be at a higher risk for this side effect. And those might be patients, again, where we think about ibrutinib as a very good option, since it’s very well tolerated even by patients who have issues with their kidneys.

So, those are some of the factors that go into it. Certainly, patient preference makes a big difference. Some patients don’t mind the idea of going on a pill, and they like the idea that it’ll control their disease in the long term. And so there, a therapy like ibrutinib may make a lot of sense. Other patients may find that they prefer what we call a time-limited strategy. And using the venetoclax plus obinutuzumab makes a lot of sense there because it’s a one-year regimen, and they can stop. But we don’t know yet the durability of those effects. So, those are some of the factors that go into making this important decision as to what to receive for a first therapy.

I think patients have an increasingly large role in making treatment decisions about what they would like to receive, especially for their first therapy for CLL. It used to be that we had very limited treatment options for CLL, and really the only choice was chemotherapy. And so, that was a pretty easy choice if you had no other options.

So now, as I’ve highlighted, we have multiple different choices. We have chemotherapy-based approaches. We have novel agent approaches, both continuous and time limited. And so, I think it’s helpful for patients to educate themselves about the pros and cons of these different options, to get input from a CLL specialist, if possible, and certainly from their oncologist as well as family members and friends, particularly if they have had friends who’ve gone through this. Getting their advice can be helpful.

And reaching out to online supports as well can be a useful thing in terms of educating oneself. And at the end of the day, the patient has to make the decision as to what they think is best for them.

And it might be a different decision for each individual patient. But the good news for patients, even though it can be challenging to make this decision, all of these options are good ones. And so, there isn’t really a wrong decision here. But there may be some that are better suited for individual patients based on their own preferences.

CLL Treatment Options: What’s Available NOW?

CLL Treatment Options: What’s Available NOW? from Patient Empowerment Network on Vimeo.

Dr. Matthew Davids reviews current chronic lymphocytic leukemia (CLL) treatment approaches and discusses the role of watch and wait.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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Transcript:

Dr. Matthew Davids:   So, we’re very fortunate in CLL that we have a number of very effective treatment options. But I would like to start by highlighting the fact that, for the majority of CLL patients when they’re first diagnosed, a watch and wait or observation strategy is generally preferred.

And this goes back to many years of research showing that there’s no survival advantage to starting early with chemotherapy-based approaches.

And we have some recent data with the newer drugs that, even with these better agents in terms of the tolerability, that early intervention strategies still probably don’t make a difference for our patients and are associated still with side effects and risks. So, the first important thing is to understand that it’s okay to be observed and go on to this watch and wait strategy, and that many patients can stay on this type of approach for many years.

However, once treatment is indicated, we do have a number of therapy options for CLL patients. And these go back to chemotherapy-based approaches, which have been around for quite a while now and now include some newer drugs that we call novel agents that are really transforming how we manage the disease. So, for younger, fitter patients, we can still think about chemoimmunotherapy, and in particular a regimen called FCR, which includes two chemotherapy drugs, fludarabine and cyclophosphamide, and a third drug which is an antibody called rituximab.

And this combination works very well, in particular for patients who are very fit and can tolerate it and remains a viable option. An advantage of this approach is that it’s time limited. It’s a six-month course. But there are some significant side effects from chemotherapy and some longer-term risks. And so, it’s something that we think carefully about before we recommend.

We really think about the novel agents now as being a good option for most of our patients with CLL. And these novel agents are typically pills that, in general, tend to be well tolerated, although each one has its unique risks and potential side effects. We’ve been using the drug ibrutinib now for a few years for the initial treatment of CLL. And this drug targets one of the pathways in the CLL that the cell relies on for its survival. And it’s a drug that patients take once per day. And once they start on it, they usually continue on it for a long period of time. We’ve had patients on this drug up to seven or eight years now who continue to do well.

Ibrutinib doesn’t tend to completely eradicate the CLL. But it often gets patients into very good remissions. And if they tolerate the drug well, then they can stay on it long term and control the disease. But typically, the drug is given as a continuous therapy. So, we don’t have as much experience with stopping it at this point. And so, that’s typically how we recommend giving it, is as a continuous drug.

Now, another new option for the initial therapy of CLL patients is called venetoclax, which is another pill that we have had a lot of experience with over the last few years in clinical trials. It was approved for patients who had previously had treatment for CLL for the last three years or so. And then just recently, the FDA gave approval to venetoclax as a first therapy for CLL patients. And we typically give this in combination with a different antibody drug called obinutuzumab, which is given intravenously.

So, this regimen, which we call venetoclax plus obinutuzumab, is typically given for a six-month combination course, followed by about six additional months of venetoclax pills. And then patients stop therapy at that point.

So, one of the advantages of this approach is that, like the chemotherapy, it’s a time-limited approach for one year. And we can often see very deep remissions that allow patients to remain off therapy for a period of time afterwards.

One of the issues so far is just that we don’t have as long-term follow up as we do with ibrutinib. So, we don’t know what’s gonna happen to these patients seven or eight years after they’ve started venetoclax plus obinutuzumab. We certainly hope that this one year of therapy provides a durable response for patients, and it certainly looks promising in that regard so far. But we currently have more long-term experience with ibrutinib as an initial treatment.

So, these are kind of the main options that we think about for patients who need their first therapy for CLL. We always think about observation first. But when patients do need treatment, we move toward either a chemoimmunotherapy-based approach with a regimen like FCR, or ibrutinib, or venetoclax plus obinutuzumab. And so, it’s great to have all these very valuable and effective options for our patients.

You’re Not a Guinea Pig: Understanding Clinical Trial Participation

You’re Not a Guinea Pig: Understanding Clinical Trial Participation from Patient Empowerment Network on Vimeo

“Will I be a guinea pig if I participate in a clinical trial?” CLL expert Dr. Brian Hill explains the clinical trial process and addresses common patient fears and misconceptions.

Dr. Brian Hill is the Director of the Lymphoid Malignancies Program at Cleveland Clinic. More about this expert.

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Transcript:

Dr. Brian Hill:

So, one of the first questions many people ask about being a clinical trial participant is, “Am I a guinea pig?” And what I would say is we’re always practicing medicine. Anything we do, we’re practicing.

But we are always trying to get better whether it’s formally on a trial or not. In terms of side effects of treatment, no matter what – if we have the treatment available, any medication can potentially cause side effects. And it’s very difficult to predict. So, even if you are not on a clinical trial, you could be treated with a standard therapy and potentially have problems or difficulty with it. In terms of clinical trials, it depends where in the sort of journey you are in. If you have never been treated before and now you need to be treated, there are trials that are appropriate for people who are at their first line of treatment.

And this is not typically where we are experimenting with new drugs. So, this is typically where we have established treatments or just sort of trying to compare which one is better. Sometimes these are randomized.

So, there’s a flip of a coin, and you can be assigned to one or another. And I understand why many patients may not want to have their treatment determined by chance. But I would keep in mind that usually if this is being done, it’s been vetted through not just the institution where they are being treated, but often times through review boards throughout the country who basically say, “We think it’s okay to have a flip of a coin decision here because if we have a great treatment which is A and a great treatment which is B and we really don’t know if A or B is better, it’s okay to sort of have a randomization where you may get A or B.”

Sometimes A is the standard and B is likely to be better, but we don’t really know that B is better. And the only way to get the second option would be to be on the clinical trial. So, in that case if you are enrolled, the “worst” option would be the standard.

But it may give you the option of being even better than the standard. And again, if we knew that the second option was better then it wouldn’t be a clinical trial, it would be our standard.  This is sort of how we make progress. And it requires a buy in from the medical community and physicians, but also, it’s important that patients feel comfortable with it. So, that’s kind of for front line treatment. In terms of subsequent therapies, again there are a lot of very good standard treatments available.

And sometimes there are new drugs that are being developed. If the new drug has never been given before to a human, that’s called a Phase One trial. And typically, those are given or offered to people who have had many other lines of therapy and may not have other good options. But sometimes we know that the new drug has been given to people, it’s safe.

The side effect profile is already known even if it hasn’t been given to large numbers of people. And in those cases that would be something around something often called a Phase Two trial where we know it’s safe, but we’d love to see how well it works. And that’s an option for patients as well.

Right. So, outside of talking with your hematologist/oncologist or CLL specialist, there are many other resources for getting information about CLL. The Lymphoma Research Foundation, The Leukemia Lymphoma Society and the CLL Society are all great organizations that have useful websites.

They have 1-800 numbers you can call into. Many of these groups have – I know the CLL Society has a support group in many cities that’s held on a regular basis. And often times there are patient meetings organized through LLS or LRF, the two groups that I mentioned, that allow patients to come and learn from each other and also ask questions of specialists who may be speaking at those events.