Webinar: Initial Results from a Health–Related Quality of Life Study in Hairy Cell Leukemia
October 6, 2022
Hosted by the Hairy Cell Leukemia Foundation with speakers Dr. Leslie Andritsos from the University of New Mexico Comprehensive Cancer Center and Dr. Mirela Anghelina from The Ohio State University. Moderated by Anna Lambertson, HCLF Executive Director.
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Transcript of Presentation
Anna Lambertson:
The Hairy Cell Leukemia Foundation is a nonprofit organization focused on research and patient education in HCL. Throughout the year, we host regular webinar presentations with HCL experts and we hold meetings for people with HCL to learn from and support each other. We fund new research in HCL to develop novel therapies with the goal of one day finding a cure for Hairy Cell Leukemia.
Today’s webinar is about health-related quality of life in hairy cell leukemia. Just last month, initial results of a study were published in Leukemia Research. This study was funded by the Hairy Cell Leukemia Foundation and the SASS Foundation for Medical Research. Two authors of this study are here today to discuss why health related quality of life is important, why this study was conducted and what these initial results can teach us.
Dr. Leslie Andritsos is a hematologist at the University of New Mexico Comprehensive Cancer Center. Dr. Andritsos has devoted a significant amount of time in her career to HCL. In partnership with the research group of Dr. Michael Grever at the Ohio State University, she has been active in developing and expanding the HCL patient data registry, and she's a frequent author or co-author on HCL related publications.
Dr. Mirela Anghelina is a biomedical informatics consultant at the Ohio State University. She holds an MPH from OSU having previously completed her MD and residency in Romania. In her role at OSU, Dr. Anghelina supports numerous HCL related studies, and she's also a critical partner in the Patient Data Registry Initiative. I'm delighted to welcome both of you here today, and I will turn the time over to you for your presentation.
Dr. Leslie Andritsos:
I want to welcome all the patients who are joining us today. I don't know if any of the patients who were the impetus behind this study are with us. We had a breakout session at our Germany meeting a few years back where we formed the basis of this study. And so we want to thank everyone that has participated and devoted their time to filling out these questionnaires.
I looked at the registration list and I see many of you are here with us today and we really appreciate so much. The participants at the quality of life breakout session at the meeting in Heidelberg and everybody who's been able to participate in this study to this point, we do want to thank the Hairy Cell Foundation and the SASS Foundation for providing funding, and all of our colleagues around the world who have participated in this study, particularly Dr. Zent and his team who enrolled a large number of patients and Dr. Banerji and Dr. Claire Dearden at CancerCare Manitoba and Royal Marsdon Hospital who are working on getting this protocol open, and of course our huge OSU team that has been instrumental in making this research possible and our colleagues at the CCTS at Ohio State.
Dr. Leslie Andritsos:
So the way this all started was, at our annual Hairy Cell Foundation meetings, we usually have patient sessions that can either be educational sessions or discussions about topics that are important to the patients participating. And so at this particular meeting, we talked to a group of German patients about their quality of life. And one of their comments was that this is something that has never actually been studied. And so they had a lot of concerns about two things. One was fatigue as a complication of their treatment, and the other one was fear of catching infection. And so the patients related to us that they were spending more time at home or isolating themselves more than they had before they had a diagnosis of hairy cell leukemia.
And so, we took this to heart. This is one of our missions, being investigators, to answer some of these questions. So we developed this longitudinal study, meaning we follow people over the course of their enrollment up to five years to see how things change with time, and this coincidentally happened during the pandemic of course. And so people entered all at different times in their treatment course.
Dr. Leslie Andritsos:
And for the purposes of this study, because this was actually the first prospective quality of life study in hairy cell, we used validated surveys. So these are surveys that have already been used in other patients with leukemia or cancer to see how our patients compared along those validated surveys. And we also developed a small side survey with the help of our epidemiologist, Dr. Michelle Notten, to look at how having a rare disease impacts your quality of life.
The way it's working, because we need to know where people are at in their treatment course, is that patients who are enrolled in the patient data registry were invited to participate in the quality of life study. So we could look at timing of therapy in relation to quality of life.
This is the paper, we're extremely happy and proud to have it published. And we wanted to emphasize the fact that this research was done at the request of our patients. And we feel like, especially for a rare disease, we need to be spending our time doing things that are important to the people with the disease. We titled this Patient Driven Research, and these are the initial results from this prospective study.
In the same month, we published the registry paper. So I have to say that this paper was a lot longer in development because we did have a major change to the structure of the registry in the middle of it. And so the initial paper that we had written had to be rewritten to reflect the fact that, as opposed to being a registry where people kept their data at their own center, now the data is stored at Ohio State University in a central data registry for a number of different reasons. But a lot of those were data sharing and security agreement concerns.
Dr. Mirela Anghelina:
I'm going to summarize how we designed this study. We created a questionnaire, a set of questions which were built in REDCap database. This is short for Research Database Capture, research capture. And the patients were able to take the questionnaire either electronically or on paper, and as Leslie said before, after we collected the data from the questionnaire, we linked the data from the questionnaire with the clinical data we had in the hairy cell leukemia patient data registry by a unique research identifier. I want to mention that both databases are secure and the information is de-identified so the researchers have access only to de-identified data.
Patients, once enrolled, had to complete a questionnaire at the time of the consent and every six months after that for up to five years. So if we do the math, the application had around 11 surveys to complete. The questionnaire, it takes 25 minutes to complete and it has a set of seven scales. Six of them are already validated for cancer, leukemia, or other chronic diseases. The first six are already validated. The last one, the hairy cell leukemia patient concerns and self-efficacy is the scale which was developed by OSU team. And we hope we are going to validate in the coming analysis.
Dr. Mirela Anghelina:
There are these six validated scales. We put accent on the first two scales and the social support scale. The first scale is called functional assessment of cancer therapy in leukemia. This scale was created to measure the quality of life of patients living with cancer, it has four subscales. And so researchers added a fifth subscale, which contained the leukemia concerns for patients living with leukemia. The second scale is a measure for fatigue for patients living with chronic illnesses.
Dr. Mirela Anghelina:
I included here a snapshot of the FACT leukemia questionnaire, the four subscales I told you about. To calculate the FACT leukemia score, which means to calculate the quality of life score, we have to calculate each subscale and add the score from all five scales. Each subscale has a set of questions and they assess physical well-being, emotional well-being, social well-being, and functional well-being. So as I said, FACT leukemia scale has five scales: physical, emotional, social, functional, and an additional one for concerns common in leukemia. For this scale, higher scores indicate better quality of life and functioning.
Dr. Mirela Anghelina:
We discussed this study with four centers initially: Ohio State University, University of Rochester, Royal Marsdon Hospital from UK, and Cancer Care Manitoba from Canada. However, only Ohio State University and University of Rochester were able to enroll patients. The other two still have pending regulatory approval, although they helped us with designing the study and writing the paper.
Dr. Mirela Anghelina:
So far we have enrolled 388 patients, 353 patients are enrolled at OSU and 35 patients enrolled at University of Rochester. In this paper, we included only 165 patients. Here is a table with the population characteristics we included in this paper. There is a lot of information here, but briefly the median age of patients included in the study was 59. We have a lot of young patients. 24% of them were younger than 50. Of course, as you expect, the majority were male and white male. However, we have good number of women participation, 23% of them were women. And also we have around 5% of patients of other races than white.
This is very important. We plan to characterize this disease in women and patients of other races. So their participation is much appreciated. The majority of patients were from academic centers, have a provider in academic centers, and of course the majority have classic hairy cell. However, there were some who have hairy cell variant or atypical hairy cell leukemia.
Dr. Mirela Anghelina:
Patients entered in the study at different disease status. The majority, I think there are around 80% or 70%. So 70% of them were in remission or stable disease. We had 9% in relapse, 8% newly diagnosed, and 7% on wait and watch. And 13% of them were on a treatment at the study entry. We summarize here, some of the scales. Patients have a median of six weekly episodes of physical activity. An episode of physical activity was an episode which was at least 20 minutes long and could have any intensity, low, moderate, or high.
Dr. Mirela Anghelina:
Around 40% of patients reported good or very good quality of life. However, when they were asked whether they were satisfied with their health, only around 60% were satisfied and very satisfied with their health. We have here the median of social support scale was 90 out of 100, which is very high. So our patients have high social support. However, the range was between 13 and 100. So there are some patients who have very, very low social support. The median score for fatigue scale was 43 out of 52 maximum for the scale. For fatigue scale, the higher score means less fatigue. So the higher score, the patient feels better and experience less fatigue. So 43 out of 52 means that they had experienced some fatigue.
Dr. Mirela Anghelina:
We looked to quality of life at the time of study entry versus disease status. We have here a figure of this analysis. On the X axis we have the disease status: newly diagnosed, wait and watch, complete remission, partial remission, hematologic response, stable disease, and relapse. And on the Y axis we have the FACT leukemia total score. This is the score for quality of life. The higher the score, the better quality of life.
Dr. Mirela Anghelina:
As you see, the newly diagnosed here have the lowest quality of life score. They are followed by patients on wait and watch and patients in relapse. When we look to those five subscales included in the FACT leukemia score, we found out that newly diagnosed patients had a worse score for physical, emotional and functional well-being, and also for leukemia concerns than other patients with other disease status.
Dr. Mirela Anghelina:
We wanted to see was there any difference in quality of life for patients enrolled before COVID or during COVID. And we didn't find any significant difference in the quality of life. To look for factors associated with quality of life score, our statistician created a statistical model. I'm not going to go into detail here, but I included the table of the model and I highlighted the factors which showed to be significantly associated with a better quality of life. And that was the older the patient, the better quality of life. Having more episodes of weekly physical activity was associated with higher quality of life. And also patients with the social support have a better quality of life.
Dr. Mirela Anghelina:
The second scale we used was to measure the level of fatigue our patients experience. As I said before, the higher score of this scale, the less fatigue. So patients with hairy cell experienced more fatigue. So here is the score. So more fatigue than general population and similar fatigue with patients with other cancers. When we look to women versus men, women experienced more fatigue. And when we look to age of the patients, patients younger than 50 experienced more fatigue. Our statistician created another model to find the factors associated with less fatigue. And again, I highlighted here the factor we found. So more episodes of weekly physical activity and good social support again were found to be associated with less fatigue.
Dr. Mirela Anghelina:
One of the questions in the fatigue scale asked patients whether they were able to work while managing this disease. And what we found was that almost 80% of patients reported they were able to work. However, around 40% of newly diagnosed patients and patients in relapse had to take sick leave during their therapy. So newly diagnosed and patients in relapse. I have the summary of this study here.
Dr. Mirela Anghelina:
Hairy cell patients reported better quality of life than patients with other chronic leukemias, as was previously published. Health related quality of life varied by patient disease status. Our hairy cell patients in remission or with stable disease had a higher quality of life than patients with other disease status. However, newly diagnosed patients had the poorest quality of life score with lowest worse score being for physical, functional, and emotional well-being, as well as for leukemia concerns scale. And as I presented before, better health related quality of life was associated with older age, being more physically active, and having a good social support, and less fatigue was associated with more physical activity and having a good social support.
Dr. Leslie Andritsos:
We had hypothesized that perhaps the reason why the younger patients were having more fatigue was maybe because they were caring for younger children or just had other responsibilities and maybe were pulled in many different directions because we didn't really have an explanation for that.
Dr. Mirela Anghelina:
We searched to see if this was reported in other cancers or other leukemia and we found a citation of women with cancer. That younger than 50 had experienced more fatigue than the older ones. And the explanation was the same, that they have their plate full caring for others and managing the disease and worrying about insurance.
Dr. Leslie Andritsos:
I think that's something that we haven't really captured yet. But that is, I think, a significant point of stress for patients if they have insurance issues or trouble obtaining the medications that they need and things like that. So these are all things that we're still working on.
Transcript of Q&A
Anna Lambertson:
I want to reiterate that these are initial results. And then as you have stated right here in this slide, the data that you've presented in this paper is only for a fraction, not quite half of the patients who have completed the survey.
I wanted to ask a quick clarifying question. I understand that there were about four different institutions involved in the study. OSU provided the vast number of patients. Can you clarify whether those OSU patients, were they all patients who were treated at OSU or were they patients who were consented at OSU for this study?
Dr. Mirela Anghelina:
Yeah, very good question, Anna. So at OSU we enrolled patients who were seen at OSU, but also patients from anywhere else in the United States. Not international patients, but any patient who wants to enroll in these two studies can contact us through the Hairy Cell Leukemia Foundation website.
Anna Lambertson:
What you're saying is individuals can complete a form to indicate their interest in joining the patient data registry and then you're utilizing the patient data registry as the platform for distributing the survey.
We have received one question in the Q&A about where this information has been published. So if you go to the footer on the Hairy Cell Leukemia Foundation website, there is a published research button. You can click on that and that takes you to a vast array of publications in Hairy Cell Leukemia from many of our centers of excellence, including this quality of life study.
One of the questions that also came in as you were doing your presentation was about how you correlate age? You talked about how older patients seem to have less fatigue and perhaps higher quality of life. Are there other learnings that you can point to or that you feel you need to study further related to the age of the patients and their health-related quality of life?
Dr. Leslie Andritsos:
The two things that were consistent across all the surveys was more physical activity resulted in better quality of life and being older resulted in a better quality of life. And at this point we can really only hypothesize why that would be. One possibility is that some people stay in remission a very long time. And so it's possible some of our older patients may have had treatment previously and then been able to maintain a long remission which resulted in just better health for a long period of time that enabled them to recover from all the toxicities of treatment and just live a normal life.
Also, hopefully people are enjoying retirement, if they are retired, and are being active and doing things that are important to them and not feeling pulled down by work and other obligations that tend to make life harder. But at this point it really is just kind of up in the air as to what factors go into that, and of course social support.
So I think as we go on, one of the things that I would really like to do is have a scientific approach to this because we know that leukemias, and especially lymphoid leukemias, which hairy cell is one, do have a tendency to secrete these proteins that cause fatigue called cytokines. And there's a lot of different medical and disease related reasons why people might be feeling more tired when they're not in remission. And so I think that would be a very interesting thing to study over the course of people's lives and treatment.
And to do that, we are going to need a tissue bio repository. And so that is something that we have been discussing at the last few Hairy Cell Foundation meetings is how we can operationalize starting to collect blood samples from patients. People who are treated at Ohio State do have the opportunity to donate blood to the leukemia tissue bank. So there may be quite a few people on this webinar that have already donated their blood to the leukemia tissue bank. And so I think that we need both a lifestyle approach to this and just to see what factors are changing in our patients as they get older and a scientific approach where we're looking at disease specific scientific reasons that might be contributing to fatigue.
Anna Lambertson:
So if you were able to collect tissue samples from, hypothetically, the patients who joined this study across a range of ages and including men and women, you might, at least from the standpoint of age, be able to compare and contrast the levels of cytokines and look at differences between patients who are perhaps newly diagnosed and those who are older and in remission for a long time.
Dr. Leslie Andritsos:
We don't have a way to quantify. Right now it's self-reported levels of fatigue, but it would be nice to have a quantifiable result to compare that to.
Anna Lambertson:
We received a question in the Q&A about how COVID influenced the survey. I know that you spoke to that a bit, but could you go into more detail? How did you pivot and integrate survey data during COVID?
Dr. Mirela Anghelina:
So what we did, we just looked to the quality of life scores before and after COVID, that's it. To go in more detailed analysis we would need information about the vaccination status, the antibody levels. All that stuff is not approved on our protocol. We have to amend our protocol for that. So at the time we did this analysis, we didn't have that information. However, this information, it is in the patient's medical records. So we can extract it and we plan to analyze it going forward.
Anna Lambertson:
Dr. Andritsos, I want to ask you a question. As a hematologist seeing patients, how do you functionally think about this data when you're treating someone who has hairy cell leukemia? What does this mean to you as a hematologist?
Dr. Leslie Andritsos:
So we only had a couple of other quality of life studies in chronic leukemias to look at and one was in chronic lymphocytic leukemia. And so we did look at all of those previous publications before we developed this study. But it was very interesting to see the things that they looked at specifically that lowered patient's quality of life.
One of the things that CLL patients had reported across the board was it really annoyed them when people would tell them how great it was to have CLL because it's a good leukemia and people do great, but especially, and I think this is especially true for hairy cell leukemia, probably much more so than for CLL. When a lot of our hairy cell patients are diagnosed, they're extremely ill. And it's not uncommon for people to need to be admitted to the hospital for treatment of a life-threatening infection. The first month or two of treatment tends to be pretty bumpy with potential complications such as pneumonia or some other serious infection.
It's a scary time, but the treatments are very effective and so people tend to recover, get back on their feet and hopefully stay in remission a long time. But we have clearly seen that the period of time where the quality of life is the lowest is at the time of diagnosis. And so I think that's when the most support needs to be provided to patients. First of all, to help them understand what they're dealing with.
A lot of patients are diagnosed in hospitals where there may not be a hematologist with expertise in hairy cell leukemia. So that's one of the things that we were trying to get at with our unvalidated survey, which was, did having a new diagnosis of a rare disease that your doctor may not know what to do about, did that impact how you felt about how things were going?
There's definitely time points in people's lives where they need more support than others and their quality of life is going to be lower, which is around the time that the disease is relapsing and they require treatment again. The Foundation website is a phenomenal resource because the data is there to show what treatments have been published, what's available. There is the mail bag where people can reach out if they need something or have a question. The international patients I think can also find their way to the Hairy Cell Leukemia Foundation with questions, even if they can't participate on the registry or quality of life study. And then just making sure that patients can get to a center of excellence in times where if things are not going well that they can be seen by an expert.
There were a lot of surprises with this study. I think the biggest one was that our hairy cell patients have better social support than not only people with other types of cancer but also the general population. We also don't have an explanation for that. That's something we're very interested to explore.
But I think I would say also as an investigator, this type of research is for the patients. And so if there's something that we're not looking at, we absolutely want feedback from the patients about what's important to them and what the unmet needs are because we don't always know that, or we don't always know if we're going in the right direction. We hope we're starting to answer some of the questions that are important to patients. But our research tends to be based around things that are important to us because we have medical questions that are unanswered, but we also want to be incorporating what's most important to patients.
Anna Lambertson:
Two questions have come into the Q&A. One is, did you capture how many relapses the patients who completed the study had experienced?
Dr. Leslie Andritsos:
So yes, we tried very hard. This was actually one of our biggest challenges to figure out exactly what type of remission our patients were in. And we spent a lot of time defining that because a lot of people never had a bone marrow biopsy. And so that became one of our biggest challenges. And that's why we have some categories that are a little bit different than what you might see in the guidelines paper, because we had to include categories for people that did not have a bone marrow.
Dr. Mirela Anghelina:
Yes, we captured all the relapse episodes. We didn't analyze this for this paper. We didn't include the number of relapses in our analysis for this paper. However, we captured this and we want to do further analysis in a longitudinal way to find out how the quality of life of patients changed during their journey.
Anna Lambertson:
Two questions that have come through the Q&A are both related to fatigue.
Consistent exercise seems to improve quality of life, to decrease these feelings of fatigue. Are you able to talk about that a little bit more from the medical perspective as to why that is helpful? And in addition to exercise, what are some other ways that you as a treating hematologist can help patients mitigate their fatigue?
Dr. Leslie Andritsos:
I would say in my medical practice this is probably the toughest thing that comes up, because the fatigue can be directly related to the underlying disease or it could also be secondary to something like the thyroid not working properly, adrenal gland dysfunction, sleep apnea is a big one, especially in New Mexico. Here at altitude we have a special kind of sleep apnea called central sleep apnea where people don't even know they're having sleep apnea.
And so first we usually try to cross the big things off the list that might be also contributing to fatigue because there is not a test right now for fatigue being caused by the leukemia. We don't have any way to test for that unless it's just directly related to severe anemia or something like that that's showing up in the blood work. But if everything looks normal and there's not another medical reason identified, it's probably something physiologically related to what I talked about earlier, which is some kind of abnormal cytokine release, something that the leukemia's doing to disrupt the normal physiology.
In terms of exercise, I have a different perspective on this, which is I feel like you have to be in training to get older if you have a chronic disease. That you have to think of exercise a little bit differently because it is a marathon. And we know that sometimes when people lose their muscle mass for whatever reason, once you're over the age of 60, it's very hard to get it back. And so maintaining a healthy muscle mass is really important to prevent this thing that happens called sarcopenia, which is your muscle starts to melt away if not using them. And then once they melt, you usually cannot get them back. And so I think the patients that are doing very well are very deliberately exercising even when they have fatigue to keep from losing their functional status.
Dr. Leslie Andritsos:
And my other point would be that this study has shown us something we already knew, which is that hairy cell patients are very tough and have a lot of grit. Most of the people that I've taken care of just do what they need to do. So I would encourage everyone to see your family doctor, make sure it's safe, but if there's not a reason not to, get started on an exercise program to maintain your muscle mass and overall health so that you can be in training for the eventuality that the leukemia could come back and you need treatment again or there's some other complication.
Dr. Leslie Andritsos:
And the other thing I would say is that you have to have a little bit of caution because something that we frequently run into is everything gets attributed to the hairy cell. And so we don't want to be missing another medical problem that is emerging like heart disease or something and just saying, “Oh, it's probably the hairy cell.” If there's a new symptom or a new condition, it always needs to be evaluated to be sure that we're not actually dealing with something that needs to be fixed in another realm.
Anna Lambertson:
Another question is also about remission. The individual says, “Wouldn't the average length of a person's remission impact their quality of life?”
Dr. Leslie Andritsos:
I certainly think so. I'm really excited to start having some of the five year data to look at the trajectory. The longer the patients are in remission, does their quality of life keep going up? And it kind of makes sense that if you feel like you're in a good place physically, you're probably going to do more and compound those healthy behaviors and be able to do the things you need to do to stay healthy.
Dr. Mirela Anghelina:
I wanted to say that we didn't look to that, but we plan to. So we have the number of remissions for each patient and the length of each remission, and we plan to include them in our longitudinal analysis.
Dr. Leslie Andritsos:
I'd just like to thank everyone again. We could not do this research without you. I know that a lot of the surveys took some time and there were some redundant questions and we really appreciate you being committed to this because we do need to use these validated surveys to get started and then hopefully we can get to more granular questions that are very specific to hairy cell patients. But we want to hear from you if there are things that we're not addressing that are important. And we don't always know what that is until we hear about it. So please feel free to reach out. And I want to thank again the Hairy Cell Leukemia Foundation for all the support over the years. This has been a long-term commitment, so we really appreciate the opportunity to present here today.
Anna Lambertson:
Thank you and thank you to everyone who logged in and joined us for this very interesting discussion.
The transcript was modified for clarity.