CLL Treatments: ASH 2022 Brian Koffman Understanding Pts with CLL
By Brian Koffman, MDCM (retired), DCFP, FCFP, DABFP, MSEd
How will understanding patients with chronic lymphocytic leukemia (CLL) help with their treatments? First, I want to say I’m very thankful to have the opportunity to present this study on behalf of my co-investigators. We presented this as a poster presentation at ASH 2022 in New Orleans. The title is “Understanding Patient Preferences for Chronic Lymphocytic Leukemia Treatments.” In the way of background, I think all clinicians know how radically the treatment paradigm in CLL (chronic lymphocytic leukemia) has shifted over the last 8 to 10 years where chemo immunotherapy was the standard of care. But now we have several excellent targeted therapy options for patients to consider in every line of therapy.
But these vary in terms of how they’re given, what the adverse events are, their efficacy, the convenience of. So understanding what’s important to patients is what motivated us to do this clinical trial. It was a web-based discreet choice experiment survey, and it was developed for CLL (chronic lymphocytic leukemia) patients and the respondents were recruited by the CLL Society, which is a nonprofit dedicated to the unmet needs of the CLL community, mostly patients and caregivers, where I serve as the Chief medical Officer and executive vice president. Respondents answered 12 DCE questions, discrete choice questions concerning small lymphocytic leukemia. And for those unfamiliar with this methodology, each question offers a choice between two hypotheticals.
These were treatment profile, that were created with an experimental design and there were seven attributes of various levels. And this allowed us to analyze at what level was important to the patient. Where did patients make that shift? What was the tipping point in terms of what was important to them in choosing therapy (Eg. targeted therapy).
And one that we looked at was achieving a progression-free survival PFS at 2 years. What were your odds? Treatments resulting in a measurable residual disease. Was that important to measure at the end or was routine testing enough? What about the frequency of administrations? Were these BID medications or daily medications?
The duration of treatment, the risk of tumor lysis syndrome, TLS, the risk of atrial fibrillation and the risk of fatigue. The estimated preference weights were used to calculate conditional relative importance of changing each attribute from the most preferred to the least preferred level. And they were also used to calculate the maximum risks of treatment related adverse events that the patients would accept in considering that therapy.
So let me go over the results, between April and June of 2022, 229 adults in the US with a self-reported diagnosis of CLL (chronic lymphocytic leukemia) for at least 3 months completed the survey. The average age was 66, which is pretty common, most clinical trials, but younger than the typical age of someone newly diagnosed with chronic lymphocytic leukemia (CLL), which is 71, 95% of the patients were white, which is what we see, and we also see preponderance of females, 59.4% were females, even though we know that CLL (chronic lymphocytic leukemia) tends to be a more of a male disease. Approximately 2/3 of the patients had received (chronic lymphocytic leukemia) treatment for CLL and 71% of the patients were currently in therapy.
The DCE results revealed that respondents placed the greatest importance on increasing the chance of progression-free survival at 2 years from 70 to 90%. This is what we would hope for. And confirming the results with MRD (minimal residual disease) testing, the MRD testing was even more important when they were looking at the importance, if they were able to achieve progression-free survival of only 70%, confirming that with MRD testing was even more important in that circumstance than under the 90%. The results also indicated that patients preferred treatment by daily oral pills over intravenous infusions administered every 4 weeks.
I don’t think that’s any big surprise. They preferred treatments of a fixed duration over treatments to progression, and they preferred treatments with a lower risk of side effects. I think all of these are intuitive, but it’s nice to see they’re confirmed. Reducing the risk of Tumor Lysis syndrome was the least important to the.
And that was reducing the risk from 3% to 0%. On average, respondents were willing to accept more than a 3% risk of tumor lysis syndrome, which was the largest risk that was presented as an option in the survey. In exchange for all of the improvements in chance of progression-free survival, duration of treatment, and mode of administration, with one exception, respondents were willing to accept a 2.7 risk of tumor lysis syndrome to confirm their results with MRD testing versus routine testing when the chances of progression-free survival was 90%, confirmation with MRD testing was more important to respondents when the chance of achieving progression-free survival was lower at 70% compared to when it was higher at 90%.
Respondents were also willing to accept greater than a 3% tumor lysis syndrome, a 6.2% risk of atrial fibrillation, and a 21.2% risk of fatigue. Have a 12 month treatment instead of a treat to progression therapy. And for the change from IV every 4 weeks to 2 pills daily. Respondents were willing to accept greater than a 3% risk of tumor lysis, a 7.7% risk of atrial fibrillation, and a 27.7% risk of fatigue.
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What is chronic lymphocytic leukemia (CLL)?
Chronic lymphocytic leukemia, sometimes known as CLL, is a subtype of chronic leukemia. The term “chronic” denotes that the progression of leukemia is often very slow. CLL is caused by the production of abnormal cells in the bone marrow (a type of white blood cell count, not red blood cells). When abnormal (cancer) cells are more numerous than healthy cells, this can lead to a higher risk of infection, as well as anemia and a tendency to hemorrhage. There is a possibility that the abnormal (cancer) cells will spread to other organs and tissues throughout the body. CLL (chronic lymphocytic leukemia) is one of the types of adult leukemia that is diagnosed most frequently. It usually occurs either during or after the middle age. Children are only rarely affected by it.
Alterations in the genetic material (DNA) of bone marrow cells are what lead to the development of CLL (chronic lymphocytic leukemia). It is difficult to determine who will develop CLL due to the absence of information regarding the causes of these genetic abnormalities. There are several other factors that could potentially make your risk higher.
What is the next step for this research?
There’s a lot of potential options here. The one that seems obvious to me. Is that we should be asking those same questions of the clinicians in terms of what’s important to them. Is it important, oral versus iv? Is it important? Fix duration versus treat to progression or intolerance is once or twice daily important when they’re writing a script for something, how important is the level of progression-free survival in the adverse events? So I think asking the same kind of survey of practitioners, the people prescribing the meds, recommending the meds, arranging for the meds would be important. I also think that there’s other questions that need to be looked at.
To keep the survey manageable, we didn’t look at a lot of potential parameters. What about progression-free survival at 5 years? What about looking at overall survival? What about looking at other adverse events during the pandemic? Should we be looking at infection risk, other things like that? So I think that there’s a lot of options both to be directed at the clinicians and also to be looked at the patients.
What are the key takeaways from this research and data on chronic lymphocytic leukemia treatment?
I think the key takeaways for clinicians is that patients are thinking. their treatment and weighing the risks and benefits of the different therapies that are offered to them. I think it’s encouraging to see that what’s most important to patients is how successful the targeted therapy can be, and that having a 90% chance of progression-free survival is the most important thing to patients want to see that results confirmed by minimal or measurable residual disease testing at the end, and even more so if that result is only, if the chance is only 70% of progression-free survival, then they really want to see it confirmed with measurable residual disease. This suggests a level of sophistication of the patients to be aware of that.
Patients are surprisingly willing to put up with adverse events to get what they want in terms. A highly efficacious therapy also in terms of a fixed duration therapy, also in terms of oral therapy. So when we’re sitting down to have discussions with our patients about what their potential options are, and there’s so many great options now to treat CLL (chronic lymphocytic leukemia). It’s important to understand what things patients are thinking about, what they’re mulling over, so the patient in front of you can help in terms of deciding together what that best possible targeted therapy is.
Is there anything else that you would like to add about this clinical trial for the oncologist and hematologist watching this video?
There has never been a better time to treat CLL, but there’s never been a more complicated time to treat CLL. And as we’ve had this explosion of therapeutic options, many of whom are very similar in terms of their outcome, I think it’s very important for us to involve our patients in terms of what their preferences are, because we know we’re gonna get better adherence to the therapy.
We’re gonna know we’re gonna get buy-in, we know we’re gonna. The patient’s more likely to put up with the inevitable adverse events that occur. So I think this research helps inform that and look forward to future research that confirms that these shared medical decision making is happening and that patients and doctors are working together to find their best possible path forward. Which, as I said, is getting increasingly complicated in CLL.
Brian Koffman, MDCM (retired), DCFP, FCFP, DABFP, MSEd – About The Author, Credentials, and Affiliations
Since his 2005 diagnosis, Dr. Koffman, a renowned physician, educator, and clinical professor, has devoted himself to teaching and assisting the CLL community. Dr. Koffman feels that his dual role as a physician and patient allows him to provide straightforward explanations of complicated situations, advocate for his fellow patients, and educate other healthcare professionals. This is particularly crucial given the continually evolving therapeutic landscape. Dr. Koffman holds both a medical degree and a Master of Science in medical education. Dr. Koffman is also a board-certified family physician in Canada and the United States, a retired clinical professor in family medicine at the Keck School of Medicine of the University of Southern California, and the former medical director of the non-profit medical educational organization Primary Care Network. Dr. Koffman co-founded CLL Society Inc. and serves as its Chief Medical Officer and Executive Vice President.