A Brighter Outlook for CML Patients
- For chronic myeloid leukemia (CML) patients, there is a promising new first-line drug approval that, according to one of the world’s leading leukemia experts, is showing “significant improvement” — and a potentially safer choice with less side effects — compared to the four other treatment options.
- The US Food and Drug Administration (FDA) recently granted accelerated approval to asciminib (Scemblix) for adult patients newly-diagnosed with Philadelphia chromosome-positive CML in chronic phase. This type of drug is a tyrosine kinase inhibitor (TKI), a targeted therapy drug.
- Asciminib was already approved in 2021 for patients with chronic-phase CML who had already been treated by two different TKIs (as a third-line treatment).
- Dr. Jorge Cortes, Director of the Georgia Cancer Center at Augusta University, tells SurvivorNet that study results showed “that the safety profile was equivalent or better in many aspects for asciminib compared to the other drugs.”
- The treatment path for CML, or deciding which drugs to use, will depend on many factors, and Dr. Cortes encourages patients to be vocal about their needs and ask their doctor any treatment-related questions that come up.
- You can check out SurvivorNet’s in-depth overview of CML here.
Chronic myelogenous leukemia, also known as CML, is a type of cancer of the white blood cells.
Read MoreTKIs are targeted therapy drugs that block the effects of BCR:ABL1 (the abnormal protein found in people with CML).
What is CML?
CML occurs when a cell in the bone marrow undergoes a breakage of two chromosomes (chromosomes 9 and 22), which then fuse to form a characteristic abnormal chromosome, called the Philadelphia chromosome (named for the city in which it was first identified). Chromosomes are structures found inside the nucleus of a cell. A chromosome is made up of proteins and DNA organized into genes. People normally have 46 chromosomes, divided into 23 pairs, in each cell. One of each pair of chromosomes comes from your mother, and the other pair comes from your father. The Philadelphia chromosome is present in the blood cells of 90% of people with CML.Asciminib: A Promising New Approval
Asciminb has already been on the market since its October 2021 FDA approval for patients with chronic-phase CML who had already been treated by two different TKIs. Previously, it could be used as a third-line treatment if the first options failed. That is why this new approval as a first-line treatment is particularly promising.
Dr. Jorge Cortes, Director of the Georgia Cancer Center at Augusta University, tells SurvivorNet the approval offers a “significant improvement” for Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) patients in chronic phase.
Dr. Cortes explains that the approval was based off of a study that “at random, assigned patients to receive either asciminib or any of the approved drugs — approved TKIs — that we have available for this condition.” Remarkably, “it also showed that the safety profile was equivalent or better in many aspects for asciminib compared to the other drugs.”
“So what that means, what this approval means, what these results mean, is that we have another option that is very valuable that seems to be very potent, very effective, but also that seems to be very safe with the information that we have so far,” Dr. Cortes says. “So it allows us to better assign the best treatment option for each one of our patients.”
“We do have four drugs, four very good drugs,” he notes, “but having an extra one and one that provides additional benefit is always beneficial when trying to do the best selection for each one of our patients.”
The Treatment Options for CML
For most people, CML is treated with an oral medication, called a tyrosine kinase inhibitor (TKI). The rates of progression have reduced significantly from over more than 20% in the pre-TKI era to less than 5% now, largely due to refinements in CML therapy and response monitoring.
This medication blocks the effects of BCR-ABL1 (the abnormal protein found in people with CML). Though most patients with CML have a normal quality and duration of life with TKI therapy, some patients progress to accelerated phase.
The most common TKI medications for CML are:
- Imatinib mesylate (brand name: Gleevec)
- Dasatinib (brand name: Sprycel)
- Nilotinib (brand name: Tasigna)
- Bosutinib (brand name: Bosulif)
- Ponatinib (brand name: Iclusig)
- Asciminib (brand name: Scemblix)
The CML Treatment Path for New Patients
When Dr. Cortes discusses an overall treatment plan with his patients, he makes sure to cover his bases, first discussing the disease as a whole and taking the time to explain all other aspects of the process.
SurvivorNet encourages CML patients to use this as a model of the level of care you should be receiving from your own doctor, with this insight and information from Dr. Cortes to help you get the most out of your medical visits.
Dr. Cortes explains that he makes sure to touch on several topics with patients, including, “What [CML] means, what are the long-term consequences if the disease is not treated, if it does not respond [to treatment], etc. And what are the goals of therapy and what these goals mean.”
What to Know About CML
- Digital Guide: Tyrosine Kinase Inhibitors (TKIs) for CML
- How Do I Pay for CML Treatment? Navigating the Cost of Care
- The Different Phases Of Chronic Myeloid Leukemia (CML) & Possible Treatments
- What Do Doctors Look For As Patients Undergo Oral Treatment (TKIs) For CML?
- What is Chronic Myeloid Leukemia (CML) and How is it Diagnosed?
RELATED: What is Chronic Myeloid Leukemia (CML) and How is it Diagnosed?
“At the very first visit, I want to talk about the potential for treatment discontinuation,” he adds, to “explain that possibility and what it takes to get there.”
“And then I discuss what are the treatment options and what are the pros and cons of each one of the multiple treatment options that we have available now and how do we go about selecting each one of them and what would be the best option for each of the patients based on the efficacy and the safety on the schedule of administration.
“Of course the coverage depending on the insurance and all these factors,” Dr. Cortes adds.
What Goes into Treatment Decisions
Another highly important element, Dr. Cortes goes on to explain how a patient’s health history and predisposition for certain side effects may define your treatment plan.
“For example, if I have a drug and one of the drugs that we use has a higher risk of giving diarrhea, if I have a patient that has already problems with their gastrointestinal system, well that’s a reason why I’m not selecting that drug or somebody that has pulmonary problems,” he explains.
RELATED: Lisa’s Story: Managing Side Effects Along the Road to Meeting CML Treatment Goals
“So that interaction between the patient’s history, comorbidities, sensitivities and what I know about the drug and then very importantly, what are the goals of the patient are my goals to eventually stop therapy where I may want to look for the drug that gives me more of that deepest response.
“So, of course, these are all integrated into one decision — and it’s a discussion with the patient. It’s not just my decision. I want to tell them these are pros and cons. ‘Now, of course, this is my recommendation, but what do you think?'”
Overall, as far as other predictors of response, Dr. Cortes says “newer generation drugs give us a better chance than the older generation.”
Genetic Factors
Genetic factors also play a key role for doctors when determining what medical route to go for CML patients.
“There are also some patients that — this is relatively new knowledge that we know — that may have abnormalities in other genes that are associated with cancer in general. And those patients tend to have lower probability of a good response … they tend to have more of a risk of progression,” Dr. Cortes explains.
RELATED: Understanding the Genetics of CML
“So that’s another subset of patients where we know that the responses may not be as good, so we always want to incorporate all of that, explain it to the patient and then incorporate it into our decisions and try to find what may work best for that patient.”
In CML, Dr. Cortes says that “the hallmark of the disease is disease fusion of two genes. Between chromosomes nine and 22.”
Long-Term Goals & ‘Better Quality of Life’
When it comes to long-term goals, Dr. Cortes says it’s important for doctors to map out what they want to achieve for the patients “and what gives us the best possibility and how do we get there best for our patients.”
He also emphasizes that sometimes doctors get distracted by “the drug being approved very recently and we sometimes don’t recognize that the drug has been available for almost 10 years now.”
“We started using it in clinical trials 10 years ago and why that’s important is because we have a lot of safety track record with the drug. So I always want to emphasize that because it tells us a lot of what to expect with the drug and sure efficacy is very important for our patients, but I think it’s also very important to emphasize to our colleagues that for patients, quality of life side effects is an important consideration and because many patients will not be able to stop the drug, a drug that gives me fewer side effects, better quality of life is very, very valuable and that’s something we should not minimize,” Dr. Cortes explains.
Learning to Manage Side Effects
Given the fact that CML has more options for treatment, doctors may have more of a “tendency” to switch drugs if the patient is suffering from side effects. However, Dr. Cortes stresses looking for ways to manage side effects rather than quickly jumping ship.
“The problem with that is that then we may end up using all of our drugs for things that probably can be fixed in another way and I don’t want to be burning all my fires with something that I can fix,” Dr. Cortes says. “So I think it is important to recognize that side effects can be managed and I think that we all need to acknowledge that there are areas that we feel more comfortable with and others.
“In my own practice, this is an area that I feel very comfortable. There are other areas where I call on my colleagues and say, ‘Hey, I have this scenario, how do you manage it? You see these more than I do, how do you manage these?’ And I think that always checking is a good thing.”
RELATED: Check out SurvivorNet’s In-depth Overview of Chronic Myeloid Leukemia
Admittedly, Dr. Cortes says that “nowadays, things are much more complex than when I started my career and it was easier to know everything.”
In the grand scheme of things, “there was very little to know,” compared to today with such a rapidly changing medical landscape with so many more treatment approvals and further knowledge of many more diseases.
“Now it’s better to ask,” he says, encouraging doctors to “look at the literature” and not to be afraid to check in with colleagues. “A lot of the side effects can be managed,” not just by giving another medication, but also adjusting the doses.
“We’ve learned that adjusting the doses is very powerful, it helps manage side effects and many patients can be treated with lower doses of the drug. Well, let’s take advantage of that and do the proper management to have the patient do as well and feel as well as possible.”
When to Lower the Drug Dose
Dr. Cortes says they’ve learned that there are two ways of doing the dosing. “One is of course when somebody is having side effects, particularly if they’re very, very severe or very inconvenient, we lower the dose to manage the side effects. But another thing that we are increasingly doing is that patients that have a good response and have a stable response, we can, and probably in many instances we should, lower the dose.
“Even in the absence of side effects or serious side effects, you can maintain a good response with lower doses than the standard. There is one study where we intentionally did that where patients, once they responded, we lowered the dose and just kept a lower dose to minimize toxicity. Well, we know that probably with many drugs we can do that and that helps the patients feel better and we don’t need to use just the label dose just because it’s on the label,” he adds.
“If we can maintain with a lower dose, and again, particularly relevant for a patient where treatment discontinuation is not an option, well let’s keep the minimum necessary through dose so that there’s fewer side effects of course may even have a benefits in terms of cost and other advantages.”
A Hopeful Future for CML Patients
Overall, Dr. Cortes says “it’s very rewarding” to see another big step in the management of CML.
“I’ve been fortunate enough to see all this progress, and then for a while we hadn’t seen any new developments, and now with this approval of [asciminib] — and now for frontline, it is very rewarding to see that you can still continue to improve the outcome of patients.”
He adds that “there’s sometimes the perception that, okay, we have a lot of drugs, we are done with CML and no. When you are in the clinic you realize we’re not done with CML patients.”
“You still need to improve the outcomes of patients in many ways, either because better efficacy, better tolerability, and this is a drug that looks very clean. It’s really another important step forward and just having been fortunate enough to be part of the development of the drug, it makes you feel good when you see that you can offer that to your patients and make them do better, feel better.”
Questions to Ask Your Doctor
For CML patients, as far as what questions you should be asking your doctor, we are fortunate to have Dr. Cortes’ guidance, as a leading expert in his field. Here is a sum-up of questions and topics that are important to address with your medical team:
- What are my options? “I think it is very important to ask about what are all my options. If I’m presented with, ‘Hey, you have CML, I’m going to give you this drug,’ always ask, ‘what are my other options? What are the pros and cons? What are my long-term goals? What are we aiming for? What are the chances with this drug? What are the chances with another drug?’ Always ask for options for the information and again, emphasize the long-term goals,” Dr. Cortes explains.
- How can I live better, have a better quality of life? “Now we know that patients can have a near normal life expectancy, but go beyond that,” Dr. Cortes recommends. “What about not only living longer, living better, how can we achieve that? Is this that you’re offering me the best option for that purpose as well? I think that asking those questions is very important.”
- What does my outcome look like? “I do think that it is very important to recognize that having another new tool for patients where we can, putting everything that we talked about, the patient characteristics, the disease characteristics, the drug characteristics, look at what’s best for the patient. Having another option and one that’s very effective and very safe is going to allow me, for a large number of patients, to provide a better outcome,” Dr. Cortes explains. “And I think we always need to look at that. And again, I always emphasize long-term goals. That’s where I want to be.”
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