Recent changes in the concept of “low-intensity anticancer therapy” in acute myeloid leukemia (AML) have opened the door to a higher share of patients being cured.
For a long time, the treatment approach for patients with AML has been “high-intensity anticancer therapy” when aiming for a cure and “low-intensity anticancer therapy” when a cure is not possible. Recently, however, patients’ conditions have determined the treatment, depending on whether or not they can undergo high-intensity anticancer therapy.
“In recent years, the results of low-intensity anticancer therapy have been outstanding, so the concept of high-intensity anticancer therapy for patients who aim for cure and low-intensity anticancer therapy for patients who do not aim for cure is a little incorrect now,” said Professor Hawk Kim of the Department of Hematology at Gachon University Gil Medical Center on the YouTube channel “Gil Medical Center TV,” pointing out the changed treatment reality.
Professor Kim said, “High-intensity anticancer therapy is the standard of care, so if we can do high-intensity therapy, we do high-intensity therapy. If high-intensity therapy is not possible, low-intensity anticancer therapy is used. The idea of high-intensity therapy because the goal of treatment is cure, and low-intensity therapy because we have given up on cure is not true now. The goals may be the same, or they may be different. It's only about whether the current condition allows for high-intensity therapy.”
It means that low-intensity anticancer therapy for patients with AML does not mean that they have given up hope of a cure. So, what are some of the circumstances under which a patient with AML might be given low-intensity chemotherapy?
First, patients 75 and older are eligible for low-intensity chemotherapy.
“After the age of 75, even if you look fine, your organs are aged a lot,” Professor Kim said. “So, high-intensity treatment may be difficult for those over 75.”
Patients with poor heart function are also treated with low-intensity chemotherapy. “The drugs that go into high-intensity therapy affect heart function,” Kim said, explaining that if the heart function itself is poor, to begin with, high-intensity therapy is challenging.
Besides, patients with AML who have very poor lung function are also candidates for low-intensity anticancer therapy. This is because pneumonia caused by chemotherapy can pose a significant threat to life. Therefore, patients with reduced lung function also choose low-intensity therapy.
Lastly, people with limited daily activities are also candidates for low-intensity chemotherapy. “If you have to stay in bed almost all day, or if your life outside of bed is less than 50 percent of the time, you are subject to low-intensity anticancer therapy,” he said. “The limitation of daily life is a criterion for choosing low-intensity chemotherapy because it represents the overall function of the patient.”
Currently, the goal of treatment for AML does not depend on whether the patient is targeted for cure but instead on whether the patient is treated with low-intensity chemotherapy in these four cases and high-intensity chemotherapy otherwise. But how much of this change in treatment concept is thanks to the improved performance of low-intensity anticancer therapy?
“The remission rate of high-intensity chemotherapy varies depending on the age and risk of the disease, but the remission rate of high-intensity anticancer therapy is usually 50 to 70 percent,” Kim said. “Low-intensity anticancer therapy (used to) have a remission rate of 25 percent, so it was natural to do high-intensity therapy instead of low-intensity therapy if possible. Now, the remission rate of low-intensity therapy is up to at least 50 percent or 60 percent, which is very similar to the therapeutic performance of high-intensity therapy.”
“With low-intensity therapy, unlike high-intensity therapy, you don't necessarily have to get a complete remission in the first treatment, but there's a fairly high percentage of patients who get a complete remission after the first (cycle) and before the second,” he said. “So, if the overall remission rate is 50-60 percent, about 70-80 percent get a complete remission in the first treatment.”
That also explains why many patients with acute AML who receive low-intensity anticancer chemotherapy devise a new treatment strategy in the medical field.
“There are quite a few patients who are undergoing low-intensity anticancer therapy at first and then undergoing stem cell transplantation to be cured,” Professor Kim said. “Initially, they could not undergo high-intensity anticancer therapy due to infections and other reasons, so they started low-intensity anticancer therapy, but when the remission went well, and the patient's condition improved, they moved on to stem cell transplantation and received treatment for cure.”
Low-intensity chemotherapy is a four-week cycle of hypomethylation (a choice of outpatient, five-day infusion, or seven-day infusion, with similar therapeutic effects) followed by an oral agent that inhibits a gene called BCL-2. It is easier to administer in many ways than high-intensity chemotherapy.
“The process of low-intensity chemotherapy is not difficult. High-intensity chemotherapy is all hospitalized, but low-intensity chemotherapy is usually outpatient,” Kim explained. “Low-intensity chemotherapy uses two drugs, and there are not many side effects of the drugs.”
Because the goal is not to achieve complete remission quickly and go on to cure, the treatment is characterized by repeated treatments. Every four weeks, patients with AML have to go through a series of injections (five or seven days of outpatient continuous infusion therapy) and medications until they relapse or change to a treatment that aims for a cure.
“Low-intensity therapy can be very good for remission, but it's not a cure. When we talk about continuing low-intensity therapy, we should think that there will be a relapse at some point,” Kim explained. “The goal is to maintain the remission or the current good status for as long as possible. This could be as short as a few months or as long as a few years.”
“In the past, a patient who would not have been able to go into remission and would have had difficulty with daily life and would have died sooner or later because of high-intensity therapy can now go into remission and live a normal life because of low-intensity therapy,” Professor Kim noted. “The ultimate goal of low-intensity anticancer therapy is to control the disease as long as possible so the patient can lead a normal life.”
If a patient with AML who is on low-intensity therapy plans to undergo a stem cell transplant for a cure, the patient should continue low-intensity anticancer therapy until the transplant to prevent the disease from getting worse.
“Low-intensity anticancer chemotherapy does not mean a cure. You must know low-intensity chemotherapy alone leads to relapses eventually,” Professor Kim pointed out. “If you start with low-intensity treatment and you're feeling well and want to switch to curative treatment, you should take low-intensity anticancer therapy until you reach such a situation.”