New advances in AML treatment boost cure rates for older patients

The cure rate for the blood cancer acute myeloid leukemia (AML) has recently increased dramatically. AML occurs mainly in adults, especially older adults, and it was known that the treatment performance of elderly patients was poor compared to younger ones.

“Old-age AML is an elderly cancer that occurs in patients with an average age of 65-67 years,” said Professor Cho Byung-sik of the Department of Hematology at the Catholic University of Korea Seoul St. Mary’s Hospital, on a YouTube channel with the same name as the hospital. “It used to be more difficult to treat older adults than younger patients, but the situation has changed recently.”

What could be the reason?

“With the recent introduction of new drugs, including targeted anticancer therapies, and the continuous improvement of hematopoietic stem cell transplantation techniques, the cure rate for patients with AML has improved considerably. These changes are occurring rapidly, especially in older adults.”

Why had older patients with AML fared worse than younger patients with AML in the past, then?

“The standard treatment for AML is high-intensity chemotherapy, often followed by a stem cell transplant,” Professor Cho said. “Both of these treatments require prolonged hospitalization and are often associated with complications that are difficult even for younger patients to endure.”

Elderly patients often have multiple comorbidities that are different from those of younger patients, and their ability to adapt and recover from the same treatment is often reduced compared to younger patients due to the decline in organ function with aging, Cho said, adding that these are risk factors for increased mortality during treatment.

There are more. The disease also tends to show poorer prognosis in older AML patients.

“Older patients often have poorer disease characteristics,” Cho said. “Taken together, these factors mean that treatment outcomes are relatively poorer in older patients than younger ones.”

For this reason, treatment strategies for elderly AML patients have changed dramatically. This is thanks largely to the development and introduction of new drugs, advances in hematopoietic stem cell transplantation techniques, and the refinement of geriatric assessment techniques through research by blood cancer doctors.

“For elderly patients, it is important to identify the basic characteristics of leukemia and evaluate the patient's systemic condition in various ways, rather than rushing treatment,” Professor Cho said. “Through these, it is most important to predict the response rate to chemotherapy and the risk of complications and to make an appropriate treatment plan accordingly.”

In the case of elderly patients, research is underway to develop an assessment method that can accurately evaluate treatment adherence and resilience to treatment through a comprehensive analysis of physical, mental, and functional factors, called 'geriatric comprehensive assessment, Professor Cho said.

It has been confirmed that patients with poor physical function and emotional status are more likely to fail treatment due to complications during high-intensity anticancer therapy. These patients are now being offered “low-intensity targeted therapy” instead of high-intensity chemotherapy to reduce complications and improve treatment outcomes, he added.

It is the emergence of the new targeted anticancer drug “venetoclax” that has made the biggest difference in the outcomes of elderly patients with AML.

“The most representative change in the treatment of elderly patients is the introduction of venetoclax,” Cho said. “Previously, elderly patients who could not receive standard anticancer treatments were treated with azacitidine, decitabine, and other drugs, which had the advantage of fewer side effects, but the response rate was disappointing at around 25 percent.”

In a recent large-scale phase 3 clinical trial, treatment with venetoclax in combination with azacitidine improved the response rate to 65 percent, and the side effects were not significantly different, so it has recently been used as a first-line treatment for patients who cannot receive high-intensity chemotherapy, according to Professor Cho. In Korea, it has been covered by insurance since the beginning of this year and is actively used in various hospitals, he added.

In addition, the effectiveness of the combination of venetoclax and decitabine has recently been demonstrated, further expanding treatment options.

“We found that the combination of venetoclax and decitabine was superior to decitabine monotherapy and almost as effective as vetetoclax and azacitidine, so it is now actively used in outpatient and inpatient settings,” Cho said.

Another factor contributing to the increased durability of advanced AML is the advancement of hematopoietic stem cell transplantation, which has expanded indications for older patients.

“Patients in the group with poor prognosis need not only chemotherapy but also advanced immune cell therapy called allogeneic stem cell transplantation. In addition, various immune-related complications that occur after transplantation are also a big mountain to overcome to be cured,” Cho said. “In the past, due to these difficulties, transplantation was only available for young patients. In recent years, however, transplantation techniques have been continuously improved, and it has become possible to apply hematopoietic stem cell transplantation to elderly patients.”

In the medical field, many transplants have been performed in older patients with AML. “For elderly patients whose goal is to cure the disease completely, it is important to have an aggressive treatment plan that includes transplantation at least until their early 70s,” Cho emphasized.

Moreover, in recent years, allogeneic stem cell transplantation has become almost impossible due to the inability to find a donor. In allogeneic stem cell transplantation, it is essential to find a stem cell donor with a matching histocompatibility antigen (HLA) genotype, and in some cases, a match cannot be found within the family.

The first step in finding a stem cell donor is to look for an HLA-matched sibling and, if not, to look for someone else. If no HLA genotype match is found, a donor with at least half of the eight HLA genes in the family is selected for transplantation.

“Recently, many families do not have children, so if there is no half-matched donor in the family, cord blood is used for transplantation,” Cho said. “In the end, transplantation is rarely unsuccessful because there is no donor, and the success rate is almost the same regardless of the donor type.”

Moreover, managing allogeneic stem cell transplantation, a high-risk procedure, continues to evolve. In allogeneic stem cell transplantation, the patient's blood is replaced with the donor's blood so that the immune cells in the donor's blood can attack and kill the leukemia cells that remain after chemotherapy, which can be fatal if the transplanted immune cells attack the patient's normal cells, known as graft-versus-host disease.

“Despite various preventive measures against graft-versus-host disease, it occurs in about half of transplant patients. Recently, various therapies have been developed, and the effectiveness of preventing and treating graft-versus-host disease is gradually improving,” Cho noted.

In conclusion, Professor Cho advised that the most important thing in treating AML is to make an accurate assessment at the time of diagnosis and to develop a good treatment plan based on that assessment.

“Although the treatment process is long and not easy, I sincerely hope that many patients will not lose hope because leukemia can be cured if treated aggressively,” he said.