'AML treatment advances hindered by limited reimbursement, government delays'

Acute myeloid leukemia (AML) remains one of the most challenging blood cancers to treat due to its diverse genetic variations and complex treatment process.

In recent years, treatment outcomes have been improved with the introduction of various targeted anticancer drugs in Korea, but only a few are covered by insurance. Many patients still rely on high-intensity chemotherapy (7-3 therapy) and hematopoietic stem cell transplantation for cure.

Korea Biomedical Review met with Professor Chung Jun-won of the Department of Hematology at Severance Hospital and chairman of the Acute Myeloid Leukemia/Myelodysplastic Syndromes (AML/MDS) research committee of the Korean Society of Hematology to learn about the latest treatment advances in AML and highlight the disease's characteristics and unmet needs in the current treatment landscape.

Professor Chung explained that the new treatment paradigm for AML is evolving due to the introduction of targeted anticancer drugs.

“AML requires a variety of approaches due to the heterogeneity and complexity of the disease, multiple gene mutations and complex clonality, differences in treatment response, and the potential for relapse,” Chung said.

Because a single gene mutation does not cause AML but various gene mutations working together to cause the disease, targeted therapies that attack one gene alone are unlikely to cure the disease and are likely to relapse.

“Furthermore, even among AML patients with the same mutation, the response to treatment varies,” Chung explained. “That’s because the individual patient's immune status and other genetic factors also play a role.”

AML has a high potential to relapse even after treatment, Professor Chung said, adding that even if a significant mutation is eliminated during initial treatment, other potentially residual mutations can reactivate and relapse, requiring more complex treatment strategies.

“Next-generation sequencing (NGS) and minimal residual disease (MRD) play a critical role in the treatment of AML,” Chung said. “These two technologies are key tools in understanding the heterogeneity and complexity of AML, monitoring treatment effectiveness, and preventing relapse.”

As AML is caused by a combination of mutations rather than a single gene, NGS is essential for understanding each patient's mutation pattern. It is also essential for selecting drugs that target specific mutations (FLT3, IDH1/2, TP53, etc.) and for developing treatment plans based on relapse risk.

“MRD is a technique that measures the small amount of cancer cells that remain in the body after treatment, and is a very important indicator for assessing whether a leukemia patient is cured and the likelihood of relapse,” Chung said. “Patients with a negative MRD have a low risk of relapse, while patients with a positive MRD have a higher risk of relapse, which may require more intense treatment and additional treatments such as hematopoietic stem cell transplantation may be considered.”

“In the past, MRD measurements were primarily performed by flow cytometry or PCR (polymerase chain reaction), but with the introduction of precision analysis technologies, including NGS, it is now possible to detect even the smallest residual cells, making it an important tool for early detection and prevention of relapse,” Professor Chung added.

Chung emphasized that as MRD becomes a key performance indicator for AML treatment, government officials responsible for reimbursement also need to better understand it.

For instance, when evaluating the efficacy or cost-effectiveness of a treatment for reimbursement, the government requires data on improvement in overall survival (OS) as the gold standard. Still, OS data is almost impossible to obtain for AML treatments that aim for a cure through hematopoietic stem cell transplantation.

Therefore, he noted that there are repeated delays in domestic reimbursement for AML drugs with MRD or PFS (progression-free survival) as the primary efficacy endpoint in all licensed clinical trials.

None of the targeted anticancer drugs licensed for AML in Korea have entered the reimbursement system except for Venetoclax and Gilteritinib. Novartis has abandoned reimbursement for Midostaurin, a first-generation FLT3 inhibitor, and Mylotarg (gemtuzumab ozogamicin), an anti-CD33 antibody, is being reviewed at the subcommittee level of the Pharmaceutical Reimbursement Evaluation Committee under the Health Insurance Review and Assessment Service after several challenges by Pfizer.

In addition, according to Chung, the government's lack of understanding of NGS and MRD has further increased the financial burden on AML patients in Korea. The government revised selective benefits for NGS late last year, increasing the patient co-payment rate from 50 percent to 80 percent for all cancers except lung cancer.

The government believes that the existing NGS reimbursement is not cost-effective except for lung cancer, for which there are many targeted anticancer drugs based on various gene mutations, which Chung said is “a typical example of the government's lack of understanding of NGS.”

“Identifying various gene variants for therapeutic exploration is one of the NGS technologies, but evaluating whether MRD is positive or negative after treatment is also done with NGS technology,” Professor Chung said, emphasizing that the government must categorize NGS fees in greater detail.

In lung cancer, NGS is used to select targeted antitumor drugs based on gene mutations, but according to Chung, in AML, NGS plays an essential role not only in the selection of therapies but also in post-treatment evaluation and post-treatment strategy.

“As AML is a heterogeneous disease with a complex interplay of various gene mutations, NGS is essential for precise diagnosis and personalized treatment,” Professor Chung said. “However, many patients face difficulties in diagnosis and treatment due to high test costs and limited insurance coverage.”

He noted that even as new drugs become available, delays in coverage continue to prevent patients from accessing the latest therapies in a timely manner.

“Above all, AML requires greater government understanding and attention to the disease and policy support that considers the nature of blood cancers and the complexity of their treatment,” Professor Chung added.