The Latest Treatment Options for Acute Myeloid Leukemia
Article Summary
- Recently approved drugs are rapidly changing the treatment of patients with acute myeloid leukemia.
- Newer options include less toxic front-line therapies and several targeted drugs.
- Researchers at Sylvester Comprehensive Cancer Center explore these new options and their impact on patients in a new commentary for JAMA Oncology.
The treatment landscape for acute myeloid leukemia (AML) is changing fast.
“It’s been an exciting time in the treatment of AML,” said Mikkael Sekeres, M.D., M.S., chief of the Division of Hematology at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.
Several new drugs have come online in the last few years—some developed in collaboration with Sylvester researchers—to expand options for patients.
Dr. Sekeres and Sylvester physician-researcher Sangeetha Venugopal, M.D., M.S., surveyed the field in a recent review in the Journal of the American Medical Association Oncology (JAMA Oncology).
“The time was ripe for an update on the biology of AML and the treatment approaches that we’ve adopted since the approval of these drugs,” said Dr. Sekeres.
Treating Vulnerable Patients
About 20,800 people are diagnosed with AML annually in the U.S., with a median onset age of 69. Only about one-third of patients live five years or longer, according to National Cancer Institute data from 2014-2020.
New drugs are beginning to brighten the outlook.
Historically, a substantial fraction of patients were unable to tolerate the first-line combination of chemotherapy drugs. Many frail, typically older patients often did not receive any active therapy.
The approval of the drug venetoclax in 2020, and similar drugs after that, enabled physicians to offer such patients a less harsh option. Venetoclax targets a molecule involved in cell death, promoting cell apoptosis. It is typically combined with the older chemotherapy drug azacitidine.
Patients generally better tolerate the azacitidine-venetoclax combination than traditional chemotherapy and often stay on it for the rest of their lives.
“Since we’ve introduced this combination, more patients are getting treated, more patients are getting treated as outpatients closer to their homes, and the people who are being treated are living longer,” said Dr. Sekeres.
Tailoring Targeted Therapies
Patients have also benefitted from therapies that target different mutations often found in AML, including in genes FLT3, IDH1 and IDH2.
The first molecularly targeted drug, midostaurin, was approved to treat AML patients with FLT3 mutations in 2017. Since then, several others have been added to the mix.
Midostaurin and another FLT3 inhibitor, quizartinib, are used as part of initial, front-line treatment in eligible patients, typically combined with conventional chemotherapy agents.
Other newer drugs are approved for patients who do not respond to first-line therapy or become resistant to it, including several drugs that target IDH1 and IDH2.
Sylvester Clinical Trials Expand Treatment Options
At Sylvester, a host of clinical trials expand the treatment options for both newly diagnosed patients and those whose cancer has relapsed. For instance, some trials are testing IDH1 and IDH2 inhibitors as first-line treatments in patients whose tumors carry mutations in these genes. Other trials are testing entirely new agents that target other mutations, such as in the genes KMT2A and NPM1c.
The future is bright for targeted therapies, said Dr. Venugopal.
“We ensure that our patients have the latest treatment options available to them when they come and see us, from the get-go,” she said.
Physicians are now also better able to assess patient tumors at the molecular level and track how they are responding, such as through measurable residual disease tests that can often catch the return of cancer in its earliest stages and inform the next therapeutic steps.
A Comprehensive Approach
When newly diagnosed AML patients are first seen at Sylvester, physicians evaluate whether they can tolerate intensive chemotherapy, said Dr. Venugopal.
“The initial treatment decision is based on tolerance and the biological age and the performance status of any particular patient,” said Dr. Venugopal.
Patients also undergo a bone marrow biopsy, which is sent to Sylvester’s pathology department for a battery of tests. Such tests can determine the types of mutations present in the tumor and guide decisions about recommendations for targeted therapies.
AML physicians meet weekly with Sylvester pathologists to discuss newly admitted patients and review laboratory and clinical findings. The oncology and pathology teams work in tandem, said Drs. Venugopal and Sekeres.
“Our pathologists are constantly thinking about patients so that they make the right diagnosis for the right person,” said Dr. Sekeres.
Both Drs. Sekeres and Venugopal credit the strength of the pathology team in helping Sylvester onboard the new treatment approaches, supporting an array of clinical trials and adapting to a fast-changing field.
Sylvester researchers were also involved in clinical trials that led to the approval of the newer drugs. Dr. Sekeres and Sylvester physician-researcher Justin Watts, M.D., chief of the Leukemia Section, helped lead the trials that resulted in the approval of quizartinib for FLT3-mutated AML, olutasidenib for IDH-mutated AML and imetelstat, recently approved for an AML precursor cancer.
Improving Patient Quality of Life
Dr. Venugopal’s and Dr. Sekeres’ new review should help physicians at other treatment centers make the best treatment recommendations, said Dr. Sekeres.
At Sylvester, the new approaches are already changing patients’ quality of life. An increasing number of patients are being treated as outpatients at one of Sylvester’s 10 satellite locations in Florida, in addition to its Miami medical campus.
If patients need more intensive care or transplantation, they have access to a fully dedicated inpatient leukemia unit in Miami. There, they interact with doctors, pharmacists, nurses, social workers and other experts specifically dedicated to people with a leukemia diagnosis.
“We all work together to make sure not only that patients get the best treatment for their diagnosis, but also the best care,” said Dr. Sekeres.
Tags: Acute Myeloid Leukemia, AML, cancer research, Dr. Mikkael Sekeres, Dr. Sangeetha Venugopal, JAMA Oncology, Sylvester Comprehensive Cancer Center