Hematologic oncologist Eytan Stein (shown here with nurse practitioner Coleen Ranaghan) has led the development of several new drugs for acute myeloid leukemia.
Acute myeloid leukemia (AML) is one of the most common types of blood cancer. The word “acute” means that the cancer can advance quickly and needs to be treated right away. The word “myeloid” refers to the type of blood cells that are cancerous.
Myeloid cells are blood cells that develop into red blood cells that carry oxygen, white blood cells that fight infection, and platelets that help blood clot. This explains why fatigue, infections, and excessive bruising and bleeding are symptoms of AML.
We recently spoke with hematologic oncologist Eytan Stein, Director of the Program for Drug Development in Leukemia at Memorial Sloan Kettering Cancer Center, about AML. Dr. Stein discussed the latest advances in treatment for this blood cancer and how people can benefit from receiving their treatment at MSK.
How common is AML?
About 20,000 people in the United States are diagnosed with AML every year. The average age at the time of diagnosis is 72, but it can develop at any age.
As the population of the United States ages, AML is becoming more common. Some people develop AML as a result of prior chemotherapy or radiation for other cancers, but for most adults, the cause is not known.
Although rare, it also is increasingly recognized that there are certain cases of AML that may be hereditary.
How is treatment for AML changing?
Until recently, there had been no new drug approvals for treating AML since 1973. But since 2017, there have been many new drugs approved. These drugs target mutant proteins that are common in patients with AML as well as proteins that are not mutated but are important in the development and persistence of AML. In addition to those targeted drugs, we now have novel formulations of chemotherapy that are used to treat people with AML that evolved from a prior myelodysplastic syndrome.
One of the new drugs is called venetoclax (Venclexta®). It targets a protein in leukemia cells called BCL-2. Targeting BCL-2 causes leukemia cells to die. This drug is used not only in AML but also in chronic lymphocytic leukemia. In AML, the combination of venetoclax with an older drug called azacytidine has been approved for older patients. This treatment has truly remarkable efficacy: Nearly 70% of patients will go into remission.
Enasidenib (Idhifa®) was approved to treat AML that carries a mutation in a gene called IDH2. Ivosidenib (Tibsovo®) targets cancers with a mutation in the related gene IDH1. Both enasidenib and ivosidenib work by converting cancer cells back into normal cells rather than killing them. MSK’s Leukemia Service led the trials that resulted in both of these drugs being approved.
In addition, we continue leading the way in investigating newer AML treatments:
- A new class of drugs called menin inhibitors are showing great promise for some cases of advanced AML. I am leading the first-ever clinical trial of the menin inhibitor revumenib, and in March 2023 we published encouraging results in Nature showing benefit in both adults and children. Menin inhibitors appear to be very well tolerated and are easy to take — everything you want in a targeted therapy.
- There also is promising research into treating AML with chimeric antigen receptor (CAR) T cell therapy. Michel Sadelain, MD, PhD is leading a team using CAR T therapy to target two different AML antigens at the same time — ADGRE2 and CD371. Anthony Daniyan, MD, and colleagues are taking a slightly different approach — targeting CD371 only but trying to enhance CAR T cells’ power by making them produce the interleukin 18 protein. This acts as a strong signal to initiate and boost the immune response so that even the AML cells without CD371 are effectively destroyed.
We’ve been able to develop all these new treatments because — thanks to research in both the lab and the clinic — we now have a much better understanding of what drives this disease. This knowledge leads to more effective ways to target malignant cells. It’s an amazing, exciting time to be doing leukemia research.
How often are stem cell or bone marrow transplants used to treat AML?
Blood or marrow stem cell transplants are recommended for many, but not all, people with AML. For those who are able to find a donor and are able to safely tolerate the transplant process, this treatment may offer the best chance for a cure.
For people whose disease is considered low risk because of its genetic characteristics, a transplant is usually not recommended. These people usually do well without that treatment.
For others, especially those who have serious, unrelated health problems, a transplant may not be recommended either. But transplants themselves have become safer and are now offered to a wider variety of patients — both old and young.
What does MSK offer people with AML that most other hospitals don’t?
MSK is on the cutting edge of treating AML. We offer a wide variety of clinical trials, both for newly diagnosed patients and those with relapsed disease. These clinical trials give patients access to the most promising new drugs that may become the standard of care in years to come.
At MSK, we are also always looking for ways to make it easier for patients to receive their treatment. We now routinely administer consolidation chemotherapy — the second part of treatment — as an outpatient treatment rather than in the hospital. In consolidation therapy, chemotherapy is given on alternating days throughout the week. This is done every week for a month.
Under our new procedure, the way it works is that patients come in on a Monday and get their first treatment. During that appointment, their chemotherapy for Wednesday and Friday is loaded into an electronic pump.
What else is special about the way MSK treats AML?
There are 20 doctors on our service who are completely focused on leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. We also have nurses and nurse practitioners with fantastic expertise in caring for people with acute leukemia. Some of them have many years of experience.
We have a team of clinical pharmacists who are dedicated to working with the Leukemia Service. They are vital for understanding all the new drugs that are being given to patients, whether as part of standard care or a clinical trial. And they’re very good at educating patients about what they need to know when taking these drugs.
We also have wonderful colleagues on the Infectious Diseases Service. They focus on the prevention and treatment of the infections that are common in people receiving leukemia therapy. They closely monitor our patients for signs of trouble. They also perform clinical and laboratory-based research that’s leading to better treatment for all people with cancer.
In addition, our experts in stem cell and bone marrow transplantation lead one of the largest programs in the country. They developed many of the protocols for transplants that are used around the world today and are continually working to improve the care of people with AML and other blood cancers through research and clinical trials.
This story was originally published in 2022 and has been updated.
