Eytan M. Stein, MD

Eytan M. Stein, MD, chief of the leukemia service and director for the program for drug development in leukemia at Memorial Sloan Kettering Cancer Center, discusses the unmet needs and challenges for treating patients with acute myeloid leukemia (AML).

Stein noted that the treatment landscape for patients with AML has undergone many positive changes in the past decade as new treatments allow for a wider patient population to be treated and treatments can be tailored to individual patients. For instance, treatment can be tailored for patients with AML who test positive for a 

 mutation or older patients with AML have shown that they can avoid intensive treatments with the use of venetoclax (Venclexta).

However, according to Stein, the median overall survival (OS) for these patients has not increased enough and more work is needed to continue these positive trends and provide treatment that continues to improve the OS in meaningful ways. Stein also discusses the work that is needed to be done for patients with 

 mutations and the complexity of their karyotype.

Even though the overall survival has improved for many, many patients, the majority of those patients are going to end up relapsing. So we went from a place where we really didn't have any treatments that worked very well, to a place where now patients have a median overall survival of maybe a year and a half if they're older than 70 or 75 [years old].As an academic oncologist, I'm like, "Oh, my god, that's amazing," right? But in real life, that's not so amazing. If I told you, you had a year and a half to live, you'd be pretty upset, and I'd be pretty upset if someone told me that.

So there are major areas where we still need to improve on this initial [treatment] success that we've had. There are some particularly poor risk groups of patients, specifically patients with what are called a complex karyotype and p53 mutations. But those patients who really don't do very well with anything, and we really need to understand the science better to understand how we can improve the outcomes for those patients as well.

Videos

Eytan M. Stein, MD, discusses the unmet needs and challenges for treating patients with acute myeloid leukemia. 

Addressing Unmet Needs and Challenges in AML

Eytan M. Stein, MD, hematologic oncologist and director of the Program for Drug Development in Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York, discusses the currently available treatment options for patients with acute myeloid leukemia (AML) and how Menin inhibitors fit into this space.

Besides recommending patients with AML to enroll in clinical trials, patients who are younger may also receive intensive induction chemotherapy. For patients who are older in age, popular combinations include a hypomethylating agent like azacytidine [Vidaza] plus venetoclax [Venclexta].

Now, Menin inhibitors are being developed for patients with relapsed/refractory AML whose previous treatment regimen may not have worked for them. Various clinical trials evaluating Menin inhibitors as single agents are ongoing in this space.

The way we currently treat AML outside of a clinical trial is that for 1 group of patients, typically those patients who are a little bit younger, we will give those patients some intensive induction chemotherapy. Then for patients who may be a little bit older, we give them the combination of a hypomethylating agent, which is typically azacytidine, with the BCL2 inhibitor, venetoclax.

Menin inhibitors now are being developed in the setting of patients who have relapsed and refractory acute myeloid leukemia. They've gotten that treatment regimen paradigm that I just described, and it either didn't work or it worked for a brief period of time, and then the patient ended up relapsing. These drugs are currently in clinical trials in the relapsed and refractory setting as single agents.

 However, there's a lot of effort now. When you have a drug that looks to be effective in the relapsed and refractory setting, you don't want to wait for a patient to relapse to give them that drug. You want to move it up into earlier lines of therapy. When you move it up into earlier lines of therapy, you want to combine it with the standard of care agent. Now, some of the new clinical trials that are being done are combining Menin inhibitors, and specifically the Syndax drug, with that intensive induction chemotherapy and with the combination of azacitidine and venetoclax.

Eytan M. Stein, MD, discusses the currently available treatment options for patients with acute myeloid leukemia and how Menin inhibitors fit into this space.

Fitting Menin Inhibitors Into the AML Landscape

Closing out their discussion, Drs Hetty Carraway and Eytan M. Stein highlight an ongoing clinical trial investigating a triplet therapy for AML.

ENHANCE-3 Trial of Magrolimab in Combination with Venetoclax and Azacitidine in AML

Dr Stein explains clinical trial data on the use of magrolimab plus azacitidine for patients with TP53-mutated AML.

ENHANCE-2 Trial of Magrolimab plus Azacitidine in AML

Dr Carraway highlights some of the most urgent unmet needs for patients with higher-risk MDS.

Unmet Needs for Patients with Higher-Risk Myelodysplastic Syndrome

Eytan M. Stein, MD, discusses how to treat patients with MDS who have IDH or TP53 mutations, and whether there is a role for targeted therapy in this patient population.

Eytan M. Stein, MD | Authors

Articles

Addressing Unmet Needs and Challenges in AML

Fitting Menin Inhibitors Into the AML Landscape

ENHANCE-3 Trial of Magrolimab in Combination with Venetoclax and Azacitidine in AML

ENHANCE-2 Trial of Magrolimab plus Azacitidine in AML

Unmet Needs for Patients with Higher-Risk Myelodysplastic Syndrome

Treating Patients with Myelodysplastic Syndrome and IDH or TP53 Mutations