At Stanford, Gabe Mannis, MD, combines compassionate care with groundbreaking science — bringing clinical trial opportunities, like menin inhibitors, directly to his patients

“My vision was actually pretty simple: I wanted to eventually have a trial option for every AML patient that came to see me, and I wanted Stanford’s AML program to be one of the premier AML programs in the world,” Mannis says.

These new oral medications target specific genetic changes in leukemia cells and offer new hope to patients whose cancers have returned or resisted all other treatments. For many with AML that has relapsed or become drug-resistant, treatment options have been limited. Now, for a meaningful subset of patients, there is finally something new, and it’s not chemotherapy.

What Are Menin Inhibitors – and Why Do They Matter?

To understand menin inhibitors, you don’t need a PhD in molecular biology, but you do need to know this: Not all leukemia is the same. AML, for instance, is an aggressive blood cancer that arises when bone marrow makes too many abnormal white blood cells. But among AML cases, genetic mutations vary widely, which is why treatments that work for one patient may be ineffective for another.

Menin inhibitors are part of a new generation of targeted therapies – drugs designed to interrupt the specific genetic pathways that allow leukemia cells to grow unchecked.

Mannis examines a patient as part of Stanford’s menin inhibitor clinical trial program, which has helped usher in a new era of targeted leukemia therapy

“Menin inhibition is a really neat, new strategy to treat certain types of leukemia,” Mannis explains. “What makes menin inhibition so unique is that instead of killing cancer cells directly like most treatments, it switches off faulty gene signals that are blocking the cells from maturing. This allows the leukemia cells to develop into more normal, healthy blood cells – a process called differentiation, which we can actually watch unfold under the microscope in real time.”

It’s a highly precise intervention – and it’s taken over 20 years to get here.

The research that led to this discovery began in pediatric oncology, where scientists were desperate for new treatments for infants with a particularly aggressive form of leukemia. Over the years, as the biology became clearer, so did the potential: This was not just a treatment for rare childhood cases. It might benefit adults, too.

“This was truly a bench-to-bedside evolution that began in an academic lab,” Mannis reflects. “I vividly remember discussing one of the preclinical papers several years ago in my colleague Ravi Majeti, MD, PhD’s lab meeting and thinking to myself, ‘This looks like really, really good science – I need to be a part of this drug development.’”

“My vision was actually pretty simple: I wanted to eventually have a trial option for every AML patient that came to see me, and I wanted Stanford’s AML program to be one of the premier AML programs in the world.” – Gabriel Mannis, MD

Who Might Benefit?

Not every patient with leukemia will be eligible for a menin inhibitor, but for those who are, the impact could be profound. Specifically, the therapy shows promise in two genetic subtypes of acute leukemia:

• NPM1 mutations – seen in about 30% of AML cases, often in younger patients.
• KMT2A rearrangements – less common, but often more aggressive; seen in some adult AML cases and in children with acute lymphoblastic leukemia.

“Taken together, roughly 40% of patients with acute leukemia could potentially benefit from this class of therapy,” Mannis says.