Targeted Hope
At Stanford, Gabe Mannis, MD, combines compassionate care with groundbreaking science — bringing clinical trial opportunities, like menin inhibitors, directly to his patients
Targeted Hope
The Next Era of AML Care Begins at Stanford
When Gabriel Mannis, MD, associate professor of medicine, joined the hematology faculty at Stanford in 2019, he brought with him not only a deep commitment to his patients with acute myeloid leukemia (AML), but also a vision: to build a thriving clinical trials program capable of bringing the latest scientific discoveries to the bedside. Just a few years later, that vision has helped usher in a major breakthrough – FDA approval of a new class of drugs known as menin inhibitors.
“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.
Inside the Trials: What the Data Shows
Mannis served as the Stanford principal investigator on the multicenter trials that helped lead to FDA approval. One of the most promising agents to emerge is revumenib, now officially greenlit by the FDA. Other menin inhibitors – ziftomenib, bleximenib, and enzomenib – are still in development and showing strong early results:
- Response rates are around 60%.
- Complete remissions occur in roughly a quarter of patients.
- Many patients are able to proceed to stem cell transplant, which may offer longer-term remission.
Some combinations, such as ziftomenib with standard chemotherapy, have shown complete remission rates as high as 91% in early trials.
“Without trial oversight and input from skilled clinical investigators, it’s possible that effective drugs might never successfully make their way to patients,” Mannis says. “For me, it’s like being one of the first people in the world to work with a new iPhone prototype, except instead of just testing more realistic Memojis, I get to offer my patients potentially life-saving drugs.”
Known for his warmth, Mannis brings a smile to both patients and colleagues — an approach that sustains compassion in the face of challenging work
A Stanford-Led Push Toward Progress
Targeted cancer therapies have been reshaping the oncology landscape for years – think HER2 inhibitors in breast cancer or EGFR inhibitors in lung cancer.
The approval of revumenib marks the beginning of a similar new chapter in leukemia treatment, particularly for patients at Stanford and across the country who have few other options. That progress is due in no small part to physician-scientists like Mannis, who not only treat patients but help design and lead the clinical trials that bring new options into the world. And at Stanford, where clinical research is tightly woven into patient care, this approval feels personal.
“Despite the significant advances in AML treatment over the past few years, the reality remains challenging – most patients still die from their leukemia,” Mannis says. “Early in my career, the emotional weight of this work would often follow me home. With experience, I’ve learned that finding moments of lightness and humor is essential for providing sustainable, compassionate care. By embracing these moments and not taking myself too seriously, I can stay present and focused on what matters most: supporting my patients through both the challenges and the victories.”
A memorable victory, he says, came in the form of a video text he received after the clinical trial.
“One of the stories I often tell is that of a woman whose leukemia relapsed shortly after a bone marrow transplant,” Mannis recalls. “She went into remission during the trial, got a second bone marrow transplant more than two years ago, and is now likely cured. A year or so after the second transplant, she texted me a video of her and her daughter dancing at Taylor Swift’s Eras Tour – and as a fellow hardcore Swiftie, this really hit home.”
