Menin Inhibitors in AML: In NYC, Experts Map the Path From Academic Centers to Community Care

Menin inhibitors have moved quickly from clinical trials into practice for adults with relapsed or refractory (R/R) acute myeloid leukemia (AML) that carries a KMT2A rearrangement (KMT2Ar) or an NPM1 mutation (NPM1m). How to deliver them safely outside a handful of large cancer centers was the focus of a Stakeholder Interchange that The American Journal of Managed Care® (AJMC®) hosted on June 24, 2026, in New York, New York.

The session was moderated by Oscar B. Lahoud, MD, chief medical officer and section chief of hematology at New York University (NYU) Langone Hospital–Brooklyn. Its objectives were to (1) outline the current therapeutic positioning of menin inhibitors in AML; (2) evaluate the role of community oncology in delivering novel targeted therapies; and (3) define best practices for collaboration and patient comanagement across care settings.

Participants were:

• Bhavana (Tina) Bhatnagar, DO, director of hematology and medical oncology, WVU Cancer Institute at Wheeling Hospital, West Virginia University
• Kelly Chung, PharmD, BCOP, clinical pharmacy specialist, leukemia, Memorial Sloan Kettering Cancer Center (MSK)
• Xiaoyi Chen, MD, PhD, hematologist/oncologist, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson University Hospital
• Kira Gritsman, MD, PhD, physician-scientist and director of blood cancer correlative research, Montefiore Einstein Comprehensive Cancer Center
• Aziz Nazha, MD, hematologist/oncologist and executive director of enterprise AI workforce transformation and education, Jefferson Health, Philadelphia
• Neil Palmisiano, MD, MS, system leader for leukemia and deputy director of phase 1 therapeutics for hematologic malignancies, Rutgers Cancer Institute of New Jersey; system leader for leukemia, RWJBarnabas Health

Unmet Need and Where Menin Inhibitors Fit

Lahoud opened by reviewing why these subgroups need new options. Although most patients with AML achieve remission after induction, many relapse, and survival after relapse is poor. NPM1 mutations, considered favorable at diagnosis, occur in approximately 30% of adult AML cases and lose that advantage in the R/R setting; KMT2A rearrangements are less common but are overrepresented in therapy-related disease. Before menin inhibitors, these patients relied on intensive chemotherapy or a hypomethylating agent with or without venetoclax (Venclexta; AbbVie/Genentech), with remission needed as a bridge to transplant.¹

Menin inhibitors block the menin-KMT2A interaction that drives HOXA9 and MEIS1 expression, allowing leukemic cells to differentiate. National Comprehensive Cancer Network (NCCN) guidelines list revumenib (Revuforj; Syndax Pharmaceuticals) for R/R KMT2Ar AML and revumenib or ziftomenib (Komzifti; Kura Oncology) for R/R NPM1m AML.¹ In the AUGMENT-101 trial (NCT04065399) of revumenib in KMT2Ar disease, the overall response rate was 63.2% and the complete remission (CR) plus CR with partial hematologic recovery (CRh) rate was 22.8%.² In KOMET-001 (NCT04067336), ziftomenib produced a 22% CR/CRh rate in NPM1m AML, with median overall survival of 6.6 months.³ The FDA approved revumenib for R/R NPM1m AML in October 2025 and ziftomenib (Komzifti) for the same indication in November 2025.⁴^,⁵

Bhatnagar summed up the group’s view. “There’s nothing else in that space,” she said. “It’s not curative. So, I think we would like to see longer overall survival, more durable remissions. But I think for this population—where there’s literally nothing—I think that’s very promising.”

Palmisiano was blunter about the alternatives. “In the relapse refractory setting…there are 27 options, but they’re all equally bad,” he said. “Our greatest unmet need is how to extend that duration of response in the relapsed/refractory setting, especially for the KMT2A” patients.

Molecular Testing Remains the First Bottleneck

The faculty uniformly described a lag between relapse and actionable results. Bhatnagar’s practice sends next-generation sequencing (NGS) to WVU’s main campus in Morgantown, which takes approximately 2 weeks, and payers often want confirmation that the mutation persists at relapse. “So, you might literally be sitting there for 2 weeks waiting for that result to come in,” she said.

In Philadelphia, Nazha said Jefferson outsourced its testing to a commercial laboratory, and results now take approximately 3 weeks. At Rutgers, Palmisiano said a rapid send-out assay for FLT3 and NPM1 returns in 3 or 4 days, but KMT2A rearrangement results from cytogenetics carry a 2-week lag, as does the in-house 56-gene NGS panel.

Sites with faster turnaround had redesigned their workflows. Gritsman said Montefiore asked pathologists to prioritize a focused in-house panel covering FLT3, NPM1, and TP53, which returns in 4 days, before a broader panel follows. Chung said MSK’s in-house MSK-IMPACT testing typically returns in 4 to 5 days for inpatients when the team asks pathology to expedite it, and “usually…a week or a week and a half if unprompted.” Lahoud said NYU partnered with outside companies and often has results within a week.

Bridging to Transplant and Switching Agents

For fit patients, the goal of treatment is remission and a prompt allogeneic transplant. The biggest challenge, Chen said, is timing: Responses can be short, and some of her patients relapsed while waiting for a donor. She described a patient with KMT2Ar AML who had relapsed after 2 transplants, achieved CR on revumenib, and, after later salvage with gemtuzumab ozogamicin (Mylotarg; Pfizer), went on to a third transplant.

Chen has also seen responses to revumenib in 3 patients whose disease progressed after ziftomenib, and her team is preparing a case series. “I personally do feel they have overlaps, but they’re not completely equivalent to each other,” she said, adding that if one inhibitor fails, the other is worth trying when it can be obtained. Chung said her team takes the same approach. “Someone progresses on [revumenib], I’m like, let’s try [ziftomenib].” Lahoud noted that resistance mutations affecting menin may still respond to next-generation agents such as bleximenib, which is being developed by Johnson & Johnson; it is being studied alone and with venetoclax-azacitidine.

Sequencing questions remained open. For a patient with FLT3 and NPM1 comutations, Palmisiano said his team usually treats FLT3 first. For a younger patient with NPM1m AML relapsing after the standard 7+3 chemotherapy backbone, Lahoud leaned toward azacitidine-venetoclax. Gritsman said most of her fit patients receive 7+3 plus venetoclax on trial, making them venetoclax-exposed at relapse so that she would favor revumenib. “If your goal is to try to get them to transplant in one piece, I typically try to go for something that’s going to preserve their functional status so that they’re able to move forward with it without any further delays,” she said.

Participants also shared their experiences with once-weekly low-dose decitabine and venetoclax, a regimen Montefiore investigators have studied in TP53-mutated disease.⁶

QTc, Drug Interactions, and Differentiation Syndrome

In the pivotal trials, any-grade differentiation syndrome occurred in 27.7% of patients receiving revumenib and 25% receiving ziftomenib; any-grade QTc prolongation occurred in 25.5% and 13%, respectively.²^,³ The revumenib label calls for an electrocardiogram (ECG) before starting, with the ECG repeated at least weekly for the first 4 weeks and at least monthly thereafter, plus a dose reduction when taken with strong CYP3A4 inhibitors.⁷ Gritsman and Lahoud said their centers follow this monitoring schedule.

Chung said the R/R population makes interactions hard to avoid. “A lot of issues with polypharmacy [involve] patients at that point who are on a lot of supportive care. They’re very neutropenic, so they have to be on prophylactic antibiotics and antifungals,” she said. “And then, all those medications can also cause QTc prolongation as well.” Lahoud said azole antifungals are the main concern and that he will hold revumenib when a patient with a serious mold infection needs one; Chung noted that dose reduction is an alternative.

Chung named differentiation syndrome as the adverse event requiring the most preparation for clinics that are considering starting revumenib in the outpatient setting. Some MSK clinicians send patients starting isocitrate dehydrogenase inhibitors home with a “pill-in-the-pocket” steroid prescription, but no other site reported doing this with menin inhibitors. Palmisiano said differentiation syndrome is uncommon when menin inhibitors are given in triplet combinations, as most of his patients receive them. Chen said she had not seen it in 4 patients treated with revumenib.

Outpatient Starts and Access Hurdles

Most sites start menin inhibitors in the outpatient setting. “The hospital is a bad place, especially for vulnerable patients,” Lahoud said, adding that waiting a week for a specialty pharmacy fill does not justify an admission. Inpatient starts happen mainly when patients are already hospitalized for other reasons. Gritsman described starting therapy in the hospital for a patient with refractory KMT2Ar disease who was too ill for discharge and needed a bridge to transplant.

Chung said MSK’s in-house specialty pharmacy can usually supply the drug within a day or two, but outside pharmacies slow things down. Inpatient status creates its own problems, she said. For patients with Medicare or Medicaid, “it’s impossible to fill an outpatient script because it shows up that they’re admitted in the hospital.” Some skilled nursing facilities, she added, will accept a patient only with an unopened bottle of oral chemotherapy.

Formulary rules can block inpatient use entirely. “We can’t write a new prescription that’s not on the formulary. And we don’t have either of the menin inhibitors on the formulary yet,” Bhatnagar said, noting her pharmacists can sometimes secure only a few doses.

Nazha explained the hospital logic: “Hospitals are worried, even if you order it, it’s not approved by the insurance, the hospital is going to swallow the cost of those medications.”

Payer mix shapes access as well. Approximately 84% of Lahoud’s Brooklyn patients have Medicare or Medicaid, and both NYU and Rutgers treat many uninsured or undocumented patients, for whom emergency Medicaid can take time. Palmisiano said Pennsylvania grants it more readily than New Jersey or New York. Lahoud said NYU partners with city hospitals, such as Bellevue, and works directly with rehabilitation facilities to ensure that weekly blood counts and ECGs continue after discharge.

Pathways Work When They Are Enforced

Lahoud argued that the breadth of NCCN guidelines leaves community clinicians without direction. “They’re called guidelines, but they don’t guide you into what’s the preferred treatment,” he said. NYU uses integrated pathway software, developed with Dana-Farber Cancer Institute, that embeds clinical trials and generates weekly reports of noncompliance across its 4 hospitals. He urged participants in leadership roles to tie compliance to incentives for quality and consistency, not only cost.

Other sites rely less on software. Nazha said Jefferson has pathways in its order sets, but adherence is uncertain. “Unless you force people to do it, it’s really hard to standardize practice,” he said, recalling that a standardized immunotherapy pathway in lung cancer at Cleveland Clinic saved $10 million over 6 months. Bhatnagar said WVU’s hub-and-spoke system is developing pathways but has met resistance from community physicians. Rutgers, Montefiore, and MSK depend on weekly leukemia tumor boards that community physicians can join. Chen said Rutgers builds an Epic template for each new agent, so ECGs and laboratory monitoring are ordered automatically, with pharmacists checking adherence.

Defining the Community’s Role

Participants disagreed about how much AML care belongs in the community. “I don’t think any leukemia patient should be treated in the community,” Nazha said, noting that oncologists who see 1 or 2 cases a year cannot be expected to master these regimens. Gritsman countered that patients often do not want to travel, and Lahoud said a trip from Brooklyn to Manhattan can feel “like going abroad” for some. Nazha framed the national challenge as “How do you give therapy closer to home? And then the second challenge, ‘How do you give clinical trials closer to home?’ ”

Bhatnagar, who practices in a community setting after 8 years at Ohio State, said the barrier is familiarity: educating patients, staff, and emergency department clinicians about drugs they rarely see. Chen described coaching a community partner prescribing a menin inhibitor through borderline QTc readings. “I keep telling her this is the last treatment I have for the patient,” she said. “If…you’re worried about the QT of 450 or something, then we don’t have any treatment.” Lahoud added, “This is where clinical pathways will only get you so far.”

The group converged on a shared-care model. Induction and menin inhibitor initiation happen at the academic center. After the first month, once the risks of QTc prolongation and differentiation syndrome have eased, community practices can handle transfusions and routine monitoring if they offer same-day transfusion, which many cannot. Palmisiano said community sites can manage neutropenic fever, but decisions about holding the drug should stay with specialists. “The issue of when to start and stop the menin inhibitors, I think, is a huge one, which should be just give it, I think, most of the time.”

References

1. NCCN. Clinical Practice Guidelines in Oncology. Acute myeloid leukemia, version 5.2026. Updated July 15, 2026. Accessed October 15, 2026. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf
2. Issa GC, Aldoss I, Thirman MJ, et al. Menin inhibition with revumenib for KMT2A-rearranged relapsed or refractory acute leukemia (AUGMENT-101). J Clin Oncol. 2025;43(1):75-84. doi:10.1200/JCO.24.00826
3. Wang ES, Montesinos P, Foran J, et al; KOMET-001. Ziftomenib in relapsed or refractory NPM1-mutated AML. J Clin Oncol. 2025;43(31):3381-3390. doi:10.1200/JCO-25-01694
4. Joszt L. Revumenib granted FDA approval for R/R NPM1-mutated AML. AJMC. October 24, 2025. Accessed October 16, 2026. https://www.ajmc.com/view/revumenib-granted-fda-approval-for-r-r-npm1-mutated-aml
5. Joszt L. FDA approves ziftomenib for R/R NPM1-mutated AML. AJMC. November 13, 2025. Accessed October 16, 2026. https://www.ajmc.com/view/fda-approves-ziftomenib-for-r-r-npm1-mutated-aml
6. Goldfinger M, Mantzaris I, Shastri A, et al. Treatment of TP53-mutated myelodysplastic syndrome and acute myeloid leukemia with low-intensity metronomic decitabine and venetoclax. Haematologica. 2026;111(10):3308-3317. doi:10.3324/haematol.2026.300534
7. Revuforj. Prescribing information. Syndax Pharmaceuticals; 2025. Accessed October 16, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218944s003lbl.pdf