At an AJMC® Stakeholder Interchange in Los Angeles, leukemia specialists described a region where hospital formularies push menin inhibitor starts into the clinic, emergency department (ED) physicians may not recognize differentiation syndrome, and capitated insurance contracts steer some patients with acute myeloid leukemia away from academic centers.
The Los Angeles, California, metropolitan area has several large academic leukemia programs, but specialists say a fragmented health care market shapes how menin inhibitors reach patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) as much as the drugs’ clinical profiles do.
At a Stakeholder Interchange convened by The American Journal of Managed Care® (AJMC®), topics such as insurance contracts, the region’s many independent hospitals, and the reach of community oncology groups dominated a July 21, 2026, small group discussion. The session included a faculty member from Seattle, Washington, for a comparative perspective.
The session was moderated by Anthony Stein, MD, professor in the Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, and codirector of the Gehr Family Center for Leukemia Research, City of Hope. Its objectives matched those of earlier sessions: (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:
Participants agreed that menin inhibitors menin inhibitors have their clearest and earliest role in KMT2A-rearranged (KMT2Ar) disease”, where relapse comes fast and alternatives are few. Walter, who joined from Seattle, said the case is less clear for NPM1-mutated (NPM1m) relapses after a long remission. “To me, it’s kind of a glass half full, half empty,” he said. “The drug works to some degree, but…it’s not a game-changing effect. It’s sort of somewhat sad in a way for the mechanism that is so fundamental for these leukemias.” Merin noted that many patients with NPM1m disease also carry FLT3 mutations, in which case FLT3-targeted therapy typically takes priority.
Al Malki pointed out that single-agent trial results came largely from patients who had already received venetoclax, which may understate the drugs’ activity. Stein said combinations are where the field is headed. In the KOMET-007 trial (
Blackmon raised a gap specific to therapy-related disease. “I keep having therapy-related patients with KMT2A that are not qualified for these studies because of prior malignancies,” she said. Stein said frontline trial eligibility should change for patients whose earlier cancer has been in remission for a year or more, since etoposide-related KMT2Ar leukemia often arises soon after treatment.
In Los Angeles, hospital economics largely decide where therapy starts. Merin said Cedars-Sinai does not build disease-specific pathways for menin inhibitors; instead, oral targeted drugs are kept off the inpatient formulary. “The whole point of the institutional treatment pathways is to prevent people from prescribing it inpatient. They don’t care what you do outpatient. Outpatient is profitable, inpatient it’s money-losing,” he said. He supports the policy, noting that many community physicians hold privileges at Cedars-Sinai and that the rule moves patients out of the hospital and onto transfusion support and targeted therapy. Insurers rarely object to combining menin inhibitors with other agents in relapsed disease, he added.
Blackmon said City of Hope also relies on outpatient prescription coverage, although staff sometimes arrange for a family member to bring the drug to the hospital when a patient will be discharged within 7 to 10 days. Stein said patients with rapidly rising white blood cell counts still need admission for cytoreduction and tumor lysis prophylaxis before a menin inhibitor is added; he noted that KMT2Ar disease can climb from 5000 to 50,000 cells/µL within days.
The threshold for outpatient starts depends on the setting. “If it’s a cancer center with sufficient outpatient support, you can see the patient 3 times a week, get infusion quickly, then you can do outpatient earlier,” Cai said. “But if it’s a community center, some of the oncologists—they probably keep the patient for a longer time.”
Turnaround for the tests that qualify patients varied widely across the region. Stein said City of Hope’s rapid panel returns NPM1 results in 3 to 5 working days, with KMT2A rearrangements identified by fluorescence in situ hybridization (FISH) or cytogenetics; Blackmon said FISH for KMT2A is now reflexive for all AML cases there and returns in about a week. At Cedars-Sinai, KMT2A testing is done in-house, but next-generation sequencing goes to an outside laboratory and can take 2 to 3 weeks.
USC lacks in-house molecular testing. “We don’t have it in-house, unfortunately, so it takes a while. You guys all have it in-house, which is nice,” O’Connell said. Walter said Seattle’s program can return preliminary cytogenetics and FISH in 2 days when pushed.
Minimal residual disease (MRD) testing posed a separate problem. Merin said NPM1 MRD samples are sent out and take approximately 3 weeks to be returned. “By the time you get the result back, it’s 3 weeks old, which means you would have relapsed already,” he said.
Outpatient starts shift safety monitoring to clinics, pharmacists, and EDs. Amanam said QTc risk is often hidden in routine supportive care. “You have medications that are QT prolonging, and then you add the menin inhibitor; I think sometimes that’s missed. So, I think that’s very important for kind of all the different services to be aware of that.” Stein named ondansetron and levofloxacin (Levaquin; Janssen) as common culprits.
Participants discussed how agents differ in ways that matter for these medication lists. Revumenib (Revuforj; Syndax Pharmaceuticals) requires a dose reduction with strong CYP3A4 inhibitors such as azole antifungals, whereas ziftomenib requires closer monitoring but no dose change; ziftomenib should not be taken with proton pump inhibitors, and revumenib has no such restriction.²,³ Both labels call for an electrocardiogram (ECG) at least weekly for the first 4 weeks and at least monthly thereafter.”.2,3
Merin said Cedars-Sinai’s specialty pharmacists check the ECG before releasing an outpatient prescription and call patients to review their medications. Artz said City of Hope’s inpatient pharmacy support is more robust. “But I think outpatient, it’s a little thin, to be honest,” he said. “Usually for us, we’ve stabilized them by the time they’re outpatient, but I do think the outpatient is a challenge, too.”
For differentiation syndrome, the larger worry was recognition. “Outside of a few leukemia docs, differentiation syndrome is not what’s on the mind if someone comes into the [ED] with shortness of breath,” Walter said. “Once you have the diagnosis, it’s trivial. But not missing it is the problem.”
That risk is sharper in Los Angeles, Merin said, because patients may land at any of roughly 85 hospitals; Cedars-Sinai relies on a 24-hour answering service. Stein recommended giving patients a wallet card. “It’s always good to probably have a card for the patient saying, I’m on X drug, and these are the 2 black box warnings,” he said. He suggested a home steroid supply makes more sense for rural patients than for those who can reach care quickly in the city.
O’Connell, who has treated patients with menin inhibitors only on trials, described the hesitation clinicians feel before a first outpatient start. “I have someone ready to start it, and I am worried about them, because it takes some training for the patient to know what to recognize,” she said.
The sharpest disagreement concerned community treatment of AML. “It shouldn’t be treated in the community, period,” Merin said, citing practices that cannot anticipate transfusion needs or give same-day transfusions. He traced the problem to small Affordable Care Act, Medi-Cal, and Medicare Advantage plans that capitate oncology care to large community groups, some with dozens of offices across Southern California, rather than to hospitals with hematologists. Amanam recalled his first patient with commercial insurance on revumenib: the insurer would not pay for care at City of Hope, so the City of Hope team coached the community physician through differentiation syndrome over the phone.
Al Malki said education alone cannot close the gap. “They have 1000 other cancers that they need to be educated on, and they’re generalists. This is very specialized for them,” he said. Walter countered that community treatment is expanding regardless. Oral regimens and lower-intensity backbones have “opened the floodgate,” he said, and patients now often begin therapy locally before reaching an academic center. Blackmon agreed that community oncologists can adapt. “They finally figured out HMAs in the community; they’re handling it,” she said, referring to hypomethylating agents. “It takes a little time and feeling like you’ve got a few cases under your belt, but they can do it.”
Cai described the model Kaiser Permanente uses: academic-level specialists start treatment, then return patients to local oncologists with telemedicine follow-up. Merin said that hub-and-spoke approach works within a large integrated system but not across Los Angeles’ smaller plans. Amanam said trust is the missing ingredient. “Especially in Southern California, a lot of community practices are very worried that they’re going to see you and then the patient—they’ll never see the patient again,” he said. “So, I think if we have kind of a built-in system where there’s some level of trust…and we’re not going to take the patient from you, I think it would be helpful.” Merin was skeptical that such partnerships would form in such a fractured market.
Most participants said payer restrictions influence, rather than dictate, whether a community patient starts a novel therapy. O’Connell said patients often arrive at USC for a second opinion after their oncologist could not obtain a drug, and her team gets the patient started, secures approval of the drug, and sends them back.
Merin said the manufacturer of revumenib offers a $0 co-pay program for commercially insured patients and an income-based assistance program. He added that clinical trials play an outsized financial role in Los Angeles: “Managed care is very interested in clinical trials because [with] clinical trials, the sponsor is subsidizing the care.”
Amanam cited California rules that give patients in capitated plans better access to a second opinion at a cancer center, although Artz noted that this covers only the consultation, not ongoing care. Blackmon said lodging and caregiving needs remain unaddressed for adults. “In pediatrics, they have this in place, but for adults, too bad if you don’t have a caregiver for a transplant,” she said. Stein and Merin noted that this is a particular problem, as high housing costs have pushed some patients to the high desert, far from leukemia centers and reliable transfusion support.
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