At this year’s American Society of Hematology meeting, investigators rolled out striking early data for an all‑oral regimen built around revumenib (Revuforj). The phase 1/2 SAVE trial tested revumenib together with oral decitabine/cedazuridine and venetoclax in patients with newly diagnosed, menin‑susceptible acute myeloid leukemia (AML). The headline numbers grabbed attention: an objective response rate of 86% and deep minimal residual disease (MRD) clearance in most responders — results that hint at a potential shift away from inpatient chemotherapy for selected patients.
The outcomes in plain numbers
Across the newly diagnosed cohort (n = 21) the SAVE regimen produced an overall response rate of about 86%. Complete remissions (CR) were common — roughly three quarters of patients — and many of those remissions were MRD‑negative at a sensitivity of 10^-4 by multiparameter flow cytometry. At a median follow‑up of nine months, median duration of response and overall survival had not been reached; the estimated 12‑month DOR rate was approximately 70% and the 12‑month overall survival rate close to 57%.
Responses were seen in both molecular subgroups the investigators targeted: patients with NPM1 mutations and those with KMT2A rearrangements each showed high response rates and substantial MRD negativity. That consistency across genotypes is one reason clinicians at ASH described the findings as encouraging rather than merely provocative.
Why an all‑oral approach matters — and where it falls short
Oral therapy matters for patients and caregivers. Taking treatment at home, avoiding long infusions, and fewer admissions are real quality‑of‑life gains — especially for older adults who make up a large portion of the AML population. But the SAVE data also sounded cautionary notes.
Hematologic toxicity was substantial. Nearly half of patients experienced febrile neutropenia, and significant rates of thrombocytopenia, neutropenia, and infection were reported. There were three grade 5 events (two bacteremias and one bronchopulmonary hemorrhage) and two early deaths in the cohort. Differentiation syndrome occurred in about one in five patients, occasionally at grade 3 or higher, though these episodes responded to steroids when recognized and treated.
Those safety signals underscore a recurring theme in targeted AML therapy: deep, rapid responses can come with a risk of profound myelosuppression and infectious complications. Investigators stress that careful monitoring, prompt management of differentiation syndrome, and rigorous dose optimization are essential if menin‑inhibitor combinations move into broader frontline use.
Dosing nuance and resistance
Revumenib dosing in the combination was adjusted based on CYP3A4 interactions. Investigators identified a recommended phase 2 dose that reflects that interaction: 160 mg twice daily when given with strong CYP3A4 inhibitors, and 270 mg twice daily without such inhibitors. That pharmacologic nuance matters clinically because many common drugs modulate CYP3A4 and could alter revumenib exposure.
Resistance mechanisms are already being investigated. The team developed assays to detect MEN1 point mutations that can emerge under selective pressure from menin inhibition; at least one known MEN1 variant was observed at relapse in this program. Those findings suggest that, while combinations may deepen initial responses, escape pathways will still need workarounds — whether second‑generation menin inhibitors, sequential strategies, or combination partners that forestall resistance.
Where this sits in the regulatory and trial landscape
Revumenib already has regulatory precedent in the relapsed/refractory setting: the FDA has cleared the drug for patients with KMT2A translocations and — more recently — for those with susceptible NPM1 mutations in relapsed/refractory AML. See the agency announcements here: the original approval for KMT2A‑rearranged disease and the later action for NPM1‑mutant AML. The SAVE study (NCT05360160) is explicitly testing whether combining revumenib with hypomethylating agents and venetoclax can extend benefit to first‑line, non‑intensive settings; the trial is listed on ClinicalTrials.gov.
The practical takeaway for clinicians and patients
These are early‑phase data from a small cohort with short follow‑up, so enthusiasm should be measured. But the combination’s high CR and MRD‑negative rates are meaningful — especially for older or unfit patients who are poor candidates for intensive chemotherapy. The tradeoff is clear: potentially less hospital time and oral convenience versus a higher burden of myelosuppression and infection risk that will require careful outpatient management and dose individualization.
Larger, confirmatory studies and longer follow‑up will be needed to determine whether the promise translates into durable survival benefit with an acceptable safety profile. In the meantime, the SAVE results add fuel to an evolving strategy in AML care: targeted, orally delivered regimens that aim to replace or reduce the role of traditional inpatient chemotherapy for selected molecular subtypes.
For clinicians who want to review the trial record, the SAVE study is registered at ClinicalTrials.gov. For the regulatory context around revumenib, see the FDA summaries linked above.