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Purpose: Medication prior authorization (mPA) occurs commonly in US cancer care. While medical oncologists report potential harm resulting from this requirement, the impact of mPA in pediatric oncology is unknown. This study's primary aim was to test the feasibility of prospectively collecting multi-institutional data on mPA in pediatric oncology, while secondarily assessing for resultant delays in care., Methods: Pediatric patients with cancer were enrolled between September 2021 and December 2022 at three Children's Oncology Group institutions participating in the National Cancer Institute Community Oncology Research Program. Data collected for each mPA event included the name of the medication, indication, desired initiation date, and actual date administered., Results: Among 68 patients enrolled at three institutions, 38 (56%) were subject to at least one mPA. A total of 69 mPAs occurred in these 38 patients, with 36 (52%) for supportive care and 33 (48%) for treatment medications. Ultimately, 61 of 69 (88%) mPAs were approved as prescribed (33 of 33 treatment mPAs) with a range of 5-240 minutes of provider/staff time required to resolve. MPAs delayed care in 15 of 69 (22%) cases with a range of 1-21 days. Most providers reported minimal or no additional burden to characterizing mPA data., Conclusion: Despite the complexity and variability of institutional mPA processes, it is feasible to prospectively collect multi-institutional mPA data. No cancer treatment mPA request led to alterations in prescriptions. Delays in care because of mPA affect roughly one quarter of pediatric patients with cancer, the consequences of which remain unknown.

Purpose: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with KMT2A -rearranged ( KMT2Ar ) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) KMT2Ar acute leukemia., Methods: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R KMT2Ar acute leukemia or with AML and nucleophosmin 1 ( NPM1 ) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m 2 if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all KMT2Ar treated patients; efficacy was assessed in those with centrally confirmed KMT2Ar . The separate NPM1 cohort of the trial is ongoing., Results: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% ( P = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease., Conclusion: Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.