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The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1–2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4–5 events. The 9-year CI of grade 1–2 cardiac failure was 1.3%, grade 3–4 was 15%, and grade 5 was 2.1%; of grade 1–2, arrhythmia was 1.9%, grade 3–4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3–4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.

Simple Summary Studies addressing the economic costs and burden of secondary acute myeloid leukemia (sAML) are scarce in the literature. We analyzed this topic in a real-life population of sAML patients between 60-75 years receiving intensive chemotherapy induction. In elderly patients with sAML and intensive regimens, it entails an increase in costs and a longer hospital stay. In these specific patients, almost a third of the time is spent hospitalized after the diagnosis of sAML. There are no studies with this type of population and diagnosis, which gives added value to the results obtained. Pharmacoeconomic studies in patients with AML are being carried out due to the need to evaluate the cost-effectiveness of new oral drugs, therapeutic schemes with higher costs than previous treatments. Background: Information regarding the impact on healthcare systems of secondary acute myeloid leukemia (sAML) is scarce. Methods: A retrospective review of medical charts identified patients aged 60-75 years with sAML between 2010 and 2019. Patient information was collected from diagnosis to death or last follow-up. Outpatient resource use, reimbursement, frequency and duration of hospitalization, and transfusion burden were assessed. Forty-six patients with a median age of 64 years were included. Anthracycline plus cytarabine regimens were the most common induction treatment (39 patients, 85%). The ratio of the total days hospitalized between the total follow-up was 29%, with a sum of 204 hospitalizations (average four/patient; average duration 21 days). The total average reimbursement was EUR 90,008 per patient, with the majority (EUR 77,827) related to hospital admissions (EUR 17,403/hospitalization). Most hospitalizations (163, mean 22 days) occurred in the period before the first allogeneic hematopoietic stem cell transplant (alloHSCT), costing EUR 59,698 per patient and EUR 15,857 per hospitalization. The period after alloHSCT (in only 10 patients) had 41 hospitalizations (mean 21 days), and a mean reimbursement cost of EUR 99,542 per patient and EUR 24,278 per hospitalization. In conclusion, there is a high consumption of economic and healthcare resources in elderly patients with sAML receiving active treatments in Spain.

Context: Mutations in the FLT3 tyrosine kinase and in IDH1/IDH2 (collectively IDHm) co-occur in up to 30% of adults with acute myeloid leukemia (AML). SEL24/MEN1703 is an orally available, first-in-class, dual PIM/FLT3 kinase inhibitor. Preliminary results from the phase 1/2 first-in-human DIAMOND-01 trial (NCT03008187) demonstrated antitumor activity of single-agent SEL24/MEN1703 in adult patients with relapsed/refractory (R/R) IDHm AML, where 3 of 8 IDHm patients responded. Objective: To report the first safety and efficacy results from an additional expansion cohort of the DIAMOND-01 trial in 20 patients with R/R IDHm AML. Design: DIAMOND-01 is a phase 1/2, open-label, multicenter study consisting of 2 parts: dose escalation and cohort expansion, including an additional expansion cohort (IDHm) that is ongoing. Patients: Patients with R/R IDHm AML and no standard therapeutic options were eligible. Intervention(s): Patients received the recommended dose of 125 mg SEL24/MEN1703 orally, once daily for 14 days over a 21-day cycle until disease progression or unacceptable toxicity. Main Outcome Measure(s): The number and frequency of adverse events (AEs; primary) and overall response rate (ORR; secondary). Results: As of 10 January 2022, 14 patients were enrolled in the IDHm cohort. Seven patients had IDH2, 1 had IDH1/2, and 4 had IDH1 mutations. Two patients had a concomitant FLT3-ITD mutation. Safety data (N=12) showed that grade ≥3 TEAEs (≥10% of patients) were pneumonia (33%) and asthenia (17%), both unrelated to the study drug. Of the 7 patients who completed ≥1 treatment cycle and had ≥1 post-baseline assessment or clear disease progression, ORR was 28.6%; 1 patient achieved a complete response with incomplete blood count recovery at cycle 3 and underwent hematopoietic stem cell transplant, and 1 patient had a partial response at cycle 4 (confirmed at cycle 7 and still on treatment). Among the 7 remaining patients, 3 discontinued before completion of cycle 1 without progression or response, and 4 patients are ongoing and have not yet undergone post-baseline assessments. Conclusions: SEL24/MEN1703 had a manageable safety profile and single-agent activity in adult patients with R/R IDHm AML and may be a feasible therapeutic option in this difficult-to-treat population.

Prognosis for relapsed or refractory (R/R) acute myeloid leukemia (AML) despite salvage therapy is dismal. This phase I dose-escalation trial assessed the safety and preliminary clinical activity of selinexor, an oral exportin-1 (XPO1) inhibitor, in combination with FLAG-Ida in younger R/R AML patients. The aim was to find the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD). Fourteen patients were included, and selinexor dosage was 60 mg (3 patients), 80 mg (3 patients), and 100 mg (7 patients) weekly. No dose-limiting toxicities were reported. Grade ≥3 non-hematologic adverse events (AEs) occurred in 78.6% of patients. Two patients were non MTD evaluable due to early death, and overall, 3 out of 14 patients (21.4%) had fatal AEs. Five out of 12 (42%) response and MTD evaluable patients achieved a complete remission (CR; n=4) or CR with incomplete hematologic recovery (CRi, n=1), and 4 patients (33%) subsequently underwent allogeneic transplantation. The median overall survival (OS) and event-free survival (EFS) were 6.0 (range 0.9-19.3) and 1.1 months (range 0.7-19.3), respectively. Using selinexor 100 mg/weekly, CR/CRi rate of 66.7%, OS 13.6 months (range, 1.6-19.3), and EFS 10.6 months (range, 0.9-19.3). At last follow-up, 3 patients were alive. Selinexor 100 mg/weekly with FLAG-Ida combination in R/R AML showed acceptable tolerability and efficacy, establishing the RP2D of this regimen in future clinical trials. ClinicalTrials.gov Identifier: NCT03661515.