Healthcare Utilization and Costs Among Patients with Acute Myeloid Leukemia Receiving Oral Azacitidine Maintenance Therapy Versus No Maintenance: A US Claims Database Study.

INTRODUCTION: The substantial economic burden of acute myeloid leukemia (AML) could be reduced with post-remission maintenance therapies that delay relapse. Real-world healthcare resource utilization (HCRU) data and costs among patients with AML receiving oral azacitidine (Oral-AZA) maintenance therapy or no maintenance are not well understood. We characterize HCRU and costs among these patients in clinical practice in the USA. METHODS: Data from IQVIA PharMetrics® Plus (January 1, 2016-June 30, 2022) were used. Patients ≥ 18 years who were newly diagnosed with AML, received first-line systemic induction therapy, and attained disease remission were eligible. Patients receiving Oral-AZA maintenance and those receiving no maintenance ("watch and wait" [W&W]) were matched 1:3 on baseline characteristics using propensity score matching (PSM) and followed until hematopoietic stem cell transplantation or end of continuous insurance enrollment, whichever occurred first. Outcomes included treatment patterns, inpatient and outpatient visits, and costs. RESULTS: After PSM, the Oral-AZA cohort included 43 patients and the W&W cohort 129. Of the 43 patients receiving Oral-AZA, 88.4% started at the recommended dose of 300 mg and 11.6% at 200 mg. The Oral-AZA cohort had significantly (p = 0.0025) longer median (95% CI) time to relapse from the index maintenance date (median not reached [NR; 9.0 months-NR] vs 3.3 months [0.8 months-NR]), and fewer per person per month (PPPM) hospitalizations (0.23 vs 0.61; p = 0.0005) and overall outpatient visits (5.77 vs 7.58; p = 0.0391) than the W&W cohort. Despite higher AML drug costs PPPM in the Oral-AZA cohort ($16,401 vs $10,651 for W&W), total healthcare costs PPPM were lower ($25,786 vs $38,530 for W&W; p < 0.0001). CONCLUSIONS: Patients with newly diagnosed AML treated with Oral-AZA maintenance in clinical practice had prolonged remission and lower HCRU and costs than patients receiving no maintenance therapy. These findings underscore the clinical and economic value of Oral-AZA in clinical practice.

Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States.

Intensive chemotherapy (IC) is commonly used to achieve remission in patients with acute myeloid leukemia (AML). Venetoclax plus azacitidine (VEN-AZA) is FDA-approved to treat patients with AML aged ≥ 75 years or who are ineligible for IC. This retrospective analysis used de-identified electronic health records from the US-based Flatiron Health database from patients diagnosed 11/21/2018 to 10/31/2021 to compare treatment outcomes with VEN-AZA vs. IC. Patients were 1:1 propensity score-matched ([Formula: see text]). Assessments included rates of complete remission (CR) and hematopoietic stem cell transplant (HSCT), overall survival (OS), and relapse-free survival (RFS). CR and HSCT rates were higher with IC than with VEN-AZA (60.9% vs. 44.2% [P = 0.006] and 18.1% vs. 8.0% [P = 0.012], respectively). Median OS was 17.7 months in patients treated with IC and 11.3 months with VEN-AZA without censoring (P = 0.278) and 13.7 vs. 10.6 months, respectively, with censoring at HSCT (P = 0.584). Median RFS was 12.0 months in patients treated with IC vs. 9.5 months with VEN-AZA without censoring (P = 0.431) and 6.4 vs. 7.4 months, respectively, with censoring at HSCT (P = 0.444). No OS or RFS differences observed between the two arms reached statistical significance. Randomized controlled trials comparing the two approaches are warranted, as are novel approaches to reduce relapse rates following CR.

Patient-reported outcome measures in studies of myelodysplastic syndromes and acute myeloid leukemia: Literature review and landscape analysis.

OBJECTIVES: This study aims to describe the use of patient-reported outcome measures (PROMs) in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) studies and the PROMs landscape. METHODS: A comprehensive literature review was performed in Medline/Embase (since 2000) and ClinicalTrials.gov (since 2013) to identify PROMs used in MDS and AML clinical studies. Additionally, PROMs included in approved drug labels since 2000 were reviewed. RESULTS: Overall, 112 different PROMs were used in 168 published MDS studies and 152 PROMs were used in 172 AML studies. From ClinicalTrials.gov, 16 different PROMs were used in 22 ongoing registered studies in MDS, and 24 were reported in 41 AML studies. The most frequently used PROMs were cancer-specific (eg, EORTC QLQ-C30, FACT-An) or generic (SF-36, EQ-5D) instruments, whereas MDS- and AML-specific instruments (eg, QUALMS and QOL-E in MDS; FACT-Leu and EORTC QLQ-Leu in AML) were used in a minority of studies. Two EMA-approved drugs for MDS included PROMs in their label. EORTC QLQ-C30 is by far the most frequently used cancer-specific PROM in both MDS and AML studies. CONCLUSIONS: This research indicated an underuse of AML/MDS-specific PROMs for these two indications in clinical studies and labeling claims. However, AML/MDS-specific instruments in development might be considered in future studies.

Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi.

BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen-activated protein (MAP) kinase pathway. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. Here we report frequent somatic mutations in the heterotrimeric G protein alpha-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the Ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention.