Lefèbvre, Patrick

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease associated with non-specific symptoms, which may lead to diagnosis delays and poor outcomes. Research Question: Which symptoms and diagnostic procedures occur prior to PAH diagnosis and do they vary based on diagnosis delay? Aim: To describe PAH symptoms and diagnostic procedures among patients newly diagnosed with PAH. Methods: Adults with PAH were identified from Optum’s de-identified Clinformatics ® Data Mart Database (2016-2021). Eligible patients had continuous health plan enrollment ≥12 months (mo) before the first recorded PAH-related symptoms (i.e., index date ) and from the index date until the first recorded PAH diagnosis on a medical claim (i.e., study period ). Patients also had ≥1 fill for a PAH treatment and ≥1 right heart catheterization at any time post-index. PAH symptoms and diagnostic procedures were described during the study period, overall, and stratified by time between the index date and first PAH diagnosis (i.e., diagnosis delay ; ≤12 mo, 12–24 mo, and >24 mo). Results: The sample included 538 patients (≤12 mo: N=327; 12–24 mo: N=126; >24 mo: N=85). Mean age was 66 years, 60.6% were female, and mean (range) diagnosis delay was 11.8 (0.0–50.2) mo. During the study period, most patients had ≥2 unique symptoms recorded, but those with longer delay had more fatigue (≤12 mo: 26.6%; 12–24 mo: 55.6%; >24 mo: 54.1%), edema (29.1%; 42.9%; 51.8%), and dizziness (10.1%; 23.0%; 18.8%), among others. Mean delay was shorter when the first symptoms were ascites (4.2 mo) and syncope (6.4 mo) and longer for fatigue (14.2 mo) and dizziness (14.0 mo). On average, patients with longer delay had more diagnostic procedures pre-diagnosis (≤12 mo: 4.3; 12–24 mo: 8.2; >24 mo: 8.7), driven by more electrocardiograms (ECG; 1.9; 4.2; 4.5). Overall, 85.5% of patients had an ECG and 83.5% had a transthoracic echocardiography pre-diagnosis. Conclusions: Symptoms such as fatigue, edema, and dizziness were more common in patients with longer time to diagnosis and these patients had more diagnostic procedures. Greater physician awareness and new screening tools (e.g., predictive algorithms using ECG data) could accelerate PAH diagnosis and treatment aiming at improving patient outcomes.

Abstract Background Patients with high-risk, newly diagnosed multiple myeloma (HR-NDMM) who are ineligible for autologous stem cell transplant (ASCT) have limited first-line treatment options. Recent meta-analyses evaluating the impact of incorporating daratumumab in the backbone regimen on progression-free survival (PFS) have found mixed results in these patients. Materials and Methods A pooled analysis of patient-level data for ASCT-ineligible patients with HR-NDMM [ie, del(17p), t(4;14), t(14;16)] from the MAIA and ALCYONE trials; stratified by study identifier and adjusting for cytogenetic abnormality subtype, baseline performance status, International Staging System stage, myeloma type, and renal impairment; was conducted. Impact of daratumumab on PFS and rates of complete response or better (≥CR), minimal residual disease (MRD)-negative CR, very good partial response or better (≥VGPR), and overall response (ORR) was compared to control. Results Among 101 patients in the daratumumab and 89 patients in the control cohort, median follow-up was 43.7 months. Daratumumab reduced the risk of progression or death by 41% (adjusted hazard ratio for PFS [95% confidence interval (CI)] = 0.59 [0.41-0.85]) versus control. At 36 months, the estimated proportion of patients who did not progress and were still alive was 41.3% in the daratumumab and 19.9% in the control cohort. Rates of ≥CR (41.6% vs. 22.5%), MRD-negative CR (24.8% vs. 5.6%), ≥VGPR (75.2% vs. 46.1%), and ORR (92.1% vs. 74.2%) were higher for daratumumab versus control. Conclusion These findings demonstrate that incorporation of daratumumab in frontline treatment regimens reduced the risk of progression or death and improved response rates among ASCT-ineligible HR-NDMM patients.