Zhou, Summera

Background: A pivotal clinical trial comparing the efficacy and safety of ibrutinib with zanubrutinib in patients with Waldenström macroglobulinemia (WM) did not achieve its primary endpoint of complete response or very good partial response. In addition, median progression-free survival was not reached in either treatment arm. In the absence of treatment effectiveness differentiation based on clinical trial evidence, we conducted a real-world study to assess patient characteristics, treatment patterns, and all-cause healthcare resource utilization (HRU) in patients with WM who received ibrutinib or zanubrutinib as first-line (1L) therapy. Methods: In this retrospective cohort study, we used the ConcertAI Database to collect claims data of patients with WM aged ≥18 years who initiated single-agent ibrutinib (420 mg/day) or zanubrutinib (320 mg/day) as 1L therapy on or after 9/1/2021 (index date). A 6-month washout period of guideline-recommended WM antineoplastic agents was required to confirm 1L status. Patients were excluded if they were receiving ibrutinib and zanubrutinib concurrently, died within 30 days of the index date, had a record of hematopoietic stem cell transplant, had a record of other ibrutinib indications in the 6 months before index, or were participating in a clinical trial. Baseline demographics and clinical characteristics, therapy duration (number of days between the first and last day of the medication supply), and HRU (all-cause and WM-specific) per-patient-per-month (PPPM) were assessed. Results: The study included 51 patients (ibrutinib, n=30; zanubrutinib, n=21). In both cohorts, most participants were male (ibrutinib, n=20 [67%]; zanubrutinib, n=16 [76%]), and the mean age at baseline was 73 years and 75 years, respectively. At baseline, the median Charlson Comorbidity Index was 0, and the WM-related and ibrutinib/zanubrutinib-related clinical events were similar between the two cohorts. While the zanubrutinib cohort had a higher prevalence of infections (33% vs 3%) and musculoskeletal pain (24% vs 7%) at baseline, the ibrutinib cohort had a higher prevalence of hypertension (20% vs 14%). The baseline prevalence of anemia was similar in both cohorts (ibrutinib, 27%; zanubrutinib, 29%). Mean follow-up was 6.9 months (ibrutinib) and 6.3 months (zanubrutinib). The mean ± SD duration of therapy was 152 ± 112 days (ibrutinib) and 113 ± 99 days (zanubrutinib; p=0.195). The ibrutinib cohort had a significantly lower all-cause HRU PPPM (4.53 ± 3.96 vs 8.53 ± 6.66, p=0.020) and lower WM-specific HRU PPPM (0.11 ± 0.26 vs 0.54 ± 1.14, p=0.104). Conclusions: In this real-world analysis, patients with WM treated with 1L ibrutinib had a numerically longer duration of therapy and lower all-cause and WM-specific HRU PPPM, compared to those treated with 1L zanubrutinib. Due to a small sample size and short follow-up, these findings should be interpreted cautiously.

AbstractBackgroundUnderstanding mortality risk across the Alzheimer’s disease (AD) clinical stages is essential for resource planning and estimating the value of disease modifying therapies (DMTs), which may slow progression. Such studies are lacking.MethodThe study used the Uniform Data Set of the National Alzheimer’s Coordinating Center (NACC) from September 1, 2005 to March 1, 2021 to assess mortality risk across the AD clinical stages. It included 12,414 participants aged ≥ 50 years, who contributed to the following stages: cognitively unimpaired (CU n = 11,458), incident prodromal AD (n = 937), and AD dementia (n = 745). AD etiology and stage were established based on clinical evaluation and cognitive, behavioral, and functional scores. Study centers report mortality for actively followed participants. Participants contributed observation time until all‐cause death, disease progression, discontinuation, loss to follow‐up, data cutoff or the last visit before a longer than 36‐month gap in visits or recorded scores.Hazard ratios for each AD stage versus CU were estimated using Cox proportional hazards models. Least absolute shrinkage and selection operator facilitated final predictor selection.ResultParticipants’ mean age (SD) at study entry was 71.0 years (SD 9.2) (34.9% males). Participants with incident mild, moderate, and severe AD had increased mortality risk relative to CU after controlling for age, sex, education, apolipoprotein E ε4 genotype status, BMI, and residence type. Relative all‐cause mortality risk by AD stage decreased with increasing age; the HRs (95% CI) for mortality at 65 years of age were 6.7 (2.7‐16.9), 14.8 (8.8‐24.8), and 30.1 (16.7‐56.8) for mild, moderate and severe AD respectively; at 80 years of age, the corresponding HR (95% CI) were 2.4 (1.7‐3.3), 3.1 (2.4‐3.9), and 6.6 (4.8‐9.1). Male sex (HR = 1.75, 95% CI 1.52‐2.04) and residing in an institution (vs. private residence; HR = 3.11, 95% CI 2.28‐4.25) significantly increased relative all‐cause mortality risk.ConclusionRelative all‐cause mortality risk increases with AD severity, and more so at younger ages. Despite data limitations, findings are significant as efforts to delay disease, for instance with DMTs, could not only improve patient and caregiver quality of life and reduce costs, but also extend the lives of patients with AD.NIA/NIH Grant U24 AG072122 funds the NACC database.