Hospital Virgen del Valle

As there are no prospective randomized studies in patients with advanced systemic mastocytosis (AdvSM), we compared clinical outcomes between patients treated with avapritinib in the Phase I EXPLORER (NCT02561988) and Phase II PATHFINDER (NCT03580655) trials (N = 176) and patients treated with midostaurin (N = 99) or cladribine (N = 49) from a global, multi-center, retrospective, chart review study. Overall survival (OS) and duration of treatment (DOT) were compared between the cohorts using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards models, and maximum reduction in serum tryptase levels was compared using adjusted generalized linear models. Median OS was not reached (95% confidence interval [CI]: 46.9 months, not estimable) for avapritinib, 28.6 (18.2, 44.6) months for midostaurin, and 23.4 (14.8, 40.6) months for cladribine. The avapritinib cohort had significantly longer OS compared to midostaurin (hazard ratio [HR] [95% CI]: 0.59 [0.36, 0.97]) and cladribine (0.32 [0.15, 0.67]), longer DOT (vs. midostaurin: 0.63 [0.41, 0.96]; vs. cladribine: 0.14 [0.09, 0.23]), and greater reduction in serum tryptase levels with mean difference [95% CI] vs. midostaurin of -72.8 % [-101.1 %, -44.6 %] and vs. cladribine of -25.0 % [-32.4 %, -17.7 %] (all p < 0.05). Results were similar in treatment-naïve (1 L) and previously treated (2 L+) patients; there was improved OS in 1 L avapritinib vs. 1 L midostaurin patients (HR: 0.14 [0.05, 0.42]; p < 0.001) and in 2 L+ avapritinib vs. 2 L+ cladribine patients (0.34 [0.16, 0.71]; p = 0.004). Together, we show that avapritinib treatment resulted in significantly improved OS, longer DOT, and greater reduction in serum tryptase levels compared to midostaurin or cladribine in real-world clinical practice.

Background: There is no gold standard definition of sarcopenic obesity (SO). Our objective is to evaluate the benefit of using the new definition proposed by the European Association for the Study of Obesity (EASO) in older people. Methods: Data from the Toledo Study of Healthy Aging, a study based on a cohort of community-dwelling older adults, were used. SO was defined according to the EASO and by a composite of the Foundation for the National Institute of Health (FNIH) for the diagnosis of sarcopenia and the WHO’s criteria for obesity (Body Mass Index, BMI ≥ 30 kg/m2; waist circumference, &gt;88 cm for women and &gt;102 cm for men). Frailty [Frailty Phenotype (FFP) and Frailty Trait Scale-5 (FTS5)] and disability (Katz Index) statuses were assessed at baseline and at the follow-up (median 2.99 years). Mortality at a 5-year follow-up was also assessed. The Logistic and Cox regression models were used to assess the associations. Results: Of the 1559 subjects (age 74.79 ± 5.76 years; 45.54% men), 30.15% (EASO/ESPEN) vs. 16.36% (FNIH) met the SO criteria (Kappa = 0.42). SO was associated with the prevalence of frailty by both the EASO’s [OR(95%CI): FFP: 1.70 (1.33–2.16); FTS-5 binary: 2.29 (1.60–3.27); β(95%CI): FTS-5 continuous 3.63 (3.00–4.27)] and FNIH+WHO’s criteria [OR (95%CI): 2.20 (1.61, 3.00)]. The FNIH + WHO’s criteria were cross-sectionally associated with disability [OR: 1.52 (1.07, 2.16); p-value 0.018], while the EASO’s criteria were not. The EASO’s criteria did not show any association at the follow-up, while the FNIH + WHO’s criteria were associated with incident frailty. Conclusions: The EASO’s new criteria for sarcopenic obesity demonstrate moderate agreement with the traditional definition and are cross-sectionally associated with adverse events, but they do not effectively predict the outcomes generally associated with sarcopenic obesity in older adults. Therefore, the performance of the EASO’s criteria in older people raises the need for refinement before recommending it for generalized use in this population.

Introduction: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. Methods: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried’s criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. Results: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962–2,043] pg/mL vs. 1,212 [963–1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36–3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30–4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91–3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: −72.8, −47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.