Immunotherapy (IO) has improved prognosis of non-small cell lung cancer (NSCLC); however, some patients experience primary IO resistance (PIR). CXCL13 could be a promising PIR biomarker due to its role in antitumor immune responses. 177 patients with stage IV NSCLC receiving IO from the observational, multicenter, real-world study BLI-O were included from 15 centers in Spain. CXCL13 and 39 other cytokines were measured in 158 baseline (BS1) and 98 post-first-cycle of IO (BS2) plasma samples. Additionally, peripheral T and B cell BS2 immunophenotypes were determined. CXCL13 levels were also measured in plasma samples from 38 stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy from the NADIM II trial (NCT03838159). PIR was defined as disease progression within 3 months in non-surgical cases or incomplete pathological response in surgical cases. Metastatic PIR patients had higher CXCL13 plasma levels compared to non-PIR patients, especially in BS2 samples, and exhibited a greater increase of CXCL13 levels after the first cycle of IO. Patients with high BS2 CXCL13 levels showed shorter PFS (p = 0.0002) and OS (p = 0.0007). Females showed a lower percentage of high CXCL13 cases compared to male cases. CXCL13 did not influence the growth of NSCLC cell lines in vitro. Moreover, the expression of the CXCL13/CXCR5 axis was restricted to the immune compartment of tumors. Plasmatic CXCL13 levels were not associated with PD-L1 TPS expression nor TLS density in tumor tissue. However, at systemic level, patients with high CXCL13 levels exhibited impaired B and T cell phenotypes, along with elevated levels of inflammatory cytokines, after first IO cycle. Finally, high BS2 CXCL13 levels in resectable cases were also associated with PIR. Elevated CXCL13 levels after the first cycle of IO are associated with PIR and an altered peripheral immune profile in NSCLC, supporting its potential as a prognostic biomarker in these patients.
Epidemiological data from Sapin are lacking, especially in a publication relating Spanish data and prevalence of programmed cell death ligand-1 (PD-L1) expression. This study aimed to evaluate the prevalence of PD-L1 expression by Combined Positive Score (CPS) ≥ 5 in patients with advanced esophagogastric adenocarcinoma (aEGAC) in Spain. This observational, retrospective, and multicenter study collected sociodemographic and clinical data from adult patients with locally advanced unresectable, recurrent, or metastatic EGAC across 21 centers in the AGAMENON-SEOM registry. CPS PD-L1 expression was centrally analyzed using the IHC 28–8 pharmDx. A total of 166 patients were included, with 144 valid and evaluable samples. The primary tumor locations were stomach (70.1
NPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in FLT3-ITD, DNMT3A, IDH1/IDH2, and TET2 genes, was applied to a training cohort of NPM1-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the NPM1-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.
OBJECTIVES:Treatment of GCA still requires substantial exposure to glucocorticoids (GCs), which are associated with significant toxicity. This study compares the efficacy and safety of the GC-only standard of care (SOC) with a regimen combining intravenous methylprednisolone (IVMP) pulses, MTX and lower doses of prednisone, in newly diagnosed patients with GCA. METHODS:A usual clinical practice study was conducted in three Spanish academic hospitals. One hundred and fifty-one patients diagnosed with GCA were treated with SOC prednisone (40-60 mg/d) or with IVMP (125-500 mg/d ×3) followed by lower-dose prednisone (≤30 mg/d) and MTX (IVMP/MTX), with a follow-up of 2 years. A propensity score was used to adjust for baseline differences in the multivariate analyses. RESULTS:Seventy-nine (52.3%) patients received SOC prednisone and 72 (47.7%) IVMP/MTX. The clinical characteristics at baseline were similar in both the groups. Hundred percent patients achieved remission after a median time of 4 weeks, without differences between the groups. Relapse rates were also similar. Patients receiving IVMP/MTX had significantly lower cumulative GC doses and reached prednisone ≤5 mg/d faster than SOC patients (mean 13.8 vs 56.5 weeks; P < 0.001). Patients in the IVMP/MTX group were less likely to suffer any GC-related adverse effect (adjusted OR 0.35, 95% CI 0.14-0.85; P = 0.021). CONCLUSIONS:The combination IVMP/MTX with lower-dose prednisone is as effective as the SOC in inducing remission and preventing relapses in GCA. The IVMP/MTX scheme significantly reduces GC exposure and GC-associated adverse effects. IVMP/MTX could be a potential GC-sparing strategy, especially in patients with GCA at higher risk of GC toxicity.
