Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients wih lower risk myelodysplastic syndromes

Background: Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of ironoverload and associated organ damage, and death. Emerging evidence indicates that iron chelation ther-apy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especiallythose classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1).Methods: Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centersin Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). Results: Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 g/L. Of the 80chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox followingdeferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patientschelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiacmortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1years for non-chelated patients (p < 0.001). For patients chelated ≥6 m or patients classified as adequatelychelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusionintensity (HR = 1.08, p = 0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m(HR = 0.24, p < 0.001). Conclusion: Six or more months of adequate ICT is associated with markedly better overall survival. Thissuggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals