Background This systematic review and meta-analysis evaluates the safety and efficacy of immune checkpoint inhibitors (ICIs) combined with hypomethylating agents (HMAs) in patients with treatment-naïve acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (HR-MDS). Methods We systematically searched PubMed, Scopus, and Web of Science from inception to 5 July 2026, and also searched ClinicalTrials.gov and Google Scholar. We included single-arm and controlled studies involving treatment-naïve AML and HR-MDS patients. We performed quantitative meta-analyses of overall response rates (ORR), complete response (CR) rates, and toxicities in HR-MDS studies with sufficient data, using a random-effects model for all outcomes. We assessed risk of bias using the MINORS tool for single-arm studies and the RoB 2 tool for randomized trials. Results The systematic review included 15 articles. Of these, 8 studies contributed treatment-naïve HR-MDS populations and were included in the quantitative meta-analysis; the remaining AML-only and mixed-population studies were synthesized narratively. The pooled ORR was 68 (95% CI: 0.62–0.74). The CR rate was 23 (95% CI: 0.15–0.32). Hematologic toxicities (grade ≥3) included neutropenia (51%), thrombocytopenia (47%), febrile neutropenia (36%), and anemia (33%). Among non-hematologic toxicities, constipation of any grade was most common (52%), while grade ≥3 diarrhea was less frequent (5%). Conclusion ICI-HMA combinations showed descriptive clinical activity in treatment-naïve HR-MDS, with descriptive toxicity rates from single-arm studies, but the certainty of this evidence is low to very low, and randomized trials to date have not demonstrated improved outcomes with the addition of ICIs to HMAs. Quantitative evidence is limited to HR-MDS, highlighting the need for further studies, especially in AML.
Gastric cancer remains a major global health challenge, highlighting the need to investigate novel compounds with potential biological activity. This study evaluated the effects of a cell-free Lactobacillus gasseri extract on MTT-based metabolic activity in AGS human gastric adenocarcinoma cells following 24, 48, and 72 h of exposure. The extract was associated with a dose- and time-dependent reduction in MTT signal, with statistically significant reductions observed at 31.25 µL/mL after 24 h, 15.6 µL/mL after 48 h, and 7.81 µL/mL after 72 h (p < 0.001). The estimated IC₅₀ values decreased from approximately 45 µL/mL at 24 h to 22 µL/mL at 48 h and 8 µL/mL at 72 h. Higher concentrations (250–500 µL/mL) resulted in near-complete suppression of the MTT signal at all incubation times. These findings indicate that the cell-free extract is associated with reduced MTT-based metabolic activity in AGS cells under the tested in vitro conditions. However, because MTT measures metabolic activity rather than directly establishing cell death, and the study involved only one cancer cell line and one assay, these results should be interpreted as preliminary exploratory observations. Further investigations using appropriate assay-interference controls, non-cancerous cell models, and complementary assays are required to validate the findings and assess selectivity. The present results do not establish a specific mechanism of action or therapeutic potential.
