A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes.

Azacitidine-mediated hypomethylation promotes tumor cell immune recognition but may increase the expression of inhibitory immune checkpoint molecules. We conducted the first randomized phase 2 study of azacitidine plus the immune checkpoint inhibitor durvalumab vs azacitidine monotherapy as first-line treatment for higher-risk myelodysplastic syndromes (HR-MDS). In all, 84 patients received 75 mg/m2 subcutaneous azacitidine (days 1-7 every 4 weeks) combined with 1500 mg intravenous durvalumab on day 1 every 4 weeks (Arm A) for at least 6 cycles or 75 mg/m² subcutaneous azacitidine alone (days 1-7 every 4 weeks) for at least 6 cycles (Arm B).

A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML.

Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged ≥65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1 through 7 with (Arm A, n = 64) or without (Arm B, n = 65) durvalumab 1500 mg on day 1 every 4 weeks.

Bone marrow microenvironments that contribute to patient outcomes in newly diagnosed multiple myeloma: A cohort study of patients in the Total Therapy clinical trials.

Background: The tumor microenvironment (TME) is increasingly appreciated as an important determinant of cancer outcome, including in multiple myeloma (MM). However, most myeloma microenvironment studies have been based on bone marrow (BM) aspirates, which often do not fully reflect the cellular content of BM tissue itself. To address this limitation in myeloma research, we systematically characterized the whole bone marrow (WBM) microenvironment during premalignant, baseline, on treatment, and post-treatment phases.

Computational tools for metabolic engineering.

A great variety of software applications are now employed in the metabolic engineering field. These applications have been created to support a wide range of experimental and analysis techniques. Computational tools are utilized throughout the metabolic engineering workflow to extract and interpret relevant information from large data sets, to present complex models in a more manageable form, and to propose efficient network design strategies.