Hematology

Venetoclax/azacitidine rivals intensive chemotherapy in younger, non-favorable–risk AML and efficiently bridges to allo-HSCT

Younger adults ≤60 years with newly diagnosed non-favorable–risk AML received frontline venetoclax 600 mg plus azacitidine irrespective of intensive chemotherapy fitness. Overall response was 69%, with 53% complete remissions and 68% of responders achieving MRD negativity. Over half of patients (53%) proceeded to allogeneic stem cell transplant in first remission, and most non-responders were salvaged with intensive chemotherapy. Compared with matched intensive chemotherapy controls, venetoclax/azacitidine improved response rate, transplant rate, and progression-free survival. Venetoclax/azacitidine was associated with fewer hospital days, transfusions, and infectious complications while maintaining at least comparable efficacy to intensive chemotherapy. 1

Bomedemstat demonstrates high cytoreductive and molecular response rates in difficult-to-treat essential thrombocythemia

This phase 2 trial evaluated daily oral bomedemstat in 73 essential thrombocythemia patients needing cytoreduction after inadequate response or intolerance to standard therapy. At 24 weeks, 77% of evaluable patients achieved platelet counts ≤400×10^9/L without new thromboembolic events. Durable platelet and white blood cell count reductions were common, while hemoglobin levels generally remained stable. Variant allele frequencies of driver mutations decreased in most evaluable patients, suggesting potential disease-modifying activity. Grade 3–4 adverse events occurred in nearly half, prompting treatment interruption or discontinuation in a minority, but no treatment-related deaths were reported. 2

Six-year data show sustained FIX expression and very low bleeding after fidanacogene elaparvovec in hemophilia B

Adults with severe hemophilia B received a single infusion of fidanacogene elaparvovec and were followed for six years. Mean FIX activity remained in the mild-deficiency range, around 25% at year 2 and 26% at year 6 among completers. Mean treated annualized bleeding rates stayed below one per year, with a median of zero and 71% experiencing no treated bleeds. No participants resumed FIX prophylaxis, and there were no FIX inhibitors, thrombotic events, liver masses, or treatment-related serious adverse events. Patient-reported outcomes and target joint status improved and were maintained throughout long-term follow-up, supporting durable clinical benefit. 3

Matched unrelated and haploidentical donors approach sibling outcomes for thalassemia transplantation, at the cost of more GVHD

This multicenter phase 4 study enrolled 823 transfusion-dependent thalassemia patients receiving allo-HSCT from matched sibling, matched unrelated, or haploidentical donors. Two-year overall and event-free survival exceeded 93% across all donor types, with slightly higher rates in matched sibling recipients. Transplant-related mortality was low at 4.4%, and graft failure was rare at 0.5%. Alternative donor grafts had significantly higher rates of acute grade 2–4 and moderate–severe chronic GVHD compared with matched siblings. These results support expanding allo-HSCT to patients lacking matched siblings, with careful GVHD risk counseling and management. 4