Hematology

Venetoclax–HMA rivals CPX-351 in older/secondary AML with fewer infections

In this 600-patient Mayo series, Ven-HMA and CPX-351 achieved similar CR/CRi rates in newly diagnosed, mostly older AML, including AML-MR. Despite CPX-351 being used in younger, fitter patients, transplant-censored overall survival was similar between regimens. Ven-HMA caused fewer infectious complications than CPX-351, important for frail and comorbid patients. Ven-HMA yielded higher CR/CRi in males, de novo AML, and STAG2- or CEBPA-mutated disease, whereas CPX-351 favored SF3B1-mutated cases. 1

Real-world NPM1-mut AML data validate marrow MRD cutoffs for relapse and allo-SCT use

This registry included 141 NPM1-mut AML patients in CR/CRi after two induction cycles with bone marrow RT-qPCR MRD assessment. Patients achieving <0.1% mutNPM1/ABL after cycle two saw no clear RFS or OS benefit from allo-SCT in first remission. High-level MRD (≥0.1%) at end-of-treatment or follow-up predicted imminent relapse and supported early intervention. Undetectable or very low MRD (<0.01%) allowed observation, while low-level MRD (≥0.01%–<0.1%) required close monitoring for escalation. The 0.1% post–cycle two and 0.01% follow-up cutoffs provide actionable thresholds for MRD-guided risk stratification and transplant planning. 2

Isa-KRd quadruplet deepens MRD negativity in transplant-eligible myeloma

In the phase 3 EMN24 IsKia trial, 302 transplant-eligible NDMM patients ≤70 years were randomized to Isa-KRd versus KRd. Post-consolidation NGS MRD negativity at 10⁻⁵ and 10⁻⁶ was significantly higher with Isa-KRd than KRd. Deep MRD responses were faster and more durable with Isa-KRd, including higher 1-year sustained 10⁻⁶ MRD negativity. Grade 3–4 non-hematologic toxicity, discontinuations, and fatal adverse events were similar between arms, and progression-free survival data remain immature. 3

Base-edited autologous HSPCs achieve durable transfusion independence in β-thalassemia

This phase 1 trial infused CS-101, base-edited autologous CD34+ cells targeting BCL11A binding motifs, into five β-thalassemia patients. Median neutrophil and platelet engraftment occurred at 16 and 25 days, indicating prompt hematopoietic recovery. All patients became transfusion independent, with the last red cell transfusion at a median of 18 days post-infusion. By month three, mean hemoglobin was 12.4 g/dL with HbF 11.5 g/dL, maintained or higher through a median 23-month follow-up. Adverse events resembled busulfan conditioning and autologous transplant, with no deaths or cancers reported. 4