Hematology

CPX-351 benefit is restricted to WHO5 myelodysplasia-related AML, not TP53-mutated disease

This correlative analysis sequenced 184 patients from the pivotal CPX-351 versus 7+3 phase 3 AML trial and reclassified disease by molecular subtype. Two-year overall survival differed markedly: 7% for TP53-AML, 19% for AML-MR, 37% for other-AML, and 70% for DDX41-AML. CPX-351 improved survival versus 7+3 only in AML-MR (median 9.7 vs 6.8 months), with no advantage in TP53-AML or other-AML. Among transplanted patients, CPX-351 was associated with markedly higher 2-year survival, primarily in AML-MR cases. Multihit TP53 had substantially worse survival than single-hit TP53, indicating allelic state dominated prognosis and was not rescued by CPX-351. 1

Peripheral blood flow MRD is highly concordant with marrow and prognostic in AML

Investigators compared multicolor flow MRD in 53 paired bone marrow and peripheral blood samples, then prospectively evaluated 118 AML patients. Peripheral blood and marrow MRD showed 100% qualitative concordance in the pilot set with strong quantitative correlation. In the larger cohort, peripheral blood MRD had 96% sensitivity, 99% specificity, and 98% concordance versus marrow, with 95% adequacy. Peripheral blood MRD levels were lower than marrow yet significantly correlated, supporting blood as a reliable, less invasive matrix. Peripheral blood MRD positivity predicted inferior relapse-free and overall survival, including in post-induction remission patients. 2

Younger haploidentical donors outperform older HLA-matched siblings in severe aplastic anemia

The CBMTRG registry analyzed 795 severe aplastic anemia patients undergoing allogeneic HSCT from matched sibling, haploidentical, or unrelated donors. Overall survival, failure-free survival, and GVHD-free/failure-free survival were high, all above 75% in this contemporary cohort. Donor age ≥50 years independently predicted inferior GVHD-free/failure-free survival, overall survival, and failure-free survival, with hazard ratios around 2. Stratification by donor type and age showed younger haploidentical donors achieved superior survival compared with older HLA-matched siblings. These data indicate donor age exerts greater prognostic impact than HLA compatibility in SAA given current haploidentical platforms. 3

Donor-derived Treg infusions show promising activity in steroid-refractory chronic GVHD

This phase I/II program treated 33 steroid-refractory or steroid-dependent chronic GVHD patients with freshly isolated donor regulatory T-cell infusions. Treg purification via CliniMACS and infusion were feasible and safe across dose levels. Global responses occurred in 71% of patients, and 52% achieved at least a 2-point improvement in cGVHD severity scores. Clinical improvement enabled tapering of corticosteroids, ruxolitinib, mycophenolate, and discontinuation of calcineurin inhibitors in many patients. Infused Treg clonotypes were detectable up to 12 months, supporting biological persistence despite the study not being powered for definitive efficacy. 4