30-Second Takeaway
- Intensified double-induction 7+3 can match CPX-351 survival in older t-AML/AML-MRC despite higher remission rates.
- KIT-TKD and FLT3-ITD add MRD-independent relapse risk in CBF-AML and should guide consolidation and transplant decisions.
- AZA/VEN is a viable bridge-to-allo-HSCT in R/R AML, with post-transplant outcomes comparable to intensive salvage.
- Dynamic PANGEA-SMM risk modeling sharpens progression prediction in smoldering myeloma, incorporating evolving biomarkers and renal/hemoglobin changes.
- Early IST discontinuation, refined comorbidity scoring with PTCy, and graft-source flexibility can fine-tune allo-HSCT long-term outcomes.
Week ending March 28, 2026
Targeted refinements in AML, myeloma precursors, transplant practice, and early myelofibrosis
Intensified 7+3 double induction rivals CPX-351 in older t-AML/AML-MRC
In older t-AML/AML-MRC patients meeting CPX-351 trial criteria, intensified 7+3 double induction achieved higher CR/CRi than CPX-351 (67.8% vs 47.7%). Despite deeper remissions, median OS was similar for intensified 7+3 versus CPX-351 (10.1 vs 8.9 months; HR 0.99, p=0.95). Thirty-day mortality and key toxicities, including febrile neutropenia, were comparable between regimens. These data support obligatory double-induction 7+3 as a reasonable alternative to CPX-351 for fit older patients with t-AML/AML-MRC.
KIT-TKD and FLT3-ITD drive MRD-independent relapse risk in CBF-AML
This combined retrospective and prospective cohort included 656 adults with CBF-AML in first CR, with centralized 36-gene sequencing and MRD assessment. In LASSO models adjusting for early MRD response, KIT-TKD in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 independently increased relapse risk. Adding these lesions to MRD improved risk discrimination, with 3-year cumulative relapse 22% in low-risk versus 53% in high-risk patients. Results were validated prospectively, supporting mandatory inclusion of these mutations in CBF-AML risk stratification and post-remission planning.
Allo-HSCT after AZA/VEN salvage yields encouraging 2-year survival in R/R AML
This multicenter real-world study evaluated 75 R/R AML patients undergoing allo-HSCT after azacitidine/venetoclax salvage from the VENAURA registry. Estimated 2-year OS after transplant was 61.4%, with a 2-year relapse incidence of 35.1% and NRM 10.6%. Early cytologic response after cycle 1 of AZA/VEN independently predicted both OS and relapse risk. Matched comparison with 75 patients salvaged by intensive chemotherapy showed similar OS and no significant increase in relapse after AZA/VEN. There was a trend toward lower 2-year NRM with AZA/VEN, suggesting a favorable toxicity profile for bridge-to-transplant use.
PANGEA-SMM dynamic model improves prediction of smoldering myeloma progression
The PANGEA-SMM model was developed in 2,344 SMM patients from seven international centers with longitudinal clinical and biologic data. Four evolving biomarkers independently associated with shorter time to progression were rising M-protein, rising FLC ratio, creatinine increase, and hemoglobin decline. PANGEA-SMM outperformed 20/2/20 and IMWG models, with C-statistic 0.79 using full trajectories and 0.78 without biomarker history or recent marrow. An open-access PANGEA-SMM tool and validation utilities are provided to compare performance versus established models in clinical and trial settings.
References
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Additional Reads
Optional additional studies from this edition.