Metformin Triggers Ferroptosis in AML Through Lipid Remodeling: A Repurposing Opportunity for Metabolic Subtypes

Metformin Triggers Ferroptosis in AML Through Lipid Remodeling: A Repurposing Opportunity for Metabolic Subtypes

A new ex vivo study shows metformin induces ROS-driven ferroptosis in acute myeloid leukemia (AML), particularly in samples with altered lipid metabolism (IDH2, FLT3 mutations). Lipidomic remodeling, CD36-mediated fatty acid uptake, and DGAT1 activity determine sensitivity—suggesting biomarker-guided repurposing strategies and combination approaches.
Community Health Workers Halt Decline in Quality of Life During Transition to Adult Care for Young Adults With Sickle Cell Disease

Community Health Workers Halt Decline in Quality of Life During Transition to Adult Care for Young Adults With Sickle Cell Disease

A multicenter randomized trial found that community health worker support produced modest but durable improvements in health-related quality of life for young adults with sickle cell disease during transition to adult care, whereas a mobile health intervention provided transient benefit.
Ramantamig (JNJ-79635322): A Trispecific T‑Cell Engager Targeting BCMA and GPRC5D Shows Potent Preclinical Activity in Multiple Myeloma

Ramantamig (JNJ-79635322): A Trispecific T‑Cell Engager Targeting BCMA and GPRC5D Shows Potent Preclinical Activity in Multiple Myeloma

Ramantamig (JNJ-79635322), a trispecific antibody that engages BCMA, GPRC5D and CD3, demonstrates sub-nanomolar cytotoxicity, ex vivo depletion of patient plasma cells, and antitumor activity in xenograft models—supporting ongoing phase 1 trials in relapsed/refractory multiple myeloma.
CPX‑351 in Down Syndrome–Associated Myeloid Leukemia: a dose‑sensitivity mismatch that reduced event‑free survival in the ML‑DS 2018 trial

CPX‑351 in Down Syndrome–Associated Myeloid Leukemia: a dose‑sensitivity mismatch that reduced event‑free survival in the ML‑DS 2018 trial

In the ML‑DS 2018 trial, substituting reduced‑intensity induction with CPX‑351 led to lower 24‑month event‑free survival (69% vs 90%) despite excellent overall survival and minimal treatment‑related mortality; MRD by GATA1 NGS, trisomy 8 and complex karyotype predicted relapse.
Age‑Adapted Chemotherapy Plus MRD‑Directed Transplantation Improves Safety Without Sacrificing Efficacy in Ph‑Negative Adult ALL: Key Findings from GRAALL‑2014

Age‑Adapted Chemotherapy Plus MRD‑Directed Transplantation Improves Safety Without Sacrificing Efficacy in Ph‑Negative Adult ALL: Key Findings from GRAALL‑2014

The GRAALL‑2014 trial shows that age‑adapted chemotherapy with MRD‑guided alloHSCT reduces early mortality and transplant use while maintaining disease‑free survival in adults (18–59) with Ph‑negative ALL; 4‑year DFS was 57.1% and overall survival improved across age groups.
DAGO2 (daunorubicin/cytarabine + fractionated gemtuzumab) Outperforms CPX‑351 in Older Adults with Non‑Adverse‑Risk AML: NCRI AML18 Results

DAGO2 (daunorubicin/cytarabine + fractionated gemtuzumab) Outperforms CPX‑351 in Older Adults with Non‑Adverse‑Risk AML: NCRI AML18 Results

In older adults (≥60 years) with non‑adverse‑risk AML enrolled in NCRI AML18, daunorubicin/cytarabine plus fractionated gemtuzumab (DAGO2) produced higher early MRD‑negative CR rates and superior 3‑year EFS and OS versus CPX‑351, with particular molecular subgroups showing no benefit or harm from CPX‑351.
DAGO2 (daunorubicin+cytarabine+fractionated gemtuzumab) outperforms CPX‑351 in older adults with non‑adverse‑risk AML: insights from NCRI AML18

DAGO2 (daunorubicin+cytarabine+fractionated gemtuzumab) outperforms CPX‑351 in older adults with non‑adverse‑risk AML: insights from NCRI AML18

In NCRI AML18 (n=439, median age 68), DAGO2 produced higher early CR/MRD‑negative rates and superior 3‑year EFS and OS versus CPX‑351 in older adults without adverse‑risk cytogenetics; survival differences persisted across key subgroups including NPM1 and FLT3 mutations.
Venetoclax plus gilteritinib shows potent preclinical activity in FLT3‑mutant BCL11B‑a lineage‑ambiguous leukemia: translational opportunities and trial design considerations

Venetoclax plus gilteritinib shows potent preclinical activity in FLT3‑mutant BCL11B‑a lineage‑ambiguous leukemia: translational opportunities and trial design considerations

Preclinical work shows that combining the BCL‑2 inhibitor venetoclax with the FLT3 inhibitor gilteritinib produces deep, reproducible anti‑leukemia activity in FLT3‑mutant, BCL11B‑activated lineage‑ambiguous leukemias. BH3 profiling and single‑cell transcriptomics reveal mechanisms of resistance and biology of residual cells, supporting rapid clinical evaluation.