Vyxeos (cytarabine/daunorubicin liposomal formulation)

Recent advances have led to the development of novel therapeutic strategies, such as BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, enasidenib), CD47 inhibitors (magrolimab), TIM-3 inhibitors (sabatolimab), XPO1 inhibitors (eltanexor), NEDD8-activating enzyme inhibitors (pevonedistat), TP53-targeted agents (eprenetapopt), liposomal chemotherapy (CPX-351), and oral HMA formulations. Combinations of hypomethylating agents with these new drugs, as first-line treatment, have to date not proven more efficacious than HMA monotherapy. This review summarizes the current therapeutic landscape on novel therapies for HR-MDS, highlighting their mechanism of action, efficacy, and demonstrates the unmet clinical need for more effective therapies.

P1, N=24, Recruiting, Thomas Jefferson University | Suspended --> Recruiting | Trial completion date: Jan 2026 --> Jan 2029 | Trial primary completion date: Jan 2026 --> Jan 2028

sAML/AML-MRC with an adverse karyotype had a dismal outcome. These findings provide a benchmark for risk stratification in the pre- CPX-351 era.

The OS benefit of CPX-351 observed in the trial was driven by AML-MR with no benefit of CPX-351 in TP53-AML, where the primary prognostic factor was allelic state. Clinical Trial Information: NCT01696084.

P1/2, N=52, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P2, N=21, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=46 --> 21 | Trial primary completion date: Jan 2027 --> Jun 2025

P1, N=18, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2025 --> Apr 2027 | Trial primary completion date: Nov 2025 --> Apr 2027

Despite these gains, the absolute survival benefit remains modest, prolonged cytopenias are universal, and outcomes in TP53-mutated or younger adverse-risk patients are still poor, raising legitimate questions about cost-effectiveness and generalizability. Nonetheless, CPX-351 stands as the first clinically validated example of ratiometric nanomedicine in oncology, proving that reformulating established drugs can yield meaningful progress where novel agents have often failed.

P3, N=1186, Recruiting, Children's Oncology Group | Trial completion date: Sep 2027 --> Jun 2029 | Trial primary completion date: Sep 2027 --> Jun 2029

P=N/A, N=113, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Feb 2026 --> Oct 2025 | Trial primary completion date: Feb 2026 --> Oct 2025

P2, N=46, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended