CPX-351 (liposomal daunorubicin/cytarabine) vs CLAG-M (high-dose cytarabine backbone) in unfit AML: higher CR/CRi with CLAG-M, no OS win overall

CPX-351 is a fixed-ratio liposomal formulation of daunorubicin + cytarabine, while CLAG-M combines cladribine + high-dose cytarabine + G-CSF + mitoxantrone (intensive cytarabine-based chemotherapy). In this single-institution randomized Phase 2 trial (NCT04195945) of medically unfit, newly diagnosed AML/other high-grade myeloid neoplasms with TRM score ≥13.1 (n=60; 68% ECOG 3–4), 3-month OS was 70% with CLAG-M vs 60% with CPX-351 (P=0.41) and CR/CRi was 73% vs 47% (P=0.064), but median OS was not significantly different (10.5 vs 5.8 months; P=0.76) and relapse-free survival was similarly non-significant (37.6 vs 19.9 months; P=0.80). As a real-world benchmark for “unfit” AML today, azacitidine+venetoclax delivers median OS ~14.7 months in VIALE-A (vs 9.6 months with azacitidine alone), so the medians here (especially CPX-351 at 5.8 months) look below contemporary HMA/VEN expectations—though cross-trial comparisons are shaky given this study’s very high baseline frailty (TRM-selected; mostly ECOG 3–4).