Magrolimab Plus Azacitidine Versus Placebo Plus Azacitidine in Patients With Untreated Higher-Risk Myelodysplastic Syndromes: The Phase III ENHANCE Study

Sallman, DA; Garcia-Manero, G; Daver, N; Abboud, CN; Stein, E; Larkin, K; Halpern, AB; McCurdy, SR; Al Malki, MM; Subramanian Guru Murthy, G; Silverman, LR; Larson, RA; Greenberg, P; Gojo, I; Wrobel, T; Platzbecker, U; Forsyth, C; Vachhani, P; Dong, M; Shao, J; Johnson, LDS; Tan, A; Lee, C; Doshi, P; Vyas, P; Wei, AH

Author(s): Sallman, DA; Garcia-Manero, G; Daver, N; Abboud, CN; Stein, E; Larkin, K; Halpern, AB; McCurdy, SR; Al Malki, MM; Subramanian Guru Murthy, G; Silverman, LR; Larson, RA; Greenberg, P; Gojo, I; Wrobel, T; Platzbecker, U; Forsyth, C; Vachhani, P; Dong, M; Shao, J; Johnson, LDS; Tan, A; Lee, C; Doshi, P; Vyas, P; Wei, AH;
Details: Publication Year 2026-09-10,Volume 44,Issue #26,Page 2529-2542
Journal Title: Journal of Clinical Oncology
Abstract: PURPOSE: To evaluate the efficacy and safety of the cluster of differentiation 47-targeted antibody magrolimab plus azacitidine (Magro/Aza) versus azacitidine alone in treatment-naive patients with higher-risk myelodysplastic syndromes (MDS) in the phase III ENHANCE study (ClinicalTrials.gov identifier: NCT04313881). METHODS: Based on the Revised International Prognostic Scoring System, patients with intermediate- to very-high-risk MDS were randomly assigned to receive Magro (1 mg/kg on days [D]1 and 4; 15 mg/kg on D8; 30 mg/kg on D11 and D15, and then once per week for five doses, followed by 30 mg/kg maintenance doses once every 2 weeks)/Aza (75 mg/m(2) daily on D1-7 or on D1-5 and 8-9 in 28-day cycles) or matched placebo plus azacitidine (Placebo/Aza). Dual primary end points were complete remission (CR) rate (per 2006 International Working Group criteria) and overall survival (OS). RESULTS: At final analysis, 539 patients were randomly assigned to Magro/Aza (n = 268) or Placebo/Aza (n = 271) arms. Baseline characteristics were generally well balanced between treatment arms. In the Magro/Aza versus Placebo/Aza arms, the CR rate was 21.3% versus 23.6% (odds ratio, 0.876 [95% CI, 0.585 to 1.312]; P = .5218), and median OS was 15.9 versus 18.6 months (hazard ratio, 1.203 [95% CI, 0.947 to 1.528]; P = .1299). Magro/Aza had a higher incidence of grade >/=3 adverse events (AEs; 92.8% v 79.2%), AE-associated study drug discontinuations (24.0% v 12.1%), serious AEs (71.9% v 51.5%), and fatal AEs (15.2% v 9.8%) versus Placebo/Aza. CONCLUSION: ENHANCE did not meet the primary end points of CR rate and OS, and showed more frequent severe AEs in patients treated in the Magro/Aza arm.
Publisher: ASCO
Keywords: Humans; *Azacitidine/administration & dosage/adverse effects/therapeutic use; *Myelodysplastic Syndromes/drug therapy/mortality; Female; Male; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; Aged; *Antibodies, Monoclonal, Humanized/administration & dosage/adverse; effects/therapeutic use; Middle Aged; Aged, 80 and over; Double-Blind Method
Research Division(s): Blood Cells and Blood Cancer
PubMed ID: 42441929
Publisher's Version: https://doi.org/10.1200/JCO-25-00617
Open Access at Publisher's Site: https://doi.org/10.1200/JCO-25-00617
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-07-15 09:14:54

Last Modified: 2026-09-07 09:10:51