Magrolimab plus azacitidine vs physician’s choice for untreated <i>TP53</i>-mutated acute myeloid leukemia: the ENHANCE-2 study

Patients with TP53-mutated acute myeloid leukemia (AML) have an extremely poor prognosis, necessitating new treatments. The global, randomized, phase 3 ENHANCE-2 trial evaluated the anti-CD47 monoclonal antibody magrolimab plus azacitidine (Magro/Aza) for previously untreated TP53-mutated AML. Patients determined ineligible for intensive therapy were randomized to receive Magro/Aza or venetoclax plus Aza (Ven/Aza); those eligible for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy. The primary end point was overall survival (OS) in the nonintensive arm. At interim analysis, nonintensive-arm OS hazard ratio (HR) between treatment groups was 1.191 (95% confidence interval [CI], 0.744-1.906), meeting the study's definition for futility and resulting in study termination. At final analysis, median OS was 4.4 vs 6.6 months (HR, 1.132; 95% CI, 0.783-1.637; P = .5070) in the nonintensive arm (n = 205) and 7.3 vs 11.1 months (HR, 1.434; 95% CI, 0.635-3.239; P = .3798) in the intensive arm (n = 52) between Magro/Aza and control groups, respectively. Incidences of grade ≥3 adverse events were similar across Magro/Aza and control groups (nonintensive, n = 194: 96.9% and 95.9%; intensive, n = 50: 92.6% and 95.7%), including grade ≥3 anemia (nonintensive: 27.1% and 23.5%; intensive: 25.9% and 21.7%). Grade ≥3 infections were observed in 50.0% and 53.1% of patients in the nonintensive arm and 44.4% and 65.2% of intensive-arm patients. ENHANCE-2 did not meet its primary end point of OS in TP53-mutated AML but provides important data informing future studies in this challenging population. This trial was registered at www.clinicaltrials.gov as #NCT04778397.

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Journal
Blood
Published
2025-02-26
DOI
https://doi.org/10.1182/blood.2024027408
Citations
40
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
70.80
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article

Magrolimab plus azacitidine vs physician’s choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study

Pau Montesinos, Christian Récher, Anoop Kumar Enjeti, Jenny O’Nions et al.
40 citations
Blood
Acute Myeloid Leukemia Research
70.80
article

Magrolimab plus azacitidine vs physician’s choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study

Pau Montesinos, Christian Récher, Anoop Kumar Enjeti, Jenny O’Nions, David Andrew Sallman, Naval Guastad Daver, Joshua F. Zeidner, Thomas Pabst, Cristina Papayannidis, Devendra Hiwase, Lisa D. Johnson, Julie Y. Huang, Richard A. Larson, Paresh Vyas, Lindsay Wilde, Ichiro Kawashima, Gal Hacohen-Kleiman, Calvin Lee, Anskar YH Leung, Mei Dong, Taravat Bagheri
article en
40 citations

Abstract

Patients with TP53-mutated acute myeloid leukemia (AML) have an extremely poor prognosis, necessitating new treatments. The global, randomized, phase 3 ENHANCE-2 trial evaluated the anti-CD47 monoclonal antibody magrolimab plus azacitidine (Magro/Aza) for previously untreated TP53-mutated AML. Patients determined ineligible for intensive therapy were randomized to receive Magro/Aza or venetoclax plus Aza (Ven/Aza); those eligible for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy. The primary end point was overall survival (OS) in the nonintensive arm. At interim analysis, nonintensive-arm OS hazard ratio (HR) between treatment groups was 1.191 (95% confidence interval [CI], 0.744-1.906), meeting the study's definition for futility and resulting in study termination. At final analysis, median OS was 4.4 vs 6.6 months (HR, 1.132; 95% CI, 0.783-1.637; P = .5070) in the nonintensive arm (n = 205) and 7.3 vs 11.1 months (HR, 1.434; 95% CI, 0.635-3.239; P = .3798) in the intensive arm (n = 52) between Magro/Aza and control groups, respectively. Incidences of grade ≥3 adverse events were similar across Magro/Aza and control groups (nonintensive, n = 194: 96.9% and 95.9%; intensive, n = 50: 92.6% and 95.7%), including grade ≥3 anemia (nonintensive: 27.1% and 23.5%; intensive: 25.9% and 21.7%). Grade ≥3 infections were observed in 50.0% and 53.1% of patients in the nonintensive arm and 44.4% and 65.2% of intensive-arm patients. ENHANCE-2 did not meet its primary end point of OS in TP53-mutated AML but provides important data informing future studies in this challenging population. This trial was registered at www.clinicaltrials.gov as #NCT04778397.

BloodVol. 146(5)
University of North Carolina at Chapel Hill (US), Royal Adelaide Hospital (AU), University College London Hospitals NHS Foundation Trust (GB), The University of Texas MD Anderson Cancer Center (US), Université Toulouse III - Paul Sabatier (FR), Thomas Jefferson University (US), Universitat de València (ES), Queen Mary Hospital (CN), University Hospital of Bern (CH), John Radcliffe Hospital (GB), LMU Klinikum (DE), Hospital Universitari i Politècnic La Fe (ES), Moffitt Cancer Center (US), Centre Hospitalier Universitaire de Toulouse (FR), University of Oxford (GB), University of Chicago (US), Sidney Kimmel Cancer Center (US), MRC Weatherall Institute of Molecular Medicine (GB), University of Yamanashi Hospital (JP), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), Gilead Sciences (Spain) (ES), MRC Human Immunology Unit (GB), Gilead Sciences (United States) (US), University of Hong Kong - Shenzhen Hospital (CN), Calvary Mater Newcastle Hospital (AU), Oxford University Hospitals NHS Trust (GB), Istituti di Ricovero e Cura a Carattere Scientifico (IT), UNC Lineberger Comprehensive Cancer Center, Central Adelaide Local Health Network, University College London (GB), University of Yamanashi (JP), University of Newcastle Australia (AU), Ludwig-Maximilians-Universität München (DE), University of Hong Kong (HK)
Good health and well-being
Openalex Percentile: Top 0%
Acute Myeloid Leukemia Research
70.80
DOIOpen Access PDFOpenAlex
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