The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab
or placebo for untreated AML unfit for intensive therapy

J 2025

The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy

DAVER, Naval; Paresh VYAS; Gerwin HULS; Hartmut DOHNER; Sebastien MAURY et al.

Základní údaje

Originální název

The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy

Autoři

Vydání

Blood, AMSTERDAM, ELSEVIER, 2025, 0006-4971

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 23.100 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00143874

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

The ENHANCE-3 study; venetoclax; azacitidine; magrolimab; placebo; untreated AML; unfit for intensive therapy

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 3. 2026 09:08, Mgr. Tereza Miškechová

Anotace

V originále

Patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) have limited treatment options. The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine. Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, and then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles. The primary end point was overall survival (OS); key secondary end points included complete remission (CR) rate and safety. After randomization of 378 patients, the trial was stopped at a prespecified interim analysis owing to futility. At fi final analysis, with median follow-up of 7.6 months (magrolimab arm) vs 7.4 months (control arm), median OS was 10.7 vs 14.1 months (hazard ratio, 1.178; 95% confidence interval, 0.848-1.637). The CR rate within 6 cycles was 41.3% vs 46.0%. Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs 6.5%) and respiratory events (2.6% vs 0%). There were similar incidences of any-grade infections, febrile neutropenia, and neutropenia between arms. These results highlight the difficulty in improving outcomes for patients with AML who were ineligible for IC. This trial was registered at www.clinicaltrials.gov as #NCT05079230.

Citovat

DAVER, Naval; Paresh VYAS; Gerwin HULS; Hartmut DOHNER; Sebastien MAURY; Jan NOVAK; Cristina PAPAYANNIDIS; Carmen Martinez CHAMORRO; Pau MONTESINOS; Rabin NIROULA; Pierre FENAUX; Jordi ESTEVE; Shang-Ju WU; De Voeght ADRIEN; Jiří MAYER; Peter J M VALK; Lisa JOHNSON; Mei DONG; Liu KE; Sowmya KUWAHARA; Kenneth CALDWELL a Guru Subramanian Guru MURTHY. The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy. Blood. AMSTERDAM: ELSEVIER, 2025, roč. 146, č. 5, s. 601-611. ISSN 0006-4971. Dostupné z: https://doi.org/10.1182/blood.2024027506.

@article{2558439,
   author = {Daver, Naval and Vyas, Paresh and Huls, Gerwin and Dohner, Hartmut and Maury, Sebastien and Novak, Jan and Papayannidis, Cristina and Chamorro, Carmen Martinez and Montesinos, Pau and Niroula, Rabin and Fenaux, Pierre and Esteve, Jordi and Wu, ShangandJu and Adrien, De Voeght and Mayer, Jiří and Valk, Peter J M and Johnson, Lisa and Dong, Mei and Ke, Liu and Kuwahara, Sowmya and Caldwell, Kenneth and Murthy, Guru Subramanian Guru},
   article_location = {AMSTERDAM},
   article_number = {5},
   doi = {https://doi.org/10.1182/blood.2024027506},
   keywords = {The ENHANCE-3 study; venetoclax; azacitidine; magrolimab; placebo; untreated AML; unfit for intensive therapy},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy},
   url = {https://ashpublications.org/blood/article/146/5/601/536723/The-ENHANCE-3-study-venetoclax-and-azacitidine},
   volume = {146},
   year = {2025}
}

TY  - JOUR
ID  - 2558439
AU  - Daver, Naval - Vyas, Paresh - Huls, Gerwin - Dohner, Hartmut - Maury, Sebastien - Novak, Jan - Papayannidis, Cristina - Chamorro, Carmen Martinez - Montesinos, Pau - Niroula, Rabin - Fenaux, Pierre - Esteve, Jordi - Wu, Shang-Ju - Adrien, De Voeght - Mayer, Jiří - Valk, Peter J M - Johnson, Lisa - Dong, Mei - Ke, Liu - Kuwahara, Sowmya - Caldwell, Kenneth - Murthy, Guru Subramanian Guru
PY  - 2025
TI  - The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy
JF  - Blood
VL  - 146
IS  - 5
SP  - 601-611
EP  - 601-611
PB  - ELSEVIER
SN  - 00064971
KW  - The ENHANCE-3 study
KW  - venetoclax
KW  - azacitidine
KW  - magrolimab
KW  - placebo
KW  - untreated AML
KW  - unfit for intensive therapy
UR  - https://ashpublications.org/blood/article/146/5/601/536723/The-ENHANCE-3-study-venetoclax-and-azacitidine
N2  - Patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) have limited treatment options. The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine. Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, and then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles. The primary end point was overall survival (OS); key secondary end points included complete remission (CR) rate and safety. After randomization of 378 patients, the trial was stopped at a prespecified interim analysis owing to futility. At fi final analysis, with median follow-up of 7.6 months (magrolimab arm) vs 7.4 months (control arm), median OS was 10.7 vs 14.1 months (hazard ratio, 1.178; 95% confidence interval, 0.848-1.637). The CR rate within 6 cycles was 41.3% vs 46.0%. Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs 6.5%) and respiratory events (2.6% vs 0%). There were similar incidences of any-grade infections, febrile neutropenia, and neutropenia between arms. These results highlight the difficulty in improving outcomes for patients with AML who were ineligible for IC. This trial was registered at www.clinicaltrials.gov as #NCT05079230.
ER  -

DAVER, Naval; Paresh VYAS; Gerwin HULS; Hartmut DOHNER; Sebastien MAURY; Jan NOVAK; Cristina PAPAYANNIDIS; Carmen Martinez CHAMORRO; Pau MONTESINOS; Rabin NIROULA; Pierre FENAUX; Jordi ESTEVE; Shang-Ju WU; De Voeght ADRIEN; Jiří MAYER; Peter J M VALK; Lisa JOHNSON; Mei DONG; Liu KE; Sowmya KUWAHARA; Kenneth CALDWELL a Guru Subramanian Guru MURTHY. The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy. \textit{Blood}. AMSTERDAM: ELSEVIER, 2025, roč.~146, č.~5, s.~601-611. ISSN~0006-4971. Dostupné z: https://doi.org/10.1182/blood.2024027506.

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