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  3. Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML

Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Marchione D.M.
  • Recher C.
  • Heuser M.
  • Vives S.
  • Zarzycka E.
  • Wang J.
  • Riva M.
  • Calado R.T.
  • Schuh A.C.
  • Yeh S.-P.
  • Tron A.E.
  • Hui J.
  • Gianolio D.A.
  • Choe S.
  • Patel P.
  • De Botton S.
  • DiNardo C.D.
  • Döhner H.

Grupos

Abstract

In the phase 3 AGILE study, after a 12.4-month median follow-up, ivosidenib, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, combined with azacitidine significantly improved event-free survival, overall survival (OS), and complete remission rates compared with placebo-azacitidine in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML), who were unfit for intensive chemotherapy. This post hoc analysis reports long-term follow-up results from AGILE after a median follow-up of 28.6 months. Overall, 148 patients were randomized to receive ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75). Median OS was significantly longer with ivosidenib (29.3 months; 95% confidence interval [CI], 13.2 to not reached) than with placebo (7.9 months; 95% CI, 4.1-11.3; hazard ratio, 0.42 [95% CI, 0.27-0.65]; P < .0001). Hematologic recovery was faster, more durable, and conversion to transfusion independence (53.8% vs 17.1%; P = .0004) was more common with ivosidenib than with placebo. Of 33 ivosidenib-treated patients evaluable for molecular measurable residual disease (MRD), 10 converted to MRD negativity. Although OS did not differ significantly between MRD-negative and MRD-positive responders at the 0.1% variant allele frequency (VAF) threshold, MRD-negative patients had numerically longer survival. MRD status appeared more predictive of long-term OS when an exploratory 1% VAF threshold was applied. MRD response was not associated with IDH1 variant, VAF, inferred clonality, or number of baseline comutations. The previously reported safety profile was maintained. These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy–ineligible patients with IDH1-mutated AML. This trial was registered at www.ClinicalTrials.gov as #NCT03173248. © 2025 The American Society of Hematology

Datos de la publicación

ISSN/ISSNe:
2473-9529, 2473-9537

Blood Advances  ELSEVIER

Tipo:
Article
Páginas:
5177-5189
PubMed:
40706052
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
2,795 SCImago ℠
Cuartil:
Q1 SCImago ℠

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Keywords

  • azacitidine; CD135 antigen; DNA methyltransferase 3A; isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; isocitrate dehydrogenase inhibitor; ivosidenib; Janus kinase 2; placebo; protein p53; protein tyrosine phosphatase SHP 2; transcription factor ETV6; transcription factor EZH2; transcription factor RUNX1; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; anemia; Article; asthenia; blood biochemistry; blood sampling; cancer diagnosis; chemotherapy; constipation; controlled study; cryopreservation; diarrhea; disease exacerbation; double blind procedure; drug efficacy; drug safety; febrile neutropenia; fever; gene mutation; human; hypokalemia; leukocytosis; loss of appetite; major clinical study; multiple cycle treatment; nausea and vomiting; neutropenia; overall survival; peripheral edema; phase 3 clinical trial; pneumonia; progression free survival; randomized controlled trial; thrombocytopenia

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