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Clinical Trial
. 2025 May 27;9(10):2542-2552.
doi: 10.1182/bloodadvances.2024014901.

Safety run-in and part 1 of GIMEMA AML1718: venetoclax combined with FLAI as induction treatment in non-low-risk AML

Giovanni Marconi  1   2 , Alfonso Piciocchi  3 , Ernesta Audisio  4 , Cristina Papayannidis  5 , Marco Cerrano  4 , Clara Minotti  6 , Francesca Paoloni  3 , Fabio Guolo  7   8 , Monica Bocchia  9 , Michela Rondoni  10 , Albana Lico  11 , Matteo G Carrabba  12 , Matteo Giovanni Della Porta  13 , Marco Frigeni  14 , Luisa Giaccone  15 , Germana Beltrami  16 , Chiara Cattaneo  17 , Maria Chiara Di Chio  18 , Bianca Serio  19 , Enrico Crea  3 , Roberto Freilone  4 , Saveria Capria  6 , Antonio Curti  5 , Paola Minetto  7 , Edoardo la Sala  3 , Jacopo Nanni  20 , Beatrice Anna Zannetti  10 , Giorgia Simonetti  21 , Maria Teresa Bochicchio  21 , Giuseppe Saglio  15 , Roberto M Lemoli  7 , Adriano Venditti  22 , Marco Vignetti  3 , Paola Fazi  3 , Giovanni Martinelli  5   20
Affiliations
Clinical Trial

Safety run-in and part 1 of GIMEMA AML1718: venetoclax combined with FLAI as induction treatment in non-low-risk AML

Giovanni Marconi et al. Blood Adv. .

Abstract

The standard induction treatment for acute myeloid leukemia (AML) has limited efficacy for patients with non-low-risk AML. We conducted a multicenter study phase 1b/2, Gruppo Italiano Malattie EMatologiche dell'Adulto AML1718, to investigate the safety and efficacy of venetoclax (VEN) combined with fludarabine, cytarabine, and idarubicin (V-FLAI) as an induction therapy for patients with non-low-risk AML aged <65 years and at intermediate or high European LeukemiaNet risk. After a safety run-in, patients were randomly allocated to VEN 400 mg or VEN 600 mg cohorts. The primary objectives were safety and composite complete remission (bone marrow blasts of <5% with any recovery). We report a predefined interim analysis after 57 patients. Median exposure to VEN during induction was 22 days. Effectiveness and safety were similar between VEN 400 mg and VEN 600 mg cohorts. The 60-day mortality rate was 5.8%. Prolonged aplasia was observed in patients receiving high doses of cytarabine during consolidation. Composite CR was achieved in 84% of patients. With a median follow-up of 20.6 months, 1-year overall survival was 71%, 1-year disease-free survival was 66.2%, and 1-year cumulative incidence of relapse was 24%. V-FLAI is an effective induction therapy for young and fit patients. Fifty-five more patients will be enrolled in part 2; they will receive VEN 400 mg + FLAI as predefined and will be evaluated centrally for measurable residual disease. This trial was registered at www.clinicaltrials.gov as #NCT03455504.

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Conflict of interest statement

Conflict-of-interest disclosure: G. Marconi acts as a consultant/speakers' bureau member of AbbVie, Astellas, AstraZeneca, Immunogen, Menarini/Stemline, Pfizer, Ryvu, Servier, Syros, and Takeda, and reports research support from AbbVie, Astellas, AstraZeneca, and Pfizer. E.A. received honoraria from AbbVie. C.P. served on an advisory board of, and/or received honoraria from, Amgen, Pfizer, Astellas, AbbVie, Blueprint, Novartis, Delbert Pharma, GlaxoSmithKline, Stemline, Incyte, Janssen, and Bristol Myers Squibb. F.G. acts as a consultant for Jazz and Astellas. M.C. received honoraria from AbbVie. G. Martinelli acts as a consultant/advisor/speakers' bureau member of Ariad/Incyte, Pfizer, Celgene/Bristol Myers Squibb, Amgen, Roche, AbbVie, GlaxoSmithKline, Astellas, Daiichi Sankyo, Takeda, and Janssen, and received research support from Pfizer, AbbVie, AstraZeneca, Daiichi Sankyo, Takeda, and Ariad/Incyte. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram of the AML1718 trial safety run-in and part 1. CRi, complete response without platelet and neutrophils recovery; PR, partial response; pts, patients; Rel, relapse; SCT, stem cell transplant; SD, stable disease.
Figure 2.
Figure 2.
Adverse events grade 2+ reported in >5% of patients, classified according to NCI-CTCAE version 5.0. Adverse events are presented as related or not related according to the investigator’s judgment. Infections are presented in detail. CNS, central nervous system; NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events.
Figure 3.
Figure 3.
Time for platelet and neutrophil recovery after induction in VEN 400 mg + FLAI and VEN 600 mg + FLAI arms. PMN, polymorphonucleated cells; PLT, platelets.
Figure 4.
Figure 4.
OS and event-free survival for VEN 400 mg + FLAI and VEN 600 mg + FLAI combinations.
See this image and copyright information in PMC

References

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