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

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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Publication Details

Journal
Blood Advances
Published
2025-03-06
DOI
https://doi.org/10.1182/bloodadvances.2024014901
Citations
2
Primary Topic
Synthetic Organic Chemistry Methods
Type
article
Field-Weighted Citation Impact
1.87
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article

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

Monica Bocchia, Fabio Guolo, Francesca Paoloni, Maria Teresa Bochicchio et al.
2 citations
Blood Advances
Synthetic Organic Chemistry Methods
1.87
article

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

Monica Bocchia, Fabio Guolo, Francesca Paoloni, Maria Teresa Bochicchio, Roberto Massimo Lemoli, Matteo Giovanni Carrabba, Beatrice Anna Zannetti, Paola Fazi, Michela Rondoni, Roberto Freilone, Giuseppe Saglio, Giovanni Marconi, Jacopo Nanni, Maria Chiara Di Chio, Edoardo La Sala, Chiara M. Cattaneo, Alfonso Piciocchi, Marco Cerrano, Clara Minotti, Cristina Papayannidis, Enrico Crea, Marco Frigeni, Giorgia Simonetti, Albana Lico, Paola Minetto, Antonio Curti, Giovanni Martinelli, Marco Vignetti, Luisa Giaccone, Bianca Serio, Matteo Giovanni Della Porta, Saveria Capria, Germana Beltrami, Ernesta Audisio, Adriano Venditti
article en
2 citations

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.

Blood AdvancesVol. 9(10)
University of Siena (IT), University of Rome Tor Vergata (IT), Humanitas University (IT), Policlinico Umberto I (IT), San Raffaele University of Rome (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), ASL Roma (IT), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale Papa Giovanni XXIII (IT), Azienda Unità Sanitaria Locale Della Romagna (IT), Fondazione Gimema Onlus (IT), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), IRCCS Ospedale San Raffaele (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Azienda Ospedaliera Universitaria Senese (IT), Associazione Italiana Ematologia Oncologia Pediatrica (IT), Ospedale Policlinico San Martino (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), IRCCS Humanitas Research Hospital (IT), University of Turin (IT), University of Genoa (IT), Sapienza University of Rome (IT), University of Bologna (IT)
Openalex Percentile: Top 17%
Synthetic Organic Chemistry Methods
1.87
DOIOpen Access PDFOpenAlex
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