Details

Autor(en) / Beteiligte

• Cluzeau, Thomas
• Sebert, Marie
• Rahmé, Ramy
• Cuzzubbo, Stefania
• Lehmann-Che, Jacqueline
• Madelaine, Isabelle
• Peterlin, Pierre
• Bève, Blandine
• Attalah, Habiba
• Chermat, Fatiha
• Miekoutima, Elsa
• Rauzy, Odile Beyne
• Recher, Christian
• Stamatoullas, Aspasia
• Willems, Lise
• Raffoux, Emmanuel
• Berthon, Céline
• Quesnel, Bruno
• Loschi, Michael
• Carpentier, Antoine F
• Sallman, David A
• Komrokji, Rami
• Walter-Petrich, Anouk
• Chevret, Sylvie
• Ades, Lionel
• Fenaux, Pierre

Titel

Eprenetapopt Plus Azacitidine in TP53 -Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myélodysplasies (GFM)

Ist Teil von

• Journal of clinical oncology, 2021-05, Vol.39 (14), p.1575-1583

Ort / Verlag

United States: Wolters Kluwer Health

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• -mutated ( ) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have very poor outcome irrespective of the treatment received, including 40% responses (20% complete remission [CR]) with azacitidine (AZA) alone, short response duration, and a median overall survival (OS) of approximately 6 months. Eprenetapopt (APR-246), a novel first-in-class drug, leads to p53 protein reconformation and reactivates its proapoptotic and cell-cycle arrest functions. This phase II study assessed the safety and efficacy of eprenetapopt in combination with AZA in untreated high or very high International Prognostic Scoring System-R MDS and AML patients. Fifty-two patients (34 MDS, 18 AML [including seven with more than 30% blasts]) were enrolled. In MDS, we observed an overall response rate (ORR) of 62%, including 47% CR, with a median duration of response at 10.4 months. In AML, the ORR was 33% including 17% CR (27% and 0% CR in AML with less than and more than 30% marrow blasts, respectively). Seventy-three percent of responders achieved next-generation sequencing negativity (ie, variant allele frequency < 5%). The main treatment-related adverse events were febrile neutropenia (36%) and neurologic adverse events (40%), the latter correlating with a lower glomerular filtration rate at treatment onset ( < .01) and higher age ( = .05), and resolving with temporary drug interruption without recurrence after adequate eprenetapopt dose reduction. With a median follow-up of 9.7 months, median OS was 12.1 months in MDS, and 13.9 and 3.0 months in AML with less than and more than 30% marrow blasts, respectively. In this very high-risk population of MDS and AML patients, eprenetapopt combined with AZA was safe and showed potentially higher ORR and CR rate, and longer OS than reported with AZA alone.