Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort

Edmond Chiche (1, 2) , Ramy Rahme (3) , Sarah Bertoli (4, 5) , Pierre-Yves Dumas (6) , Jean-Baptiste Micol (7, 8, 9) , Yosr Hicheri (10) , Florence Pasquier (7, 8) , Pierre Peterlin (11) , Patrice Chevallier (11) , Xavier Thomas (12) , Michael Loschi (2, 13) , Alexis Genthon (14) , Ollivier Legrand (14, 15) , Mohamad Mohty (15, 14) , Emmanuel Raffoux (3) , Patrick Auberger (13) , Alexis Caulier (16) , Magalie Joris (16) , Caroline Bonmati (17) , Gabrielle Roth-Guepin (17) , Caroline Lejeune (18) , Arnaud Pigneux (6) , Norbert Vey (10) , Christian Recher (4, 5) , Lionel Ades (3, 19) , Thomas Cluzeau (13, 2)

1 UCA Faculté Médecine - Université Côte d'Azur - Faculté de Médecine
2 CHU Nice - Centre Hospitalier Universitaire de Nice
3 AP-HP - Hopital Saint-Louis [AP-HP]
4 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
5 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
6 CHU Bordeaux [Bordeaux]
7 IGR - Institut Gustave Roussy
8 Université Paris-Saclay
9 Département d'hématologie [Gustave Roussy]
10 Institut Paoli-Calmettes
11 CHU Nantes - Centre hospitalier universitaire de Nantes
12 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
13 C3M - Centre méditerranéen de médecine moléculaire
14 CHU Saint-Antoine [AP-HP]
15 CRSA - Centre de Recherche Saint-Antoine
16 CHU Amiens-Picardie
17 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
18 Institut de Cancérologie Lucien Neuwirth
19 UPCité - Université Paris Cité

CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD,1023 was achieved in 57% of complete response (CR)/CR with incomplete hematological recovery (CRi) patients. Only the presence of mutated TP53 (P = .02) or PTPN11 (P = .004) predicted lower response in multivariate analysis. Interestingly, high-risk molecular prognosis subgroups defined by 2017 European LeukemiaNet risk stratification, including ASXL1 and RUNX1 mutations, were not associated with a significantly lower response rate using CPX-351. With amedian follow-up of 8.6 months, median overall survival (OS) was 16.1 months. Thirty-six patients underwent allogeneic stem cell transplantation with a significantly longer median OS compared with nontransplanted patients (P<.001). In multivariate analyses, only spliceosome mutations were associated with better OS (P=.04). In comparison with intensive chemotherapy, there was no difference in OS for patients,60 years. These data confirm the efficacy and safety of CPX-351 in high-risk AML(t-AML and MRC-AML) in a real-life setting. CPX-351 is a treatment of choice for patients aged >60 years.

Domaines: Sciences du Vivant [q-bio]

Edmond Chiche, Ramy Rahme, Sarah Bertoli, Pierre-Yves Dumas, Jean-Baptiste Micol, et al.. Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort. Blood Advances, 2021, 5 (1), pp.176-184. ⟨10.1182/bloodadvances.2020003159⟩. ⟨hal-03605963⟩