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. 2021 Jan 12;5(1):176-184.
doi: 10.1182/bloodadvances.2020003159.

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

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

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

Edmond Chiche et al. Blood Adv. .

Abstract

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 <10-3 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 a median 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.

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Conflict of interest statement

Conflict-of-interest disclosure: P.P., A.P., C.R., and T.C. have served as an advisor or consultant for Jazz Pharmaceuticals. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Frequencies of mutated genes (n = 74).
Figure 2.
Figure 2.
Integrated matrix of the 80 assigned patients and mutations. Mutated genes are grouped by broad biological pathways and according to Lindsley’s classifier.
Figure 3.
Figure 3.
Survivals using CPX-351 in a real-life setting. Median OS (A) in the French cohort and subgroup analyses of median OS according to allogeneic hematopoietic cell transplantation (B), 2017 ELN prognostic group (C), and Lindsley’s classifier (D).
See this image and copyright information in PMC

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