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4255 Long-Term Real-World Experience of CPX-351 in Combined French-Italian Cohorts Identified High Rate of Negative Measurable Residual Disease (MRD) and Prolonged Overall Survival

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Hematology Disease Topics & Pathways:
AML, Research, Acute Myeloid Malignancies, Clinical Research, Diseases, Therapies, real-world evidence, Myeloid Malignancies, Minimal Residual Disease
Monday, December 11, 2023, 6:00 PM-8:00 PM

Thomas Cluzeau, MD, PhD1, Fabio Guolo, MD, PhD2*, Edmond Chiche3*, Paola Minetto, MD4, Ramy Rahmé, MD, MSc5*, Sarah Bertoli6*, Livio Pagano, MD7*, Jean-Baptiste Micol, MD8, Michele Gottardi9*, Pierre Peterlin10*, Sara Galimberti, MD, PhD11*, Xavier Thomas, MD, PhD12*, Giuliana Rizzuto, PhD13*, Mohamad Mohty, MD, PhD14, Michela Rondoni15*, Emmanuel Raffoux, M.D.16*, Giambattista Bertani, MD17*, Alexis Caulier, MD, PhD18*, Michelina Dargenio, MD19*, Caroline Bonmati, MD20*, Atto Billio21*, Caroline Lejeune22*, Barbara Scappini23*, Arnaud Pigneux, MD, PhD24*, Patrizia Zappasodi, MD25*, Christian Recher, MD, PhD26*, Norbert Vey, MD27, Francesco Grimaldi, MD28*, Lionel Ades, MD, PhD29 and Roberto Massimo Lemoli, MD30*

1Nice University Hospital, Nice, Provence Alpes Cote d'Azur, France
2Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
3Nice University Hospital, Nice, FRA
4University of Genoa, Genova, ITA
5Clinical Hematology, Avicenne University Hospital, Assistance Publique – Hôpitaux de Paris, Bobigny, France
6Toulouse University Hospital, Toulouse, FRA
7Dipartimento di Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
8Institut Gustave Roussy, Villejuif, FRA
9Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, Padova, ITA
10Hematology Department, Hôpital Hotel Dieu, NANTES CEDEX 1, France
11Department of Clinical and Experimental Medicine, Hematology, University of Pisa, Pisa, Italy
12Centre Hospitalier Lyon-Sud, Pierre Benite, FRA
13Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, ITA
14Department of Haematology, Saint Antoine Hospital, Paris, France
15Hematology Unit & Metropolitan Transplant Network, Ravenna, AUSL Romagna, Ravenna, ITA
16Hôpital Saint-Louis, Hematology Department, AP-HP, Paris, France
17S.C. Ematologia, ASST Grande Ospedale Metropolitano, Niguarda Ca' Granda, Milano, Italy
18Hematology Department, CHU Amiens, Amiens, France
19Divisione di Ematologia e Centro Trapianti, CSE Vito Lazzi, Lecce, Italy
20Hematology Department, CHU Nancy, Nancy, France
21Ospedale di Bolzano, Bolzano - Bozen, ITA
22Hematology department, ICLN, CHU Saint-Etienne, Saint etienne, France
23SOD Ematologia, Università di Firenze, AOU Careggi, Firenze, Italy
24Hôpital Haut-Lévèque, Hematology Department, CHU Bordeaux, Pessac, France
25Division of Hematology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy, Pavia, ITA
26Hematology Department, IUCT-ONCOPOLE, Toulouse, France
27Paoli-Calmette Cancer Institute, Marseille, France
28University of Naples Federico II, Naples, Italy, Napoli, ITA
29Hôpital Saint-Louis, Hematology Department, Hopital Saint Louis, Paris, France
30Clinic of hematology, Department of Internal medicine (DiMI), University of Genoa, Genoa, Italy


CPX-351 is a liposomal formulation of cytarabine and daunorubicin packaged at a 5:1 molar ratio. This drug has been approved by the FDA and EMEA for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML) according to the WHO 2016 AML classification. Real world experience from several countries (France, Italy, Germany, UK and US) showed similar results of phase 3 clinical registration but with short follow-up. Lancet et al. published a long-term update of phase 3 clinical trial and confirmed long-term remission and improvement of overall survival (OS) (Lancet Haematology 2021). Thus, the primary objective of this study was to analyze the efficacy of CPX-351 in a real-life setting with a longer follow-up, evaluating the impact of measurable residual disease (MRD) in responding patients.


We retrospectively collected data from patients treated with CPX-351 in thirty-six centers in France and Italy. Overall response rate (ORR) was defined by complete remission (CR) and CR with incomplete hematological recovery (CRi). Among the patients in CR or CRi, 62 (61%) had MRD evaluation assessed by next-generation sequencing (NGS) or flow cytometry. OS was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analysis were performed using SPSS v.22 software (IBM SPSS Statistics).


Between April 2018 and October 2019, 170 patients treated with CPX-351 were included in this study. The sex ratio male/female was 80/90 and the median age was 66 years (range 20-83). AML subtypes were MRC-AML in 117 (69%) and t-AML 48 (28%) patients. According to the European LeukemiaNet (ELN) 2017 classification, genetic risk was favorable, intermediate, and adverse in 8 (5%), 61 (36%), and 98 (58%) (missing for 3 patients), respectively. According to the ELN 2022 classification, genetic risk was favorable, intermediate, and adverse in 8 (5%), 16 (9%) and 143 (84%), respectively. Thirty percent and 19% of patients had complex and monosomal karyotypes, respectively. Assessed by NGS the most frequent mutated genes were: TP53 (n=35, 21%), RUNX1 (n=30, 18%), ASXL1 (n=22, 13%) and TET2 (n=18, 11%) among the XX were NGS was available (sinon ca fait des % qui ne tombe pas juste sur les 170 pts). According to a genetic ontogeny-based classifier (Lindsley et al., Blood 2015), 28 %, 39% and 33% had de novo/pan-AML, secondary type mutations AML, and TP53 mutated AML, respectively.

The ORR was 102/170 (60%) after one (n=91) or two (n=11) inductions including 53% CR and 6% CRi. Among the 102 CR/CRi patients, 62 (61%) were evaluable for MRD after induction or after first consolidation. Forty (65%) patients had MRD below the threshold of 10-3. ELN2017 and ELN2022 were identified as factors predicting CR/CRi rate (P=0.032 and P=0.043, respectivelyà but the Lindsley classifier did not predict response (P= 0.060).

After 3-years of follow-up, in a univariate analysis, only MRD >10-3 (P=0.031); ELN 2017 classification (P=0.027) and presence of TP53 mutation (P=0.017) but not ELN 2022 or the Lindsley classifier; were associated with a significantly poorer median OS. In a multivariate analysis, only MRD >10-3 was associated with a poorer OS (hazard ratio [HR]=2.6, 95% CI 1.2-5.5, P=0.013). Median OS was 40.9 months vs. 10.6 months for patients with MRD <10-3 vs. ≥10-3, respectively (P=0.006).

Sixty (35%) patients underwent an allogeneic hematopoietic stem cell transplant (HSCT) with an improved median OS compared to non-transplanted patients (not-reached vs. 9.1 months, P<0.0001). We also observed a trend towards a better median OS in transplanted patients who underwent an HSCT with MRD <10-3 (not reached vs. 26.0 months, P=0.06).


After 3 years of follow-up, the improved OS with CPX-351 was confirmed in the real- life setting. Achievement of MRD negativity contributed to improvement of OS in the overall population and, maybe, in transplanted patients. These data provide the rationale for the ongoing ALFA-2101 phase III clinical trial evaluating CPX-351 vs. 3+7 (daunorubicin and cytarabine) in non-MRC-AML and non-t-AML using MRD as the primary endpoint.

Disclosures: Cluzeau: Jazz Pharma: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Incyte: Speakers Bureau; BMS: Consultancy, Speakers Bureau; Keros: Speakers Bureau; Syros: Speakers Bureau. Pagano: Gilead: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; Jazz: Honoraria; Moderna: Honoraria; Janseen: Honoraria; Menarini: Honoraria; Pfizer: Honoraria. Micol: Servier: Honoraria; JazzPharmaceuticals: Honoraria; Abbvie: Honoraria; Gilead: Honoraria. Galimberti: Abbvie, Janssen, Novartis, Roche, Jazz, Astra Zeneca, Pfizer, Incyte: Speakers Bureau. Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding. Raffoux: Pfizer, Inc.: Honoraria; Celgene: Honoraria; AbbVie: Honoraria; Astellas: Honoraria; Daiichi-Sankyo: Honoraria. Pigneux: BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings, Research Funding; Gilead: Honoraria; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Novartis: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Zappasodi: Amgen, Pfizer, Abbvie, Astellas: Honoraria. Ades: BMS: Consultancy, Research Funding; ROCHE: Honoraria; Abbvie: Consultancy, Research Funding; AMGEN: Consultancy; jazz: Honoraria; Novartis: Consultancy, Research Funding; KEROS: Consultancy.

*signifies non-member of ASH