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

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4255-4255
• Main Authors: Cluzeau, Thomas, Guolo, Fabio, Chiche, Edmond, Minetto, Paola, Rahmé, Ramy, Bertoli, Sarah, Pagano, Livio, Micol, Jean-Baptiste, Gottardi, Michele, Peterlin, Pierre, Galimberti, Sara, Thomas, Xavier, Rizzuto, Giuliana, Mohty, Mohamad, Rondoni, Michela, Raffoux, Emmanuel, Bertani, Giambattista, Caulier, Alexis, Dargenio, Michelina, Bonmati, Caroline, Billio, Atto, Lejeune, Caroline, Scappini, Barbara, Pigneux, Arnaud, Zappasodi, Patrizia, Recher, Christian, Vey, Norbert, Grimaldi, Francesco, Ades, Lionel, Lemoli, Roberto Massimo
• Format: Article
• Language: English
• Subjects: Human health and pathology; Life Sciences
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-177951

Introduction 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. Methods 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). Results 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, respect