Dp090 | Cpx-351 Leads to High Response Rates and Durable Outcomes in Npm1 Mutated Acute Myeloid Leukemia: an Italian Multicentric Retrospective Study
Year: 2025
Type: article
Abstract: Introduction: CPX-351 has been approved for treatment of Acute Myeloid Leukemia (AML) with Myelodysplastic Related Changes (AML-MRC) or therapy-related AML (t-AML) as per former WHO 2016 classification. Italian Real-World Experience confirmed benefit of CPX-351 in high-risk AML, and CPX-351 is now being explored as frontline treatment for de novo AML. However, data on the efficacy in NPM1 mutated AML remain limited, given rarity of this subgroup among t-AML, and results still immature from frontline trials. Aims: to analyze efficacy and outcome of CPX-351 in NPM1-mutated AML. Patients and results: 59 patients (median age 64 years, range 46-74, 52,5% aged≥65) (28/31, male/female) from 29 Italian Centers were retrospectively included in this study. Complete diagnostic testing were performed locally, and HSCT given as per local policy. Diagnosis of t-AML or AML-MRC were 19(32,2%) and 40(67,8%), respectively. Type A was most prevalent (88%) NPM1 mutation, while FLT3 was mutated in 12 patients (20%). Cytogenetics showed complex karyotype (>3 abnormalities) in 14 patients (23,7%). NGS data at diagnosis were available in 20 patients, with DNMT3a and IDH1/2 as prevalent mutations (19% respectively). Median number of comorbidities was 1 (Range 0-4). After induction 1, 47/59 patients (79%) achieved complete remission (CR); 2 achieved CR after induction 2, with a final CR rate of 83% (63% achieving MRD negativity). After inductions, 10 patients resulted refractory (16%). Complex karyotype was more frequent in refractory patients (p<0,005) with an OR of 3.12 (p=NS in a logistic stepwise regression analysis). Among responding patients, 8 (16,3%), 17 (34,8%) and 24 (48,9%) received none, one or two consolidation cycles, respectively. HSCT consolidation in first CR was performed in 17/49 responding patients (34,6%). Median RFS was of 19.6 months (CI 95% 14.8 - NA), and median of OS was of 20.2 months (CI 95% 17.21 – NA). In a Cox multivariate analysis RFS was significantly influenced by t-AML diagnosis (HR 48.5, p=0.026), FLT3 status (HR 32.1, p=0.035), number of consolidation (2 vs other)(HR 0,07, p=0.021) and HSCT in CR1 (HR 0.01, p=0.032), while OS was significantly influenced only by age (HR 1,34, p=0.012), with HSCT not significantly impacting on survival (Figure 1). Conclusions: In this large cohort of NPM1-mutated AML, CPX-351 was associated with good response and optimal survival outcome. Combinatory strategies with newer agents may further improve these results.
Authors: F. Grimaldi, F. Guolo, C. Vetro, L. Fianchi, P. Chiusolo, C. Riva, P. Minetto, C. Alati, S. Vitiello, L. Ammirati, B. Serio, V. Cardinali, V. Carluccio, M. Cimminiello, M. Molica, C. Pasciolla, M.G. Rascato, E. Vigna, M.A. Urbano, M. Memoli, S. Avilia, L. Esposito, G. Battipaglia, M. Annunziata, E. Todisco, RM. Lemoli, F. Pane
Institutions: Federico II University Hospital, University of Naples Federico II, Ospedale Policlinico San Martino, University of Genoa, Paracelsus Medical University, Azienda Sanitaria dell'Alto Adige, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Azienda ospedaliera "Bianchi-Melacrino-Morelli", Ospedale Antonio Cardarelli, AOU San Giovanni di Dio e Ruggi d'Aragona, University of Perugia, Azienda Ospedaliero-Universitaria "Renato Dulbecco", Azienda Ospedaliera S.Giuseppe Moscati, Ospedale A. Perrino, Ospedale di Circolo di Busto Arsizio, Azienda Socio Sanitaria Territoriale della Valle Olona, European Institute of Oncology
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123334
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