Temporal Trends in Real‐World Outcomes With CPX‐351 in Secondary/High‐Risk Acute Myeloid Leukemia: A PETHEMA Study
Josefina Serrano, Alicia Aguirre, David Martínez‐Cuadrón, Rosa Ayala, Juan Bergua, Julio García‐Suárez, Valle Gómez‐García de Soria, Pilar Marí, Daniel García‐Belmonte, Carmen Martínez‐Chamorro, Celina Benavente, Mayte Olave, Teresa Bernal, Eduardo Rodríguez‐Arboli, Maria‐Angeles Foncillas, Lorenzo Algarra, Juan M. Alonso, Almudena Laiglesia, Esther Prados de la Torre, Montse Arnan, Carlos Rodríguez‐Medina, Rosalía Riaza, Susana Vives, Mar Tormo, Mercedes Colorado, Jorge Labrador, Olga Salamero, Cristina Gil, Raimundo García‐Boyero, Soraya Lorente, Ana Alfonso, Olga Arce, Victor Noriega, Esperanza Lavilla, Beatriz DeRueda, Laura Torres, Joaquin Sánchez‐García, Pau Montesinos,ABSTRACT
CPX‐351, a liposomal formulation of cytarabine and daunorubicin, has been approved patients with secondary/high‐risk acute myeloid leukemia including therapy‐related acute myeloid leukemia or AML with myelodysplasia‐related changes according to the WHO 2016 classification. The aim of this study was to determine the efficacy and safety of CPX‐351 in 283 patients with AML registered in the PETHEMA database. Evolving outcome results were analyzed comparing early treated patients (before‐2022, N = 147) with those treated after Spanish financial approval (since‐2022, N = 136). The CR/CRi rate was 54% in the overall cohort, without significant differences comparing both time periods. By contrast, early death rates at day + 30 and day + 60 were higher in early period patients (11.6 vs. 5.1% and 17 vs. 8.1%, p = 0.03 and p = 0.031). Consequently, more patients could undergo HSCT in the latter treatment period (33.8% vs. 25.2%, p = 0.04). Patients treated with CPX‐351 since 2022 showed a significantly higher unadjusted 2‐year OS probability compared with patients treated earlier [40.3% (95% CI: 26.3–62.4) versus 25.2% (95% CI: 18.6–34.1), P = 0.017]. However, treatment period was not independently associated with OS in multivariable analysis. Only TP53 wild‐type status [HR 0.51 (95% CI: 0.25–1.05)] and achievement of MRD negativity after induction [HR 0.54 (95% CI: 0.29–1.0)] remained independently associated with improved OS. Overall, outcomes after CPX‐351 appeared to improve over time in unadjusted analyses; however, the absence of an independent effect of treatment period and differences in patient selection between periods preclude attributing this improvement specifically to a temporal learning effect.