Year: 2025
Type: conference-abstract
Abstract: Introduction: CPX-351 is a dual liposomal drug (daunorubicin and cytarabine) approved for the treatment of high-risk acute myeloid leukemia (AML), following the results of the pivotal trial. This study showed significant longer survival in patients aged 60-75 years treated with CPX-351 compared to 7+3 with therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC) with similar safety profile and clear benefit for patients proceeding to allogeneic stem cell transplant (SCT). Since then, several real-world studies (RW) from different countries, confirmed the efficacy observed in the phase 3 and generating important insights into the use of CPX-351. Additionally, they have addressed important data not included in the pivotal study such as its use in younger patients, measurable residual disease (MRD) or response according to molecular alterations in myelodysplasia-related genes (MRg) included in the current classifications. Our aim is to analyze the the efficacy of CPX-351 in a real-life setting, evaluating the impact of MRD in a broader population of high-risk-AML. Methods: Retrospective, observational, multicenter study of newly diagnosed high-risk AML (t-AML and AML-MRC) treated with CPX-351 in 21 Spanish centers (May 2018 to July 2025). For this purpose, we collected data from medical records of AML patients treated with CPX-351 and investigated efficacy outcomes derived from the follow-up analysis between clinical parameters:overall survival (OS) and ORR(complete remission (CR) or CR with incomplete hematology recovery (CRi)) and [1] age ( ≤ 60 y) [2] MRD, assesed by multiparametric flow cytometry (*negative: below the threshold of 10 –3) [3] cytogenetic and molecular alterations [4], consolidation with SCT. The study was approved by Ethics Committee of the Coordinating Center. Statistical analysis was performed using SPSS v. 26. Results: A total of 219 patients with high-risk-AML treated with CPX-351 were included. Median age was 65y (range 20-78), 53 (24.2%) were younger than 60y and 135 (61,6%) were male. Median bone marrow blast at diagnosis was 30% (IQR 21-53.5). Among 195 patients with cytogenetics available:74 (33.8%) was normal, 87(39.7%) showed myelodysplasia-related cytogenetic (CM) with53 (60.9%) complex karyotype and 34 (15%) presented other alterations. Molecular profile was available in 188: 99 (52.7%) showed MRg and 40 (21.3 %) were TP53 mutated. ELN2022 risk stratification was: 12 (5.5%) favorable, 33 (15.1%) intermediate and 174 (79.5%) adverse. Among 193 patients evaluable for response, the overall response rate (ORR) was 63.7%, with 86.1% responders after 1 st cycle and MRD negative in 58% of responders. Consolidation (at least 1 cycle, 1-3) was given to 73 patients. A total of 100 (45.6%) patients underwent SCT. Early mortality at 30 and 60 days was 1.4% and 6.1% respectively. With a median follow-up time (IQR) of 8.6 months, the 1-y OS and relapse free survival (RFS) were 56.5% and 59.8%, respectively. Response to CPX-351 induction was statistically associated with better 1-y OS (68 vs 43.9%), regardless the number of induction cycles (1 cycle 68 vs 2 cycles 69%). End of induction MRD negativity was associated with a trend towards better 1y-OS (73.8 vs 60.4%, p=0.09). TP53 muation, del17p and CM were associated with end-of-induction MRD positivity. SCT was also associated with better 1-y OS (79.6% vs 35.8%). We found no difference in terms of OS regarding age(<60 66.5 vs >60 53.3%, p=0.1). Despite the lack of differences in response between younger and older in terms of ORR(64% vs 78%) or MRD response(67 vs 52%), there is a significant difference (p<0.05) in reaching SCT between both groups: 38 (71.7% vs 37.3%). Presence of del17p or TP53 mutation were predictive of worse 1y-OS (16.7 vs 62.4%; 34.2 vs 61.6%, respectively), load of TP53 disfunction was predictive of worse OS(no hit 64.1%, single hit 40.8%, double hit 14%). Efficacy of CPX-351 was not affected by mutations in MRg vs not mutated (57.9% vs 53.4%). No differences were found in ORR or OS based on whether AML was defined by cytogenetic alterations and/or prior MDS(58.6%) or solely the presence of MRg (64%) (p=0.14). Regarding safety profile, a 44 % of patients experienced mucositis, most of them low grade (1-2) in 97.9%. Conclusions: Our preliminary results support the previous evidence that CPX-351 improves overall survival in high-risk AML regardless of patients age and with acceptable safety profile.
Source: Blood
Authors: Manuel Fernández-Villalobos, Pilar Lancho-Lavilla, Virginia Pradillo Fernandez, Javier Ortiz, Angela Figuera, Sandra García-Lázaro, Rosalia Riazza, Almudena De Laiglesia, Marta Polo, Laura Solán Blanco, Montserrat Arnan, Ana Mellado, Carlos Rodríguez-Medina, Mar Tormo, Jordi Esteve, Marina Díaz-Beyá, Ferran Vall-Llovera Calmet, Irene Sanchez Vadillo, Teresa Olave, Maria del Mar Moles, Maria Isabel Gomez Roncero, Pilar Martinez Sanchez, Maria Foncillas, Alicia Roldán-Pérez, Ana Alfonso-Pierola, Aitor Abuin Blanco, Concha Alaez, Ramon Garcia-Sanz, Gabriela Rodriguez Macias
Institutions: Hospital General Universitario Gregorio Marañón, Hospital Universitario Quirónsalud Madrid, IDCQ Hospitales y Sanidad, S.L.U., Hospital Universitario de La Princesa, Hospital Universitario Severo Ochoa, Hospital Universitario Puerta de Hierro Majadahonda, Hospital Clínico San Carlos, Hospital Universitario Fundación Jiménez Díaz, Institut Català d'Oncologia, Duran i Reynals Hospital, Hospital Universitario de Gran Canaria Doctor Negrín, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Hospital Clínic de Barcelona, University Hospital Mútua de Terrassa, Mútua Terrassa, Hospital Universitario La Paz, Hospital Clínico Universitario Lozano Blesa, Complejo Hospitalario Universitario de Toledo, Hospital Universitario 12 De Octubre, Hospital Universitario Infanta Leonor, Hospital Universitario Infanta Sofía, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Universidad de Navarra, Instituto de Investigación Sanitaria Gregorio Marañón
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417019837
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