Treatment patterns and outcomes of 2310 patients with secondary acute myeloid leukemia: a PETHEMA registry study

David Martínez-Cuadrón, Juan E Megías-Vericat, Josefina Serrano, Pilar Martínez-Sánchez, Eduardo Rodríguez-Arbolí, Cristina Gil, Eliana Aguiar, Juan Bergua, José L López-Lorenzo, Teresa Bernal, Ana Espadana, Mercedes Colorado, Carlos Rodríguez-Medina, María López-Pavía, Mar Tormo, Lorenzo Algarra, María-Luz Amigo, María J Sayas, Jorge Labrador, Juan I Rodríguez-Gutiérrez, Celina Benavente, Lissette Costilla-Barriga, Raimundo García-Boyero, Esperanza Lavilla-Rubira, Susana Vives, Pilar Herrera, Daniel García-Belmonte, María Mar Herráez, Graça Vasconcelos Esteves, Maria I Gómez-Roncero, Ana Cabello, Guiomar Bautista, Amaia Balerdi, José Mariz, Blanca Boluda, Miguel Á Sanz, Pau Montesinos, David Martínez-Cuadrón, Juan E Megías-Vericat, Josefina Serrano, Pilar Martínez-Sánchez, Eduardo Rodríguez-Arbolí, Cristina Gil, Eliana Aguiar, Juan Bergua, José L López-Lorenzo, Teresa Bernal, Ana Espadana, Mercedes Colorado, Carlos Rodríguez-Medina, María López-Pavía, Mar Tormo, Lorenzo Algarra, María-Luz Amigo, María J Sayas, Jorge Labrador, Juan I Rodríguez-Gutiérrez, Celina Benavente, Lissette Costilla-Barriga, Raimundo García-Boyero, Esperanza Lavilla-Rubira, Susana Vives, Pilar Herrera, Daniel García-Belmonte, María Mar Herráez, Graça Vasconcelos Esteves, Maria I Gómez-Roncero, Ana Cabello, Guiomar Bautista, Amaia Balerdi, José Mariz, Blanca Boluda, Miguel Á Sanz, Pau Montesinos

Abstract

Secondary acute myeloid leukemia (sAML) comprises a heterogeneous group of patients and is associated with poor overall survival (OS). We analyze the characteristics, treatment patterns, and outcomes of adult patients with sAML in the Programa Español de Tratamientos en Hematología (PETHEMA) registry. Overall, 6211 (72.9%) were de novo and 2310 (27.1%) had sAML, divided into myelodysplastic syndrome AML (MDS-AML, 44%), MDS/myeloproliferative AML (MDS/MPN-AML, 10%), MPN-AML (11%), therapy-related AML (t-AML, 25%), and antecedent neoplasia without prior chemotherapy/radiotherapy (neo-AML, 9%). Compared with de novo, patients with sAML were older (median age, 69 years), had more Eastern Cooperative Oncology Group ≥2 (35%) or high-risk cytogenetics (40%), less FMS-like tyrosine kinase 3 internal tandem duplication (11%), and nucleophosmin 1 (NPM1) mutations (21%) and received less intensive chemotherapy regimens (38%) (all P < .001). Median OS was higher for de novo than sAML (10.9 vs 5.6 months; P < .001) and shorter in sAML after hematologic disorder (MDS, MDS/MPN, or MPN) compared with t-AML and neo-AML (5.3 vs 6.1 vs 5.7 months, respectively; P = .04). After intensive chemotherapy, median OS was better among patients with de novo and neo-AML (17.2 and 14.6 months, respectively). No OS differences were observed after hypomethylating agents according to type of AML. sAML was an independent adverse prognostic factor for OS. We confirmed high prevalence and adverse features of sAML and established its independent adverse prognostic value. This trial was registered at www.clinicaltrials.gov as #NCT02607059.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials (CONSORT) diagram for secondary AML adult patients.
Figure 2.
Figure 2.
Description of disorders diagnosed before AML. (A) Type of previous MDS in patients included in MDS-AML group. Patients with nonspecified and unclassifiable MDS were not included in this figure. (B) Type of previous MDS/MPN in patients included in MDS/MPN-AML group. (C) Type of previous MPN in patients included in MPN-AML group. (D) Type of previous therapy in patients included in t-AML group. (E) Type of previous neoplasm in treated patients included in t-AML group. (F) Type of previous solid neoplasm in patients with cancer antecedents without prior treatment.
Figure 3.
Figure 3.
OS of the AML patients included in the study according to different disease characteristics or therapeutic approach. (A) OS in the entire cohort of 8521 patients with AML according to type of AML (P < .001). (B) OS in secondary AML according to therapeutic approach (P < .001). (C) OS in secondary AML according to cytogenetic risk (P < .001). (D) OS in secondary AML according to NPM1 mutation (P < .001). (E) OS in secondary AML according to FLT3-ITD mutation (P = .45). (F) OS in secondary AML according to the different subgroups (P = .04).

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