Improved outcomes in 17,908 acute myeloid leukemia patients across last three decades: Results from the multinational pethema registry

Abstract Background: The therapeutic landscape of acute myeloid leukemia (AML) has evolved substantially over the past three decades. While intensive chemotherapy (IC) was the mainstay until the mid-2000s, the advent of hypomethylating agents (HMA), venetoclax-based regimens, and targeted therapies (e.g., FLT3 or IDH1 inhibitors) has changed clinical practice, especially in older or unfit patients. However, population data describing the evolution of patient characteristics, treatment allocation, and outcomes remain limited. Methods: Out of 21,371 patients, we retrospectively analyzed 17,908 evaluable adult patients with newly diagnosed AML (non-APL) reported to the PETHEMA epidemiologic registry (NCT02607059) between 1990 and 2024 (Spain, Portugal, Colombia, Chile, Mexico, and Uruguay). Patients were grouped into three eras based on major therapeutic changes: 1990–2006 (one size fits all), 2007–2016 (tailored therapies), and 2017–2024 (targeted therapies). Variables included baseline characteristics, treatment and outcomes. Survival analyses used Kaplan-Meier and Cox regression. Results: Median age at diagnosis increased over time, from 62 years in 1990–2006 to 65 years in 2017–2024 (p<0.001), with patients aged ≥80 increasing from 6.9% to 14%. Despite this, baseline ECOG ≥2 decreased from 31% to 21% (p<0.001). Secondary AML increased from 20% to 31%, while extramedullary disease declined from 25% to 16% (p<0.001). No significant differences were observed in sex distribution. Hemoglobin levels declined slightly (median 9.0 to 8.8 g/dL; p=0.019), while median white blood cell and platelet counts remained stable through eras. Serum creatinine and bilirubin slightly decreased (p<0.001), and albumin increased modestly (p<0.001), suggesting improved baseline condition at diagnosis. Frontline treatment strategies evolved markedly. IC remained predominant but declined from 80% (in 1990-2006) to 67% (in 2017-2024), p<0.001. Non-intensive therapies rose from 1.1% to 23% (p<0.001), while best supportive care (BSC) declined from 20% to 10%, indicating broader access to active treatment. Within the IC group, conventional 7+3-like regimens remained dominant until 2016 (around 90%) but decreased to 71% in 2017–2024, with increasing use of CPX-351 (5.2%), IC+FLT3 inhibitors (10%), and IC+gemtuzumab ozogamicin (2.7%). In the non-intensive setting, venetoclax + HMA combinations emerged as a key component (31% in 2017-2024), although HMA monotherapy remained the most frequently administered option (48%). In contrast, low-dose cytarabine-based regimens declined from 65% to 16%. CR/CRi rates remained stable in the three periods for IC (65% vs. 61% vs. 63%%). The proportion of patients transplanted in first CR/CRi remained stable (23% vs. 18% vs. 20%). A shift from autologous to allogeneic transplant was evident: autologous transplant use declined from 15% to 3%, while allogeneic transplant increased from 8% to 17% (p<0.001). Among 17,908 patients, median overall survival (OS) improved significantly from 9.3 months in 1990–2006, 9.3 months in 2007-2016, and 12.8 months in 2017–2024 (p<0.001). In univariate analysis, OS improved in most subgroups during the last diagnostic period, including all age categories, both sexes, patients with ECOG <2, de novo AML, those treated with front-line IC (from 12.9 to 20.4 months), those who underwent allogeneic or autologous transplantation, and even among non-transplanted patients. However, no significant gains were observed in patients with ECOG ≥2, secondary AML, or those treated with non-intensive therapies or BSC. Median OS among patients aged <50 increased from 27.2 to 65.8 months, from 5.8 to 10.3 months among those aged 65–74, and from 3.0 to 6.1 months among those aged 75–79. Median OS for ECOG ≥2 patients remained poor across all periods (approximately 3 months). Survival in the BSC group declined from 1.6 to 0.6 months. In multivariate analyses, the diagnostic period remained independently associated with OS after adjusting for age, sex, AML type, ECOG status, transplant, and treatment strategy (p<0.001). Conclusions:This large real-world study spanning more than three decades highlights substantial improvements in survival and evolving treatment patterns in AML. Despite an older population, better functional status and supportive care, and increased use of both intensive and non-intensive active therapies likely contributed to improved outcomes.

Authors

Institutions

Publication Details

Journal
Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-40
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Improved outcomes in 17,908 acute myeloid leukemia patients across last three decades: Results from the multinational pethema registry

Pilar Martínez‐Sánchez, Pau Montesinos, Olga Salamero, Joana Brioso Infante et al.
Blood
Acute Myeloid Leukemia Research
article

Improved outcomes in 17,908 acute myeloid leukemia patients across last three decades: Results from the multinational pethema registry

Pilar Martínez‐Sánchez, Pau Montesinos, Olga Salamero, Joana Brioso Infante, Rebeca Rodríguez‐Veiga, Esperanza Lavilla, Mar Tormo, Bernardo González, David Martínez‐Cuadrón, José Mariz, Luis Felipe Casado Montero, Juan Manuel Alonso‐Domínguez, Jorge Labrador, Diana Cuervo, Marcela Espinoza, Víctor Noriega Concepción, Juan Miguel Bergua Burgués, Manuel Pérez‐Encinas, Lorenzo Algarra, Beatriz De Rueda Ciller, María Lourdes Amador Barciela, M. Madrigal, Verónica Lizama, Josefina Serrano, Pilar Herrera Puente, Cristina Gil, Raimundo García‐Boyero, Eduardo Rodríguez‐Arbolí, Evelyn Acuña‐Cruz, María Teresa Olave Rubio, Claudia Sossa, Maria Jose Sayas Lloris, Teresa Bernal, Mercedes Colorado, Antonio Solana‐Altabella, Olga Arce‐Fernández, Manuel Barrios García, María García‐Fortes, Susana Vives, Emília Cortesão, Ágata Almela, Isabel Cano, Carmen Montes, Celina Benavente, Rosa Fernández, Armando Mena Duran, Maria Vidriales Vicente, Fernanda Trigo, Carlos Rodríguez‐Medina, María Luz Amigo, Christine Rojas, M.J. Cremades Romero, ANA Yurena Oliva Hernandez, Esther Pérez‐Santaolalla, Marta Valero-Nuñez
article en

Abstract

Abstract Background: The therapeutic landscape of acute myeloid leukemia (AML) has evolved substantially over the past three decades. While intensive chemotherapy (IC) was the mainstay until the mid-2000s, the advent of hypomethylating agents (HMA), venetoclax-based regimens, and targeted therapies (e.g., FLT3 or IDH1 inhibitors) has changed clinical practice, especially in older or unfit patients. However, population data describing the evolution of patient characteristics, treatment allocation, and outcomes remain limited. Methods: Out of 21,371 patients, we retrospectively analyzed 17,908 evaluable adult patients with newly diagnosed AML (non-APL) reported to the PETHEMA epidemiologic registry (NCT02607059) between 1990 and 2024 (Spain, Portugal, Colombia, Chile, Mexico, and Uruguay). Patients were grouped into three eras based on major therapeutic changes: 1990–2006 (one size fits all), 2007–2016 (tailored therapies), and 2017–2024 (targeted therapies). Variables included baseline characteristics, treatment and outcomes. Survival analyses used Kaplan-Meier and Cox regression. Results: Median age at diagnosis increased over time, from 62 years in 1990–2006 to 65 years in 2017–2024 (p<0.001), with patients aged ≥80 increasing from 6.9% to 14%. Despite this, baseline ECOG ≥2 decreased from 31% to 21% (p<0.001). Secondary AML increased from 20% to 31%, while extramedullary disease declined from 25% to 16% (p<0.001). No significant differences were observed in sex distribution. Hemoglobin levels declined slightly (median 9.0 to 8.8 g/dL; p=0.019), while median white blood cell and platelet counts remained stable through eras. Serum creatinine and bilirubin slightly decreased (p<0.001), and albumin increased modestly (p<0.001), suggesting improved baseline condition at diagnosis. Frontline treatment strategies evolved markedly. IC remained predominant but declined from 80% (in 1990-2006) to 67% (in 2017-2024), p<0.001. Non-intensive therapies rose from 1.1% to 23% (p<0.001), while best supportive care (BSC) declined from 20% to 10%, indicating broader access to active treatment. Within the IC group, conventional 7+3-like regimens remained dominant until 2016 (around 90%) but decreased to 71% in 2017–2024, with increasing use of CPX-351 (5.2%), IC+FLT3 inhibitors (10%), and IC+gemtuzumab ozogamicin (2.7%). In the non-intensive setting, venetoclax + HMA combinations emerged as a key component (31% in 2017-2024), although HMA monotherapy remained the most frequently administered option (48%). In contrast, low-dose cytarabine-based regimens declined from 65% to 16%. CR/CRi rates remained stable in the three periods for IC (65% vs. 61% vs. 63%%). The proportion of patients transplanted in first CR/CRi remained stable (23% vs. 18% vs. 20%). A shift from autologous to allogeneic transplant was evident: autologous transplant use declined from 15% to 3%, while allogeneic transplant increased from 8% to 17% (p<0.001). Among 17,908 patients, median overall survival (OS) improved significantly from 9.3 months in 1990–2006, 9.3 months in 2007-2016, and 12.8 months in 2017–2024 (p<0.001). In univariate analysis, OS improved in most subgroups during the last diagnostic period, including all age categories, both sexes, patients with ECOG <2, de novo AML, those treated with front-line IC (from 12.9 to 20.4 months), those who underwent allogeneic or autologous transplantation, and even among non-transplanted patients. However, no significant gains were observed in patients with ECOG ≥2, secondary AML, or those treated with non-intensive therapies or BSC. Median OS among patients aged <50 increased from 27.2 to 65.8 months, from 5.8 to 10.3 months among those aged 65–74, and from 3.0 to 6.1 months among those aged 75–79. Median OS for ECOG ≥2 patients remained poor across all periods (approximately 3 months). Survival in the BSC group declined from 1.6 to 0.6 months. In multivariate analyses, the diagnostic period remained independently associated with OS after adjusting for age, sex, AML type, ECOG status, transplant, and treatment strategy (p<0.001). Conclusions:This large real-world study spanning more than three decades highlights substantial improvements in survival and evolving treatment patterns in AML. Despite an older population, better functional status and supportive care, and increased use of both intensive and non-intensive active therapies likely contributed to improved outcomes.

BloodVol. 146(Supplement 1)
Universidad de Las Palmas de Gran Canaria (ES), Hebron University (PS), Universidad Autónoma de Bucaramanga (CO), Instituto Cajal (ES), Hospital Universitario Insular de Gran Canaria (ES), Hospital Universitario de Canarias (ES), Hospitais da Universidade de Coimbra (PT), Hospital Clínico San Carlos (ES), Hospital de São João (PT), Hospital Universitari i Politècnic La Fe (ES), Universidad Distrital Francisco José de Caldas (CO), Hospital Universitario Nuestra Señora de Candelaria (ES), Hospital Universitario Virgen Macarena (ES), Hospital General Universitario Morales Meseguer (ES), Hospital de Basurto (ES), Hospital Clínico Universitario de Valencia (ES), Complejo Hospitalario Universitario de Santiago (ES), Hospital Universitario de Gran Canaria Doctor Negrín (ES), Hospital del Salvador (CL), Complejo Hospitalario de Salamanca (ES), Marqués de Valdecilla University Hospital (ES), Biogipuzkoa Health Research Institute (ES), Vall d'Hebron Institut de Recerca (ES), Instituto Português de Oncologia Francisco Gentil (PT), Hospital Regional Universitario de Málaga (ES), Hospital San Pedro de Alcántara (ES), Hospital Universitario Miguel Servet (ES), Hospital Universitario de Burgos (ES), Hospital Arnau de Vilanova (ES), Hospital Regional de Concepción (CL), Hospital Universitario Reina Sofía (ES), Hospital General Universitari de Castelló (ES), Hospital Universitario Doctor Peset (ES), Vall d'Hebron Hospital Universitari (ES), Hospital General Universitario De Valencia (ES), Hospital Virgen de la Concha (ES), Hospital Universitario Fundación Jiménez Díaz (ES), Hospital Universitario Central de Asturias (ES), Hospital Clínico Universitario Lozano Blesa (ES), Badalona Serveis Assistencials (ES), Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES), Hospital Universitario HM Sanchinarro (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Donostiako Unibertsitate Ospitalea (ES), Complexo Hospitalario Universitario A Coruña (ES), Hospital Dr. Gustavo Fricke (CL), Hospital Universitario Lucus Augusti (ES), Hospital General Universitario de Albacete (ES), Instituto Português de Oncologia de Coimbra Francisco Gentil (PT), Hospital de Santa Maria (PT), Hospital Universitario Virgen del Rocío (ES), Hospital Universitari Germans Trias i Pujol (ES), Clínica Dávila (CL), Hospital Clínico Universitario Virgen de la Victoria (ES), Complejo Hospitalario de Pontevedra (ES), Hospital Universitario de León (ES), Hospital Universitario Ramón y Cajal (ES), Hospital Universitario Infantil San José (CO)
Openalex Percentile: Top 44%
Acute Myeloid Leukemia Research
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.