Identifying patients with indolent Acute Myeloid Leukemia: Long term survivors after best supportive care only, results from the pethema registry

Abstract Introduction: Most patients with acute myeloid leukemia (AML) who receive palliative best supportive care (BSC) alone experience poor outcomes, with reported median overall survival (OS) below two months. However, a subset of these patients not deemed for active therapy may survive significantly longer (i.e, more than those receiving non intensive chemotherapy approaches), suggesting the presence of a clinically indolent AML (iAML) phenotype. Identifying such patients could have meaningful implications for therapeutic decision-making and trial design. Objectives: We analyze clinical and biological characteristics of patients aged ≥60 years with indolent AML (i.e, receiving BSC only and surviving ≥9 months), comparing them with other AML patients aged ≥60 years receiving BSC only and surviving <9 months. Methods: We conducted a retrospective analysis of the PETHEMA epidemiological AML Registry (NCT02607059), including patients aged ≥60 years diagnosed between 1990 and 2024 who received BSC only. BSC included transfusions and other supportive measures, with or without oral cytoreductive agents (e.g., hydroxyurea, melphalan, mercaptopurine or thioguanine). iAML was defined as OS ≥9 months. Patients alive at last follow-up with <9 months of observation were excluded. Baseline characteristics and outcomes were compared between iAML and non-iAML groups (i.e, those aged ≥60 years receiving BSC only and surviving <9 months). A multivariate logistic regression model was used to identify independent predictors of iAML. Results: Of 2,506 eligible patients (i.e, aged ≥60 years receiving BSC only and follow-up ≥9 months), 192 (7.6%) met criteria for iAML (survival ≥9 months). Median OS was 14.8 months (95% CI, 13.2–16.4) in iAML vs. 0.85 months (95% CI, 0.78–0.93) in non-iAML patients (p<0.001). Compared with non-iAML patients, the iAML group had lower leukocyte counts (median 4.4 vs. 12.5 ×10⁹/L, p<0.001), higher platelet counts (median 82 vs. 49 ×10⁹/L, p<0.001), lower peripheral blood blast percentage (median 14% vs. 29%, p<0.001) and lower bone marrow blast percentage (median 35% vs. 56%, p<0.001). They also showed lower lactate dehydrogenase (LDH) levels (median 360 vs 535 U/L, p<0.001) and higher serum albumin levels (median 3.72 vs. 3.30 g/dL, p<0.001), reflecting a less proliferative disease profile. Performance status was better among iAML patients, with 52.9% having ECOG <2 compared to 32.6% in the non-iAML (p<0.001). Secondary and/or therapy-related AML was more frequent in the iAML group (48.7% vs. 36.7%, p=0.001). Fever at diagnosis, was more frequent among non-iAML patients (37.0% vs 18.4%, p<0,001). No significant differences were observed in sex distribution, creatinine levels, or bilirubin levels. Baseline karyotype was available in 68.5% of iAML patients and 63.5% of non-iAML patients, with no significant difference in the frequency of normal karyotypes (51.1% vs. 60.8% among evaluable patients; p=0.063). Among patients with available molecular data, NPM1 mutations were less frequent in the iAML group (11.9% vs. 23.7%; p=0.078), and FLT3-ITD positivity was low and similar between groups (8.7% vs. 14.6%; p=0.268). In multivariate analysis the following variables were independently associated with iAML: bone marrow blasts <50% (OR 3.36; 95% CI, 1.60–7.06, p=0.001), platelets ≥50 ×10⁹/L (OR 2.64; 95% CI, 1.31–5.32, p=0.007), and albumin ≥3.5 g/dL (OR 2.21; 95% CI, 1.15–4.28, p=0.018). Conclusions:Approximately 8% of elderly AML patients treated exclusively with BSC show unexpectedly long survival, consistent with an indolent clinical course, reflecting that in the absence of more efficacious therapeutic regimens, some patients could benefit from less invasive approaches. Easily measurable clinical parameters such as bone marrow blasts, platelet count, and serum albumin may help identify these patients. Further prospective and molecular studies are warranted to validate these findings and elucidate the biological underpinnings of iAML.

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Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-875
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Acute Myeloid Leukemia Research
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article

Identifying patients with indolent Acute Myeloid Leukemia: Long term survivors after best supportive care only, results from the pethema registry

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

Identifying patients with indolent Acute Myeloid Leukemia: Long term survivors after best supportive care only, results from the pethema registry

Pilar Martínez‐Sánchez, Pau Montesinos, Olga Salamero, Joana Brioso Infante, Rebeca Rodríguez‐Veiga, Esperanza Lavilla, Mar Tormo, David Martínez‐Cuadrón, José Mariz, Luis Felipe Casado Montero, Juan Manuel Alonso‐Domínguez, Jorge Labrador, Bernardo González González, Diana Cuervo, Marcela Espinoza, Víctor Noriega Concepción, Manuel Pérez‐Encinas, Lorenzo Algarra, Beatriz De Rueda Ciller, Cristina Gil, María Lourdes Amador Barciela, M. Madrigal, Verónica Lizama, Josefina Serrano, Pilar Herrera Puente, Raimundo García‐Boyero, Eduardo Rodríguez‐Arbolí, Evelyn Acuña‐Cruz, María Teresa Olave Rubio, Juan Bergua, 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 Introduction: Most patients with acute myeloid leukemia (AML) who receive palliative best supportive care (BSC) alone experience poor outcomes, with reported median overall survival (OS) below two months. However, a subset of these patients not deemed for active therapy may survive significantly longer (i.e, more than those receiving non intensive chemotherapy approaches), suggesting the presence of a clinically indolent AML (iAML) phenotype. Identifying such patients could have meaningful implications for therapeutic decision-making and trial design. Objectives: We analyze clinical and biological characteristics of patients aged ≥60 years with indolent AML (i.e, receiving BSC only and surviving ≥9 months), comparing them with other AML patients aged ≥60 years receiving BSC only and surviving <9 months. Methods: We conducted a retrospective analysis of the PETHEMA epidemiological AML Registry (NCT02607059), including patients aged ≥60 years diagnosed between 1990 and 2024 who received BSC only. BSC included transfusions and other supportive measures, with or without oral cytoreductive agents (e.g., hydroxyurea, melphalan, mercaptopurine or thioguanine). iAML was defined as OS ≥9 months. Patients alive at last follow-up with <9 months of observation were excluded. Baseline characteristics and outcomes were compared between iAML and non-iAML groups (i.e, those aged ≥60 years receiving BSC only and surviving <9 months). A multivariate logistic regression model was used to identify independent predictors of iAML. Results: Of 2,506 eligible patients (i.e, aged ≥60 years receiving BSC only and follow-up ≥9 months), 192 (7.6%) met criteria for iAML (survival ≥9 months). Median OS was 14.8 months (95% CI, 13.2–16.4) in iAML vs. 0.85 months (95% CI, 0.78–0.93) in non-iAML patients (p<0.001). Compared with non-iAML patients, the iAML group had lower leukocyte counts (median 4.4 vs. 12.5 ×10⁹/L, p<0.001), higher platelet counts (median 82 vs. 49 ×10⁹/L, p<0.001), lower peripheral blood blast percentage (median 14% vs. 29%, p<0.001) and lower bone marrow blast percentage (median 35% vs. 56%, p<0.001). They also showed lower lactate dehydrogenase (LDH) levels (median 360 vs 535 U/L, p<0.001) and higher serum albumin levels (median 3.72 vs. 3.30 g/dL, p<0.001), reflecting a less proliferative disease profile. Performance status was better among iAML patients, with 52.9% having ECOG <2 compared to 32.6% in the non-iAML (p<0.001). Secondary and/or therapy-related AML was more frequent in the iAML group (48.7% vs. 36.7%, p=0.001). Fever at diagnosis, was more frequent among non-iAML patients (37.0% vs 18.4%, p<0,001). No significant differences were observed in sex distribution, creatinine levels, or bilirubin levels. Baseline karyotype was available in 68.5% of iAML patients and 63.5% of non-iAML patients, with no significant difference in the frequency of normal karyotypes (51.1% vs. 60.8% among evaluable patients; p=0.063). Among patients with available molecular data, NPM1 mutations were less frequent in the iAML group (11.9% vs. 23.7%; p=0.078), and FLT3-ITD positivity was low and similar between groups (8.7% vs. 14.6%; p=0.268). In multivariate analysis the following variables were independently associated with iAML: bone marrow blasts <50% (OR 3.36; 95% CI, 1.60–7.06, p=0.001), platelets ≥50 ×10⁹/L (OR 2.64; 95% CI, 1.31–5.32, p=0.007), and albumin ≥3.5 g/dL (OR 2.21; 95% CI, 1.15–4.28, p=0.018). Conclusions:Approximately 8% of elderly AML patients treated exclusively with BSC show unexpectedly long survival, consistent with an indolent clinical course, reflecting that in the absence of more efficacious therapeutic regimens, some patients could benefit from less invasive approaches. Easily measurable clinical parameters such as bone marrow blasts, platelet count, and serum albumin may help identify these patients. Further prospective and molecular studies are warranted to validate these findings and elucidate the biological underpinnings of iAML.

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)
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