Dynamics of Mutant Hematopoietic Progenitor Cells Are Not Associated with Clinical Outcomes in Multiple Myeloma
Year: 2025
Type: article
Study design: Observational Study
Abstract: Mutant hematopoietic progenitor cells (HPC) may expand under high-dose melphalan- and lenalidomide-based regimens and give rise to hematologic second primary malignancies (SPM) in multiple myeloma. To determine whether genetic screening of mutant HPCs may facilitate individualized treatment to minimize the risk of SPMs, we sequenced a myeloid gene panel in 555 longitudinal CD34+ samples from 348 patients with multiple myeloma treated with lenalidomide-containing regimens and found that 23% carried mutant HPCs at diagnosis, which was associated with higher tumor burden and altered myelo-erythropoiesis, although not with inferior survival nor the development of SPMs. There was considerable fluctuation of mutant HPCs, particularly during maintenance, including the frequency of TP53 mutations increasing from 1% at diagnosis to 7% after treatment. Whereas these findings could speculate on the interest of monitoring mutant HPCs during maintenance for the potential identification of patients at greater risk of developing SPMs, overall, our study does not support the genetic screening for clonal hematopoiesis (CH) in multiple myeloma. Significance: SPMs that develop in patients with multiple myeloma have a deleterious impact on survival. Patients with CH may be at risk of developing SPMs, which could potentially be avoided through individualized treatment. However, our results suggest that screening for CH at diagnosis has limited utility.
Source: Blood Cancer Discovery
Authors: Camila Guerrero, Maria-Jose Larrayoz, Irache Erdozain, Noemi Puig, Maria-Teresa Cedena, Catarina Maia, Amagoia Mañu, Natalia Gordillo, Oihane Churruca, Diego Alignani, Sarai Sarvide, Iria Vazquez, Cristina Perez, Albert Oriol, Laura Rosinol, Rafael Ríos-Tamayo, Marta-Sonia Gonzalez-Perez, Ana-Pilar Gonzalez-Rodriguez, Felipe de Arriba, Jose M. Moraleda, Jesus Martin, Luis Palomera, Valentin Cabañas, Maria-Jose Calasanz, Joaquin Martinez-Lopez, Maria-Victoria Mateos, Joan Bladé, Juan-Jose Lahuerta, Jesus F. San-Miguel, Bruno Paiva
Institutions: Navarre Institute of Health Research, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer, Hospital Universitario 12 De Octubre, Hospital Universitari Germans Trias i Pujol, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Hospital Universitario Virgen de las Nieves, Complejo Hospitalario Universitario de Santiago, Hospital Universitario Central de Asturias, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, Hospital Universitario Virgen de la Arrixaca, Hospital Universitario Virgen del Rocío, Hospital Clínico Universitario Lozano Blesa
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Fondazione AIRC per la ricerca sul cancro ETS, International Myeloma Foundation, Cancer Research UK, European Commission, Fundación Científica Asociación Española Contra el Cáncer, Fondazione Regionale per la Ricerca Biomedica, Instituto de Salud Carlos III, HORIZON EUROPE European Research Council
OpenAlex ID: W4409480446