Metabolic shift of chronic myeloid leukemia patients under imatinib–pioglitazone regimen and discontinuation

• Published in: Medical oncology (Northwood, London, England) London, England), 2021-09, Vol.38 (9), p.100-100, Article 100
• Main Authors: Póvoa, Valquíria Mariane Oliveira, Delafiori, Jeany, Dias-Audibert, Flávia Luísa, de Oliveira, Arthur Noin, Lopes, Ana Beatriz Pascoal, de Paula, Erich Vinícius, Pagnano, Katia Borgia Barbosa, Catharino, Rodrigo Ramos
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomarkers, Tumor - metabolism; Female; Follow-Up Studies; Hematology; Humans; Imatinib Mesylate - administration & dosage; Internal Medicine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Longitudinal Studies; Male; Medicine; Medicine & Public Health; Metabolic Diseases - chemically induced; Metabolic Diseases - metabolism; Metabolic Diseases - pathology; Metabolism; Metabolites; Metabolome; Middle Aged; Non-Randomized Controlled Trials as Topic; Oncology; Original Paper; Pathology; Pioglitazone - administration & dosage; Prognosis; Prospective Studies; Retrospective Studies; Targeted cancer therapy; Withholding Treatment; Young Adult
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-021-01551-5

The Estudo de Descontinuação de Imatinibe após Pioglitazona (EDI-PIO) is a single-center, longitudinal, prospective, phase 2, non-randomized, open, clinical trial (NCT02852486, August 2, 2016 retrospectively registered) for the discontinuation of imatinib after concomitant use of pioglitazone, being the first of its kind in a Brazilian population with chronic myeloid leukemia. Due to remaining of leukemic quiescent cells that are not affected by tyrosine kinase inhibitors, it has been suggested the use of pioglitazone, a PPARγ agonist, together with imatinib as a strategy for the maintenance of deep molecular response. The clinical benefit to this association is still controversial, and the metabolic alteration along this process remains unclear. Therefore, we applied a metabolomic protocol using high-resolution mass spectrometry to profile plasmatic metabolic response of a prospective cohort of ten individuals under discontinuation of imatinib and pioglitazone protocol. By comparing patients under pioglitazone and imatinib treatment with imatinib monotherapy and discontinuation phase, we were able to annotate 41 and 36 metabolites, respectively. The metabolic alterations observed during imatinib–pioglitazone combined therapy are associated with an extensive lipid remodeling, with activation of β-oxidation pathway, in addition to the presence of markers that suggest mitochondrial dysfunction. Graphic abstract