Early Prediction of Subsequent Molecular Response to Nilotinib in Patients with Chronic Myeloid Leukemia Comparison of the Quantification of BCR-ABL1 Ratios Using ABL1 or GUSB Control Genes
Por:
Stuckey, R, Casado, LF, Colomer, D, Gomez-Casares, MT, Casas, L, Garcia-Gutierrez, V, Sastre, JL, Ramirez-Payer, A, Vall-Llovera, F, Goni, MA, Xicoy, B, Godoy, AC, Nunez, J, Mora, I, Vallansot, R, Lopez-Lorenzo, JL, Palomera, L, Conesa, V, Noya, MS, Sanchez-Guijo, F, Pena, A, Bautista, G and Steegmann, JL
Publicada:
1 oct 2020
Ahead of Print:
17 jul 2020
Resumen:
Molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). Quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to frontline nilotinib was studied using data from 60 patients with chronic-phase CML from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) substudy. Effects of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early time points as independent variables on subsequent MR were determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses. From day 45, concordance was found for both control genes' early transcript kinetics and ability to predict subsequent deep MR at 18 months. From baseline to 3 months, transcripts descended linearly with both control genes. Use of ABL1 allowed for an earlier prediction (2 months) of subsequent MR than with GUSB (3 months), with cut-off values of 1.5% and 0.19%, respectively. The dynamic determination of BCR-ABL1 transcripts using either internal control gene is valid and predictive of subsequent MR. The use of GUSB to predict an earlier and more accurate response than ABL1 is not supported in the results. Accurate early indicators of MR are essential to identify patients likely to have inferior outcomes who may benefit from treatment with an alternative tyrosine kinase inhibitor.
Filiaciones:
Stuckey, R:
Hosp Univ Gran Canaria Dr Negrin, Dept Hematol, Las Palmas Gran Canaria, Spain
Casado, LF:
Hosp Virgen Salud, Dept Hematol, Toledo, Spain
Colomer, D:
Hosp Clin Univ, Hematopathol Unit, Barcelona, Spain
Gomez-Casares, MT:
Hosp Univ Gran Canaria Dr Negrin, Dept Hematol, Las Palmas Gran Canaria, Spain
Casas, L:
Dynam Solut, Madrid, Spain
Garcia-Gutierrez, V:
Hosp Ramon & Cajal, Raman y Cajal Hlth Res Inst, Madrid, Spain
Sastre, JL:
Hosp Univ Orense, Dept Hematol, Orense, Spain
Ramirez-Payer, A:
Hosp Univ Cent Asturias, Dept Hematol, Oviedo, Spain
Vall-Llovera, F:
Hosp Univ Mutua Terrassa, Dept Hematol, Terrassa, Spain
Goni, MA:
Complejo Hosp Navarra, Dept Hematol, Pamplona, Spain
:
Hosp Badalona Germans Trias & Pujol, Dept Hematol, Badalona, Spain
Godoy, AC:
Hosp Miguel Servet, Dept Hematol, Zaragoza, Spain
Nunez, J:
Hosp Univ Marquis Valdecilla, Dept Hematol, Santander, Spain
Mora, I:
Complejo Hosp Navarra, Dept Hematol, Navarra, Spain
Vallansot, R:
Hosp Univ Joan XXIII, Hematol Serv, Tarragona, Spain
Lopez-Lorenzo, JL:
Hosp Fdn Jimenez Diaz, Dept Hematol, Madrid, Spain
Palomera, L:
Hosp Clin Univ Lozano Blesa, Aragon Inst Hlth Invest, Zaragoza, Spain
Conesa, V:
Hosp Gen Univ Elche, Dept Hematol, Elche, Spain
Noya, MS:
Complexo Hosp Univ A Coruna, Dept Hematol, La Coruna, Spain
Sanchez-Guijo, F:
Hosp Clin Univ Salamanca, Dept Hematol, Salamanca, Spain
Pena, A:
Hosp Clin San Carlos, Dept Hematol, Madrid, Spain
Bautista, G:
Hosp Univ Puerta Hierro, Dept Hematol, Majadahonda, Spain
Steegmann, JL:
Hosp la Princess, Dept Hernatol, Madrid, Spain
Bronze
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