Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array
García-Sanz R (1), Corchete LA (1), Alcoceba M (1), Chillon MC (1), Jiménez C (1), Prieto I (1), García-Álvarez M (1), Puig N (1), Rapado I (2), Barrio S (2), Oriol A (3), Blanchard MJ (4), de la Rubia J (5), Martínez R (6), Lahuerta JJ (2), González Díaz M (7), Mateos MV (1), San Miguel JF (8), Martínez-López J (2), Sarasquete ME (1); GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group.
(1) Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
(2) Hospital 12 de Octubre, Madrid, Spain.
(3) Hospital Germans Trias i Pujol, Badalona, Spain.
(4) Hospital Universitario Ramón y Cajal de Madrid, Madrid, Spain.
(5) Hospital Dr Peset de Valencia, Valencia, Spain.
(6) Hospital Clínico de San Carlos de Madrid, Madrid, Spain.
(7) Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
(8) Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, Pamplona, Spain.
Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them.
Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN.
Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide.
We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708).
Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either.
In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment.
CITATION Hematol Oncol. 2016 Sep 8. doi: 10.1002/hon.2337