A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

Effect Evaluation of Strychnos nux-vomica L.with Integrative Methods for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma Patients:A Self-Controlled Clinical Trial

Objective:To explore the clinical effect and adverse reactions of Strychnos nux-vomica in bortezomib-induced peripheral neuropathy(BIPN)of patients with multiple myeloma(MM).Methods:A total of 19 MM patients with BIPN were enrolled and Nux Vomica Capsule(NVC,0.4 g,thrice daily)were orally administrated for 30 days.Comparative analysis on parameters between pre-and post-therapy,including peripheral neuropathy(PN)grade,neurotoxicity score,Chinese medicine(CM)syndrome score,total neuropathy score(TNS),coagulation function,and serum nerve growth factor(NGF)levels were conducted.The adverse events were monitored.Results:In BIPN of MM patients who received NVC,PN grade was lowered,neurotoxicity score was obviously decreased(P 0.01),and both CM syndrome score and TNS were remarkably decreased(P<0.01).After the therapy,activated partial thromboplastin time was prolonged(P<0.01)and fibrinogen was declined(P<0.05),showing improvement in the hypercoagulable state of patients.No significant difference of NGF recovery degrees was detected between pre-and post-therapy(P>0.05).No evident adverse reactions were observed during the course of treatment.Conclusion:Strychnos nux-vomica L.has significantly effect with a good safety in treatment of BIPN in MM patients.