HLA genotyping in Japanese patients with multiple myeloma receiving bortezomib: An exploratory biomarker study of JCOG1105 (JCOG1105A1)

Masaki Ri, Shinsuke Iida, Dai Maruyama, Aya Sakabe, Ryo Kamei, Takuto Nakashima, Masahiro Tohkin, Satoshi Osaga, Kensei Tobinai, Noriko Fukuhara, Kana Miyazaki, Norifumi Tsukamoto, Hideki Tsujimura, Makoto Yoshimitsu, Kenichi Miyamoto, Kunihiro Tsukasaki, Hirokazu Nagai

Research output: Contribution to journalArticlepeer-review

Abstract

Bortezomib (Btz) shows robust efficacy in patients with multiple myeloma (MM); however, some patients experience suboptimal responses and show specific toxicities. Therefore, we attempted to identify specific HLA alleles associated with Btz-related toxicities and response to treatment. Eighty-two transplant-ineligible patients with newly diagnosed MM enrolled in a phase II study (JCOG1105) comparing two less intensive melphalan, prednisolone, plus Btz (MPB) regimens were subjected to HLA typing. The frequency of each allele was compared between the groups, categorized based on toxicity grades and responses to MPB therapy. Among 82 patients, the numbers of patients with severe peripheral neuropathy (PN; grade 2 or higher), skin disorders (SD; grade 2 or higher), and pneumonitis were 16 (19.5%), 15 (18.3%), and 6 (7.3%), respectively. Complete response was achieved in 10 (12.2%) patients. Although no significant HLA allele was identified by multiple comparisons, several candidates were identified. HLA-B*40:06 was more prevalent in patients with severe PN than in those with less severe PN (odds ratio [OR] = 6.76). HLA-B*40:06 and HLA-DRB1*12:01 were more prevalent in patients with SD than in those with less severe SD (OR = 7.47 and OR = 5.55, respectively). HLA-DRB1*08:02 clustered in the group of patients with pneumonitis (OR = 11.34). Complete response was achieved in patients carrying HLA-DQB1*03:02, HLA-DQB1*05:01, and HLA-DRB1*01:01 class II alleles. HLA genotyping could help predict Btz-induced toxicity and treatment efficacy in patients with MM, although this needs further validation.

Original languageEnglish
Pages (from-to)5011-5019
Number of pages9
JournalCancer science
Volume112
Issue number12
DOIs
Publication statusPublished - 2021 Dec

Keywords

  • HLA
  • Japanese
  • bortezomib
  • multiple myeloma
  • peripheral neuropathy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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