Bortezomib is a proven treatment for patients with multiple myeloma (MM), however, some patients achieve suboptimal responses or experience specific toxicities. As such, Masaki Ri, MD, PhD, from the Department of Hematology and Oncology at the Nagoya City University Hospital in Nagoya, Japan, and colleagues attempted to identify specific human leukocyte antigen (HLA) alleles associated with bortezomib–related toxicities and treatment response. The team was unable to identify a significant allele via multiple comparisons; however, they did note several candidates, including HLA-B*40:06 and HLA-DRB1*12:01.
The report in Cancer Science was still hopeful, suggesting that “HLA genotyping could serve as a potential biomarker for predicting bortezomib-induced toxicity and treatment response,” before the initiation of therapy.
The investigators performed HLA typing on 82 transplant–ineligible patients with newly diagnosed MM from a phase II study comparing less intensive regimens of melphalan, prednisolone, and bortezomib. Allele frequency was compared between groups and categorized according to toxicity grade and treatment response.
No HLA alleles were identified with significance, but the team listed several observations that identified potential candidates. For instance, the HLA-B*40:06 allele was more prevalent in patients with severe peripheral neuropathy than in those with less severe peripheral neuropathy (odds ratio [OR] = 6.76). Additionally, HLA-B*40:06, as well as HLA-DRB1*12:01, were more prevalent in patients with skin disorders than in those with less severe disorders (OR = 7.47 and OR = 5.55, respectively). Further, the HLA-DRB1*08:02 allele clustered in patients with pneumonitis (OR = 11.34). Lastly, complete responses were achieved in patients carrying HLA-DQB1*03:02, HLA-DQB1*05:01, and HLA-DRB1*01:01 alleles.
In short, though no specific HLA alleles were significantly associated with bortezomib treatment response and toxicities, the authors still theorized that HLA phenotypes could help identify higher-risk patients and inform the development of personalized treatment plans for patients with MM. They suggested that a study with a larger patient sample size is warranted to further investigate the allele candidates found in this study.