Department of Hematology and Oncology, Nagoya City University Hospital, Nagoya, Japan.
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Cancer Sci. 2021 Dec;112(12):5011-5019. doi: 10.1111/cas.15158. Epub 2021 Oct 26.
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-B40:06 was more prevalent in patients with severe PN than in those with less severe PN (odds ratio [OR] = 6.76). HLA-B40:06 and HLA-DRB112:01 were more prevalent in patients with SD than in those with less severe SD (OR = 7.47 and OR = 5.55, respectively). HLA-DRB108:02 clustered in the group of patients with pneumonitis (OR = 11.34). Complete response was achieved in patients carrying HLA-DQB103:02, HLA-DQB105:01, 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.
硼替佐米（Btz）在多发性骨髓瘤（MM）患者中显示出强大的疗效；然而，一些患者的反应不理想，并表现出特定的毒性。因此，我们试图确定与 Btz 相关毒性和治疗反应相关的特定 HLA 等位基因。82 名不适合移植的新诊断 MM 患者参加了一项比较两种不太强化的美法仑、泼尼松加 Btz（MPB）方案的 II 期研究（JCOG1105），对这些患者进行了 HLA 分型。根据毒性分级和对 MPB 治疗的反应，将两组之间的等位基因频率进行比较。在 82 名患者中，严重周围神经病变（PN；2 级或更高级别）、皮肤疾病（SD；2 级或更高级别）和肺炎的患者分别为 16 例（19.5%）、15 例（18.3%）和 6 例（7.3%）。10 例（12.2%）患者达到完全缓解。尽管多次比较未发现显著的 HLA 等位基因，但仍发现了一些候选基因。与较轻的 PN 相比，严重 PN 患者中 HLA-B40:06 更为常见（比值比[OR] = 6.76）。与较轻的 SD 相比，SD 患者中 HLA-B40:06 和 HLA-DRB112:01 更为常见（OR = 7.47 和 OR = 5.55）。HLA-DRB108:02 在肺炎患者中聚集（OR = 11.34）。携带 HLA-DQB103:02、HLA-DQB105:01 和 HLA-DRB1*01:01 Ⅱ类等位基因的患者达到完全缓解。HLA 基因分型有助于预测 MM 患者中 Btz 诱导的毒性和治疗效果，尽管这需要进一步验证。
