Usmani Saad Z, Khan Imran, Chiu Christopher, Foureau David, Druhan Lawrence J, Rigby Katherine, Casneuf Tineke, Sasser A Kate
Levine Cancer Institute/Carolinas Health Care System, 1021 Morehead Medical Drive, Charlotte, NC 28204 USA.
2Janssen Research & Development, LLC, Raritan, NJ USA.
Exp Hematol Oncol. 2018 Feb 7;7:3. doi: 10.1186/s40164-018-0096-7. eCollection 2018.
Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy.
A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation. The patient's disease, which was considered high risk with a deletion of chromosome 17p, advanced quickly and was triple refractory 2 years after diagnosis leaving few treatment options. He was treated with daratumumab monotherapy in the SIRIUS clinical trial resulting in a stringent complete response and clearance of minimal residual disease. The duration of the patient's clinical response is now over 3.5 years without relapse, compared with a median of 7.6 months for similarly treated patients. The patient's immunophenotype revealed CD8 T-cell expansion, clonal expansion of the T-cell receptor repertoire, and decreases in regulatory T cells during daratumumab therapy, suggesting a robust adaptive immune response. This immune response was still present 32 months into daratumumab therapy.
The results from this case report showed that a patient with advanced multiple myeloma, who had exhausted all treatment options with existing regimens, mounted an ongoing, deep, and durable response to daratumumab monotherapy. Further investigation of the immunologic profile provided additional patient-level evidence of an immunomodulatory mechanism of action of daratumumab. ClinicalTrials.gov Identifier number NCT01985126. Submitted 22 July 2013.
达雷妥尤单抗是一种人源CD38单克隆抗体，具有直接的抗肿瘤和免疫调节作用机制，在接受过一种或多种先前治疗方案的多发性骨髓瘤患者中，作为单药治疗或与既定方案联合使用时均显示出临床获益。
一名男性患者，2011年诊断为多发性骨髓瘤时70岁，在接受包括自体干细胞移植在内的五线治疗后复发。该患者的疾病被认为具有17号染色体短臂缺失的高危特征，进展迅速，诊断后2年出现三重难治性，几乎没有治疗选择。他在SIRIUS临床试验中接受了达雷妥尤单抗单药治疗，结果达到严格完全缓解并清除微小残留病。该患者的临床缓解持续时间现已超过3.5年且未复发，而类似治疗患者的中位缓解持续时间为7.6个月。患者的免疫表型显示在达雷妥尤单抗治疗期间CD8 T细胞扩增、T细胞受体库的克隆性扩增以及调节性T细胞减少，提示有强大的适应性免疫反应。这种免疫反应在达雷妥尤单抗治疗32个月时仍然存在。
该病例报告的结果表明，一名晚期多发性骨髓瘤患者在现有方案用尽所有治疗选择后，对达雷妥尤单抗单药治疗产生了持续、深度和持久的反应。对免疫特征的进一步研究提供了更多关于达雷妥尤单抗免疫调节作用机制的患者层面证据。ClinicalTrials.gov标识符编号NCT01985126。2013年7月22日提交。
