Memorial Sloan Kettering Cancer Center, New York, New York.
University of California San Francisco, San Francisco, California.
Clin Cancer Res. 2023 Dec 1;29(23):4784-4796. doi: 10.1158/1078-0432.CCR-23-0235.
Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating multiple myeloma-reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (auto-HCT).
In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared with control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of multiple myeloma-specific immunity at 1-year posttransplant.
The study enrolled 203 patients, with 140 randomized posttransplantation. Vaccine production was successful in 63 of 68 patients. At 1 year, rates of CR were 52.9% (vaccine) and 50% (control; P = 0.37, 80% CI 44.5%, 61.3%, and 41.6%, 58.4%, respectively), and rates of VGPR or better were 85.3% (vaccine) and 77.8% (control; P = 0.2). Conversion to CR at 1 year was 34.8% (vaccine) and 27.3% (control; P = 0.4). Vaccination induced a statistically significant expansion of multiple myeloma-reactive T cells at 1 year compared with before vaccination (P = 0.024) and in contrast to the nonvaccine arm (P = 0.026). Single-cell transcriptomics revealed clonotypic expansion of activated CD8 cells and shared dominant clonotypes between patients at 1-year posttransplant.
DC/MM fusion vaccination with lenalidomide did not result in a statistically significant increase in CR rates at 1 year posttransplant but was associated with a significant increase in circulating multiple myeloma-reactive lymphocytes indicative of tumor-specific immunity. Site-specific production of a personalized cell therapy with centralized product characterization was effectively accomplished in the context of a multicenter cooperative group study. See related commentary by Qazilbash and Kwak, p. 4703.
树突状细胞（DC）/多发性骨髓瘤（MM）融合疫苗接种已被证明可在自体造血细胞移植（auto-HCT）后诱导循环多发性骨髓瘤反应性淋巴细胞的扩增和临床反应的巩固。
在这项随机的 II 期试验（NCT02728102）中，我们评估了 DC/MM 融合疫苗接种、GM-CSF 和来那度胺维持治疗与 GM-CSF 和来那度胺对照组或单独来那度胺维持治疗对移植后 1 年时临床反应率和多发性骨髓瘤特异性免疫诱导的影响。
该研究纳入了 203 例患者，其中 140 例在移植后进行了随机分组。68 例患者中有 63 例成功生产疫苗。在 1 年时，完全缓解（CR）率分别为 52.9%（疫苗组）和 50%（对照组；P=0.37，80%CI 44.5%，61.3%，和 41.6%，58.4%），非常好的部分缓解（VGPR）或更好的缓解率分别为 85.3%（疫苗组）和 77.8%（对照组；P=0.2）。1 年内转换为 CR 的比例分别为 34.8%（疫苗组）和 27.3%（对照组；P=0.4）。与接种前相比，疫苗接种在 1 年时可显著扩增多发性骨髓瘤反应性 T 细胞（P=0.024），与非疫苗组相比也有显著差异（P=0.026）。单细胞转录组学揭示了移植后 1 年时，激活的 CD8 细胞的克隆扩增和患者之间共享的优势克隆型。
在移植后 1 年时，DC/MM 融合疫苗接种联合来那度胺并未显著提高 CR 率，但与循环多发性骨髓瘤反应性淋巴细胞的显著增加相关，表明存在肿瘤特异性免疫。在多中心合作组研究的背景下，成功地实现了个性化细胞治疗的局部生产和集中产品特征描述。请参阅 Qazilbash 和 Kwak 的相关评论，第 4703 页。
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