Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses.
Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses.
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DOI：
10.1158/1078-0432.ccr-11-1221
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发表时间：
2012-03-01
期刊：
影响因子：
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通讯作者：
Borrello I
中科院分区：
文献类型：
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作者：
Noonan K;Rudraraju L;Ferguson A;Emerling A;Pasetti MF;Huff CA;Borrello I
证明免疫调节药物来那度胺可用于复发性多发性骨髓瘤患者以增强疫苗反应。对接受过至少一种既往治疗的多发性骨髓瘤患者进行的早期临床试验。患者接受单药来那度胺治疗，并随机接受按不同时间表接种两次肺炎球菌七价结合疫苗（PCV）疫苗。队列 A 在开始使用来那度胺之前接受了第一次 PCV 疫苗接种，并在使用来那度胺期间接受了第二次疫苗接种。 B 组在服用来那度胺期间接受了两种疫苗接种。 B 组中的 PCV 特异性体液和细胞反应比 A 组中的更大，并且在骨髓中比在血液中更明显，这表明当两种疫苗与来那度胺同时施用时，可以实现最大的疫苗功效。具有临床骨髓瘤反应的患者表现出肿瘤特异性免疫反应的证据，其中骨髓瘤特异性 IFN-γ+ T 细胞增加，Th-17 细胞减少。这是第一个临床证据表明来那度胺可增强患者的疫苗反应和内源性抗肿瘤免疫力，因此可以作为癌症和可能的感染性疫苗的佐剂。
To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses. Early phase clinical trial of patients with multiple myeloma who received at least one prior therapy. Patients were treated with single-agent lenalidomide and randomized to receive two vaccinations with pneumococcal 7-valent conjugate vaccine (PCV) on different schedules. Cohort A received the first PCV vaccination prior to the initiation of lenalidomide and the second vaccination while on lenalidomide. Cohort B received both vaccinations while on lenalidomide. PCV-specific humoral and cellular responses were greater in cohort B than A and were more pronounced in the bone marrow than the blood, suggesting that maximal vaccine efficacy was achieved when both vaccines were administered concomitantly with lenalidomide. Patients with a clinical myeloma response showed evidence of a tumor-specific immune response with increases in myeloma-specific IFN-γ+ T cells and reductions in Th-17 cells. This is the first clinical evidence showing that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines.