Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois, USA
Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois, USA.
J Immunother Cancer. 2020 Jan;8(1). doi: 10.1136/jitc-2019-000286.
Progression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.
We performed a randomized study to evaluate two methods of Treg depletion in patients with MM undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 monoclonal antibody (basiliximab 20 mg IV) was administered on day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. Tregs were depleted from autologous stem cell (ASC) grafts with anti-CD25 microbeads and the CliniMACS device in the ex vivo Treg depletion (EVTRD) arm.
Fifteen patients were enrolled, five in each arm. The conditioning regimen was melphalan 200 mg/m. Primary objectives included assessments of efficiency of IVTRD/EVTRD, kinetics of Treg depletion and recovery following ASCT, and safety. EVTRD removed 90% of CD4CD25 cells from ASC grafts. IVTRD and EVTRD led to reductions in Treg frequency between days +7 and +90 post-transplant compared with the control (p=0.007 and p<0.001, respectively).
IVTRD and EVTRD are feasible and significantly reduce and delay Treg recovery post-ASCT for MM, and serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes.
NCT01526096.
多发性骨髓瘤（MM）患者在接受大剂量马法兰联合自体造血干细胞移植（ASCT）后病情进展，部分原因可能与免疫功能障碍有关。ASCT 后调节性 T（Treg）细胞迅速重建，并抑制针对骨髓瘤细胞的免疫反应。
我们进行了一项随机研究，以评估两种方法在接受 ASCT 的 MM 患者中清除 Treg 的效果。对照组患者不接受 Treg 清除，仅在 ASCT 后第 1 天静脉给予抗 CD25 单克隆抗体（巴利昔单抗 20mg IV）。在体内 Treg 清除（IVTRD）组中，ASCT 后第 1 天给予抗 CD25 单克隆抗体进行体内 Treg 清除；在体外 Treg 清除（EVTRD）组中，用抗 CD25 微珠和 CliniMACS 设备从自体干细胞（ASC）移植物中清除 Treg。
共纳入 15 例患者，每组 5 例。预处理方案为马法兰 200mg/m2。主要研究目的包括评估 IVTRD/EVTRD 的效率、ASCT 后 Treg 清除和恢复的动力学以及安全性。EVTRD 可从 ASC 移植物中清除 90%的 CD4+CD25+细胞。与对照组相比，IVTRD 和 EVTRD 分别导致移植后第 7 天至第 90 天 Treg 频率降低（p=0.007 和 p<0.001）。
IVTRD 和 EVTRD 是可行的，可显著减少和延迟 MM 患者 ASCT 后 Treg 的恢复，为使用移植后免疫疗法改善 ASCT 后结局提供了平台。
NCT01526096。
