Internal Medicine, Division of Hematology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, Netherlands.
Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, Netherlands.
Ann Hematol. 2021 Jan;100(1):181-187. doi: 10.1007/s00277-020-04303-z. Epub 2020 Oct 28.
Disease relapse is an important problem after allogeneic stem cell transplantations in multiple myeloma (MM). To test the hypothesis that natural killer (NK) cell alloreactivity in the setting of a haploidentical stem cell transplantation (haploSCT) can reduce the risk of myeloma relapse, we performed a small prospective phase 2 study in which we transplanted poor-risk MM patients using a killer cell immunoglobulin-like receptor (KIR)-ligand mismatched haploidentical donor. Patients received bone marrow grafts after reduced-intensity conditioning, with post-transplantation cyclophosphamide (PTCY) graft-versus-host-disease (GVHD) prophylaxis. The primary endpoint was 1.5-year progression-free survival (PFS); stopping rules were installed in case interim results made a benefit of 50% PFS at 1.5 years unlikely. After inclusion of 12 patients, of which 9 were evaluable for the primary endpoint, all patients relapsed within a median time of 90 days. All except 1 patient showed engraftment, with a median time to neutrophil recovery of 18 (12-30) days. The study was prematurely terminated based on the predefined stopping rules after the inclusion of 12 patients. With this small study, we show that in chemo-resistant myeloma patients, NK cell KIR-mismatch is not superior to conventional alloSCT. This strategy, however, can serve as a platform for new treatment concepts.Clinical Trial Registry: NCT02519114.
疾病复发是多发性骨髓瘤（MM）异基因干细胞移植后一个重要问题。为了验证自然杀伤（NK）细胞同种异体反应性在单倍体干细胞移植（haploSCT）背景下可以降低骨髓瘤复发风险的假设，我们进行了一项小型前瞻性 2 期研究，使用杀手细胞免疫球蛋白样受体（KIR）配体错配的单倍体供体移植高危 MM 患者。患者接受减强度预处理后接受骨髓移植，并进行移植后环磷酰胺（PTCY）移植物抗宿主病（GVHD）预防。主要终点为 1.5 年无进展生存（PFS）；如果中期结果使 1.5 年时 50%的 PFS 获益不太可能，则安装停止规则。纳入 12 例患者后，其中 9 例可评估主要终点，所有患者均在中位数 90 天内复发。除 1 例患者外，所有患者均出现植入，中性粒细胞恢复的中位数时间为 18（12-30）天。在纳入 12 例患者后，根据预设的停止规则，该研究提前终止。通过这项小型研究，我们表明在化疗耐药性骨髓瘤患者中，NK 细胞 KIR 错配并不优于常规 alloSCT。然而，这种策略可以作为新治疗概念的平台。临床试验注册：NCT02519114。
