Pandey Arjun, Roos Kim, Jiang Yidi, Mangoff Kathryn, Klein Gail, Forward Nick, Stewart Douglas, Laneuville Pierre, Bence-Bruckler Isabelle, Mangel Joy, Tomlinson George, Berinstein Neil L
Sunnybrook Health Sciences Centre Toronto Canada.
Sunnybrook Research Institute Toronto Canada.
EJHaem. 2024 Dec 12;6(1):e1062. doi: 10.1002/jha2.1062. eCollection 2025 Feb.
Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have an unmet medical need. The objective of this trial was to assess the efficacy and toxicities of a novel triple immunotherapy regimen-pembrolizumab, low-dose cyclophosphamide, and maveropepimut-S (MVP-S). This regimen was designed to activate tumor-specific T cells by targeting the tumor-associated antigen survivin with MVP-S and reducing two important T cell inhibitory pathways: T cell exhaustion and regulatory T cells with pembrolizumab and metronomic cyclophosphamide, respectively.
This was a single-arm Phase II clinical trial in 25 participants with R/R DLBCL-SPiReL trial (NCT03349450).
The median overall survival was 10.1 months and a third of participants survived over 2 years. Enhanced long-term survival was associated with favorable clinical characteristics and enhanced immune reactivity, as assessed by ELISpot and ISR-immune reactive responses. The regimen was well-tolerated with minimal Grade 3-4 toxicities.
Combination immunotherapy regimens such as this could offer a promising alternative to other treatments with significant toxicities for select patients.
复发/难治性弥漫性大B细胞淋巴瘤(R/R DLBCL)患者存在未满足的医疗需求。本试验的目的是评估一种新型三联免疫疗法方案——帕博利珠单抗、低剂量环磷酰胺和马韦罗培穆单抗-S(MVP-S)的疗效和毒性。该方案旨在通过MVP-S靶向肿瘤相关抗原生存素来激活肿瘤特异性T细胞,并分别通过帕博利珠单抗和节拍性环磷酰胺减少两条重要的T细胞抑制途径:T细胞耗竭和调节性T细胞。
这是一项针对25名R/R DLBCL患者的单臂II期临床试验——SPiReL试验(NCT03349450)。
中位总生存期为10.1个月,三分之一的参与者存活超过2年。通过ELISpot和ISR免疫反应评估,长期生存的提高与良好的临床特征和增强的免疫反应性相关。该方案耐受性良好,3-4级毒性最小。
这样的联合免疫疗法方案对于特定患者而言,可能是其他具有显著毒性的治疗方法的一个有前景的替代方案。