在首次缓解的情况下，化疗免疫疗法后接受自体干细胞移植的巩固性高剂量治疗是适应身体状况良好的边缘区淋巴瘤（MCL）患者的标准初步治疗；然而，在新疗法时代，治疗模式正在发展。Lenalidomide是一种已知用于治疗MCL的免疫调节剂。我们进行了一项单中心、研究者发起的二期临床研究，该研究纳入了高危MCL患者，并结合了不含自体干细胞移植巩固的免疫化疗中加入Lenalidomide的方案（NCT02633137）。患者接受了四个疗程的Lenalidomide-R-CHOP、两个疗程的R-HiDAC和六个疗程的R-lenalidomide。主要终点是3年无进展生存率。我们在每个治疗阶段以及治疗结束后6个月使用基于下一代测序（NGS）的检测方法测量了MRD。我们纳入了49名患者，其中47名患者的反应可评估。按意向治疗分析，总体反应和完全反应的比例相当，为88％（43/49），有1名患者病情稳定，研究期间有2名患者病情进展；3年无进展生存率为63％（未达到主要终点），并且根据TP53状态有所不同（WT为78％，ALT为38％，P = 0.043）。MRD状态是预后因素，可以预测R-HiDAC治疗和治疗结束后6个月的长期结果。在一种节省高剂量治疗的密集治疗方案中，我们在TP53野生型MCL患者中取得了良好的结果，包括高危情况。我们证实序贯MRD评估是一种强大的预后工具，在MCL患者中具有重要意义。

Chemoimmunotherapy followed by consolidative high-dose therapy with autologous stem cell rescue was a standard upfront treatment for fit patients with mantle cell lymphoma (MCL) in first remission; however, treatment paradigms are evolving in the era of novel therapies. Lenalidomide is an immunomodulatory agent with known efficacy in treating MCL. We conducted a single-center, investigator-initiated, phase II study of immunochemotherapy incorporating lenalidomide, without autologous stem cell transplant consolidation, enriching for patients with high-risk MCL (NCT02633137). Patients received four cycles of lenalidomide-R-CHOP, two cycles of R-HiDAC, and six cycles of R-lenalidomide. The primary endpoint was rate of 3-year progression-free survival. We measured MRD using an NGS-based assay after each phase of treatment and at 6 months following end-of-treatment. We enrolled 49 patients of which 47 were response evaluable. By intent-to-treat, rates of overall and complete response were equivalent at 88% (43/49), one patient with stable disease, and two patients had disease progression during study; 3-year progression-free survival was 63% (primary endpoint not met) and differed by TP53 status (78% WT versus 38% ALT, P = 0.043). MRD status was prognostic and predicted long-term outcomes following R-HiDAC and at 6 months following end-of-treatment. In a high-dose therapy-sparing, intensive approach, we achieved favorable outcomes in TP53-wildtype MCL, including high-risk cases. We confirmed that sequential MRD assessment is a powerful prognostic tool in patients with MCL.