Kiesewetter Barbara, Simonitsch-Klupp Ingrid, Kornauth Christoph, Dolak Werner, Lukas Julius, Mayerhoefer Marius E, Raderer Markus
Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Hematol Oncol. 2018 Feb;36(1):62-67. doi: 10.1002/hon.2472. Epub 2017 Aug 22.
Lenalidomide is an active agent for the treatment of MALT lymphoma. Recently, high expression levels of cereblon (CRBN) and MUM1 have been associated with better response rates in multiple myeloma treated with lenalidomide. However, there are no data on CRBN and MUM1 expression in MALT lymphoma. In the current study, we have systematically investigated a potential correlation of CRBN/MUM1 immunohistochemical expression and response to lenalidomide-based therapy in a series of 46 patients with MALT lymphoma treated at the Medical University Vienna 2009 to 2014. In total, 28% (13/46) of biopsy specimens derived from gastric tissues, while 72% (33/46) originated from extragastric MALT lymphoma. In terms of CRBN, 54% showed high expression (CRBN+, ≥50% positive cells); the remaining 46% were classified as low expression (CRBN-). In contrast to other reports, there was a non-significant trend towards worse response rates in CRBN+ (68% versus 86%, P = 0.161). Relapse rates (P = 0.592) and PFS (P = 0.306) did not differ between CRBN+/CRBN-, but all 3 patients progressing on lenalidomide were CRBN+ and both patients completely lacking CRBN expression responded to treatment. Concerning MUM1, 62% were MUM1-negative (MUM1-) and 38% positive (MUM1+). There was no difference in response to lenalidomide by MUM1-status (MUM1+ 71% versus MUM1- 79%, P = 0.546) and also relapse rates (P = 0.828) and PFS (P = 0.681) did not differ. Interestingly, a subgroup analysis of gastric lymphoma revealed a significantly better PFS for CRBN- and MUM1- patients, respectively (both P < 0.05). To conclude, there was no significant difference in response to lenalidomide between patients with low or high expression of CRBN/MUM1 in a general population of MALT lymphoma, and immunohistochemical CRBN/MUM1 assessment cannot be recommended in the clinical routine.
来那度胺是治疗黏膜相关淋巴组织（MALT）淋巴瘤的一种有效药物。最近，在接受来那度胺治疗的多发性骨髓瘤患者中，脑啡肽酶（CRBN）和多发性骨髓瘤锌指蛋白1（MUM1）的高表达水平与更高的缓解率相关。然而，关于MALT淋巴瘤中CRBN和MUM1表达的数据尚无报道。在本研究中，我们系统地调查了2009年至2014年在维也纳医科大学接受治疗的46例MALT淋巴瘤患者中，CRBN/MUM1免疫组化表达与基于来那度胺治疗反应之间的潜在相关性。总共，28%（13/46）的活检标本来自胃组织，而72%（33/46）起源于胃外MALT淋巴瘤。就CRBN而言，54%显示高表达（CRBN+，≥50%阳性细胞）；其余46%被归类为低表达（CRBN-）。与其他报道相反，CRBN+患者的缓解率有变差的非显著趋势（68%对86%，P = 0.161）。CRBN+/CRBN-之间的复发率（P = 0.592）和无进展生存期（PFS，P = 0.306）没有差异，但在来那度胺治疗中进展的所有3例患者均为CRBN+，而完全缺乏CRBN表达的2例患者对治疗有反应。关于MUM1，62%为MUM1阴性（MUM1-），38%为阳性（MUM1+）。MUM1状态对来那度胺的反应没有差异（MUM1+为71%对MUM1-为79%，P = 0.546），复发率（P = 0.828）和PFS（P = 0.681）也没有差异。有趣的是，胃淋巴瘤的亚组分析显示，CRBN-和MUM1-患者的PFS分别显著更好（均P < 0.05）。总之，在MALT淋巴瘤总体人群中，CRBN/MUM1低表达或高表达患者对来那度胺的反应没有显著差异，不建议在临床常规中进行免疫组化CRBN/MUM1评估。
