Immunomodulatory treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents “IMiDs” thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.     

Longer‐term follow‐up and outcome by tumour cell proliferation rate (Ki‐67) in patients with relapsed/refractory mantle cell lymphoma treated with lenalidomide on MCL‐001(EMERGE) pivotal trial

Patients with mantle cell lymphoma (MCL) generally respond to first‐line immunochemotherapy, but often show chemoresistance upon subsequent relapses, with poor outcome. Several studies of the immunomodulator, lenalidomide, have demonstrated its activity in MCL including the MCL‐001 study in relapsed/refractory patients who had failed defined prior therapies of anthracyclines or mitoxantrone, cyclophosphamide, rituximab and also bortezomib. We present here the long‐term efficacy follow‐up of the prospective phase II MCL‐001 study (N = 134), including new exploratory analyses with baseline Ki‐67 (MIB1), a biological marker of tumour proliferation. With longer follow‐up, lenalidomide showed a 28% overall response rate [ORR; 8% complete response (CR)/CR unconfirmed (CRu)]. Median duration of response (DOR), progression‐free survival and overall survival were 16·6, 4·0 and 20·9 months, respectively. Myelosuppression continued to be the most common grade 3/4 toxicity. Several studies of MCL patients treated with chemotherapy, rituximab and bortezomib have shown an inverse association between survival and Ki‐67. Ki‐67 data in 81/134 MCL‐001 patients showed similar ORRs in both low (<30% or <50%) versus high (≥30% or ≥50%) Ki‐67–expressing groups, yet lower Ki‐67 levels demonstrated superior CR/CRu, DOR and survival outcomes. Overall, lenalidomide showed durable efficacy with a consistent safety profile in heavily pretreated, relapsed/refractory MCL post‐bortezomib.     

来那度胺的合成

N-苄氧羰基-L-谷氨酰胺经酯化和氢化脱保护制得中间体L-谷氨酰胺甲酯(4),另用2-甲基-3-硝基苯甲酸(5)经酯化和溴化制得另一中间体2-溴甲基-3-硝基苯甲酸甲酯(7).4与7经缩合、氢化还原、分子内环合制得来那度胺,总收率约33%(以5计).     

新型免疫调节药来那度胺的药理及临床研究进展

来那度胺是一种新型免疫调节药，主要用于治疗多赶性骨髓瘤和骨髓增生异常综合征，一本品为沙利度胺的衍生物，通过相列小的结构修饰，提高药效，减少不良尺应。现对其作用机制、药动学、临床应用、不良反应、药物相互作用等做一综述。     

沙利度胺的研究及临床应用新进展

沙利度胺及其衍生物来那度胺在治疗骨髓瘤及骨髓增生异常综合征方面有着确切的疗效,已经通过了美国FDA的审批。近年来,沙利度胺在治疗实体瘤、血液恶性肿瘤以及其他炎性疾病方面的研究层出不穷。本文以近2年来国内外有关沙利度胺研究的最新文献报道为基础,对沙利度胺在临床前及临床方面研究的最新进展进行了综述。     

维持治疗方案改善多发性骨髓瘤患者的生存与预后

目的:分析多发性骨髓瘤（multiple myeloma,MM）患者维持治疗及方案与无进展生存期（PFS）、总生存期（OS）的联系,为临床指导治疗。方法:回顾性分析2015年03月至2020年09月在我院住院治疗的所有MM患者,总结其随访结果,分析是否维持治疗以及维持治疗方案对PFS以及OS的影响。结果:维持治疗的患者PFS与OS均优于不维持治疗者（P=0.000,P=0.002）。以来那度胺为主的维持治疗方案疗效最佳（PFS:P=0.000,OS:P=0.005）。单因素分析结果显示MM ISS分期与PFS有关(P=0.040),多因素分析结果提示MM ISS分期和是否维持治疗及维持治疗方案均对PFS有显著影响(P=0.033,P=0.017,P=0.027),是否维持治疗对OS有影响(P=0.016)。结论:维持治疗有利于MM患者生存。以来那度胺为主的维持治疗方案疗效佳,可作为首选。     

Angiogenesis inhibitors in the treatment of prostate cancer

Importance of the field: Prostate carcinoma is the most common non-cutaneous malignancy in U.S. men. The efficacy of docetaxel and prednisone in metastatic castrate-resistant prostate cancer (mCRPC) has been shown to improve overall survival; however, its effect is not durable, highlighting the need for new therapies.

Areas covered in this review: We will review the development of some of the leading compounds with direct and indirect antiangiogenic activity in prostate cancer including antibodies to VEGF and its receptors, small-molecule inhibitors of downstream signaling, immunomodulatory drugs with antiangiogenic activity, and compounds thought to directly inhibit or destroy vascular endothelial cells.

What the reader will gain: The reader will gain a basic understanding of the role of angiogenesis in prostate cancer growth and metastasis. Current and potential targets of angiogenesis and their corresponding drugs under development for prostate cancer are discussed.

Take home message: There are now multiple early-phase clinical trials of antiangiogenic agents alone or in combination in prostate cancer. Several of these agents are now in Phase III development. Combined therapy with two antiangiogenic compounds may improve the activity of either compound alone. Multiple targets in the angiogenesis pathway continue to be elucidated and should remain an active area of investigation for the treatment of prostate cancer.