Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma

Background: The goal of this retrospective study was to compare the efficacy and toxicity of lenalidomide–dexamethasone (len/dex) vs. melphalan–prednisone–lenalidomide (MPR) as upfront therapy for newly diagnosed elderly patients with myeloma. Methods: Data from 51 patients enrolled in an Italian phase I/II trial and treated with MPR were analyzed and compared with data from 38 patients, seen at the Mayo Clinic, treated with len/dex and enrolled in phase II/III trials. Results: On intention‐to‐treat analysis, time to progression (median: 24.7 vs. 27.5 months in MPR and len/dex groups, respectively, P = 0.903), progression‐free survival (median: 24.7 vs. 27.5 months in MPR and len/dex groups, respectively, P = 0.926), and overall survival (2‐yr overall survival: 86.2% in MPR vs. 89.1% in len/dex, P = 0.730) were not significantly different between the two groups. Results were confirmed when the analysis was restricted to MPR and len/dex matched pair mates. Hematologic grade 3–4 toxicities were more common with MPR (neutropenia: 66.7% vs. 21.1%, P < 0.001; thrombocytopenia: 31.4% vs. 2.6%, P < 0.001). Grade 3–4 gastrointestinal events (13.2% vs. 3.9%, P = 0.132), thrombotic events (13.2% vs. 5.9%, P = 0.279), and fatigue (10.5% vs. 3.9%, P = 0.395) were more common with len/dex. Conclusions: Results show that both MPR and len/dex are efficacious regimens for elderly patients with myeloma. Randomized trials are needed to confirm these results.     

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。     

Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study

Low baseline NK-cell counts (NKCCs) in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a poor prognosis. The REMARC phase III trial (NCT01122472) showed that lenalidomide maintenance prolonged PFS in rituximab–chemotherapy responders. We conducted a REMARC ancillary study analysing the impact of lenalidomide maintenance on the prognostic value of low NKCCs. Blood samples from 335 elderly French patients enrolled in the REMARC trial were analysed by flow cytometry to obtain NKCCs at diagnosis (n = 220), at randomization (n = 186) and/or six months after randomization (n = 184). Baseline NKCCs < 100 cells/μl were associated with shorter PFS and OS (HRs = [2.2 (1.4, 3.3), p < 0.001] and [2.8 (1.7, 4.5), p < 0.001], respectively), independently of aaIPI. In a competing risk analysis, low NKCCs at baseline were associated with a higher risk of relapse/progression (p = 0.0025), but not of death without progression (p = 0.33). Lenalidomide did not affect the prognosis value of low baseline NKCCs (p  = 0.6349). Similar results were obtained for low NKCCs at randomization. Our results demonstrate that low NKCCs at baseline and post rituximab–chemotherapy are robust prognostic factors in DLBCL and reveal that lenalidomide has no impact on this parameter. Other therapeutic strategies aiming at improving NK-cell function could improve outcomes in DLBCL.