lenalidomide

来那度胺
  • 文章类型: Journal Article
    弥漫性大B细胞淋巴瘤(DLBCL)约占美国每年B细胞非霍奇金淋巴瘤新病例的24%。高达50%的患者复发或难以接受标准一线治疗(R/R)。R-CHOP.抗CD19单克隆抗体他法西他单抗,联合来那度胺(LEN),是针对R/RDLBCL移植不合格患者的NCCN首选方案,并在美国(2020年7月)获得了加速批准,并在欧洲(2021年8月)和其他国家获得了有条件的营销授权,基于L-MIND研究的数据。他他他单抗的推荐剂量为12mg/kg,通过静脉输注,与LEN25mg联合给药12个周期,然后是他法他他单抗单药治疗,直到疾病进展或不可接受的毒性。Tafasitamab+LEN与R/RDLBCL患者的持续反应相关。大多数临床上显着的治疗相关不良事件可归因于LEN,可以通过剂量调整和支持疗法进行管理。我们为常规临床实践中使用他法他单抗和LEN治疗的R/RDLBCL患者提供管理指南。包括老年患者和肾和肝损害患者,以及关于患者教育的建议,作为全面患者参与计划的一部分。我们的建议包括如果不能耐受推荐剂量的患者需要以减少的剂量给予LEN。在特殊患者人群中,塔法他单抗不需要剂量修改。
    Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 24% of new cases of B-cell non-Hodgkin lymphoma in the US each year. Up to 50% of patients relapse or are refractory (R/R) to the standard first-line treatment option, R-CHOP. The anti-CD19 monoclonal antibody tafasitamab, in combination with lenalidomide (LEN), is an NCCN preferred regimen for transplant-ineligible patients with R/R DLBCL and received accelerated approval in the US (July 2020) and conditional marketing authorization in Europe (August 2021) and other countries, based on data from the L-MIND study. The recommended dose of tafasitamab is 12 mg/kg by intravenous infusion, administered in combination with LEN 25 mg for 12 cycles, followed by tafasitamab monotherapy until disease progression or unacceptable toxicity. Tafasitamab + LEN is associated with durable responses in patients with R/R DLBCL. The majority of clinically significant treatment-associated adverse events are attributable to LEN and can be managed with dose modification and supportive therapy. We provide guidelines for the management of patients with R/R DLBCL treated with tafasitamab and LEN in routine clinical practice, including elderly patients and those with renal and hepatic impairment, and advice regarding patient education as part of a comprehensive patient engagement plan. Our recommendations include LEN administration at a reduced dose if required in patients unable to tolerate the recommended dose. No dose modification is required for tafasitamab in special patient populations.
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    文章类型: Journal Article
    Multiple myeloma is the second most common blood cancer in New Zealand with higher incidence in Māori and Pacific Island populations. It remains an incurable disease but the rapidly changing treatment landscape has led to improved outcome. In response to recent changes in funding of anti-myeloma therapy in New Zealand, the New Zealand Myeloma Interest Group has reviewed the latest literature and updated the treatment pathway of transplant-eligible patients with newly diagnosed multiple myeloma.
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  • 文章类型: Practice Guideline
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  • 文章类型: Comparative Study
    欧洲白血病网(ELN)治疗骨髓增生异常综合征(MDS)的指南将异质性MDS亚组与许多治疗选择联系起来,从最佳支持治疗到异基因干细胞移植(alloSCT)。然而,目前尚不清楚坚持指南建议是否能提高生存率.杜塞尔多夫MDS注册表的庞大数据库使我们能够解决这个问题。我们首先进行了一项回顾性分析,包括1698名患者(队列1),我们回顾性地应用了ELN指南。我们将根据指南治疗的患者与偏离指南的患者进行了比较,要么是因为他们接受了某种治疗,尽管不推荐,要么是因为他们没有接受这种治疗,尽管他们是合格的。我们还对381名患者(队列2)进行了一项前瞻性研究,这些患者在我们部门就诊并接受了基于指南的专家建议。再一次,我们比较了后续指南依从和非依从治疗的影响.对于大多数治疗选择(最佳支持治疗,来那度胺,低甲基化剂,低剂量化疗,和强化化疗),我们发现,在队列1中,坚持ELN指南并不能改善生存率.当通过MDS专家提供的基于指南的治疗建议(队列2)前瞻性地加强患者管理时,情况也是如此。唯一的例外是alloSCT和铁螯合(ICT)。按照建议接受ICT和alloSCT的患者的表现明显优于符合条件但接受其他治疗的患者。我们的分析强调了大多数MDS疗法对生存的影响有限,并建议在所有合适的候选人中采用alloSCT。图形抽象。
    The European Leukemia Net (ELN) guidelines for treatment of myelodysplastic syndromes (MDS) connect heterogeneous MDS subgroups with a number of therapeutic options ranging from best supportive care to allogeneic stem cell transplantation (alloSCT). However, it is currently unknown whether adherence to guideline recommendations translates into improved survival. The sizeable database of the Duesseldorf MDS Registry allowed us to address this question. We first performed a retrospective analysis including 1698 patients (cohort 1) to whom we retrospectively applied the ELN guidelines. We compared patients treated according to the guidelines with patients who deviated from it, either because they received a certain treatment though it was not recommended or because they did not receive that treatment despite being eligible. We also performed a prospective study with 381 patients (cohort 2) who were seen in our department and received guideline-based expert advice. Again, we compared the impact of subsequent guideline-adherent versus non-adherent treatment. For the majority of treatment options (best supportive care, lenalidomide, hypomethylating agents, low-dose chemotherapy, and intensive chemotherapy), we found that adherence to the ELN guidelines did not improve survival in cohort 1. The same was true when patient management was prospectively enhanced through guideline-based treatment advice given by MDS experts (cohort 2). The only exceptions were alloSCT and iron chelation (ICT). Patients receiving ICT and alloSCT as recommended fared significantly better than those who were eligible but received other treatment. Our analysis underscores the limited survival impact of most MDS therapies and suggests to pursue alloSCT in all suitable candidates. Graphical abstract.
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  • 文章类型: Journal Article
    Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI.
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  • 文章类型: Journal Article
    The development of novel agents for treating multiple myeloma (MM) has markedly improved the treatment outcome and has caused a major paradigm shift in treatment strategies. In Japan, bortezomib and lenalidomide have been approved for the initial treatment; additionally, seven novel drugs, including next-generation proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors, and monoclonal antibodies, have been approved for relapsed and/or refractory MM treatment. Of these novel agents, daratumumab-containing regimens have been reported to induce a deep response, such as minimal residual disease-negative status, even in relapsed patients. Thus, compared with the initial therapy, many efficacious choices are available for treatment at the time of MM relapse; and salvage therapy is currently considered to be the most important treatment strategy for MM. In clinical practice, it is desirable to consider patient, disease, and therapeutic factors to make an optimal treatment decision for each patient.
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  • 文章类型: Journal Article
    Renal impairment (RI) is a common complication of multiple myeloma (MM), which is presented as chronic kidney disease (CKD) or acute kidney injury (AKI). The typical pathological feature is cast nephropathy. Presently international system staging (ISS) is used in evaluating MM. Although the classic Durie-Salmon staging system could be still used in clinical practice, it may miss out some patients with renal impairment. For evaluations of RI in MM patients with CKD, it\'s recommended to assess the estimated glomerular filtration rate (eGFR) by creatinine based formula CKD-epidemiology collaboration (EPI) or modification of diet in renal disease(MDRD) and to stage the renal injuries according to 2013 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines. For MM patients with AKI, KDIGO AKI guidelines is recommended for evaluation. Renal biopsy is not a routine procedure in all MM patients. It\'s necessary for patients presenting with glomerular injuries such as albuminuria > 1 g/24 h to eliminate immunoglobulin associated amyloidosis (AL) and monoclonal immunoglobulin deposition disease (MIDD). The effective treatment of MM can reduce serum light chain concentration and improve renal function. The basis of the RI treatment in MM is bortizomib-based regimen, which does not require dosage adjustment in patients with dialysis or renal insufficiency. Thalidomide and lenalidomide are two major immunomodulators in MM treatment. Thalidomide can be used effectively in RI patients without dosage adjustment while lenalidomide should be used cautiously in patients with mild or moderate RI with dosage adjustment and serum toxicity surveillance. High-dose therapy (HDT) and autologous peripheral blood stem cell transplantation (APBSCT) can be therapeutical options for RI patients younger than 65 y, and they should be considered more prudently in patients with severe renal insufficiency (GFR<30 ml/min). For patients who are not suitable for the treatment mentioned above, they can be treated with conventional chemotherapy, including VAD (vincristine, adriamycin and dexamethasone), MP (mephalan and prednisolone) and high-dose dexamethasone regimen. Adequate hydration (at least 3 litres of fluid intake a day or 2 L·m(-2)·d(-1)) and correcting reversible causes of RI are key points for the supportive care. Renal replacement therapy (more often hemodialysis) should be started in patients with severe AKI and end stage renal disease (ESRD). High flux or high cut-off membrane are recommended because routine hemodialysis could not remove the serum free light chain (sFLC) effectively. Plasmapheresis (PE) is recommended for patients with hyperviscosity syndrome or cast nephropathy presented with AKI, which may help to increase the dialysis-independency.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    Therapeutic advancements following the introduction of autologous stem cell transplantation and \'novel\' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians.
    A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review.
    Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients\' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide.
    In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options.
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  • 文章类型: Journal Article
    Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used \'off-label\'. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first-line or second-line topical therapeutic option. Antimalarials are recommended as first-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first-line treatment in highly active and/or severe CLE. Second- and third-line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy-refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B-cell- or interferon α-targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.
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