Daratumumab: Beyond Multiple Myeloma

Daratumumab (DARA) is the biological name of an Immunoglobulin G1k human monoclonal antibody. DARA the first-in-class therapy targeting CD38 expressing- plasma cells (PC) and plasma blasts. It has been approved for the treatment of multiple myeloma. It is also being examined in the setting of other hematologic malignancies. As DARA targets PCs, it could potentially be used to treat many other disease processes that are antibody mediated. In fact, several case reports and case series report experiences of using DARA to treat a variety of antibody-mediated disorderss. The aim of this review is to present a summary of the literature thus far regarding the application of DARA beyond its uses in multiple myeloma and other hematologic diseases. Specifically, we address uses of DARA as an immunologic modulator in various antibody mediated processes.     

Preclinical Comparison of Near-Infrared-Labeled Cetuximab and Panitumumab for Optical Imaging of Head and Neck Squamous Cell Carcinoma

Purpose

Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC).

Procedures

Antigen specificities and in vitro imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (n?=?22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology.

Results

Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (K _D?=?0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW in vitro. In vivo, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19: p?=?0.08 SPY, p?=?0.48 Pearl; SCC-1: p?=?0.77 SPY, p?=?0.59 Pearl; paired t tests).

Conclusions

There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC.     

CD38 Monoclonal Antibodies in Relapsed/Refractory Multiple Myeloma

Multiple myeloma remains an incurable disease. CD38 is a desirable target for therapeutic antibodies, including isatuximab and daratumumab. Nurse practitioners working in the oncology setting play an essential role in the management and education of patients receiving these therapies. This article provides a practical overview of anti-CD38 antibodies for oncology nurse practitioners, including infusion reaction mitigation, laboratory interpretation, and clinical decision making.     

多发性骨髓瘤的影像诊断

目的：为了提高对多发性骨髓瘤(multiple myeloma，MM)的影像诊断水平。材料与方法：选择经骨髓涂片证实的MM49例，对其治疗前49例的多部位X线平片表现和其中16例的脊柱磁共振成像(Magnetic resonance imaging，MRI)表现进行回顾性分析，归纳其影像特点。结果：有X线表现的42例(85．71％)，其中颅骨阳性发现29例，脊柱阳性发现21例，骨盆阳性发现17例。肋骨阳性发现16例，肱骨阳性发现15例，股骨阳性发现10例，此外，锁骨阳性发现5例，肩胛骨阳性发现4例。脊柱MRI有阳性发现16例(100％)，多数病变呈长T1、长T2信号。结论：MM的X线表现比较典型，X线平片检查在MM的诊断上有重要作用。MRI对MM的早期骨髓内侵润敏感，对早期疑似病例在X线平片检查的基础上做MRI检查，可提高对MM的影像诊断水平。     

多发性骨髓瘤的影像学评估

多发性骨髓瘤具有独特的骨病表现,由于破骨细胞激活和成骨细胞功能抑制导致溶骨性破坏和严重骨质疏松。骨病严重程度对患者生活质量和生存均有负面影响。普通X线检出骨病的灵敏度很低,CT的灵敏度虽明显提高,但难以检出骨外病变。功能性影像方法(主要包括磁共振弥散加权成像和正电子发射断层显像/计算机体层成像)不仅能发现早期溶骨病灶,且在评估全身肿瘤负荷和缓解后微小残留病变方面更有优势。本文将对这些方面的进展进行综述。     

多发性骨髓瘤治疗进展

对多发性骨髓瘤（Multiple Myeloma，MM）治疗进展综述如下。     

CD138/Syndecan-1在多发性骨髓瘤免疫表型中的意义

为了建立多发性骨髓瘤（MM）免疫分型的测定方法,分析各种抗原的表达特点,并分选高纯度原代骨髓瘤细胞,应用CD45/侧向角（SSC）设门的三色免疫荧光流式细胞术（FCM）测定18例MM患者、20例急性白血病（AL）患者和7例正常人骨髓免疫分型特点;应用抗CD138和免疫磁珠从MM患者的骨髓中分选骨髓瘤细胞.结果表明：骨髓瘤细胞CD45阴性或弱阳性,SSC介于有核红细胞和中性粒细胞之间,CD138和CD38均阳性,T、B细胞及髓系抗原多为阴性,CD56阳性率为83.3%,HLA-DR阳性率为44.4%.与MM患者相比,AL患者CD138均阴性,而CD38为100%阳性,CD56阳性率为25%.正常人CD138和CD56均为阴性.磁珠分选获得的原代骨髓瘤细胞纯度在73%-95%之间,平均为86%.结论：CD45/SSC设门的三色免疫荧光FCM是测定MM免疫分型的稳定可靠方法,CD138是骨髓瘤细胞表面较为特异的抗原标志,应用抗CD138和免疫磁珠可以获得高度富集的原代骨髓瘤细胞.     

First-line Daratumumab in Addition to Chemotherapy for Newly Diagnosed Multiple Myeloma Patients Who are Transplant Ineligible: A Cost-Effectiveness Analysis

PurposeDaratumumab is a standard-of-care treatment for newly diagnosed multiple myeloma (NDMM). According to the ALCYONE trial, the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) provides significantly longer overall survival and progression-free survival than bortezomib, melphalan, and prednisone (VMP) in patients with NDMM. However, considering the high price of daratumumab, it is necessary to conduct further research on its efficacy and cost. This study evaluated the cost-effectiveness, from the US payer perspective, of D-VMP vs VMP in the first-line setting for patients with NDMM who are not eligible for autologous stem cell transplantation.MethodsA Markov model was developed to estimate the lifetime cost and effectiveness of VMP with or without daratumumab as the first-line therapy for patients with NDMM. Univariable sensitivity analysis and probabilistic sensitivity analysis were performed to address the model robustness and uncertainty. Expected value of perfect information analysis was conducted to explore the uncertainty of decision-making and future costs.FindingsD-VMP provides an additional 2.417 quality-adjusted life years (QALYs), at a cost of $30,893 per QALY. Sensitivity analysis revealed that the transition probability of progression-free survival in D-VMP strategy, the price of daratumumab, and body weight of the patient influenced the model results most strongly. Probabilistic sensitivity analysis showed that D-VMP versus VMP has a 90.8% probability of being cost-effective at the $150,000/QALY willingness-to-pay (WTP) threshold. The population expected value of perfect information was $2150 million at a WTP threshold of $50,000/QALY and $1481 million at $100,000/QALY.ImplicationsIn this study, D-VMP was estimated to be cost-effective compared with VMP for patients with NDMM at a WTP threshold of $150,000/QALY.     

A Multimode Optical Imaging System for Preclinical Applications In Vivo: Technology Development, Multiscale Imaging, and Chemotherapy Assessment

Purpose

Several established optical imaging approaches have been applied, usually in isolation, to preclinical studies; however, truly useful in vivo imaging may require a simultaneous combination of imaging modalities to examine dynamic characteristics of cells and tissues. We developed a new multimode optical imaging system designed to be application-versatile, yielding high sensitivity, and specificity molecular imaging.

Procedures

We integrated several optical imaging technologies, including fluorescence intensity, spectral, lifetime, intravital confocal, two-photon excitation, and bioluminescence, into a single system that enables functional multiscale imaging in animal models.

Results

The approach offers a comprehensive imaging platform for kinetic, quantitative, and environmental analysis of highly relevant information, with micro-to-macroscopic resolution. Applied to small animals in vivo, this provides superior monitoring of processes of interest, represented here by chemo-/nanoconstruct therapy assessment.

Conclusions

This new system is versatile and can be optimized for various applications, of which cancer detection and targeted treatment are emphasized here.     

核素骨显像对多发性骨髓瘤诊断的研究

目的研究核素骨显像对诊断多发性骨髓瘤(Multiple Myeloma,MM)的价值.方法50例经临床确诊为MM的患者,均行全身骨显像、X线平片检查、骨髓穿刺涂片及相关实验室检查,结合骨穿及其它检查结果,分析核素骨显像对MM的诊断意义,并对部分患者进行追踪观察,评价核素骨显像对MM治疗效果的动态监测作用.结果50例MM患者中,核素骨显像阳性38例,X线阳性34例.对8例患者进行追踪,治疗后复查核素骨显像示骨质代谢异常的范围缩小,骨髓穿刺证实病情好转.结论核素骨显像在MM的诊断中有重要价值,可作为MM患者的常规检查之一.核素骨显像对MM疗效的监测有一定的指导意义.     

CD269和CD317在多发性骨髓瘤中的表达及临床意义

目的 通过研究多发性骨髓瘤(multiple myeloma,MM)患者骨髓细胞中CD269和CD317的抗原表达情况,分析其与反映MM疾病进展实验室指标的相关性,并评估其在临床诊疗中的价值。方法 采用病例对照性研究,选取63例初诊MM患者作为研究组,35例缺铁性贫血(IDA)患者作为对照组,应用流式细胞术检测两组患者骨髓血中CD269和CD317表达率以及63例MM患者骨髓血中其他抗原(CD19,CD20,CD56,CD117)的表达率; 分别检测MM患者血清血红蛋白(Hb)、血清β2微球蛋白(β2-MG)和乳酸脱氢酶(LDH)的浓度; 统计学分析CD269和CD317的表达水平并比较与其他实验室相关指标检测水平的相关性。结果 研究组和对照组的CD269阳性率分别为(86.6±2.35)%vs(4.33±1.69)%,差异具有统计学意义(t=4.256,P<0.05); CD317阳性率分别为(71.42±0.62)% vs(8.32±3.89)%,差异具有统计学意义(t=3.102,P<0.05); 在其他抗原表达上,CD269和CD317阳性组CD56的表达水平显著高于阴性组(t=4.032,P<0.05),而CD117的表达水平阳性组显著低于阴性组(t=2.832,P<0.05),CD19,CD20的表达两组间差异无统计学意义(P>0.05); MM患者CD269和CD317表达水平与CD56表达水平呈正相关(r=0.392,P<0.05),与CD117表达水平呈负相关(r=-0.210,P<0.05)。Hb含量阳性组明显低于阴性组(t=3.012,P<0.05),血清β2-MG 水平阳性组低于阴性组(t=2.024,P<0.05),血清LDH水平两组间差异无统计学意义(P>0.05); MM患者CD269和CD317表达水平与血清Hb含量呈负相关(r=-0.212,P<0.05),与血清β2-MG水平呈负相关(r=-0.312,P<0.05)。结论 MM患者骨髓细胞高表达CD269和CD317; MM的病情进展与患者CD56升高或CD117降低有关; 与血清Hb含量和β2-MG水平降低有关,有助于判断病情严重程度及评估预后。     

经抗-CD38单抗Daratumumab治疗的多发性骨髓瘤患者产生抗-Leb 1例

目的 探讨经抗-CD38单抗Daratumumab治疗的多发性骨髓瘤患者抗-Leb的鉴定及输血策略.方法 血型鉴定、直接抗球试验、交叉配血及抗体鉴定均采用试管法.为了排除抗-CD38的干扰,凝聚胺试管法用于交叉配血试验.结果 患者血型为BRhD(+),直接抗球试验阴性,患者血浆中存在无临床意义的IgM性质抗-Leb.患...     

Clini MACS纯化自体外周血CD34+造血干细胞移植治疗多发性骨髓瘤1例

多发性骨髓瘤（ＭＭ）在自体造血于细胞移植（ＡＳＣＴ）后复发的主要原因,除骨髓清除治疗后患者体内存有残留的肿瘤细胞外,还与干细胞采集物中的肿瘤细胞污染有关［１］。移植动员治疗及细胞因子应用后,伴随ＣＤ３４＋造血干细胞的增加循环中肿瘤细胞也增加。分选外周血干细胞（ＰＢＳＣ）,即可富集ＣＤ３４＋造血干细胞,又可清除骨髓瘤细胞的污染［２］。我们利用此技术,对多发性骨髓瘤病人的自体外周血干细胞移植物进行了体外净化。１ 资料与方法１．１病人情况 中年男性,有左肩胛骨及胸骨上段隆起约３ｃｍ,质硬有压病;骨扫描示…     

多发性骨髓瘤的影像诊断(附84 例报告)

目的 研究多发性骨髓瘤的影像学表现及其诊断价值。方法 分析８４例多发生性骨髓瘤的影像表现。所有病人均摄Ｘ线照片,２２例ＣＴ和１０例脊椎ＭＲＩ。结果 在Ｘ线片上,１２例正常,４例骨质疏松,６８例骨质破坏,２３例伴软组织肿块。ＣＴ示１００％均有骨破坏,８例伴软组织肿块。１０例脊椎ＭＲＩ均示病变呈长Ｔ１、长Ｔ２信号。弥漫型３例,灶型２例,弥漫加灶型３例,“盐和胡椒”型２例。２例增强后示病变和增厚的硬脊膜