利妥昔单抗联合ESHAP方案治疗复发非霍奇金淋巴瘤临床观察

目的 观察利妥昔单抗(Rituximab)联合ESHAP方案(依托泊苷、甲基强的松龙、顺铂、阿糖胞苷)治疗复发的CD20阳性B细胞性非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)的临床疗效及安全性.方法 回顾性分析我院以利妥昔单抗联合ESHAP方案及单用ESHAP方案治疗复发的CD20阳性B细胞性非霍奇金淋巴瘤的临床资料.32例复发的CD20阳性的B细胞非霍奇金淋巴瘤患者,随机分为利妥昔单抗联合ESHAP方案组(治疗组)及单用ESHAP方案组(对照组),每21 d为1个周期,重复治疗.全部32例患者完成4个周期化疗后进行疗效评价.结果 治疗组完全缓解率(CR)为37.5%,总有效率为87.5%;对照组分别为25%、56.3%,两组有效率有显著性差异(P<0.05).两组患者不良反应主要为轻中度骨髓抑制、脱发和消化道反应.不良反应发生率相近(P>0.05),均可耐受.治疗组1例(6.25%)出现利妥昔单抗输注相关的不良反应,经对症处理后好转.结论 利妥昔单抗联合ESHAP方案治疗复发的CD20阳性B细胞性非霍奇金淋巴瘤安全有效,患者耐受良好,应推荐使用.     

美罗华治疗B细胞性非霍奇金淋巴瘤临床观察

目的观察利妥昔单抗（美罗华）联合CHOP方案治疗非霍奇金淋巴瘤的疗效及毒副反应。方法9例经病理组织学证实为CD20阳性的B细胞非霍奇金淋巴瘤患者接受利妥昔单抗375mg／m^2,静脉滴注,每3周1次。共4～6次。其间联用CHOP方案治疗4—6个疗程。结果9例患者治疗后,完全缓解6例,部分缓解2例,无变化1例,总有效率88．9％。所有患者均未见严重的不良反应。结论利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤临床疗效较好,毒副反应较小。     

利妥昔单抗联合CHOP方案治疗初治B细胞非霍奇金淋巴瘤的疗效观察

目的探讨利妥昔单抗联合CHOP治疗初治B细胞非霍奇金淋巴瘤(NHL)的近期疗效和毒副反应。方法 65例初治B细胞NHL随机分为两组,观察组35例接受利妥昔单抗联合CHOP方案治疗,对照组30例仅接受CHOP方案化疗,并比较观察两组的近期疗效和毒副反应。结果观察组总有效率及临床获益率分别为71.43%、94.29%,均高于对照组的50.00%、70.00%,差异有统计学意义(P均0.05)。观察组出现3例利妥昔单抗相关的轻度发热。两组化疗相关毒副反应均较轻,且发生率比较差异均无统计学意义(P均0.05)。所有毒副反应均未影响治疗的顺利进行。结论利妥昔单抗联合CHOP方案治疗初治B细胞NHL疗效较单纯CHOP方案好,但毒副反应未增加,值得临床推广应用。     

利妥昔单抗联合CHOP方案治疗NHL的临床疗效评价

目的:探讨利妥昔单抗联合环磷酰胺、阿霉素、长春新碱、强的松(CHOP)方案治疗非霍奇金淋巴瘤(NHL)的疗效及安全性。方法:62例NHL患者,其中32例接受利妥昔单抗联合CHOP方案治疗者为治疗组;30例接受CHOP方案治疗者为对照组。每周期21d,共进行6个疗程。结果:治疗组与对照组总有效率分别为75.00%、60.00%(P<0.05);2组毒副作用基本相似(P>0.05);治疗组的生活质量改善情况明显高于对照组(P<0.05)。结论:利妥昔单抗联合CHOP方案对NHL患者有较好疗效,且化疗药物的毒副作用未见增加。     

加拿大通报利妥昔单抗致肠梗阻和穿孔的不良事件

2006年11月10日,霍夫曼-罗氏有限公司与加拿大卫生部共同发布信息,通报了与利妥昔单抗(Rituximab,商品名:Rituxan)相关的肠梗阻和胃肠穿孔的不良事件。利妥昔单抗是一种嵌合型抗CD20单克隆抗体,用于治疗B细胞非霍奇金淋巴瘤(NHL)和类风湿性关节炎(RA)。基于上市后及临床研究数据,罗氏公司与加拿大卫生部强调以下事实和建议:(1)已观察到患者使用利妥昔单抗出现腹痛、肠梗阻和穿孔的病例,甚至导致一些患者死亡。大部分(包括所有死亡报告)发生于使用利妥昔单抗与化疗联合治疗NHL期间。(2)利妥昔单抗与这些病例间的因果关系尚未建立。(3)…     

利妥昔单抗联合CHOP方案治疗非霍奇金淋巴瘤的疗效观察

目的探讨利妥昔单抗联合CHOP方案治疗非霍奇金淋巴瘤(NHL)的临床疗效。方法收集2008年1月至2012年1月,我院收治的NHL患者58例,随机分为观察组与对照组,观察组予以利妥昔单抗联合CHOP方案治疗,对照组单独应用CHOP方案治疗,比较两组的临床疗效。结果观察组的治疗总有效率为89.7%,显著高于对照组的72.4%(P<0.05);观察组不良反应与对照组无明显差异(P>0.05)。结论妥昔单抗联合CHOP方案治疗非霍奇金淋巴瘤疗效显著,不增加不良反应,值得推广应用。     

利妥昔单抗在儿童血液病中的应用

抗CD20人鼠嵌合型单克隆抗体利妥昔单抗可通过多种机制杀伤B细胞,目前广泛应用于治疗CD20阳性淋巴瘤以及某些免疫相关性疾病,如免疫性血小板减少性紫癜、自身免疫性溶血性贫血、Evans综合征、移植后淋巴增殖性疾病和系统性红斑狼疮等.本文综述利妥昔单抗在儿童血液病中的临床应用.     

以B细胞为靶标的类风湿性关节炎的治疗

类风湿性关节炎(RA)是人类的一种系统性自身免疫性疾病。利妥昔单抗(rituximab)作为一种针对B细胞特异性抗原CD20的人-鼠嵌合单克隆抗体,是首个以B细胞为靶标治疗RA的药物。根据美国类风湿学学会(ACR)20,50,70反应标准,甲氨蝶呤与利妥昔单抗联用能显著减轻类风湿因子血清阳性的RA的体征和症状,且比较安全。在一项双盲对照的Ⅱ期临床试验中,贝利单抗(belimumab)有较好的耐受性和良好的效应。     

利妥昔单抗联合化疗及造血干细胞移植治疗难治性弥漫大B细胞淋巴瘤临床观察

目的 探讨利妥昔单抗联合化疗及造血干细胞移植治疗难治性弥漫大B细胞淋巴瘤(DL-BCL)的临床疗效和安全性评价.方法 回顾性分析1例应用利妥昔单抗联合化疗及造血干细胞移植治疗的难治性DLBCL患者的临床资料,并结合文献复习对此方法治疗难治性DLBCL的临床疗效和安全性进行评价.结果 1例难治性DLBCL患者先后予各种方案化疗后未获得缓解,改为利妥昔单抗联合化疗及造血干细胞移植治疗后,造血重建顺利,取得完全缓解,相关并发症控制较好,随访至2010年11月1日一直长期无病生存.结论 利妥昔单抗联合化疗及造血干细胞移植治疗难治性DLBCL是安全有效的治疗手段.

Abstract：

Objective To report the clinical efficacy and safety of rimximab combined with autologous hematopoietic stem cell transplantation in a case of refractory diffuse large B cell lymphoma.Methods Clinical data of a case in rituximab combined chemotherapy and hematopoietic stem eell transplantation for refractory difluse large B cell lymphonm was analyzed.The efficacy and safety for the program with literature review were evaluated.Results The patient did not achieve remission with various chemotherapy regimens.After using autologous hematopoietic stem cell translplantation with rituximab,the hematopoietic was rebuilded successfuly,symptoms were complete reIieved,complications wero well controlled.Follow-up to November 1,2010,tIle patient was discasc-free survival.Conclusion Rituximab combined with autologous hematopoietie stem cell transplantation is a safe and effective treatment of refractory diffuse large B cell lymphoma.     

西妥昔单抗联合化疗治疗转移性结直肠癌的观察

目的 观察西妥昔单抗联合化疗方案治疗转移性结直肠癌的近期疗效及不良反应.方法 11例经病理组织学确诊的转移性结直肠癌患者,给予西妥昔单抗联合FOLFOX方案治疗,西妥昔单抗首次给予负荷剂量400 mg/m2,每周给予维持剂量为250 mg/m2.结果 全组11例患者中,完全缓解1例,部分缓解5例,稳定2例,进展3例,有效率54.5％ (6/11),疾病控制率为72.7％ (8/11),中位肿瘤进展时间为8.4个月.主要不良反应为痤疮样皮疹(9例)和腹泻(6例).5例合并肝转移患者中经治疗后1例转化为可切除病灶.患者耐受良好,无治疗相关死亡.结论 西妥昔单抗联合FOLFOX方案治疗转移性结直肠癌疗效较好,不良反应多可耐受.     

Rituximab in autologous stem cell transplantation for follicular lymphoma

Contamination of stem cell harvests with residual tumor cells is a significant problem hampering the success of autologous peripheral blood stem cell transplantation in non-Hodgkin's lymphoma (NHL). Techniques have therefore been introduced to attempt to remove these cells, either in vivo, prior to harvesting, or ex vivo, before reinfusion into the patient. Rituximab is a human-mouse chimeric anti-CD20 monoclonal antibody that has been administered to patients prior to stem cell harvesting, to purge the blood of residual malignant cells. Clinical studies have shown that rituximab is safe to use during stem cell mobilization since administration did not adversely affect the yield of CD34+ stem cells or the functional capability of these progenitors. Rituximab was also effective in purging stem cell harvests of malignant cells. Translocation of the bcl-2 gene was found in a significantly smaller proportion of stem cell harvests from patients who had received a purging infusion of rituximab than controls. Rituximab may also be useful as salvage therapy following post-transplant relapse or as maintenance therapy for patients in remission. Prospective randomized trials will ultimately define the role of rituximab in the autologous transplantation setting.     

Rituxan immunotherapy and zevalin radioimmunotherapy in the treatment of non-Hodgkin's lymphoma

Immunotherapy with the anti-CD20 monoclonal antibody rituximab has been shown in clinical trials to be effective in the treatment of both indolent and aggressive non-Hodgkin's lymphomas (NHL). Recent studies have demonstrated improved clinical benefit with extended dose and maintenance therapies in patients with indolent lymphomas and chronic lymphocytic leukemia. Rituximab's label was recently expanded to include treatment of bulky disease, retreatment of patients previously treated with rituximab, and an eight-week extended treatment schedule. Rituximab has also been effectively combined with chemotherapy, resulting in higher response rates and longer response durations in randomized trials in patients with aggressive lymphoma. Studies continue to evaluate and expand the role of rituximab in the treatment of NHL, including its use in combined immunotherapy approaches and autologous stem cell transplant as well as in the treatment of autoimmune disorders. Radioimmunotherapy with the rituximab and ibritumomab tiuxetan (Zevalin) regimen was recently approved for the treatment of relapsed or refractory low-grade, follicular or CD20+ transformed NHL, including rituximab refractory follicular NHL. The regimen is delivered on an outpatient basis over the course of a week. Studies are currently exploring sequential dose therapy, radioimmunotherapy with rituximab maintenance, and ibritumomab tiuxetan radioimmunotherapy as part of autologous stem cell transplant. Current understanding of the mechanisms of action of rituximab and the use of rituximab and ibritumomab tiuxetan in patients with indolent and aggressive NHL will be discussed.     

Ten years of rituximab in NHL

Background: Rituximab, a chimeric mouse/human monoclonal antibody targeting the pan-B-cell antigenic marker CD20, was the first monoclonal antibody licensed for use in the treatment of cancer. Objective: This review focuses on the impact of rituximab in the treatment of patients with B-cell non-Hodgkin lymphoma (NHL). Methods: Three key areas related to the use of rituximab in B-cell NHL are discussed: mechanism of action, clinical efficacy in both indolent and aggressive disease, and safety of its use as both monotherapy and in combination with chemotherapy. Results/conclusions: Rituximab has demonstrated significant clinical efficacy in the treatment of NHL, particularly in combination with chemotherapy, and its use has revolutionized the treatment of both indolent and aggressive B-cell NHL over the past decade. Furthermore, consistent toxicity data have been obtained with a safe and tolerable profile in most patients.     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents. The latter was a randomised comparison of eight cycles of CHOP plus rituximab 375 mg/m(2) intravenously (one dose per cycle) versus CHOP alone in previously untreated elderly patients (60 to 80 years of age) with diffuse large B-cell lymphoma. In this pivotal trial, 2-year event-free and overall survival were significantly higher with rituximab plus CHOP, and there was no increase in clinically significant adverse effects compared with CHOP alone. Treatment with rituximab is generally well tolerated, particularly in terms of adverse haematological effects and serious or opportunistic infections relative to standard chemotherapy. Infusion-related reactions occur in the majority of patients treated with rituximab; these are usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions. In approximately 10% of patients, however, severe infusion-related reactions develop (e.g. bronchospasm, hypotension). These reactions are usually reversible with appropriate interventions and supportive care but there have been rare reports of fatalities. CONCLUSIONS: Clinical trials with rituximab indicate that the drug has broad application to B-cell malignancies, although further clarification is needed to determine its optimal use in many of these clinical settings. Importantly, rituximab in combination with CHOP chemotherapy has emerged as a new treatment standard for previously untreated diffuse large B-cell lymphoma, at least in elderly patients. Compared with conventional chemotherapy, rituximab is associated with markedly reduced haematological events such as severe neutropenia, as well as associated infections. Rituximab may be particularly suitable for elderly patients or those with poor performance status, and its tolerability profile facilitates its use in combination with cytotoxic drugs. PHARMACODYNAMIC PROPERTIES: Rituximab is a mouse/human chimaeric IgG(1)-kappa monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B lymphocytes. Although treatment with rituximab induces lymphopenia in most patients, typically lasting about 6 months, a full recovery of B lymphocytes in the peripheral blood is usually seen 9-12 months after therapy, as CD20 is not expressed on haematopoietic stem cells. CD20 is, however, expressed on >90% of B-cell non-Hodgkin's lymphomas (NHL) and to a lesser degree on B-cell chronic lymphocytic leukaemia (CLL) cells.Although not fully elucidated, the cytotoxic effects of rituximab on CD20-positive malignant B cells appears to involve complement-dependent cytotoxicity, complement-dependent cellular cytotoxicity, antibody-dependent cellular cytotoxicity and induction of apoptosis. In addition, in vitro data indicate that rituximab sensitises tumour cells to the effects of conventional chemotherapeutic drugs. PHARMACOKINETIC PROPERTIES: Serum rituximab concentrations increased in proportion to dose across a wide range of single- and multiple-dose intravenous regimens in patients with B-cell NHL. When administll NHL. When administered at a dose of 375 mg/m(2) once weekly for 4 weeks in a pivotal trial in patients with relapsed or refractory indolent B-cell NHL (follicular or small lymphocytic subtypes), peak serum concentrations essentially doubled from the first (239.1 mg/L) to the fourth (460.7 mg/L) infusion, while elimination half-life (t(1/2)) increased from 76.3 to 205.8 hours (3.2 to 8.6 days). The concomitant increase in serum rituximab concentrations and t(1/2) with each successive infusion may be due, at least in part, to the elimination of circulating CD20-positive B cells and reduction or saturation of CD20-binding sites after the initial infusions of rituximab. The pharmacokinetic properties of rituximab are also characterised by wide inter-individual variability, and serum drug concentrations that are correlated with clinical response. Although pharmacokinetic data are limited in patients with aggressive forms of NHL, such as diffuse large B-cell lymphoma, rituximab appears to have a similar pharmacokinetic profile in these patients to that in patients with indolent B-cell NHL. The pharmacokinetics of rituximab are also reported to be similar whether the drug is administered with or without cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. THERAPEUTIC USE: A number of studies have demonstrated efficacy of intravenous rituximab in patients with various lymphoid malignancies of B-cell origin, including indolent (e.g. follicular lymphoma) and aggressive (e.g. diffuse large B-cell lymphoma) forms of NHL, and CLL, but the drug has not yet been approved for use in CLL, and approved indications in NHL vary between countries. In the US, for example, rituximab is available for the treatment of patients with low-grade or follicular, relapsed or refractory, CD20-positive B-cell NHL. In Europe, the drug has similar approval for relapsed or refractory follicular NHL as in the US, but has also been approved for use in combination with CHOP chemotherapy for the most common aggressive form of NHL (CD20-positive, diffuse large B-cell lymphoma). Rituximab was approved for these indications primarily on the basis of results from two pivotal trials. In Japan, rituximab has been approved for indolent B-cell NHL and mantle cell lymphoma (an aggressive form of B-cell NHL), primarily on the basis of results of a Japanese phase II trial. Indolent NHL: Results of several studies evaluating rituximab 375 mg/m(2) once weekly for 4 weeks in patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic lymphomas) showed objective response (OR) rates ranging from approximately 40-60% in those receiving the drug for relapsed or refractory indolent B-cell NHL, and slightly higher (50-70%) for those receiving rituximab as first-line therapy. In a pivotal trial in 166 patients with relapsed or refractory low-grade or follicular B-cell NHL, intent-to-treat (ITT) analysis showed an OR rate of 48%, and a projected median time to progression of 13 months.Encouraging data are also emerging on the use of rituximab in combination with chemotherapeutic agents (e.g. CHOP, fludarabine-containing regimens) or other drugs (e.g. interferon-alpha2a) in previously untreated patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic subtypes). Rates for OR were consistently around 95%, with the majority being complete responses (CRs). Follow-up data from a study in 40 patients with low-grade or follicular B-cell NHL treated with rituximab plus CHOP as first-line therapy showed that responses were durable with a progression-free survival and median duration of response >5 years.Bcl-2 gene rearrangement (t14;18) occurs in malignant cells in up to 85% of patients with follicular lymphoma, and minimal residual disease in peripheral blood and bone marrow can be monitored using polymerase chain reaction (PCR). In several studies assessing blood and/or bone marrow, rituximab has achieved molecular response (conversion from PCR-positive to PCR-negative bcl-2 status) in at least half of the patients. Aggressive NHL: Studies with rituximab as monotherapy in aggressive B-cell NHL, a potentially curable disorder, have generally been restricted to patients with relapsed or recurrent disease, since CHOP has traditionally been the standard first-line treatment regimen. However, promising results from phase II monotherapy studies prompted further clinical investigation of rituximab in conjunction with chemotherapy. Thus, most studies with rituximab in patients with aggressive forms of B-cell NHL have involved combination therapy, including a pivotal randomised trial comparing eight cycles of standard CHOP therapy plus rituximab 375 mg/m(2) (one dose per cycle) versus CHOP alone in 399 previously untreated elderly patients (60-80 years of age) with diffuse large B-cell lymphoma. Results of the pivotal trial showed a clear advantage for rituximab plus CHOP versus CHOP in terms of event-free survival (primary endpoint) at 2 years (57% vs 38%, p < 0.001). Overall survival at 2 years (70% vs 57%, p < 0.01) and CR rate (76% vs 63%, p < 0.01) were also higher with the rituximab-CHOP combination. Other, smaller trials with rituximab in combination with CHOP or other chemotherapeutic regimens, either as first-line therapy or for patients with relapsed or refractory aggressive B-cell NHL, have also shown promising results in terms of clinical response rates.CLL: In relatively small trials (n < 40) conducted primarily in patients with relapsed or refractory B-cell CLL, rituximab monotherapy (various regimens) achieved OR rates of 23-45%, with median duration of response ranging from approximately 3-10 months. (ABSTRACT TRUNCATED)     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab (MabThera, Rituxan) is an anti-CD20 monoclonal antibody that induces lysis and apoptosis of normal and malignant human B cells, and sensitises malignant B cells to the cytotoxic effect of chemotherapy. In phase III trials in patients with indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL), intravenous rituximab in combination with chemotherapy was more effective as first- or second-line therapy than chemotherapy alone in providing tumour remission and patient survival. Likewise, in patients with chronic lymphocytic leukaemia (CLL), rituximab in combination with chemotherapy appeared more effective than chemotherapy alone as either first- or second-line treatment. In addition, rituximab maintenance therapy was shown to significantly prolong tumour remission and patient survival in patients with indolent B-cell NHL or CLL. The combination of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was cost effective as first-line therapy for advanced-stage diffuse large B-cell NHL compared with CHOP alone. Rituximab, either alone or in combination with chemotherapy, was generally well tolerated in patients with NHL or CLL. Overall, rituximab in combination with chemotherapy, is a valuable option for first- and second-line therapy in patients with advanced-stage indolent or aggressive B-cell NHL, and possibly those with B-cell CLL, and is included in current treatment guidelines for these indications. The drug is also potentially useful as maintenance therapy in patients with indolent B-cell NHL or CLL.     

Rituximab: an innovative therapy for non-Hodgkin's lymphoma.

The epidemiology, etiology, classification, and treatment of non-Hodgkin's lymphoma (NHL) are reviewed, and rituximab, a newly available therapy, is discussed. NHL comprises a group of lymphoproliferative disorders the frequency of which continues to rise. Although many classification systems exist for identifying specific histological subtypes, NHL is generally divided into indolent (low-grade) and aggressive (intermediate- and high-grade) forms. Low-grade NHL is characterized by a slowly progressive, continually relapsing course, with eventual transformation to a more rapidly progressive form that is usually fatal. Several options are available for the management of indolent NHL; none is curative. Rituximab, a human-mouse monoclonal antibody that targets the CD20 antigen expressed in over 90% of B-cell NHLs, provides an alternative to conventional chemotherapy that is relatively safe and effective. In a Phase III trial involving 166 patients with relapsed or refractory low-grade B-cell NHL, rituximab produced an overall response of 48%, with 20 of 80 responders still in remission more than 36 months after treatment. Study results in patients with bulky disease and those requiring retreatment have also been encouraging. Most adverse effects associated with rituximab are mild to moderate. Infusion-related reactions occur more commonly during initial infusions and in patients with evidence of increased tumor burden but can be effectively managed with premedication, supportive care, and adjusted infusion rates. Hematologic effects are generally mild and transient, and adverse immune responses are rare. Rituximab is an alternative to conventional chemotherapy for the treatment of relapsed or refractory low-grade or follicular CD20-positive B-cell NHL.     

利妥昔单抗治疗类风湿关节炎的临床研究进展

利妥昔单抗是一种特异性针对CD20分子的基因工程抗体,能与B淋巴细胞表面的CD20结合,并通过补体介导的细胞毒作用等机制对B淋巴细胞进行特异性清除,从而达到治疗作用.利妥昔单抗最初作为抗淋巴瘤药物首先获得美国FDA认证,近年来被应用于类风湿关节炎等自身免疫病的治疗,取得了较好的疗效.现对其治疗类风湿关节炎的作用机制、临床应用和研究进展做一综述.     

Rituximab therapy for indolent non-Hodgkin's lymphoma

Indolent non-Hodgkin's lymphomas (NHLs) are essentially incurable with current treatments. Rituximab is a specific anti-CD20 chimeric monoclonal antibody against the CD20 antigen, which is stably expressed on most B-cells (from the pre-B-cell stage). Compared with chemotherapy, rituximab has an excellent tolerability profile, making it a good therapeutic option for patients with indolent NHL. In the pivotal study for rituximab, patients with relapsed or refractory indolent or follicular lymphoma (FL) had an overall response rate of 50%. There is evidence that first-line rituximab therapy may be associated with better response rates; in previously untreated FL with a low tumor burden, rituximab monotherapy has produced an overall response rate of 73%. Attempts to improve response rates to rituximab by increasing the dose or frequency of dosing showed that the addition of four extra infusions of rituximab (in addition to the standard treatment schedule) resulted in an overall response rate of 76% in patients with FL. Augmenting rituximab with cytokines is also an option for increasing response rates in patients with indolent NHL. In a trial by the Nordic Lymphoma Study Group in patients with previously untreated or first-relapse indolent NHL, who had stable disease or a partial response after four doses of rituximab, 48% of the patients treated with rituximab plus interferon-alpha2a achieved a complete response. A further option is to combine rituximab with chemotherapy. Interim analyses from the East German Study Group have shown that rituximab plus mitoxantrone, chlorambucil and prednisolone (MCP) resulted in overall response rates of 89% in patients with untreated indolent lymphoma. Rituximab is therefore an excellent treatment option both as first-line and as salvage therapy for patients with indolent NHL.     

Mechanism of action of rituximab

Rituximab, the humanized chimeric anti-CD20 monoclonal antibody, represents a powerful tool for treating B-cell malignancies and is licensed for the treatment of relapsed or chemorefractory low-grade or follicular non-Hodgkin's lymphoma (NHL). It has a unique mode of action and can induce killing of CD20+ cells via multiple mechanisms. The direct effects of rituximab include complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and the indirect effects include structural changes, apoptosis, and sensitization of cancer cells to chemotherapy. In vitro studies have made a significant contribution to the understanding of these mechanisms of action and have led to the development of innovative and effective treatment strategies to optimize patient response. The most significant of these strategies is the combination of rituximab and CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), which is proving a highly effective combination in the treatment of NHL. However, all patients do not respond equally well to rituximab, and in vitro studies have identified a possible mechanism of resistance involving the anti-complement inhibitors CD55 and CD59. Neutralizing antibodies to CD55 and CD59 can overcome resistance to rituximab-mediated complement-mediated cytotoxicity in vitro. This paper overviews our understanding of the mechanisms of action of rituximab and identifies how this knowledge could be applied in a clinical setting to maximize response in both sensitive and resistant patients.