BACKGROUND Marginal zone lymphoma(MZL)is an indolent subtype of non-Hodgkin lymphoma(NHL),which is rare clinically with severe rashes as the initial symptom.CASE SUMMARY This study reports a case of MZL with generaliz...BACKGROUND Marginal zone lymphoma(MZL)is an indolent subtype of non-Hodgkin lymphoma(NHL),which is rare clinically with severe rashes as the initial symptom.CASE SUMMARY This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge.First-line treatment with rituximab combined with zanubrutinib had poor effects.However,after switching to obinutuzumab combined with zanubrutinib,the case was alleviated,and the rashes disappeared.CONCLUSION For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody(mAb)combination therapy,switching to a type II anti-CD20 mAb combination regimen may be considered.This approach may provide a new perspective in the treatment of MZL.展开更多
Backgrounds:GALLIUM is a global phase Ⅲ study that demonstrated significant improvements in progression-free survival(PFS)for obinutuzumab plus chemotherapy(G-chemo)vs.rituximab plus chemotherapy(R-chemo)in previousl...Backgrounds:GALLIUM is a global phase Ⅲ study that demonstrated significant improvements in progression-free survival(PFS)for obinutuzumab plus chemotherapy(G-chemo)vs.rituximab plus chemotherapy(R-chemo)in previously untreated patients with follicular lymphoma(FL).This study aimed to report the results of a subgroup of patients in China.Methods:Patients were randomized to G-chemo or R-chemo.Responders received maintenance therapy for 2 years or until disease progression.The primary endpoint was investigator(INV)-assessed PFS.Secondary endpoints included the overall response rate(ORR)and complete response rate(CRR)at the end of induction chemotherapy,overall survival(OS),and safety.Results:Overall,58 patients with FL were randomized to the G-chemo(n=25)and R-chemo arms(n=33).The INV-assessed PFS rate at 3 years was 81.8%in the G-chemo arm,vs.70.2%in the R-chemo arm(hazard ratio 0.35;95%confidence interval:0.09-1.34;P=0.1120).The INV-assessed CRRs(without positron emission tomography[PET])in these arms were 24.0%and 21.2%,respectively,whereas the ORRs were 80.0%and 90.9%,respectively.INV-assessed CRR-PET was 52.6%in the G-chemo,vs.60.9%in the R-chemo.Median OS was not reached in either arm.Grade 3 to 5 adverse events were more frequent in the R-chemo arm(97.0%vs.88.0%).Conclusions:The results of this subgroup analysis were consistent with those of the global population,and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.Trial registration:ClinicalTrials.gov,No.NCT01332968.展开更多
Background:Patients with relapsed/refractory B-cell lymphomas have limited treatment options.GERSHWIN is an open-label,single-arm,phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically docu...Background:Patients with relapsed/refractory B-cell lymphomas have limited treatment options.GERSHWIN is an open-label,single-arm,phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically docu-mented CD20+relapsed/refractory chronic lymphocytic leukemia(CLL),diffuse large B-cell lymphoma(DLBCL),or follicular lymphoma(FL).The primary outcome measure of pharmacokinetics has been previously reported.We now present data on the secondary endpoint measures(e.g.,safety,and efficacy and pharmacodynamics).Methods:Patients received 1000 mg obinutuzumab intravenously on days 1,8,and 15 of cycle 1(CLL patients;first dose split over 2 days),and on day 1 of cycles 2-8.Each cycle lasted for 21 days;the treatment period was 24 weeks.All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety,efficacy,as well as pharmacodynamics.Results:A total of 48 patients(>18 years of age)were enrolled(CLL:12;DLBCL:23;FL:13).The subjects received a median of two lines of anticancer treatment prior to the enrollment.Thirty-five patients(72.9%)had at least one adverse event(AE).The most frequent AE was infusion-related reactions(15 patients;31.3%),followed by pyrexia(11 patients;22.9%).Treatment-related AEs were reported in 28 patients(58.3%),and included one death(interstitial lung disease).End-of-treatment(EoT)response rate was 33.3%.Best overall response rate was 47.9%.Most CLL patients achieved a partial response at EoT(58.3%).CD19+depletion occurred in 75.0%of the patients with CLL,and all patients with FL and DLBCL.Conclusions:The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients;no new safety signals were observed.展开更多
Objectives： The molecular targeting drugs for the treatment of B-cell lymphoma have been dramatically developed. Recently, novel drugs of monoclonal antibodies and small molecules are approved by US FDA （Food and Dr...Objectives： The molecular targeting drugs for the treatment of B-cell lymphoma have been dramatically developed. Recently, novel drugs of monoclonal antibodies and small molecules are approved by US FDA （Food and Drug Administration）. Key Findings： This review summarizes characteristics, mechanisms, and results of the trials in the novel molecular targeting drugs for B-cell lymphoma such as obinutuzumab, polatuzumab vedotin, ibrutinib, idelalisib, and venetoclax. Summary： As a novel anti-CD20 antibody, obinutuzumab has been clinically developed on going. ADC （antibody drug conjugate） against CD79b molecules is also developed for B-cell lymphoma. BCR pathway is one of the most crucial pathways, and ibrutinib is a BTK （Bruton＇s tyrosine kinase） inhibitor that is under development for the treatment of B-cell malignancies, including CLL （chronic lymphocytic leukemia）, MCL （mantle cell lymphoma）, and DLBCL （diffuse large B-cell lymphoma）, as well as FL （follicular lymphoma）. BCL-2 family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax, which is a highly selective BCL-2 inhibitor, a mimic for its BCL2 homolog 3-domain to induce apoptosis, is also reported to be active against B-cell malignancies. Conclusions： Mechanism-based combination regimens including these drugs may be required in the future.展开更多
目的:系统评价奥妥珠单抗联合化疗治疗滤泡性淋巴瘤的药物经济学价值以及经济性研究中的模型运用,为卫生政策的制订和临床决策提供参考依据。方法:检索PubMed、ScienceDirect、Cochrane系统评价数据库、Medline、Embase、Web of Scienc...目的:系统评价奥妥珠单抗联合化疗治疗滤泡性淋巴瘤的药物经济学价值以及经济性研究中的模型运用,为卫生政策的制订和临床决策提供参考依据。方法:检索PubMed、ScienceDirect、Cochrane系统评价数据库、Medline、Embase、Web of Science、中国知网和万方数据知识服务平台等数据库,时间段为各自建库至2023年9月,并辅以手工检索和文献追溯等方法,纳入公开发表的奥妥珠单抗的药物经济学相关文献。根据纳入标准筛选出的文献,按照《卫生经济学评价报告标准共识》(2022版)量表对文章进行质量评价,并对纳入文献中使用的模型以及得到的研究结果进行分析和总结。结果:共纳入文献7篇,从模型来看,有5篇使用了马尔科夫模型,2篇使用了分区生存模型;从方法来看,7篇均采用成本-效果分析,其中2篇同时使用了成本-效用分析。经统计,奥妥珠单抗联合化疗的增量成本效果比值均在各国意愿支付值之内。结论:本研究显示奥妥珠单抗联合化疗比利妥昔单抗联合化疗更具有经济性,这为我国卫生决策、医院药品遴选和医保准入进一步提供证据。展开更多
文摘BACKGROUND Marginal zone lymphoma(MZL)is an indolent subtype of non-Hodgkin lymphoma(NHL),which is rare clinically with severe rashes as the initial symptom.CASE SUMMARY This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge.First-line treatment with rituximab combined with zanubrutinib had poor effects.However,after switching to obinutuzumab combined with zanubrutinib,the case was alleviated,and the rashes disappeared.CONCLUSION For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody(mAb)combination therapy,switching to a type II anti-CD20 mAb combination regimen may be considered.This approach may provide a new perspective in the treatment of MZL.
基金The GALLIUM study was sponsored by F.Hoffmann-La Roche Ltd。
文摘Backgrounds:GALLIUM is a global phase Ⅲ study that demonstrated significant improvements in progression-free survival(PFS)for obinutuzumab plus chemotherapy(G-chemo)vs.rituximab plus chemotherapy(R-chemo)in previously untreated patients with follicular lymphoma(FL).This study aimed to report the results of a subgroup of patients in China.Methods:Patients were randomized to G-chemo or R-chemo.Responders received maintenance therapy for 2 years or until disease progression.The primary endpoint was investigator(INV)-assessed PFS.Secondary endpoints included the overall response rate(ORR)and complete response rate(CRR)at the end of induction chemotherapy,overall survival(OS),and safety.Results:Overall,58 patients with FL were randomized to the G-chemo(n=25)and R-chemo arms(n=33).The INV-assessed PFS rate at 3 years was 81.8%in the G-chemo arm,vs.70.2%in the R-chemo arm(hazard ratio 0.35;95%confidence interval:0.09-1.34;P=0.1120).The INV-assessed CRRs(without positron emission tomography[PET])in these arms were 24.0%and 21.2%,respectively,whereas the ORRs were 80.0%and 90.9%,respectively.INV-assessed CRR-PET was 52.6%in the G-chemo,vs.60.9%in the R-chemo.Median OS was not reached in either arm.Grade 3 to 5 adverse events were more frequent in the R-chemo arm(97.0%vs.88.0%).Conclusions:The results of this subgroup analysis were consistent with those of the global population,and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.Trial registration:ClinicalTrials.gov,No.NCT01332968.
基金GERSHWIN was sponsored by F.Hoffmann-La Roche Ltd.Medical Writing supportunder the direction of the lead author,was provided by Elizabeth Johnson of Gardiner-Caldwell Communications,and was funded by F.Hoffmann-La Roche Ltd.
文摘Background:Patients with relapsed/refractory B-cell lymphomas have limited treatment options.GERSHWIN is an open-label,single-arm,phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically docu-mented CD20+relapsed/refractory chronic lymphocytic leukemia(CLL),diffuse large B-cell lymphoma(DLBCL),or follicular lymphoma(FL).The primary outcome measure of pharmacokinetics has been previously reported.We now present data on the secondary endpoint measures(e.g.,safety,and efficacy and pharmacodynamics).Methods:Patients received 1000 mg obinutuzumab intravenously on days 1,8,and 15 of cycle 1(CLL patients;first dose split over 2 days),and on day 1 of cycles 2-8.Each cycle lasted for 21 days;the treatment period was 24 weeks.All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety,efficacy,as well as pharmacodynamics.Results:A total of 48 patients(>18 years of age)were enrolled(CLL:12;DLBCL:23;FL:13).The subjects received a median of two lines of anticancer treatment prior to the enrollment.Thirty-five patients(72.9%)had at least one adverse event(AE).The most frequent AE was infusion-related reactions(15 patients;31.3%),followed by pyrexia(11 patients;22.9%).Treatment-related AEs were reported in 28 patients(58.3%),and included one death(interstitial lung disease).End-of-treatment(EoT)response rate was 33.3%.Best overall response rate was 47.9%.Most CLL patients achieved a partial response at EoT(58.3%).CD19+depletion occurred in 75.0%of the patients with CLL,and all patients with FL and DLBCL.Conclusions:The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients;no new safety signals were observed.
文摘Objectives： The molecular targeting drugs for the treatment of B-cell lymphoma have been dramatically developed. Recently, novel drugs of monoclonal antibodies and small molecules are approved by US FDA （Food and Drug Administration）. Key Findings： This review summarizes characteristics, mechanisms, and results of the trials in the novel molecular targeting drugs for B-cell lymphoma such as obinutuzumab, polatuzumab vedotin, ibrutinib, idelalisib, and venetoclax. Summary： As a novel anti-CD20 antibody, obinutuzumab has been clinically developed on going. ADC （antibody drug conjugate） against CD79b molecules is also developed for B-cell lymphoma. BCR pathway is one of the most crucial pathways, and ibrutinib is a BTK （Bruton＇s tyrosine kinase） inhibitor that is under development for the treatment of B-cell malignancies, including CLL （chronic lymphocytic leukemia）, MCL （mantle cell lymphoma）, and DLBCL （diffuse large B-cell lymphoma）, as well as FL （follicular lymphoma）. BCL-2 family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax, which is a highly selective BCL-2 inhibitor, a mimic for its BCL2 homolog 3-domain to induce apoptosis, is also reported to be active against B-cell malignancies. Conclusions： Mechanism-based combination regimens including these drugs may be required in the future.
文摘目的:系统评价奥妥珠单抗联合化疗治疗滤泡性淋巴瘤的药物经济学价值以及经济性研究中的模型运用,为卫生政策的制订和临床决策提供参考依据。方法:检索PubMed、ScienceDirect、Cochrane系统评价数据库、Medline、Embase、Web of Science、中国知网和万方数据知识服务平台等数据库,时间段为各自建库至2023年9月,并辅以手工检索和文献追溯等方法,纳入公开发表的奥妥珠单抗的药物经济学相关文献。根据纳入标准筛选出的文献,按照《卫生经济学评价报告标准共识》(2022版)量表对文章进行质量评价,并对纳入文献中使用的模型以及得到的研究结果进行分析和总结。结果:共纳入文献7篇,从模型来看,有5篇使用了马尔科夫模型,2篇使用了分区生存模型;从方法来看,7篇均采用成本-效果分析,其中2篇同时使用了成本-效用分析。经统计,奥妥珠单抗联合化疗的增量成本效果比值均在各国意愿支付值之内。结论:本研究显示奥妥珠单抗联合化疗比利妥昔单抗联合化疗更具有经济性,这为我国卫生决策、医院药品遴选和医保准入进一步提供证据。
