BACKGROUND Allogeneic hematopoietic stem cell transplantation(Allo-HSCT)is currently the only viable method of curing patients with acute myeloid leukaemia.In 30%to 50%of patients,donors and recipients have some level...BACKGROUND Allogeneic hematopoietic stem cell transplantation(Allo-HSCT)is currently the only viable method of curing patients with acute myeloid leukaemia.In 30%to 50%of patients,donors and recipients have some level of ABO blood group incompatibility.ABO blood group incompatibility can cause antibodies against the donor's red blood cells to persist in the recipient's body,resulting in a delay of several months in the recovery of red blood cells.A number of different treatments have been reported for post-transplant pure red cell aplastic anaemia(PRCA),such as plasmapheresis,donor lymphocyte infusions,anti-thymocyte globulin,rituximab and steroids.CASE SUMMARY A 41-year-old female diagnosed with acute myeloid leukaemia underwent peripheral blood allogeneic haematopoietic stem cell transplantation in November 2013 from an HLA matched unrelated donor.The donor was AB-positive and the recipient was O-positive.The patient was diagnosed with PRCA three months after receiving the donor stem cell transplant.After failing multiple lines of therapy,the patient applied for daratumumab.After receiving three doses of daratumumab,the patient developed a reticulocyte response and no longer required CONCLUSION The use of daratumumab anti-CD38 for the remove of plasma cells is safe and effective and may be tried for refractory patients with PRCA after undergoing allo-HSCT for ABO incompatibility.展开更多
BACKGROUND The treatment of multiple myeloma has significantly progressed over the past half-century.The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and ...BACKGROUND The treatment of multiple myeloma has significantly progressed over the past half-century.The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and safety of daratumumab in treating multiple myeloma.AIM To explore the efficacy and safety of daratumumab in treating multiple myeloma.METHODS A systematic literature search was performed using Chinese and English databases,including the China National Knowledge Infrastructure,Wanfang,China Biology Medicine,VIP,the Cochrane Library,Embase,and PubMed.The search encompassed studies in treating multiple myeloma with daratumumab,spanning from the inception of the database to June 2023.Revman 5.1 software was used for analysis.RESULTS Our analysis included eight English articles and one Chinese article of high quality.The meta-analysis results indicated that compared to other therapies,daratumumab could improve the overall response rate(ORR)[odds ratio(OR)=2.67,95%confidence interval(CI)=2.01,3.53,Z=6.85,P<0.00001],complete remission(CR)(OR=2.87,95%CI=2.16,3.83,Z=7.23,P<0.00001)and progression-free survival(PFS)time(hazard ratio=0.48,95%CI=0.38,0.60,Z=6.54,P<0.00001)in patients with multiple myeloma.These differences were statistically significant.Additionally,these results suggested that daratumumab increases the risk of neutropenia and thrombocytopenia with minimal effect on the incidences of anemia and upper respiratory tract infections.CONCLUSION Daratumumab can improve ORR,CR rate,and PFS in patients with multiple myeloma.It also increases the risk of neutropenia and thrombocytopenia,necessitating careful monitoring during its clinical application.展开更多
目的探讨复发/难治性多发性骨髓瘤伴继发性髓外病变患者达雷妥尤单抗联合苯达莫司汀治疗的疗效和安全性。方法回顾性分析2021年1月至2023年12月于广西医科大学附属肿瘤医院住院治疗的复发/难治性多发性骨髓瘤伴继发性髓外病变患者的临...目的探讨复发/难治性多发性骨髓瘤伴继发性髓外病变患者达雷妥尤单抗联合苯达莫司汀治疗的疗效和安全性。方法回顾性分析2021年1月至2023年12月于广西医科大学附属肿瘤医院住院治疗的复发/难治性多发性骨髓瘤伴继发性髓外病变患者的临床资料。所有患者均接受至少三线治疗仍疾病进展,然后采用达雷妥尤单抗和苯达莫司汀联合治疗。分别采用国际骨髓瘤工作组(International Myeloma Working Group,IMWG)标准和美国国家癌症研究所不良事件通用术语标准(NCI-CTCAE)5.0版评估其治疗疗效和安全性。结果共12例患者纳入分析,获完全缓解2例,部分缓解4例,微小缓解2例,疾病稳定1例,疾病进展3例,总缓解率为50%,中位无进展生存期为8个月。所有患者均出现血液学毒性,其中4例为Ⅲ~Ⅳ级;3例患者在治疗期间发生肺炎;均未发生治疗相关性死亡。结论达雷妥尤单抗联合苯达莫司汀在治疗复发/难治性伴继发性髓外病变的多发性骨髓瘤中显示出有效性,且毒性作用可控,值得在更大规模的患者群体中进一步验证。展开更多
目的探讨DARA-Fab片段处理经抗CD38单克隆抗体雷达木(daratumumab,DARA)治疗后的多发性骨髓瘤(multiple myeloma,MM)患者输血相容性检测方法的可行性,并通过对比二硫苏糖醇(Dithiothreitol,DTT)方法评估其输血疗效。方法将DARA使用Pierc...目的探讨DARA-Fab片段处理经抗CD38单克隆抗体雷达木(daratumumab,DARA)治疗后的多发性骨髓瘤(multiple myeloma,MM)患者输血相容性检测方法的可行性,并通过对比二硫苏糖醇(Dithiothreitol,DTT)方法评估其输血疗效。方法将DARA使用PierceFab制备试剂盒制备成DARA-Fab片段后,确认不同体积(5、10、15、30μL)DARA-Fab片段对于抗筛细胞和抗体鉴定细胞的中和效果;DARA-Fab片段和明确相应抗原的抗筛细胞与对应的单抗试剂为试验组,以添加同体积的生理盐水为对照组孵育后离心;各选取20名经DARA治疗后的MM患者,分别使用DARA-Fab封闭RBC表面抗原和与DTT破坏红细胞表面抗原的方法来进行输血相容性检测,对其输血前后实验室指标进行统计分析,并比较2种配血方法。结果15、30μL DARA-Fab片段与抗筛细胞与混有DARA的血清孵育离心后结果为阴性,5、10μL DARA-Fab结果为阳性,15μL DARA-Fab处理抗体鉴定细胞(2、3、4、5、7、9、11)后为阴性,抗体鉴定细胞(1、6、8、10、12)经30μL DARA-Fab片段处理后,结果为阴性;添加DARA-Fab的实验组对MNS系统、Duffy、Kidd、Kell、Lewis、Rh血型系统和对照组结果一致;DARA-Fab片段这20名患者输注RBC后Hb(hemoglobin,Hb)(73.90±1.90)(g/L)比输血前(63.60±1.58)明显提高,统计学差异明显(P<0.01);患者总胆红素(total bilirubin,TBil)(μmol/L)(16.25±3.54 vs 17.87±3.57)、直接胆红素(direct bilirubin,DBIL)(μmol/L)(6.31±2.32 vs 7.10±2.80)和间接胆红素(Indirect Bilirubin,I-Bil)(9.94±1.38 vs 10.77±1.22)输注前后无明显差异,无统计学差异(P>0.05)。DTT处理方法与DARA-Fab片段封闭方法的输血前后Hb差值(10.75±1.04 vs 10.30±0.98)、TBil差值(3.31±1.47 vs 3.31±0.55)、DBIL差值(2.76±1.24 vs 2.60±0.83)和I-Bil差值(1.97±0.40 vs 2.82±0.53)无明显差异,无统计学差异(P>0.05)。结论DARA-Fab片段可通过封闭RBC表面CD38抗原,来去除DARA对红细胞输血相容性检测的干扰,这种封闭方法对于红细胞临床常见血型系统的抗原无影响,且通过这种配血方法实验室指标输血疗效明显,与DTT方法的输血疗效无差异。展开更多
Despite recent progress in multiple myeloma(MM)treatments,most patients will relapse and require additional treatment.Intravenous daratumumab,a human IgGκmonoclonal antibody targeting CD38,has shown good efficacy in ...Despite recent progress in multiple myeloma(MM)treatments,most patients will relapse and require additional treatment.Intravenous daratumumab,a human IgGκmonoclonal antibody targeting CD38,has shown good efficacy in the treatment of MM.A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions.We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab,with a shorter administration time and reduced infusion-related reaction rate in global studies.This phase 1,multicenter study(MMY1010;ClinicalTrials.gov Identifier:NCT04121260)evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line(n=1)or≥2 prior lines(n=20)of therapy,including a proteasome inhibitor and an immunomodulatory drug.Primary endpoints were pharmacokinetics and safety.Mean(standard deviation)maximum trough concentration of daratumumab was 826(335)μg/mL,which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab.Safety was consistent with safety profiles observed in other daratumumab studies,with no new safety concerns identified.Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies.At a median follow-up of 7.5 months,the overall response rate was 57.1%,with a very good partial response or better rate of 38.1%and complete response or better rate of 19.0%.Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM,potentially impacting clinical administration of daratumumab in this population.展开更多
基金Natural Science Foundation of Guizhou Province,China,No.397.
文摘BACKGROUND Allogeneic hematopoietic stem cell transplantation(Allo-HSCT)is currently the only viable method of curing patients with acute myeloid leukaemia.In 30%to 50%of patients,donors and recipients have some level of ABO blood group incompatibility.ABO blood group incompatibility can cause antibodies against the donor's red blood cells to persist in the recipient's body,resulting in a delay of several months in the recovery of red blood cells.A number of different treatments have been reported for post-transplant pure red cell aplastic anaemia(PRCA),such as plasmapheresis,donor lymphocyte infusions,anti-thymocyte globulin,rituximab and steroids.CASE SUMMARY A 41-year-old female diagnosed with acute myeloid leukaemia underwent peripheral blood allogeneic haematopoietic stem cell transplantation in November 2013 from an HLA matched unrelated donor.The donor was AB-positive and the recipient was O-positive.The patient was diagnosed with PRCA three months after receiving the donor stem cell transplant.After failing multiple lines of therapy,the patient applied for daratumumab.After receiving three doses of daratumumab,the patient developed a reticulocyte response and no longer required CONCLUSION The use of daratumumab anti-CD38 for the remove of plasma cells is safe and effective and may be tried for refractory patients with PRCA after undergoing allo-HSCT for ABO incompatibility.
文摘BACKGROUND The treatment of multiple myeloma has significantly progressed over the past half-century.The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and safety of daratumumab in treating multiple myeloma.AIM To explore the efficacy and safety of daratumumab in treating multiple myeloma.METHODS A systematic literature search was performed using Chinese and English databases,including the China National Knowledge Infrastructure,Wanfang,China Biology Medicine,VIP,the Cochrane Library,Embase,and PubMed.The search encompassed studies in treating multiple myeloma with daratumumab,spanning from the inception of the database to June 2023.Revman 5.1 software was used for analysis.RESULTS Our analysis included eight English articles and one Chinese article of high quality.The meta-analysis results indicated that compared to other therapies,daratumumab could improve the overall response rate(ORR)[odds ratio(OR)=2.67,95%confidence interval(CI)=2.01,3.53,Z=6.85,P<0.00001],complete remission(CR)(OR=2.87,95%CI=2.16,3.83,Z=7.23,P<0.00001)and progression-free survival(PFS)time(hazard ratio=0.48,95%CI=0.38,0.60,Z=6.54,P<0.00001)in patients with multiple myeloma.These differences were statistically significant.Additionally,these results suggested that daratumumab increases the risk of neutropenia and thrombocytopenia with minimal effect on the incidences of anemia and upper respiratory tract infections.CONCLUSION Daratumumab can improve ORR,CR rate,and PFS in patients with multiple myeloma.It also increases the risk of neutropenia and thrombocytopenia,necessitating careful monitoring during its clinical application.
文摘目的探讨复发/难治性多发性骨髓瘤伴继发性髓外病变患者达雷妥尤单抗联合苯达莫司汀治疗的疗效和安全性。方法回顾性分析2021年1月至2023年12月于广西医科大学附属肿瘤医院住院治疗的复发/难治性多发性骨髓瘤伴继发性髓外病变患者的临床资料。所有患者均接受至少三线治疗仍疾病进展,然后采用达雷妥尤单抗和苯达莫司汀联合治疗。分别采用国际骨髓瘤工作组(International Myeloma Working Group,IMWG)标准和美国国家癌症研究所不良事件通用术语标准(NCI-CTCAE)5.0版评估其治疗疗效和安全性。结果共12例患者纳入分析,获完全缓解2例,部分缓解4例,微小缓解2例,疾病稳定1例,疾病进展3例,总缓解率为50%,中位无进展生存期为8个月。所有患者均出现血液学毒性,其中4例为Ⅲ~Ⅳ级;3例患者在治疗期间发生肺炎;均未发生治疗相关性死亡。结论达雷妥尤单抗联合苯达莫司汀在治疗复发/难治性伴继发性髓外病变的多发性骨髓瘤中显示出有效性,且毒性作用可控,值得在更大规模的患者群体中进一步验证。
文摘目的探讨DARA-Fab片段处理经抗CD38单克隆抗体雷达木(daratumumab,DARA)治疗后的多发性骨髓瘤(multiple myeloma,MM)患者输血相容性检测方法的可行性,并通过对比二硫苏糖醇(Dithiothreitol,DTT)方法评估其输血疗效。方法将DARA使用PierceFab制备试剂盒制备成DARA-Fab片段后,确认不同体积(5、10、15、30μL)DARA-Fab片段对于抗筛细胞和抗体鉴定细胞的中和效果;DARA-Fab片段和明确相应抗原的抗筛细胞与对应的单抗试剂为试验组,以添加同体积的生理盐水为对照组孵育后离心;各选取20名经DARA治疗后的MM患者,分别使用DARA-Fab封闭RBC表面抗原和与DTT破坏红细胞表面抗原的方法来进行输血相容性检测,对其输血前后实验室指标进行统计分析,并比较2种配血方法。结果15、30μL DARA-Fab片段与抗筛细胞与混有DARA的血清孵育离心后结果为阴性,5、10μL DARA-Fab结果为阳性,15μL DARA-Fab处理抗体鉴定细胞(2、3、4、5、7、9、11)后为阴性,抗体鉴定细胞(1、6、8、10、12)经30μL DARA-Fab片段处理后,结果为阴性;添加DARA-Fab的实验组对MNS系统、Duffy、Kidd、Kell、Lewis、Rh血型系统和对照组结果一致;DARA-Fab片段这20名患者输注RBC后Hb(hemoglobin,Hb)(73.90±1.90)(g/L)比输血前(63.60±1.58)明显提高,统计学差异明显(P<0.01);患者总胆红素(total bilirubin,TBil)(μmol/L)(16.25±3.54 vs 17.87±3.57)、直接胆红素(direct bilirubin,DBIL)(μmol/L)(6.31±2.32 vs 7.10±2.80)和间接胆红素(Indirect Bilirubin,I-Bil)(9.94±1.38 vs 10.77±1.22)输注前后无明显差异,无统计学差异(P>0.05)。DTT处理方法与DARA-Fab片段封闭方法的输血前后Hb差值(10.75±1.04 vs 10.30±0.98)、TBil差值(3.31±1.47 vs 3.31±0.55)、DBIL差值(2.76±1.24 vs 2.60±0.83)和I-Bil差值(1.97±0.40 vs 2.82±0.53)无明显差异,无统计学差异(P>0.05)。结论DARA-Fab片段可通过封闭RBC表面CD38抗原,来去除DARA对红细胞输血相容性检测的干扰,这种封闭方法对于红细胞临床常见血型系统的抗原无影响,且通过这种配血方法实验室指标输血疗效明显,与DTT方法的输血疗效无差异。
文摘Despite recent progress in multiple myeloma(MM)treatments,most patients will relapse and require additional treatment.Intravenous daratumumab,a human IgGκmonoclonal antibody targeting CD38,has shown good efficacy in the treatment of MM.A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions.We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab,with a shorter administration time and reduced infusion-related reaction rate in global studies.This phase 1,multicenter study(MMY1010;ClinicalTrials.gov Identifier:NCT04121260)evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line(n=1)or≥2 prior lines(n=20)of therapy,including a proteasome inhibitor and an immunomodulatory drug.Primary endpoints were pharmacokinetics and safety.Mean(standard deviation)maximum trough concentration of daratumumab was 826(335)μg/mL,which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab.Safety was consistent with safety profiles observed in other daratumumab studies,with no new safety concerns identified.Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies.At a median follow-up of 7.5 months,the overall response rate was 57.1%,with a very good partial response or better rate of 38.1%and complete response or better rate of 19.0%.Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM,potentially impacting clinical administration of daratumumab in this population.
