Objective:To analyze the clinical efficacy and safety of toripalimab combined with the GC chemotherapy regimen in the treatment of advanced urothelial carcinoma.Methods:A retrospective study was conducted on 102 patie...Objective:To analyze the clinical efficacy and safety of toripalimab combined with the GC chemotherapy regimen in the treatment of advanced urothelial carcinoma.Methods:A retrospective study was conducted on 102 patients with advanced urothelial carcinoma treated at our hospital between March 2021 and August 2024.Based on treatment regimens,patients were divided into a chemotherapy group(n=52)and a combination group(n=50).The chemotherapy group received the GC chemotherapy regimen,while the combination group received GC chemotherapy combined with toripalimab.Both groups underwent 4-6 cycles of treatment based on patient tolerance.Clinical efficacy,immune-related factor levels,survival outcomes,and safety were observed and compared.Results:The disease control rate(DCR)and overall response rate(ORR)in the combination group were slightly higher than those in the chemotherapy group,but the differences were not statistically significant(P>0.05).After treatment,levels of IFN-γand IL-2 increased significantly,while VEGF levels decreased significantly in both groups(P<0.05),with superior outcomes observed in the combination group(P<0.05).Follow-up analysis showed progression-free survival(PFS)and median overall survival(OS)in the chemotherapy group were 5.19 and 10.15 months,respectively,compared to 8.24 and 18.23 months in the combination group,with statistically significant differences(P<0.05).During treatment,the incidence of adverse reactions such as rash,immune-related pneumonia,and immune-related diarrhea was higher in the combination group than in the chemotherapy group(P<0.05).However,the incidence of gastrointestinal reactions,fever,and leukopenia did not differ significantly between the two groups(P>0.05).Conclusion:The use of toripalimab combined with the GC chemotherapy regimen for advanced urothelial carcinoma can effectively improve clinical outcomes and extend patient survival,with good overall safety.However,attention should be given to preventing adverse reactions such as rash and pneumonia during treatment.展开更多
BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Niv...BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.展开更多
BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor an...BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective.However,we report a case of toxic epidermal necrolysis(TEN),a grade 4 toxicity,after this combination therapy.CASE SUMMARY A 39-year-old male presented with erythema,blisters and erosions on the face,neck,trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab,a PD-1 inhibitor.The skin injury covered more than 70%of the body surface area.He was previously diagnosed with liver cancer with cervical vertebra metastasis.Histologically,prominent necrotic keratinocytes,hyperkeratosis,liquefaction of basal cells and acantholytic bullae were observed in the epidermis.Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils.Direct immunofluorescence staining was negative.Thus,the diagnosis was confirmed to be TEN(associated with combination therapy with toripalimab and lenvatinib).Full-dose and long-term corticosteroids,high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered.The rashes gradually faded;however,as expected,the tumor progressed.Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the10-mo follow-up.CONCLUSIONCautious attention should be given to rashes that develop after combination therapy with PD-1inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for thetreatment of TEN associated with this combination treatment.展开更多
BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for ...BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.展开更多
The development of immune checkpoint inhibitors,such as those targeting programmed cell death protein 1(PD-1),represents a major breakthrough in cancer therapy.Although immune checkpoint blockade therapy has a favorab...The development of immune checkpoint inhibitors,such as those targeting programmed cell death protein 1(PD-1),represents a major breakthrough in cancer therapy.Although immune checkpoint blockade therapy has a favorable risk/benefit ratio,it causes significant immune-related adverse events(irAEs),such as cutaneous reactions,in particular,severe bullous skin reactions and toxic epidermal necrolysis.Here,we report a case of a 51-year-old woman with malignant thymoma who developed a severe bullous skin reaction(characterized by a systemic rash,bullae,epidermal desquamation,and Stevens-Johnson syndrome)as a result of treatment with the PD-1 inhibitor toripalimab.The patient was treated with high doses of glucocorticoid,intravenous immunoglobulin,and intensive care,and eventually recovered from the severe irAEs.The intravenous injection of anti-PD-1 antibodies induces cutaneous reactions,which are associated with higher mortality rates.High doses of glucocorticoid combined with intravenous immunoglobulin are effective in alleviating such irAEs.Thus,improving the level of care and preventing skin infections can effectively reduce the risk of death.展开更多
Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxic...Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.展开更多
Background:Several programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)antibodies have been approved for cancer treatmentworldwide.Their pharmacokinetic and pharmacodynamic characteristics have ...Background:Several programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)antibodies have been approved for cancer treatmentworldwide.Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries,but related data in Chinese patients are limited.This study was conducted to investigate the safety,efficacy,pharmacokinetics,and pharmacodynamics of an anti-PD-1 antibody,toripalimab,in Chinese patients.Methods:A single-center phase I study was conducted in Sun Yat-sen University Cancer Center.Eligible patients were adults with histologically confirmed,treatment-refractory,advanced,solitary malignant tumors.Toripalimab was intravenously infused every 2 weeks in dose-escalating cohorts at 0.3mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg.The study followed standard 3+3 design.Results:Between 15th March 2016 and 27th September 2016,25 patients were enrolled,of whom 3(12.0%),7(28.0%),6(24.0%),6(24.0%),3(12.0%)received 0.3 mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg toripalimab,respectively.After a median follow-up time of 5.0 months(range:1.5-19.8 months),we observed that the commonest treatment-related adverse events(TRAEs)were fatigue(64.0%)and rash(24.0%).No grade 3 or higher TRAEs were observed.No dose-limiting toxicity,treatment-related serious adverse events(SAEs),or treatment-related death occurred.Objective response ratewas 12.5%.The half-life of toripalimabwas 150-222 h after a single dose infusion.Most patients,including those from the 0.3 mg/kg group,maintained complete PD-1 receptor occupancy(>80%)on activated T cells since receiving the first dose of toripalimab.Conclusions:Toripalimab is a promising anti-PD-1 antibody,which was well tolerated and demonstrated anti-tumor activity in treatment-refractory advanced solitary malignant tumors.Further exploration in various tumors and combination therapies is warranted.展开更多
BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is an aggressive malignancy with limited treatment options and a poor prognosis,particularly in unresectable or metastatic cases.Tri-modal strategies combining systemic c...BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is an aggressive malignancy with limited treatment options and a poor prognosis,particularly in unresectable or metastatic cases.Tri-modal strategies combining systemic chemotherapy,targeted therapies,and immune checkpoint inhibitors have demonstrated synergistic effects in converting unresectable ICC to resectable status and improving patient survival.CASE SUMMARY A 39-year-old male presented with unresectable stage IIIB ICC(cT3N1M0),abdominal pain,and elevated carbohydrate antigen(CA)19-9 levels.He received tri-modal therapy consisting of gemcitabine-oxaliplatin hepatic arterial infusion chemotherapy(GEMOX-HAIC),lenvatinib(8 mg daily),and toripalimab(160 mg every three weeks).After five cycles,significant tumor shrinkage and normalization of CA19-9 levels enabled a left hepatectomy.Complications,including biliary stenosis and liver abscesses,were managed with biliary stenting and percutaneous drainage,which allowed for the continuation of chemotherapy.Postoperative pathological examination confirmed a pathological complete response.At the last follow-up,the patient had maintained 29 months of diseasefree survival post-resection and was continuing postoperative therapy.CONCLUSION This case highlights the potential of a tri-modal therapy combining GEMOX-HAIC,lenvatinib,and toripalimab to convert unresectable ICC to a resectable status,thereby potentially improving patient survival by surgical resection.Further clinical trials investigating this regimen are warranted.展开更多
BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare primary epithelial lung cancer associated with the Epstein-Barr virus.Standard treatment guideline for PLELC is yet not to be established,surgery r...BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare primary epithelial lung cancer associated with the Epstein-Barr virus.Standard treatment guideline for PLELC is yet not to be established,surgery remains the primary treatment for early-stage PLELC,and platinum chemotherapy is the most common first-line treatment for advanced PLELC.While targeted therapy and immunotherapy has emerged as effective way to treat various malignant tumors,including lung cancer,reports on PLELC are relatively scarce.CASE SUMMARY A 38-year-old man was diagnosed with right PLELC.Chest computed tomography(CT)revealed a mass in the medial segment of the middle lobe of the right lung,with lymph node metastasis in the mediastinum and right hilum of the lung.CT-guided lung tumor biopsy was performed and the postoperative pathological examination combined with immune phenotype analysis and in situ hybridization confirmed PLELC.Standard molecular testing for patients with non-small cell lung cancer was negative and programmed cell death ligand-1 expression was about 2%.The patient declined radiotherapy and chemotherapy.Consequently,immunotherapy was administered,which included toripalimab 240 mg on day 1 and anlotinib 10 mg on days 1-14 for 10 cycles,followed by a maintenance dose of anlotinib 10 mg daily every 3 weeks.As a result,his progression-free survival reached 48 months.CONCLUSION A combination of toripalimab and anlotinib may benefit patients with advanced diseases who have not received systematic antitumor therapy.展开更多
目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗...目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗者,观察组采用FOLFOX方案+特瑞普利单抗治疗,21 d为一个疗程,持续治疗6个疗程。比较两组患者治疗6个疗程后的治疗效果,以及治疗前、治疗3个疗程和6个疗程后的程序性细胞死亡受体-1(PD-1)/程序性细胞死亡配体-1(PD-L1)信号通路(PD-1蛋白、PD-1 m RNA、PD-L1蛋白、PD-L1 m RNA)、血管新生指标[低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、促血管生成素-2(Ang-2)、环氧合酶-2(COX-2)],同时比较两组患者治疗期间的毒副反应以及随访6个月的生存率。结果治疗6个疗程后,观察组患者的疾病控制率为63.27%,明显高于对照组的41.67%,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的PD-1蛋白分别为5.83±1.12、5.77±1.26,明显低于对照组的6.84±1.25、7.11±1.36,PD-1m RNA分别为6.12±1.33、6.01±1.34,明显低于对照组的6.91±1.34、7.20±1.30,PD-L1蛋白分别为6.30±1.05、6.19±1.11,明显低于对照组的7.02±1.33、6.88±1.40,PD-1 mRNA分别为6.41±1.24、6.33±1.25,明显低于对照组的7.19±1.36、7.10±1.38,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的VEGF分别为(224.46±25.25)ng/mL、(150.10±14.14)ng/mL,明显低于对照组的(279.79±30.44)ng/mL、(191.65±16.63)ng/mL,HIF-1α分别为(135.51±16.67)μg/L、(100.10±12.28)μg/L,明显低于对照组的(175.53±18.48)μg/L、(153.53±14.88)μg/L,Ang-2分别为(68.98±7.36)ng/mL、(46.68±5.13)ng/mL,明显低于对照组的(75.51±7.95)ng/mL、(56.64±6.11)ng/mL,COX-2分别为(31.48±4.12)ng/mL、(20.24±3.38)ng/mL,明显低于对照组的(36.64±4.20)ng/mL、(25.74±3.59)ng/mL;差异均有统计学意义(P<0.05)。两组患者治疗6个疗程后的毒副反应发生率与随访期间生存率比较差异均无统计学意义(P>0.05)。结论特瑞普利单抗联合FOLFOX方案治疗进展期胃癌,可阻断PD-1/PD-L1信号通路,增强肿瘤控制效果,且具有较好的安全性。展开更多
文摘Objective:To analyze the clinical efficacy and safety of toripalimab combined with the GC chemotherapy regimen in the treatment of advanced urothelial carcinoma.Methods:A retrospective study was conducted on 102 patients with advanced urothelial carcinoma treated at our hospital between March 2021 and August 2024.Based on treatment regimens,patients were divided into a chemotherapy group(n=52)and a combination group(n=50).The chemotherapy group received the GC chemotherapy regimen,while the combination group received GC chemotherapy combined with toripalimab.Both groups underwent 4-6 cycles of treatment based on patient tolerance.Clinical efficacy,immune-related factor levels,survival outcomes,and safety were observed and compared.Results:The disease control rate(DCR)and overall response rate(ORR)in the combination group were slightly higher than those in the chemotherapy group,but the differences were not statistically significant(P>0.05).After treatment,levels of IFN-γand IL-2 increased significantly,while VEGF levels decreased significantly in both groups(P<0.05),with superior outcomes observed in the combination group(P<0.05).Follow-up analysis showed progression-free survival(PFS)and median overall survival(OS)in the chemotherapy group were 5.19 and 10.15 months,respectively,compared to 8.24 and 18.23 months in the combination group,with statistically significant differences(P<0.05).During treatment,the incidence of adverse reactions such as rash,immune-related pneumonia,and immune-related diarrhea was higher in the combination group than in the chemotherapy group(P<0.05).However,the incidence of gastrointestinal reactions,fever,and leukopenia did not differ significantly between the two groups(P>0.05).Conclusion:The use of toripalimab combined with the GC chemotherapy regimen for advanced urothelial carcinoma can effectively improve clinical outcomes and extend patient survival,with good overall safety.However,attention should be given to preventing adverse reactions such as rash and pneumonia during treatment.
基金Supported by Chinese Research Hospital Association,No.Y2019FH-DTCC-SC3。
文摘BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.
基金Supported by Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases,No. 2018B030322012
文摘BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective.However,we report a case of toxic epidermal necrolysis(TEN),a grade 4 toxicity,after this combination therapy.CASE SUMMARY A 39-year-old male presented with erythema,blisters and erosions on the face,neck,trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab,a PD-1 inhibitor.The skin injury covered more than 70%of the body surface area.He was previously diagnosed with liver cancer with cervical vertebra metastasis.Histologically,prominent necrotic keratinocytes,hyperkeratosis,liquefaction of basal cells and acantholytic bullae were observed in the epidermis.Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils.Direct immunofluorescence staining was negative.Thus,the diagnosis was confirmed to be TEN(associated with combination therapy with toripalimab and lenvatinib).Full-dose and long-term corticosteroids,high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered.The rashes gradually faded;however,as expected,the tumor progressed.Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the10-mo follow-up.CONCLUSIONCautious attention should be given to rashes that develop after combination therapy with PD-1inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for thetreatment of TEN associated with this combination treatment.
文摘BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.
文摘The development of immune checkpoint inhibitors,such as those targeting programmed cell death protein 1(PD-1),represents a major breakthrough in cancer therapy.Although immune checkpoint blockade therapy has a favorable risk/benefit ratio,it causes significant immune-related adverse events(irAEs),such as cutaneous reactions,in particular,severe bullous skin reactions and toxic epidermal necrolysis.Here,we report a case of a 51-year-old woman with malignant thymoma who developed a severe bullous skin reaction(characterized by a systemic rash,bullae,epidermal desquamation,and Stevens-Johnson syndrome)as a result of treatment with the PD-1 inhibitor toripalimab.The patient was treated with high doses of glucocorticoid,intravenous immunoglobulin,and intensive care,and eventually recovered from the severe irAEs.The intravenous injection of anti-PD-1 antibodies induces cutaneous reactions,which are associated with higher mortality rates.High doses of glucocorticoid combined with intravenous immunoglobulin are effective in alleviating such irAEs.Thus,improving the level of care and preventing skin infections can effectively reduce the risk of death.
基金Natural Science Foundation of Gansu Province(Project No.:24JRRA615)Outstanding Talent Recruitment Program and the Doctoral Start-up Fund of Gansu Provincial Central Hospital(Project No.:GMCCH2024-2-6)。
文摘Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.
基金sponsored by Shanghai Junshi Biosciences Co.,Ltd.and supported,in part,by National Key R&D Program of China(2018YFC1313300)Science and Technology Program of Guangdong(2019B020227002)+5 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-036)National Natural Science Foundation of China(81930065)Natural Science Foundation of Guangdong Province(2014A030312015)Science and Technology Program of Guangdong(2019B020227002)Science and Technology Program of Guangzhou(201904020046,201803040019,201704020228)Guangdong Basic and Applied Basic Research Foundation(2019A1515110171).
文摘Background:Several programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)antibodies have been approved for cancer treatmentworldwide.Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries,but related data in Chinese patients are limited.This study was conducted to investigate the safety,efficacy,pharmacokinetics,and pharmacodynamics of an anti-PD-1 antibody,toripalimab,in Chinese patients.Methods:A single-center phase I study was conducted in Sun Yat-sen University Cancer Center.Eligible patients were adults with histologically confirmed,treatment-refractory,advanced,solitary malignant tumors.Toripalimab was intravenously infused every 2 weeks in dose-escalating cohorts at 0.3mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg.The study followed standard 3+3 design.Results:Between 15th March 2016 and 27th September 2016,25 patients were enrolled,of whom 3(12.0%),7(28.0%),6(24.0%),6(24.0%),3(12.0%)received 0.3 mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg toripalimab,respectively.After a median follow-up time of 5.0 months(range:1.5-19.8 months),we observed that the commonest treatment-related adverse events(TRAEs)were fatigue(64.0%)and rash(24.0%).No grade 3 or higher TRAEs were observed.No dose-limiting toxicity,treatment-related serious adverse events(SAEs),or treatment-related death occurred.Objective response ratewas 12.5%.The half-life of toripalimabwas 150-222 h after a single dose infusion.Most patients,including those from the 0.3 mg/kg group,maintained complete PD-1 receptor occupancy(>80%)on activated T cells since receiving the first dose of toripalimab.Conclusions:Toripalimab is a promising anti-PD-1 antibody,which was well tolerated and demonstrated anti-tumor activity in treatment-refractory advanced solitary malignant tumors.Further exploration in various tumors and combination therapies is warranted.
基金Supported by Shenzhen Clinical Research Center for Gastroenterology(Gastrointestinal Surgery),No.LCYSSQ20220823091203008.
文摘BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is an aggressive malignancy with limited treatment options and a poor prognosis,particularly in unresectable or metastatic cases.Tri-modal strategies combining systemic chemotherapy,targeted therapies,and immune checkpoint inhibitors have demonstrated synergistic effects in converting unresectable ICC to resectable status and improving patient survival.CASE SUMMARY A 39-year-old male presented with unresectable stage IIIB ICC(cT3N1M0),abdominal pain,and elevated carbohydrate antigen(CA)19-9 levels.He received tri-modal therapy consisting of gemcitabine-oxaliplatin hepatic arterial infusion chemotherapy(GEMOX-HAIC),lenvatinib(8 mg daily),and toripalimab(160 mg every three weeks).After five cycles,significant tumor shrinkage and normalization of CA19-9 levels enabled a left hepatectomy.Complications,including biliary stenosis and liver abscesses,were managed with biliary stenting and percutaneous drainage,which allowed for the continuation of chemotherapy.Postoperative pathological examination confirmed a pathological complete response.At the last follow-up,the patient had maintained 29 months of diseasefree survival post-resection and was continuing postoperative therapy.CONCLUSION This case highlights the potential of a tri-modal therapy combining GEMOX-HAIC,lenvatinib,and toripalimab to convert unresectable ICC to a resectable status,thereby potentially improving patient survival by surgical resection.Further clinical trials investigating this regimen are warranted.
基金Supported by Chinese Medicine Administration Bureau of Guangxi Zhuang Autonomous Region,No.GXZYB20220472.
文摘BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare primary epithelial lung cancer associated with the Epstein-Barr virus.Standard treatment guideline for PLELC is yet not to be established,surgery remains the primary treatment for early-stage PLELC,and platinum chemotherapy is the most common first-line treatment for advanced PLELC.While targeted therapy and immunotherapy has emerged as effective way to treat various malignant tumors,including lung cancer,reports on PLELC are relatively scarce.CASE SUMMARY A 38-year-old man was diagnosed with right PLELC.Chest computed tomography(CT)revealed a mass in the medial segment of the middle lobe of the right lung,with lymph node metastasis in the mediastinum and right hilum of the lung.CT-guided lung tumor biopsy was performed and the postoperative pathological examination combined with immune phenotype analysis and in situ hybridization confirmed PLELC.Standard molecular testing for patients with non-small cell lung cancer was negative and programmed cell death ligand-1 expression was about 2%.The patient declined radiotherapy and chemotherapy.Consequently,immunotherapy was administered,which included toripalimab 240 mg on day 1 and anlotinib 10 mg on days 1-14 for 10 cycles,followed by a maintenance dose of anlotinib 10 mg daily every 3 weeks.As a result,his progression-free survival reached 48 months.CONCLUSION A combination of toripalimab and anlotinib may benefit patients with advanced diseases who have not received systematic antitumor therapy.
文摘目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗者,观察组采用FOLFOX方案+特瑞普利单抗治疗,21 d为一个疗程,持续治疗6个疗程。比较两组患者治疗6个疗程后的治疗效果,以及治疗前、治疗3个疗程和6个疗程后的程序性细胞死亡受体-1(PD-1)/程序性细胞死亡配体-1(PD-L1)信号通路(PD-1蛋白、PD-1 m RNA、PD-L1蛋白、PD-L1 m RNA)、血管新生指标[低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、促血管生成素-2(Ang-2)、环氧合酶-2(COX-2)],同时比较两组患者治疗期间的毒副反应以及随访6个月的生存率。结果治疗6个疗程后,观察组患者的疾病控制率为63.27%,明显高于对照组的41.67%,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的PD-1蛋白分别为5.83±1.12、5.77±1.26,明显低于对照组的6.84±1.25、7.11±1.36,PD-1m RNA分别为6.12±1.33、6.01±1.34,明显低于对照组的6.91±1.34、7.20±1.30,PD-L1蛋白分别为6.30±1.05、6.19±1.11,明显低于对照组的7.02±1.33、6.88±1.40,PD-1 mRNA分别为6.41±1.24、6.33±1.25,明显低于对照组的7.19±1.36、7.10±1.38,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的VEGF分别为(224.46±25.25)ng/mL、(150.10±14.14)ng/mL,明显低于对照组的(279.79±30.44)ng/mL、(191.65±16.63)ng/mL,HIF-1α分别为(135.51±16.67)μg/L、(100.10±12.28)μg/L,明显低于对照组的(175.53±18.48)μg/L、(153.53±14.88)μg/L,Ang-2分别为(68.98±7.36)ng/mL、(46.68±5.13)ng/mL,明显低于对照组的(75.51±7.95)ng/mL、(56.64±6.11)ng/mL,COX-2分别为(31.48±4.12)ng/mL、(20.24±3.38)ng/mL,明显低于对照组的(36.64±4.20)ng/mL、(25.74±3.59)ng/mL;差异均有统计学意义(P<0.05)。两组患者治疗6个疗程后的毒副反应发生率与随访期间生存率比较差异均无统计学意义(P>0.05)。结论特瑞普利单抗联合FOLFOX方案治疗进展期胃癌,可阻断PD-1/PD-L1信号通路,增强肿瘤控制效果,且具有较好的安全性。
