BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to...BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.展开更多
BACKGROUND Oncologic immunotherapy is attracting attention as an effective strategy for cancer treatment. Currently, there are two kinds of inhibitors: Anti-PD-1 antibodies and anti-PD-L1 antibodies. These inhibitors ...BACKGROUND Oncologic immunotherapy is attracting attention as an effective strategy for cancer treatment. Currently, there are two kinds of inhibitors: Anti-PD-1 antibodies and anti-PD-L1 antibodies. These inhibitors have shown significant implications in improving the outcomes of certain cancer types in recent years.However, along with its effectiveness, adverse events cannot be ignored. As an anti-PD-1 antibody, camrelizumab(SHR-1210) has some side effects in tumor immunotherapy. The most common adverse event is reactive capillary hemangioma. While it is widely reported to occur in the skin, gingival reactive capillary hemangioma is rarely reported.CASE SUMMARY A 54-year-old man complained of gingival overgrowth on the anterior aspect of the maxilla and mandible for more than 6 mo. He had been placed on SHR-1210 for lung cancer for 7 mo. A gingival mass extending from canine to canine was noted on the lingual surfaces of the mandible. Gingival enlargement was noted in the front teeth. A clinical diagnosis of gingival reactive capillary hemangioma and chronic periodontitis was made. The treatment involved a complex local treatment(repeated local applications of an antibiotic paste, scaling and root planning, and surgery). The excised tissue was sent for histopathological examination, which confirmed the diagnosis of capillary hemangioma. After the operation, most of the gingival enlargement was reduced. At the 2-mo follow-up,it was noted that the gingival overgrowth was immediately reduced after the replacement of the anti-PD-1 agent with an anti-PD-L1 agent.CONCLUSION As the prescription for SHR-1210 has increased considerably in recent years, the occurrence of its possible side effects, including gingival reactive capillary hemangioma, has increased. It is recommended that regular oral examinations be performed before and during the treatment of tumors with SHR-1210.展开更多
BACKGROUND Camrelizumab(SHR-1210),an immune checkpoint inhibitor,is clinically used as a therapeutic option for various types of tumors.However,reports of adverse reactions associated with camrelizumab are gradually i...BACKGROUND Camrelizumab(SHR-1210),an immune checkpoint inhibitor,is clinically used as a therapeutic option for various types of tumors.However,reports of adverse reactions associated with camrelizumab are gradually increasing.Anaphylactic shock due to camrelizumab has not been reported previously,until now.We report here,for the first time,a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma.CASE SUMMARY An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago.He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis(Tx N1 M1)and received the first immunotherapy(camrelizumab 200 mg/each time,once every 3 wk)dose in December 2020,with no adverse reactions.Three weeks later,a generalized rash was noted on the chest and upper limbs;palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy.Electrocardiograph monitoring revealed a 70 beats/min pulse rate,69/24 mm Hg(1 mm Hg=0.133 k Pa)blood pressure,28 breaths/min respiratory rate,and 86%pulse oximetry in room air.The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid,adrenaline,dexamethasone sodium phosphate,calcium glucosate,and noradrenaline.Approximately 2 h after treatment,the patient’s anaphylactic shock symptoms had been completely relieved.CONCLUSION Due to the widespread use of camrelizumab,attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.展开更多
An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanom...An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.展开更多
BACKGROUND There has been no report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive programmed death-ligand 1(PD-L1)expression and high tumor mutational burden(TMB).More effect...BACKGROUND There has been no report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive programmed death-ligand 1(PD-L1)expression and high tumor mutational burden(TMB).More effective predictors of bladder cancer immunotherapy have yet to be explored,and the combination of multiple factors may be more predictive than a single factor.CASE SUMMARY We report the case of a 74-year-old male patient with recurrent metastatic bladder cancer,which demonstrated positive PD-L1 expression and high TMB.The immune checkpoint inhibitor camrelizumab was administered to the patient in combination with gemcitabine and cisplatin.The patient achieved a partial response with a progression-free survival of 11 mo.CONCLUSION This is the first report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive PD-L1 expression and high TMB.展开更多
Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1...Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1)inhibitor camrelizumab are used as treatments for ESCC,the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported.Therefore,this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.Methods:Fifty-eight patients with advanced ESCC undergoing second-line therapy,either with anlotinib plus camrelizumab or anlotinib plus S-1,were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021.The primary endpoint was progression-free survival(PFS),with secondary endpoints including the objective response rate(ORR),disease control rate(DCR),and assessment of toxicity.Results:In patients with advanced ESCC,the anlotinib plus camrelizumab group(N=32)exhibited longer PFS(8.00 vs.4.53 months,P<0.001),higher ORR(28.1 vs.19.2%,P=0.431),and higher DCR(87.5 vs.65.4%,P=0.045)than those in the anlotinib plus S-1 group(N=26).Treatment-related adverse events(TRAEs)were predominantly grade 1/2 in both groups,with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab(P=0.033).Two patients(6.3%)developed grade 1/2 immune-related pneumonia.The incidence of grade 3/4 TRAEs did not differ significantly between the two groups.Multivariable Cox regression analysis identified that the drug regimen(P<0.001),Eastern Cooperative Oncology Group performance status(P=0.008),and differentiation grade(P=0.008)were independent prognostic factors for PFS.Conclusions:Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.展开更多
This editorial comments on a study by Zuo et al.The focus is on the efficacy of he-patic arterial infusion chemotherapy combined with camrelizumab and apatinib(the TRIPLET regimen),alongside microwave ablation therapy...This editorial comments on a study by Zuo et al.The focus is on the efficacy of he-patic arterial infusion chemotherapy combined with camrelizumab and apatinib(the TRIPLET regimen),alongside microwave ablation therapy,in treating advanced hepatocellular carcinoma(HCC).The potential application of this combination therapy for patients with advanced HCC is evaluated.展开更多
Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into t...Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).展开更多
Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited...Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16 F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic(PK)and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.展开更多
Immune checkpoint inhibitors are generally contraindicated for post-transplant patients.However,we report two patients with metastatic hepatocellular carcinoma(HCC)treated with camrelizumab(SHR-1210),an anti-programme...Immune checkpoint inhibitors are generally contraindicated for post-transplant patients.However,we report two patients with metastatic hepatocellular carcinoma(HCC)treated with camrelizumab(SHR-1210),an anti-programmed cell death 1(PD-1)agent,after liver transplant.Before undergoing immunotherapy,both patients underwent liver allograft biopsy and obtained negative PD-L1 expression in tumor and liver graft specimens by immunohistochemistry.Then,camrelizumab(200 mg)was administered once every 3 weeks.During immunotherapy,the targeted therapy was continued,and the immunosuppression regimen was adjusted to a low-dose level.No graft rejection or other severe adverse reactions were observed.The disease remained stable(SD,mRECIST)for 3 months in one patient and 10 months in the other.Therefore,camrelizumab may have safety and potential benefits in advanced HCC after liver transplant.展开更多
BACKGROUND Primary liver cancer is the sixth most common cancer worldwide,with hepato-cellular carcinoma(HCC)being the most prevalent form.Despite the current availability of multiple immune or immune combination trea...BACKGROUND Primary liver cancer is the sixth most common cancer worldwide,with hepato-cellular carcinoma(HCC)being the most prevalent form.Despite the current availability of multiple immune or immune combination treatment options,the prognosis is still poor,so how to identify a more suitable population is extremely important.AIM To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus(HBV)-related HCC in Barcelona Clinic Liver Cancer(BCLC)stages B/C,considering various body mass index(BMI)in diffe-rent categories.METHODS Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab.Patients were divided into two groups based on BMI:The non-overweight group(BMI<25 kg/m2,n=51)and the overweight/obese group(BMI≥25 kg/m2,n=75).Short-term prognosis was evaluated using mRECIST criteria,with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.RESULTS Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group.Similarly,the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group.The objective remission rate and disease control rate for the two groups of patients were,respectively,objective remission rate(5.88%vs 28.00%)and disease control rate(39.22%vs 62.67%).Fatigue was more prevalent in the obese/overweight group,while other adverse effects showed no statistically significant differences(P>0.05).Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients,with obese patients showing the best outcomes.Multifactorial regression analysis identified BCLC grade,alpha-fetoprotein level,portal vein tumor thrombosis,and BMI as independent prognostic factors for OS.The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis,followed by alpha-fetoprotein level,BCLC classification,and portal vein tumor thrombosis.CONCLUSION BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab,and obese/overweight patients have a better prognosis.展开更多
BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(H...BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.展开更多
文摘BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.
文摘BACKGROUND Oncologic immunotherapy is attracting attention as an effective strategy for cancer treatment. Currently, there are two kinds of inhibitors: Anti-PD-1 antibodies and anti-PD-L1 antibodies. These inhibitors have shown significant implications in improving the outcomes of certain cancer types in recent years.However, along with its effectiveness, adverse events cannot be ignored. As an anti-PD-1 antibody, camrelizumab(SHR-1210) has some side effects in tumor immunotherapy. The most common adverse event is reactive capillary hemangioma. While it is widely reported to occur in the skin, gingival reactive capillary hemangioma is rarely reported.CASE SUMMARY A 54-year-old man complained of gingival overgrowth on the anterior aspect of the maxilla and mandible for more than 6 mo. He had been placed on SHR-1210 for lung cancer for 7 mo. A gingival mass extending from canine to canine was noted on the lingual surfaces of the mandible. Gingival enlargement was noted in the front teeth. A clinical diagnosis of gingival reactive capillary hemangioma and chronic periodontitis was made. The treatment involved a complex local treatment(repeated local applications of an antibiotic paste, scaling and root planning, and surgery). The excised tissue was sent for histopathological examination, which confirmed the diagnosis of capillary hemangioma. After the operation, most of the gingival enlargement was reduced. At the 2-mo follow-up,it was noted that the gingival overgrowth was immediately reduced after the replacement of the anti-PD-1 agent with an anti-PD-L1 agent.CONCLUSION As the prescription for SHR-1210 has increased considerably in recent years, the occurrence of its possible side effects, including gingival reactive capillary hemangioma, has increased. It is recommended that regular oral examinations be performed before and during the treatment of tumors with SHR-1210.
基金Supported by the National Natural Science Foundation of China,No.81873317the Natural Science Foundation of Zhejiang,No.LSY19H030002the Science and Technology Projects of Hangzhou City,No.20181228Y22。
文摘BACKGROUND Camrelizumab(SHR-1210),an immune checkpoint inhibitor,is clinically used as a therapeutic option for various types of tumors.However,reports of adverse reactions associated with camrelizumab are gradually increasing.Anaphylactic shock due to camrelizumab has not been reported previously,until now.We report here,for the first time,a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma.CASE SUMMARY An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago.He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis(Tx N1 M1)and received the first immunotherapy(camrelizumab 200 mg/each time,once every 3 wk)dose in December 2020,with no adverse reactions.Three weeks later,a generalized rash was noted on the chest and upper limbs;palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy.Electrocardiograph monitoring revealed a 70 beats/min pulse rate,69/24 mm Hg(1 mm Hg=0.133 k Pa)blood pressure,28 breaths/min respiratory rate,and 86%pulse oximetry in room air.The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid,adrenaline,dexamethasone sodium phosphate,calcium glucosate,and noradrenaline.Approximately 2 h after treatment,the patient’s anaphylactic shock symptoms had been completely relieved.CONCLUSION Due to the widespread use of camrelizumab,attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.
基金Supported by a grant from the Qingdao 2020 Medical Scientific Research Guidance Plan(No.2020-WJZD036)。
文摘An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.
文摘BACKGROUND There has been no report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive programmed death-ligand 1(PD-L1)expression and high tumor mutational burden(TMB).More effective predictors of bladder cancer immunotherapy have yet to be explored,and the combination of multiple factors may be more predictive than a single factor.CASE SUMMARY We report the case of a 74-year-old male patient with recurrent metastatic bladder cancer,which demonstrated positive PD-L1 expression and high TMB.The immune checkpoint inhibitor camrelizumab was administered to the patient in combination with gemcitabine and cisplatin.The patient achieved a partial response with a progression-free survival of 11 mo.CONCLUSION This is the first report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive PD-L1 expression and high TMB.
文摘Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1)inhibitor camrelizumab are used as treatments for ESCC,the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported.Therefore,this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.Methods:Fifty-eight patients with advanced ESCC undergoing second-line therapy,either with anlotinib plus camrelizumab or anlotinib plus S-1,were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021.The primary endpoint was progression-free survival(PFS),with secondary endpoints including the objective response rate(ORR),disease control rate(DCR),and assessment of toxicity.Results:In patients with advanced ESCC,the anlotinib plus camrelizumab group(N=32)exhibited longer PFS(8.00 vs.4.53 months,P<0.001),higher ORR(28.1 vs.19.2%,P=0.431),and higher DCR(87.5 vs.65.4%,P=0.045)than those in the anlotinib plus S-1 group(N=26).Treatment-related adverse events(TRAEs)were predominantly grade 1/2 in both groups,with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab(P=0.033).Two patients(6.3%)developed grade 1/2 immune-related pneumonia.The incidence of grade 3/4 TRAEs did not differ significantly between the two groups.Multivariable Cox regression analysis identified that the drug regimen(P<0.001),Eastern Cooperative Oncology Group performance status(P=0.008),and differentiation grade(P=0.008)were independent prognostic factors for PFS.Conclusions:Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.
文摘This editorial comments on a study by Zuo et al.The focus is on the efficacy of he-patic arterial infusion chemotherapy combined with camrelizumab and apatinib(the TRIPLET regimen),alongside microwave ablation therapy,in treating advanced hepatocellular carcinoma(HCC).The potential application of this combination therapy for patients with advanced HCC is evaluated.
基金This study was supported by the Chinese Society of Clinical Oncology(CSCO)-Hengrui Oncology Research Fund(No.Y-HR2018-364)。
文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).
文摘Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16 F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic(PK)and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.
基金Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province of China(CXPJJH12000001-2020218).
文摘Immune checkpoint inhibitors are generally contraindicated for post-transplant patients.However,we report two patients with metastatic hepatocellular carcinoma(HCC)treated with camrelizumab(SHR-1210),an anti-programmed cell death 1(PD-1)agent,after liver transplant.Before undergoing immunotherapy,both patients underwent liver allograft biopsy and obtained negative PD-L1 expression in tumor and liver graft specimens by immunohistochemistry.Then,camrelizumab(200 mg)was administered once every 3 weeks.During immunotherapy,the targeted therapy was continued,and the immunosuppression regimen was adjusted to a low-dose level.No graft rejection or other severe adverse reactions were observed.The disease remained stable(SD,mRECIST)for 3 months in one patient and 10 months in the other.Therefore,camrelizumab may have safety and potential benefits in advanced HCC after liver transplant.
文摘BACKGROUND Primary liver cancer is the sixth most common cancer worldwide,with hepato-cellular carcinoma(HCC)being the most prevalent form.Despite the current availability of multiple immune or immune combination treatment options,the prognosis is still poor,so how to identify a more suitable population is extremely important.AIM To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus(HBV)-related HCC in Barcelona Clinic Liver Cancer(BCLC)stages B/C,considering various body mass index(BMI)in diffe-rent categories.METHODS Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab.Patients were divided into two groups based on BMI:The non-overweight group(BMI<25 kg/m2,n=51)and the overweight/obese group(BMI≥25 kg/m2,n=75).Short-term prognosis was evaluated using mRECIST criteria,with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.RESULTS Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group.Similarly,the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group.The objective remission rate and disease control rate for the two groups of patients were,respectively,objective remission rate(5.88%vs 28.00%)and disease control rate(39.22%vs 62.67%).Fatigue was more prevalent in the obese/overweight group,while other adverse effects showed no statistically significant differences(P>0.05).Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients,with obese patients showing the best outcomes.Multifactorial regression analysis identified BCLC grade,alpha-fetoprotein level,portal vein tumor thrombosis,and BMI as independent prognostic factors for OS.The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis,followed by alpha-fetoprotein level,BCLC classification,and portal vein tumor thrombosis.CONCLUSION BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab,and obese/overweight patients have a better prognosis.
文摘BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.
