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Objective:To compare the clinical efficacy of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer (NSCLC) , and to explore its impact on tumor marker levels and immune function index, as well as to perform safety analysis.Methods:A total of 87 patients with advanced NSCLC who were treated in Hai'an People's Hospital of Jiangsu Province from May 2019 to May 2021 were selected as the research objects. According to the treatment scheme, the patients were divided into camrelizumab group ( n=41) and sintilimab group ( n=46) . The clinical efficacy, prognosis, tumor marker levels, immune function index and immune related adverse reactions of the two groups were compared. Results:There were no statistically significant differences in objective response rate [48.78% (20/41) vs. 39.13% (18/46) , χ2=0.82, P=0.365] or disease control rate [78.05% (32/41) vs. 71.74% (33/46) , χ2=0.46, P=0.499] in both camrelizumab and sintilimab group. The median progression-free survival (PFS) in the camrelizumab group was 9.1 months, and the median overall survival (OS) was 15.4 months. The median PFS in the sintilimab group was 9.7 months, and the median OS was 15.7 months. There were no statistically significant differences in median PFS and median OS between the two groups ( χ2=0.18, P=0.633; χ2=0.15, P=0.697) . Before treatment, there were no statistically significant differences in carcinoembryonic antigen (CEA) [ (47.68±8.12) ng/ml vs. (49.03±8.70) ng/ml, t=0.75, P=0.458], cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) [ (18.06±3.41) ng/ml vs. (17.25±3.78) ng/ml, t=1.05, P=0.299], and carbohydrate antigen 125 (CA125) [ (72.26±21.06) U/ml vs. (74.03±22.10) U/ml, t=0.38, P=0.704] levels between the camrelizumab group and sintilimab group. After treatment, there were no statistically significant differences in CEA [ (28.11±7.68) ng/ml vs. (27.63±5.71) ng/ml, t=0.33, P=0.740], CYFRA21-1 [ (9.29±1.88) ng/ml vs. (9.06±1.80) ng/ml, t=0.15, P=0.814], and CA125 [ (61.39±21.22) U/ml vs. (60.51±11.03) U/ml, t=0.25, P=0.806] levels between the two groups, but CEA, CYFRA21-1, and CA125 levels decreased after treatment compared with those before treatment in both groups (all P<0.05) . Before treatment, there were no statistically significant differences in T cells CD4 + [ (41.15±3.24) % vs. (41.17±2.90) %, t=0.03, P=0.976], CD8 + [ (68.82±3.94) % vs. (70.06±4.08) %, t=1.44, P=0.154], and CD4 +/CD8 + (1.88±0.33 vs. 1.76±0.25, t=1.92, P=0.058) between the two groups. After treatment, there were no statistically significant differences in T cells CD4 + [ (47.08±3.22) % vs. (48.53±5.07) %, t=1.57, P=0.120], CD8 + [ (61.22±1.67) % vs. (61.45±1.66) %, t=0.64, P=0.522], and CD4 +/CD8 + (2.31±0.17 vs. 2.36±0.12, t=1.60, P=0.114) between the two groups, while T cells CD8 + was lower than that before treatment, and CD4 + as well as CD4 +/CD8 + were higher than those before treatment in both groups (all P<0.05) . The overall incidence of adverse reactions in the sintilimab group [10.87% (5/46) ] was lower than that in the camrelizumab group [31.71% (13/41) ], and with a statistically significance ( χ2=5.74, P=0.016) . Conclusion:The clinical efficacy of camrelizumab and sintilimab in NSCLC patients is basically the same, the impacts of which on tumor markers and immune function are comparable, but the safety of sintilimab is better than that of camrelizumab.
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Immune checkpoint inhibitors (ICIs) are currently used in the treatment of various tumors and play an important role in tumor treatment, resulting in many adverse reactions related to the immune system. Type 1 diabetes (T1DM) is a rare endocrine system complication, which is rarely reported at present. We report a case of T1DM after using ICIs to treat gastric cancer. The patient was a 34 year old male who developed diabetes ketoacidosis after 206 days of sintilimab monoclonal antibody use, with fasting blood glucose of 15.78 mmol/L and glycosylated hemoglobin of 8.6%. Islet related antibody: Glutamate decarboxylase antibody: 119.2 IU/mL; Insulin antibody:<2 IU/L. Fasting insulin: 0.21 mU/L; Fasting C-peptide: 0.12 μg/L. Through the analysis of patients' clinical data, it aims to improve clinicians' understanding of immune related type 1 diabetes and provide ideas for correct diagnosis and treatment.
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A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30％of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.
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Objective To investigate the clinical efficacy and safety of the combination PP(Pemetrexed+Cisplatin)regimen of sindilizumab(Sintilimab)+bevacizumab(Bevacizumab)in advanced non-squamous non-small cell lung cancer(NSCLC)with disease progression after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors.Methods Patients with advanced non-squamous NSCLC with disease progression after receiving EGFR tyrosine kinase inhibitor treatment from January 2019 to January 2022 were retrospectively selected from The Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine.According to the different treatment modalities,patients were divided into the pemetrexed+cisplatin treatment group(Chemotherapy)group and the pemetrexed+cisplatin+si ndilizumab+bevacizumab treatment(Sintilimab+Bevacizumab)group.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR)and disease control rate(DCR)were compared between the two groups and the occurrence of adverse reactions was assessed.Results A total of 107 patients were enrolled in the study,53 in the Sintilimab+Bevacizumab group and 54 in the Chemotherapy group.The median PFS and median OS were significantly higher in the Sintilimab+Bevacizumab group than in the Chemotherapy group(P＜0.05).The median PFS and median OS in the Sintilimab+Bevacizumab group were significantly higher than in the Chemotherapy group.Bevacizumab group had no statistically significant difference in ORR with Chemotherapy group(P＞0.05),while DCR was significantly higher than Chemotherapy group(P＜0.05).The main adverse reactions were similar in both groups with the most common adverse events being anemia and neutrophils decrease.Conclusion Sintilimab+Bevacizumab combined with PP regimen treatment improved DCR and prolonged PFS and OS in patients with advanced non-squamous NSCLC whose disease progressed after EGFR tyrosine kinase inhibitor treatment.
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OBJECTIVE To evaluate the cost-effectiveness of sintilimab combined with chemotherapy than single-use chemotherapy in the first-line treatment of advanced， recurrent or metastatic esophageal squamous cell carcinoma （ESCC） from the perspective of health system of our country， and provide reference for rational use of drug in clinic. METHODS Based on ORIENT-15 study data， TreeAge Pro 2011 software was used to establish a three-state Markov model of non-progressive survival （PFS）， disease progression and death for cost-utility analysis. The model period was 3 weeks， the research time limit was 10 years， and the discount rate was 5%. The main outputs of the model were total cost， quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER）. The 1-3 times of China’s GDP per capita in 2021 was taken as the threshold of willing- ness to pay （WTP）. The uncertainty of the parameters was analyzed by single factor sensitivity analysis and probability sensitivity analysis， and the cost-effectiveness of the two schemes was discussed under three situations： different discount rates， comparison with other similar treatment schemes and charitable drug donation schemes. RESULTS The results of basic analysis showed that compared with chemotherapy plan alone， the ICER of sintilimab combined with chemotherapy was 64 208.75 yuan/QALY， which was less than WTP threshold. The results of single factor sensitivity analysis show that PFS state utility value， cycle cost of sintilimab and discount rate had relatively great influence on the results. Probability sensitivity analysis showed that when WTP≥120 000 yuan， the economic probability of sintilimab combined with chemotherapy plan was 100%. The results of situational analysis showed that sintilimab combined chemotherapy was more cost- effective than single-use chemotherapy. CONCLUSIONS Sintilimab combined with chemotherapy is more cost-effective than single-use chemotherapy in the first-line treatment of advanced， recurrent or metastatic ESCC.
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Objective To investigate the clinical efficacy and safety of fruquintinib combined with sintilimab in the treatment of advanced microsatellite stable (MSS) colorectal cancer. Methods A retrospective study of 44 patients with MSS colorectal cancer treated with fruquintinib and sintilimab was conducted.The patients were divided into the fruquintinib alone (n=22) and fruquintinib combined with sintilimab (n=22) groups.The treatment regimen was as follows: The patients in the fruquintinib alone group consumed oral fruquintinib capsules at 5 mg/d once for three consecutive weeks with a one week stop in 28 day cycles.The patients in the fruquintinib combined sintilimab group were injected intravenously with sintilimab (200 mg) once per three weeks, and fruquintinib was used in the same manner as the fruquintinib alone group. Results The objective response rate (ORR) of the fruquintinib alone group was 9.09%, the disease control rate (DCR) of the fruquintinib alone group was 45.45%.The ORR of the fruquintinib combined with sintilimab group was 18.18%, and the DCR was 63.64%.The median PFS of the fruquintinib alone and fruquintinib combined with sintilimab groups were 4.4 months (IQR: 2.1-8.2) and 6.7 months (IQR: 3.9-12.6), respectively (χ2=4.372, P=0.037).Most of the adverse reactions during the treatment of the two groups were grades 1-2.In addition, no significant difference in the incidence of adverse reactions was found between two groups (P > 0.05). Conclusion Compared with fruquintinib alone, fruquintinib combined with sintilimab in the treatment of patients with MSS colorectal cancer after the failure of standard treatment has better clinical efficacy, and adverse drug reactions can be controlled.
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OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
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Humanos , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Etoposídeo , Recidiva Local de Neoplasia/tratamento farmacológico , Asparaginase , Desoxicitidina , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma Extranodal de Células T-NK/terapia , Oxaliplatina/uso terapêuticoRESUMO
Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. .
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Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
OBJECTIVE From the perspective o f China ’s h ealth service system ，to ev aluate the cost-effectiveness of sintilimab combined with chemotherapy in the first-line treatment of advanced or recurrent non-small cell lung cancer （NSCLC），so as to provide reference for the selection of clinical medication plan and medical and health decision-making. METHODS Based on the ORIENT-11 study data ，a partitioned survival model was established ，and the model period was 21 days to simulate the death of 99％ of the patients. Using quality-adjusted life years （QALY）as an output indicator ，the cost-effectiveness of sintilimab combined with chemotherapy （trial group ）versus chemotherapy alone （control group ）in the first-line treatment of advanced or recurrent NSCLC was evaluated. Cost and utility were discounted using 5％ discount rate ；sensitivity analysis and scenario analysis were used to verify the robustness of the underlying analysis results. RESULTS Under the premise that 3 times of the per capita gross domestic product （GDP）of China in 2020 was used as the threshold of willingness-to-pay （WTP），the patients in the trial group obtained more utility （0.482 QALY）and also spent nearly twice as much as the control group. The incremental cost-effectiveness ratio（ICER）was 334 974.41 yuan/QALY. Univariate sensitivity analysis showed that progression-free survival status utility value ， pemetrexed price ，utility discount rate ，cost discount rate and sintilimab price had a greater impact on ICER. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times of China ’s per capita GDP in 2020，the probability of the trial group ’s plan being cost-effective was 6.5％. The results of the scenario analysis verified the robustness of the underlying analysis results. CONCLUSIONS On the premise of taking 3 times of China ’s per capita GDP in 2020 as the WTP threshold ， sintilimab combined with chemotherapy is not cost-effective for first-line treatment of advanced or recurrent NSCLC compared with chemotherapy alone.
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OBJEC TIVE To investigate the status and clinical characteristics of adverse drug reactions （ADRs）induced by sintilimab in order to provide references for clinical rational drug use. METHODS The cases of ADR induced by sintilimab were retrieved from the databases of PubMed ，Embase，CNKI，VIP and Wanfang. RESULTS A total of 32 literature were included ， involving 33 patients among which there were 25 males（75.76％）and 8 females（24.24％）. The incidence of ADRs was higher in patients aged over 40 years（81.82％）. The dose of sintilimab was the drug instructions recommended dose （200 mg）for 30 patients and 100 mg for a patient. The earliest ADR occurred 1 h after the first medication ，the latest ADR occurred after 14 cycles of sintilimab. The 27 cases suffered from ADR cases （81.82％）within 4 months after medication ，and no reports of ADR occurred after 12 months of medication. The major manifestations of ADR were myocarditis ，diabetes mellitus ，checkpoint inhibitor pneumonitis（CIP），cytokine release syndrome （CRS）and hypothyroid myopathy （HM），etc. CRS and HM belonged to ADRs not recorded in the drug instructions. The 29 cases of recovery and 4 deaths occurred after symptomatic treatment. CONCLUSIONS ADR caused by sintilimab often occurs within 4 months after treatment ，and it is high in males and patients over 40 years old. In clinical application of sintilimab ，attention should be paid to the occurrence of myocarditis ，diabetes mellitus ，CIP，as well as CRS and HM not recorded in the drug instructions.
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Objective To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [ CI ]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95% CI : 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P =0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95% CI : 5.6-17.6) vs 2.8 months (95% CI : 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95% CI: 7.9-11.3) vs 21.9 months (95% CI : 0-44.9), P =0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95% CI : 9.0-24.2) vs 6.9 months (95% CI : 3.6-10.2), P =0.011]. Conclusion Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.
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Objective:To observe the efficacy of sintilimab combined with apatinib in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Eighty-two patients with advanced NSCLC who were admitted to Nantong Cancer Hospital from October 2019 to September 2020 were selected for a prospective controlled study. They were divided into control group (treated with apatinib) and combination group (treated with sintilimab + apatinib) using the random number table method, with 41 cases in each group. The short-term clinical efficacy, tumor markers [neuron specific enolase (NSE), cytokeratin 19 fragment antigen (CYFRA21-1)], adverse reactions during treatment and survival were compared between the two groups.Results:The objective remission rate and clinical control rate in the combination group were higher than those in the control group [41.46% (17/41) vs. 19.51% (8/41), 85.37% (35/41) vs. 58.54% (24/41)], and the differences were statistically significant ( χ2 values were 4.66 and 7.31, both P < 0.05). The levels of NSE and CYFRA21-1 in the combination group were lower than those in the control group after treatment [(19.04±2.54) ng/ml vs. (21.35±3.11) ng/ml, (4.58±1.02) μg/L vs. (6.07±1.84) μg/L], and the differences were statistically significant ( t values were 3.68 and 4.54, both P < 0.001). There were no statistical differences in the incidence rates of gastrointestinal reaction, bone marrow depression, fatigue, and liver and kidney function damage between the combination group and the control group during treatment (all P > 0.05). The survival rate of the combination group was higher than that of the control group (71.79% vs. 47.50%), and the difference was statistically significant ( χ2 = 4.84, P = 0.028). Conclusions:Sintilimab combined with apatinib may improve clinical efficacy, reduce tumor marker levels, and improve short-term survival rate of advanced NSCLC patients.
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Objective To evaluate the safety of programmed cell death protein 1 (PD-1) inhibitor in the treatment of primary liver cancer (liver cancer) before liver transplantation. Methods Clinical data of 7 recipients given with PD-1 inhibitor before liver transplantation for liver cancer were retrospectively analyzed. The incidence of immune-related adverse event (irAE) and clinical prognosis of the recipients were summarized. The safety of PD-1 inhibitor in recipients prior to liver transplantation for liver cancer was evaluated. Results Seven recipients were treated with PD-1 inhibitor with 1-20 courses before liver transplantation for liver cancer. The time interval from drug withdrawal to liver transplantation was 6-120 d. Five recipients suffered from irAE of different degrees, including fatigue in 3 cases, fever in 2 cases, alopecia in 2 cases, rash in 1 case, nausea in 1 case and myocarditis in 1 case, respectively. A majority of these irAE were classified as grade Ⅰ-Ⅱ. One recipient died from grade Ⅴ irAE (fatal myocarditis). One recipient developed rejection at postoperative 7 d, which were mitigated after glucocorticoid pulse therapy combined with increased dosage of tacrolimus. Conclusions PD-1 inhibitor can be applied in preoperative treatment before liver transplantation for liver cancer. Nevertheless, the incidence of irAE and postoperative rejection should be intimately monitored.
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Objective: To investigate the preliminary efficacy and safety of axitinib plus sintilimab in the treatment of intermediate- and high-risk advanced renal cell carcinoma. Methods: A retrospective study of patients with advanced renal cell carcinoma treated with axitinib and sintilimab was conducted in Peking University Cancer Hospital & Institute between April 2019 to December 2019. There were seven cases of clear-cell renal cell carcinoma and three cases of non-clear-cell renal cell carcinoma.All patients received 200 mg sintilimab intravenously every 3 weeks and 5 mg axitinib orally twice daily. Objective response rate (ORR), progression-free survival (PFS), and adverse effects were analyzed. Result: With the median age of 58.5 years (range 43.0-67.0), the patients were all classified as intermediate- and high-risk patients, according to the international metastatic renal cell carcinoma database consortium (IMDC) criteria. The overall ORR was 40.0% (4/10), and the disease control rate (DCR) was 90.0% (9/10). The ORR was 57.1% (4/7) in patients with clear-cell renal cell carcinoma. The main adverse effects included elevation of hepatic transaminases (number of patients, n=4; 40.0%), hypothyroidism (n=4; 40.0%), nausea (n=3; 30.0%), hypertension (n=2; 20.0%), and hand-foot skin reaction (n=2; 20.0%). Most adverse effects were of grade 1 or 2, but grade 3-4 adverse events occurred in three patients.Most adverse effects were ameliorated by effective symptomatic treatment. Conclusions: Axitinib plus sintilimab achieved promising ORR and DCR in patients with intermediate- and high-risk advanced renal cell carcinoma, with tolerable adverse effects.
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Monoclonal antibodies (mAbs) have been widely used as therapeutic drugs for treating diseases such as cancers and auto-immune diseases. When using an IgG4 isotype, one of the challenges is the instability of its hinge which is prone to Fab-arm exchange (FAE). The hinge sequence of a wild type IgG4 is -CPSC-, however, a single point mutation S228P from -CPSC- to -CPPC- can effectively diminish FAE, thereby improving hinge stability of the IgG4 molecule. Sintilimab is the fully human anti-PD-1 monoclonal antibody designed and developed for immuno-oncology, in which serine 228 in the hinge was engineered to proline to mitigate FAE. In this study, LC-MS is used to study hinge stability of sintilimab in both in vitro (PBS and human serum) and in vivo (SCID mouse) studies. The studies demonstrate that LC-MS is a fast and simple way to monitor for the occurrence of FAE in vitro and in vivo, and FAE can be eliminated by antibody engineering with a single point mutation.