AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.M...AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.展开更多
BACKGROUND A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediate...BACKGROUND A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition.CASE SUMMARY We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur.CONCLUSION Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.展开更多
Background: Following approval of ipilimumab, this observational cohort study (CA184-332) was initiated to describe patient and disease characteristics, patterns of care, survival, and adverse events (AEs) in advanced...Background: Following approval of ipilimumab, this observational cohort study (CA184-332) was initiated to describe patient and disease characteristics, patterns of care, survival, and adverse events (AEs) in advanced melanoma (AM) patients treated with first-line ipilimumab in realworld US community practice. Methods: Adult patients with treatment-naive AM who received ≥1 dose of ipilimumab 3 mg/kg between April 2011 and September 2012 were retrospectively identified at US Oncology sites. Clinical data were abstracted from patient medical records. Results: Median age of the 157 patient cohorts was 66 years (range 21 - 91). 68.2% were male, and 90.5% had a cutaneous primary site. At ipilimumab initiation, 80.9% of patients had an ECOG performance status of 0 or 1;54.1% were stage M1c;34.4% had brain metastases;24.8% had elevated lactate dehydrogenase, and 13.4% were positive for BRAF mutation. All 4 cycles of ipilimumab were completed by 55.8% of patients. At a median follow-up of 8.5 months (range 2.9 - 15.0), median overall survival was 11.5 months (95% CI: 8.9 - 16.6) and 1-year survival was 46.7% (95% CI: 38.1 - 54.9). During ipilimumab treatment, AEs were experienced by 63.7% of patients. The most frequent AEs were gastrointestinal (41.4%;diarrhea in 19.1%) and skin-related (28.0%;rash in 17.8%);17.8% of patients had an AE that led to ipilimumab discontinuation. Conclusions: These real-world results are consistent with those from clinical trials and provide evidence supporting the effectiveness and safety of first-line ipilimumab 3 mg/kg monotherapy in patients with AM treated in a community practice setting.展开更多
Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review o...Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.展开更多
Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern.The resultan...Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern.The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects.One of the most concerning effects is the development of colitis.Upwards to 8% of patients have been reported to develop colitis, with 5% being severe(Grades 3-4).While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids.Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids.We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.展开更多
Administration of ipilimumab,a cytotoxic T-lymphocyte associated antigen-4-blocking monoclonal antibody,leads to enhancement of the anti-tumor T-cell respons and as a result shows a significant survival benefit in met...Administration of ipilimumab,a cytotoxic T-lymphocyte associated antigen-4-blocking monoclonal antibody,leads to enhancement of the anti-tumor T-cell respons and as a result shows a significant survival benefit in metastatic melanoma patients.Therefore patients are currently receiving this promising therapy as a secondline strategy.Unfortunately,by activation of the T-cell immune reponse,ipilimumab therapy may lead to an unwanted induction of different autoimmune phenomena.Diarrhoea and colitis occur in up to one third of patients.Here we present a case of ipilimumab induced ileocolitis which was successfully treated with infliximab,an anti-tumor necrosis factor monoclonal antibody,after corticosteroid therapy failure.Although formal trials are lacking,recently publicated series suggest that infusional therapy of infliximab is effective in ipilimumab induced ileocolitis.展开更多
As the treatment landscape for advanced melanoma continues to evolve, it is critical to focus on unmet needs and understand the cost of therapy. While Ipilimumab (IPI), an immunotherapy indicated for unresectable adva...As the treatment landscape for advanced melanoma continues to evolve, it is critical to focus on unmet needs and understand the cost of therapy. While Ipilimumab (IPI), an immunotherapy indicated for unresectable advanced melanoma, has been a mainstay of 1<sup>st</sup>-line treatment, there was no standard of care following progression until recently. The objective of this study was to examine real-world treatment patterns and healthcare costs following IPI use in advanced melanoma patients prior to the anti-PD-1 class approval. Adult stage III or IV melanoma patients treated with IPI were selected between April 1, 2011, and September 30, 2013, from a large U.S. commercial and Medicare claims database. Patients were evaluated for therapy after IPI, with an index date set as the first systemic therapy after IPI. Per-Patient Per-Month (PPPM) healthcare costs while on active treatment were evaluated from index until treatment discontinuation, inpatient death, end of insurance enrollment, or September 30, 2013. Of 361 eligible patients, 111 (30.7%) initiated subsequent systemic therapy (mean age, 57 years;64.9% male). The most common therapies, single-agent or combination, included vemurafenib (32.4%), paclitaxel (28.8%), temozolomide (20.7%), and carboplatin (17.1%). During a median follow-up of 130 days, mean [standard deviation] PPPM all-cause total healthcare costs were $20,383 [$18,988], of which $4800 (23.6%), $5899 (28.9%), and $9684 (47.5%) were related to melanoma drug costs, medical claims with a diagnosis of melanoma, and other (non-specified) utilization, respectively. When considering total care, the costs of U.S. patients with advanced melanoma post-IPI were substantial across all commonly used agents.展开更多
The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an exp...The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV (hepatitis B virus) and HCV (hepatitis C virus) infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.展开更多
Melanoma is a malignant neoplasm that affects the melanocytes. Its treatment is based on cancer staging. In immunotherapy, it can be pointed out the ipilimumab, used in the systemic therapy for unresectable and/or met...Melanoma is a malignant neoplasm that affects the melanocytes. Its treatment is based on cancer staging. In immunotherapy, it can be pointed out the ipilimumab, used in the systemic therapy for unresectable and/or metastatic melanoma in the first or the second line treatment with increased survival. However, limiting toxicity and the low complete response discourage its use in the elderly patients. The aim of this study is to report the case of an 83-year-old man, white, with scalp melanoma measuring 3.5 cm in its major axis. After two resections was verified that the deep margin was involved, making the lesions unresectable. The evaluation of distant metastasis, by skull, chest and abdomen CT-scan (computed tomography-scan), was performed and did not detect the presence of any metastatic loci. The patient underwent the first cycle of chemotherapy with DTIC (dacarbazine) protocol. After the first cycle, the medication was discontinued due to significant myelotoxicity and Grade 3 thrombocytopenia. Underwent second line treatment with ipilimumab by four cycles. After this, the patient follow with complete local response, asymptomatic, with no signs of local recurrence or distant metastasis site, and no limiting toxicity during and after a year of treatment with ipilimumab. Thus, it is possible to suggest that the use of ipilimumab isolatedly as a second line treatment may have a good response even in elderly patients.展开更多
Immune checkpoint inhibitors are today an immense hope in the management of cancers. However, since their widespread use, many cases of insulin-requiring diabetes appearing suddenly, as fulminant diabetes have been re...Immune checkpoint inhibitors are today an immense hope in the management of cancers. However, since their widespread use, many cases of insulin-requiring diabetes appearing suddenly, as fulminant diabetes have been reported. Here, we describe 4 cases that occurred at different times after the beginning of immune checkpoint inhibitor therapy with Nivolumab alone or associated with Ipilimumab. There are 3 cases of newly diagnosed diabetes and 1 case of known type 2 diabetes formerly quite well balanced with Metformin. The clinical and biological characteristics of these patients are quite similar. They were all insulin-requiring at the discovery of diabetes and remained so throughout their follow-up. This type of diabetes which looks like type 1 diabetes seems rather to be a new entity.展开更多
1文献来源研究一:Hellmann MD,Ciuleanu TE,Pluzanski A,et al.Nivolumab plus Ipilimumab in lung cancer with a high tumor mutational burden[J].N Engl J Med,2018,378(22):2093-2104.研究二:Hellmann MD,Paz-Ares L,Bernabe Caro ...1文献来源研究一:Hellmann MD,Ciuleanu TE,Pluzanski A,et al.Nivolumab plus Ipilimumab in lung cancer with a high tumor mutational burden[J].N Engl J Med,2018,378(22):2093-2104.研究二:Hellmann MD,Paz-Ares L,Bernabe Caro R,et al.Nivolumab plus Ipilimumab in advanced non-small-cell lung cancer[J].N Engl J Med,2019,381(21):2020-2031.2证据水平1b。3背景纳武利尤单抗联合伊匹木单抗治疗非小细胞肺癌(non-small-cell lung cancer,NSCLC)在Ⅰ期临床试验中获得很好疗效,肿瘤突变负荷(tumour mutation burden,TMB)是潜在的生物标志物,但仍需Ⅲ期临床试验来探索在TMB高(≥10个突变/Mb)的人群中双免疫治疗对比含铂双药化疗的无进展生存期(progression-free survival,PFS)。展开更多
文摘AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.
文摘BACKGROUND A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition.CASE SUMMARY We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur.CONCLUSION Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.
文摘Background: Following approval of ipilimumab, this observational cohort study (CA184-332) was initiated to describe patient and disease characteristics, patterns of care, survival, and adverse events (AEs) in advanced melanoma (AM) patients treated with first-line ipilimumab in realworld US community practice. Methods: Adult patients with treatment-naive AM who received ≥1 dose of ipilimumab 3 mg/kg between April 2011 and September 2012 were retrospectively identified at US Oncology sites. Clinical data were abstracted from patient medical records. Results: Median age of the 157 patient cohorts was 66 years (range 21 - 91). 68.2% were male, and 90.5% had a cutaneous primary site. At ipilimumab initiation, 80.9% of patients had an ECOG performance status of 0 or 1;54.1% were stage M1c;34.4% had brain metastases;24.8% had elevated lactate dehydrogenase, and 13.4% were positive for BRAF mutation. All 4 cycles of ipilimumab were completed by 55.8% of patients. At a median follow-up of 8.5 months (range 2.9 - 15.0), median overall survival was 11.5 months (95% CI: 8.9 - 16.6) and 1-year survival was 46.7% (95% CI: 38.1 - 54.9). During ipilimumab treatment, AEs were experienced by 63.7% of patients. The most frequent AEs were gastrointestinal (41.4%;diarrhea in 19.1%) and skin-related (28.0%;rash in 17.8%);17.8% of patients had an AE that led to ipilimumab discontinuation. Conclusions: These real-world results are consistent with those from clinical trials and provide evidence supporting the effectiveness and safety of first-line ipilimumab 3 mg/kg monotherapy in patients with AM treated in a community practice setting.
文摘Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.
基金Supported by Med Star Georgetown University Hospital,Washington,DC,United States
文摘Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern.The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects.One of the most concerning effects is the development of colitis.Upwards to 8% of patients have been reported to develop colitis, with 5% being severe(Grades 3-4).While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids.Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids.We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.
文摘Administration of ipilimumab,a cytotoxic T-lymphocyte associated antigen-4-blocking monoclonal antibody,leads to enhancement of the anti-tumor T-cell respons and as a result shows a significant survival benefit in metastatic melanoma patients.Therefore patients are currently receiving this promising therapy as a secondline strategy.Unfortunately,by activation of the T-cell immune reponse,ipilimumab therapy may lead to an unwanted induction of different autoimmune phenomena.Diarrhoea and colitis occur in up to one third of patients.Here we present a case of ipilimumab induced ileocolitis which was successfully treated with infliximab,an anti-tumor necrosis factor monoclonal antibody,after corticosteroid therapy failure.Although formal trials are lacking,recently publicated series suggest that infusional therapy of infliximab is effective in ipilimumab induced ileocolitis.
文摘As the treatment landscape for advanced melanoma continues to evolve, it is critical to focus on unmet needs and understand the cost of therapy. While Ipilimumab (IPI), an immunotherapy indicated for unresectable advanced melanoma, has been a mainstay of 1<sup>st</sup>-line treatment, there was no standard of care following progression until recently. The objective of this study was to examine real-world treatment patterns and healthcare costs following IPI use in advanced melanoma patients prior to the anti-PD-1 class approval. Adult stage III or IV melanoma patients treated with IPI were selected between April 1, 2011, and September 30, 2013, from a large U.S. commercial and Medicare claims database. Patients were evaluated for therapy after IPI, with an index date set as the first systemic therapy after IPI. Per-Patient Per-Month (PPPM) healthcare costs while on active treatment were evaluated from index until treatment discontinuation, inpatient death, end of insurance enrollment, or September 30, 2013. Of 361 eligible patients, 111 (30.7%) initiated subsequent systemic therapy (mean age, 57 years;64.9% male). The most common therapies, single-agent or combination, included vemurafenib (32.4%), paclitaxel (28.8%), temozolomide (20.7%), and carboplatin (17.1%). During a median follow-up of 130 days, mean [standard deviation] PPPM all-cause total healthcare costs were $20,383 [$18,988], of which $4800 (23.6%), $5899 (28.9%), and $9684 (47.5%) were related to melanoma drug costs, medical claims with a diagnosis of melanoma, and other (non-specified) utilization, respectively. When considering total care, the costs of U.S. patients with advanced melanoma post-IPI were substantial across all commonly used agents.
文摘The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV (hepatitis B virus) and HCV (hepatitis C virus) infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.
文摘Melanoma is a malignant neoplasm that affects the melanocytes. Its treatment is based on cancer staging. In immunotherapy, it can be pointed out the ipilimumab, used in the systemic therapy for unresectable and/or metastatic melanoma in the first or the second line treatment with increased survival. However, limiting toxicity and the low complete response discourage its use in the elderly patients. The aim of this study is to report the case of an 83-year-old man, white, with scalp melanoma measuring 3.5 cm in its major axis. After two resections was verified that the deep margin was involved, making the lesions unresectable. The evaluation of distant metastasis, by skull, chest and abdomen CT-scan (computed tomography-scan), was performed and did not detect the presence of any metastatic loci. The patient underwent the first cycle of chemotherapy with DTIC (dacarbazine) protocol. After the first cycle, the medication was discontinued due to significant myelotoxicity and Grade 3 thrombocytopenia. Underwent second line treatment with ipilimumab by four cycles. After this, the patient follow with complete local response, asymptomatic, with no signs of local recurrence or distant metastasis site, and no limiting toxicity during and after a year of treatment with ipilimumab. Thus, it is possible to suggest that the use of ipilimumab isolatedly as a second line treatment may have a good response even in elderly patients.
文摘Immune checkpoint inhibitors are today an immense hope in the management of cancers. However, since their widespread use, many cases of insulin-requiring diabetes appearing suddenly, as fulminant diabetes have been reported. Here, we describe 4 cases that occurred at different times after the beginning of immune checkpoint inhibitor therapy with Nivolumab alone or associated with Ipilimumab. There are 3 cases of newly diagnosed diabetes and 1 case of known type 2 diabetes formerly quite well balanced with Metformin. The clinical and biological characteristics of these patients are quite similar. They were all insulin-requiring at the discovery of diabetes and remained so throughout their follow-up. This type of diabetes which looks like type 1 diabetes seems rather to be a new entity.
文摘1文献来源研究一:Hellmann MD,Ciuleanu TE,Pluzanski A,et al.Nivolumab plus Ipilimumab in lung cancer with a high tumor mutational burden[J].N Engl J Med,2018,378(22):2093-2104.研究二:Hellmann MD,Paz-Ares L,Bernabe Caro R,et al.Nivolumab plus Ipilimumab in advanced non-small-cell lung cancer[J].N Engl J Med,2019,381(21):2020-2031.2证据水平1b。3背景纳武利尤单抗联合伊匹木单抗治疗非小细胞肺癌(non-small-cell lung cancer,NSCLC)在Ⅰ期临床试验中获得很好疗效,肿瘤突变负荷(tumour mutation burden,TMB)是潜在的生物标志物,但仍需Ⅲ期临床试验来探索在TMB高(≥10个突变/Mb)的人群中双免疫治疗对比含铂双药化疗的无进展生存期(progression-free survival,PFS)。