Clinical features, treatment, and outcome of nivolumab-induced cholangitis.

BACKGROUND: Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis. METHODS: Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023. RESULTS: Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve. CONCLUSIONS: Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.

Pembrolizumab in an HIV-infected patient with glioblastoma.

Persons living with human immunodeficiency virus (PLWH) carry increased risk for developing malignancies, including glioblastoma. Despite extensive investigations, both human immunodeficiency virus (HIV) and glioblastoma are incurable. Treatment for a patient with combined glioblastoma and HIV remains an unexplored need. Preliminary evidence suggests that immunotherapy may be effective for the simultaneous treatment of both HIV and cancer by reversing HIV latency and T cell exhaustion. We present a case of glioblastoma in a PLWH who was treated with pembrolizumab. Treatment was well tolerated and safe with a mixed response. Our patient did not develop any opportunistic infections, immune-related adverse events, or worsening of his immunodeficiency. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy.

Persons living with human immunodeficiency virus (PLWH) are at increased risk for cancers, including glioblastoma. Despite extensive research, both human immunodeficiency virus (HIV) and glioblastoma are incurable. The optimal treatment for concurrent HIV and glioblastoma is unknown. Early evidence suggests that immunotherapy can deplete residual HIV and restore immune function. We present a case of glioblastoma in a PLWH treated with immunotherapy. Treatment was well tolerated and safe. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy.

Case report: Sustained remission after combined sintilimab, anti-VEGF therapy, and chemotherapy in a patient with non-small cell lung cancer harboring acquired EGFR 19Del/T790M/cis-C797S mutation resistance.

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are highly effective against tumors harboring the T790M mutation. However, patients treated with these inhibitors ultimately develop resistance, and the most common mechanism is the emergence of the EGFR C797S mutation. Few treatment regimens have been reported for this condition. In this report, we present a successful combination treatment with the programmed cell death 1 (PD-1) inhibitor sintilimab, anti-vascular endothelial growth factor (VEGF) therapy, and chemotherapy with pemetrexed and cisplatin in a patient with non-small cell lung cancer (NSCLC) who developed acquired resistance with EGFR 19 exon deletion (19Del)/T790M/cis-C797S mutation following progression with ametinib therapy. This regimen was well tolerated, and the patient has remained progression-free for 15 months. Our case provides clinical evidence that the combination of PD-1 inhibitor, anti-VEGF therapy, and chemotherapy may be an efficacious therapeutic strategy for NSCLC patients with acquired EGFR 19Del/T790M/cis-C797S mutation resistance following progression with EGFR TKI therapy.

First­line programmed cell death 1 inhibitor plus chemotherapy vs. standard treatment in patients with recurrent or metastatic oral squamous cell carcinoma: A retrospective cohort study.

Programmed cell death 1 (PD-1) inhibitor revives the killing effect of immune cells to prevent tumor progression. The present study aimed to evaluate the efficacy and safety of first-line PD-1 inhibitor + chemotherapy vs. standard treatment in recurrent or metastatic (R/M) oral squamous cell carcinoma (OSCC). A total of 51 patients with R/M OSCC were reviewed and divided into the PD-1 inhibitor + chemotherapy (n=21) and standard treatment (n=30) groups based on their actual treatments. The results of the present study demonstrated that the objective response rate (52.4 vs. 36.7%, P=0.265) and disease control rate (81.0 vs. 70.0%, P=0.377) were numerically elevated in the PD-1 inhibitor + chemotherapy group compared with those in the standard treatment group; however, the results did not reach statistical significance. The progression-free survival (PFS) was numerically increased (without statistical significance) in the PD-1 inhibitor + chemotherapy group compared with that of the standard treatment group (P=0.057). Specifically, the PD-1 inhibitor + chemotherapy group and the standard treatment group exhibited a median [95% confidence interval (CI)] PFS duration of 6.7 (1.6-11.8) and 5.2 (3.4-7.0) months, respectively. In addition, the PD-1 inhibitor + chemotherapy group demonstrated increased overall survival (OS) compared with that of the standard treatment group (P=0.032). Specifically, the PD-1 inhibitor + chemotherapy group and the standard treatment group exhibited a median (95% CI) OS duration of 18.3 (11.9-24.7) and 10.3 (7.9-12.7) months, respectively. Furthermore, multivariate Cox regression analysis indicated that PD-1 inhibitor + chemotherapy was independently associated with improved PFS [hazard ratio (HR)=0.308, P=0.002] and OS (HR=0.252, P=0.003). In addition, the incidence of grade 3-5 adverse events (AEs) was relatively low in both groups and the incidence of any grade of each AE was not significantly different between groups (all P>0.050). In conclusion, the first-line PD-1 inhibitor + chemotherapy group had improved efficacy and comparable safety compared with those of the standard treatment in patients with R/M OSCC.

PD-1 blockade immunotherapy as a successful rescue treatment for disseminated adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with Epstein‒Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion.

BACKGROUND AND AIMS: The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI. METHODS: From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0. RESULTS: Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed. CONCLUSIONS: Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Early Changes of Serum Interleukin 14α Levels Predicts the Response to Anti-PD-1 Therapy in Cancer.

Background: Programmed cell death-1 (PD-1) blockade has been shown to confer clinical benefit in cancer patients. Here, we assessed the level of serum interleukin 14α (IL14α) in patients receiving anti-PD-1 treatment. Methods: This prospective study recruited 30 patients with advanced solid cancer who received pembrolizumab treatment in Northern Jiangsu People's Hospital between April 2016 and June 2018. The western blot analysis was used to assess the expression level of serum IL14α in patients at baseline and after 2 cycles of treatment. Interleukin 14α was performed using the unpaired 2-tailed Student test. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test. Results: The early change of IL14α after 2 cycles of anti-PD-1 therapy was calculated as delta IL14α % change = (IL14α level after 2 cycles - IL14α level before treatment)/IL14α level before treatment × 100%. Receiver operating characteristic (ROC) was analyzed to get a cutoff point of delta IL14α % change as 2.46% (sensitivity = 85.71%, specificity = 62.5%; area under the ROC curve [AUC] = 0.7277, P = .034). Using this cutoff to subgroup the patients, an improved objective response rate was observed in patients with a delta IL14α change higher than 2.46% (P = .0072). A delta IL14α change over 2.46% was associated with a superior PFS (P = .0039). Conclusions: Early changes of serum IL14α levels may be a promising biomarker to predict outcomes in patients with solid cancer following anti-PD-1 treatment.

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial.

BACKGROUND: Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a treatment for advanced non-small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD-(L)1] inhibitor failure. METHODS: Nab-paclitaxel (100 mg/m2 ) was administered on Days 1, 8, and 15 of a 28-day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD-(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%-79.6%) and the DCR was 86.2% (95% CI: 65.9%-97.0%). The median PFS was 5.6 months (95% CI: 4.4-6.7 months), and PFS rates at 1- and 2-year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8-23.0 months). Good performance status and responder of previous PD-(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). CONCLUSIONS: Nab-paclitaxel therapy improved ORR after PD-(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.

Correlation and efficacy of TACE combined with lenvatinib plus PD-1 inhibitor in the treatment of hepatocellular carcinoma with portal vein tumor thrombus based on immunological features.

BACKGROUND: Although the appearance of portal vein tumor thrombus (PVTT) is significantly associated with unfavorable prognosis, there is insufficient evidence to confirm the efficacy and safety of the triple combination of transarterial chemoembolization (TACE), lenvatinib, and programmed cell death-1 (PD-1) inhibitor for patients with hepatocellular carcinoma (HCC) and PVTT. Furthermore, it remains unclear which patient type can obtain the best survival benefit from this combination therapy. METHODS: The data of 160 patients with HCC and PVTT treated with TACE combined with lenvatinib plus PD-1 inhibitor (TACE+LEN + PD-1 group) or TACE combined with lenvatinib (TACE+LEN group) were retrospectively collected and analyzed. To estimate the efficacy and safety of combination therapy for patients with advanced HCC, tumor response, progression-free survival (PFS), overall survival (OS), biochemical indices, and adverse events (AEs) were assessed in this study. More importantly, tumor immune-related cytokines were used to identify biomarkers predicting the therapeutic response of combination therapy. RESULTS: TACE+LEN + PD-1 was superior to TACE+LEN in OS (23.5 vs. 18.3 months, p = 0.0002) and PFS (7.5 vs. 4.3 months, p < 0.0001). Moreover, TACE+LEN + PD-1 achieved more preferable benefits with respect to disease control rate (80.00% vs. 56.67%) and objective response rate (38.57% vs. 24.45%) compared with TACE+LEN in patients with HCC and PVTT (p = 0.025). Multivariate analysis showed that Child-Pugh grade, PVTT classification, treatment option, and interleukin (IL)-6, IL-17, interferon (IFN)-α, and vascular endothelial growth factor (VEGF) levels were independent factors related to OS, whereas PVTT classification, treatment option, and IL-6 and IFN-α levels were independent factors related to PFS. Furthermore, the subgroup analysis illustrated that the inflammatory cytokines VEGF, IL-6, IL-17, and IFN-α might be novel biomarkers for predicting the survival prognosis of patients with advanced HCC and PVTT treated with TACE+LEN + PD-1. The safety in the combination group was acceptable. CONCLUSIONS: Compared with TACE+LEN, the triple combination treatment of TACE+LEN + PD-1 has more promising clinical outcomes and acceptable safety in patients with HCC and PVTT. Child-Pugh grade, PVTT classification, and IL-6, IL-17, IFN-α, and VEGF levels are independent prognostic factors for survival time.

Prognostic value of esophageal cancer immune prognostic index in advanced esophageal squamous cell carcinoma patients with anti-programmed cell death-1 therapy.

BACKGROUND: This study aimed to determine whether the immune prognostic index (ECIPI), based on hemoglobin (Hb) and neutrophil-to-lymphocyte ratio (NLR), could predict the prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving programmed cell death-1 (PD-1) inhibitor treatment. METHODS: Advanced ESCC patients who had been treated with PD-1 inhibitors from Jan 2016 to Oct 2021 were included. Kaplan-Meier method and Cox proportional hazards regression were used to analyze progression-free survival (PFS) and overall survival (OS). The overall response rate (ORR) was the percentage of complete and partial responses. Univariate and multivariate analyses were used for estimating hazard ratio (HR) and 95% confidence interval (CI). Patients were grouped by ECIPI (good: Hb > 105 g/L and NLR ≤ 4.3; intermediate: Hb ≤ 105 g/L and NLR ≤ 4.3, or Hb > 105 g/L and NLR < 4.3; poor: Hb ≤ 105 g/L and NLR > 4.3). Variables for the multivariate model were selected if the p-value was below 0.05 in the univariate analysis. All statistical comparisons were two-way, and a p-value below 0.05 was set as statistical significance. RESULTS: Totally, of 123 ESCC patients with stage III or IV were included in the study. Efficacy evaluation showed that patients with pretreatment ECIPI good had the best ORR compared with those with ECIPI intermediate and ECIPI poor (53% vs. 22% vs. 8%, p < 0.01). Multivariate analysis showed that ECIPI was an independent influential factor for PFS (p = 0.004) and OS (p < 0.001). Kaplan-Meier curves demonstrated that patients with ECIPI good had the longest PFS (median: 11.6 vs. 3.5 vs. 1.7 months, p < 0.0001) and OS (median: 23.6 vs. 16.7 vs. 4.0 months, p < 0.0001) compared with those with ECIPI intermediate and ECIPI poor. Subgroup analysis indicated that ECIPI good was associated with improved PFS and OS in patients with ECOG 0-1, PD-1 inhibitor plus chemotherapy, first-line treatment, and smoke (all p < 0.05). CONCLUSIONS: Pretreatment ECIPI was associated with the prognosis in advanced ESCC patients with anti-PD-1 therapy, suggesting that ECIPI may be a useful tool to identify patients likely sensitive to PD-1 inhibitors.

Acute kidney injury in advanced lung cancer patients treated with PD-1 inhibitors: a single center observational study.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy is now the stand of care for lung cancer. Due to the low incidence, the study of acute kidney injury (AKI) in lung cancer patients treated with ICIs was hardly reported. We focused on the incidence, characteristics, risk factors, and mortality of AKI in advanced lung cancer patients receiving PD-1 inhibitors. METHODS: We reviewed advanced lung cancer patients receiving PD-1 inhibitors between January 2018 to August 2020 at Jiangsu Province Hospital. Patients were followed up for 6 months. We used the logistic regression model to evaluate risk factors for AKI, and Kaplan-Meier method to assess the association between AKI and mortality. RESULTS: A total of 305 advanced lung cancer patients treated with PD-1 inhibitors. The median age was 64 years and 80.6% of patients were male. The incidence of AKI was 10.2%, and the incidence of ICI-AKI was 4.6%. Multivariate analysis showed that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 2.509; 95% CI 1.053-5.974) and renin-angiotensin-aldosterone system (RAAS) inhibitors (OR 2.656; 95% CI 1.091-6.466) were risk factors for AKI. In addition, concomitant use of NSAIDs (OR 5.170; 95% CI 1.087-24.595) and RAAS inhibitors (OR 5.921; 95% CI 1.871-18.737), and the occurrence of extra-renal immune-related adverse events (OR 4.726; 95% CI 1.462-15.280) were significantly associated with ICI-AKI. ICI-AKI was not associated with mortality while severe AKI was associated with higher risk of mortality. CONCLUSION: AKI is common in advanced lung cancer patients treated with PD-1 inhibitors. The characteristics and risk factors of ICI-AKI were similar to those previously reported in other solid organ malignancies treated with ICIs. Severe AKI may indicate higher mortality.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study / 亚洲男科学杂志(英文版)

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Programmed cell death-1 inhibitor combined with immunochemotherapy in treatment of refractory primary mediastinal large B-cell lymphoma: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy of programmed cell death-1 (PD-1) inhibitor combined with immunochemotherapy in the treatment of refractory primary mediastinal large B-cell lymphoma (PMBCL).Methods:The clinical data of 2 refractory PMBCL patients who were achieving remission after applying PD-1 inhibitor combined with immunochemotherapy in Qilu Hospital of Shandong University (Qingdao) in July 2019 and January 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The two patients were initially treated with CDOPE and R-CDOPE regimens, respectively, but the disease did not reach remission state. Later, they were adjusted to PD-1 inhibitor combined with immunochemotherapy to achieve remission. Radiotherapy and autologous hematopoietic stem cell transplantation were used as consolidation treatment, and maintenance therapy with PD-1 inhibitors was effective and had a good safety profile.Conclusions:For refractory PMBCL patients, PD-1 inhibitor combined with immunochemotherapy may have good efficacy.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer.

Background: Thyroid transcription factor-1 (TTF-1) expression in advanced non-squamous non-small cell lung cancer (NSCLC) has been associated with the efficacy of pemetrexed plus platinum chemotherapy. However, the relation between TTF-1 expression and efficacy of the combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors plus pemetrexed and platinum chemotherapy, a standard first-line treatment regimen for advanced non-squamous NSCLC, has remained unclear. Methods: We retrospectively evaluated TTF-1 expression in tumor tissue of patients with advanced or recurrent non-squamous NSCLC treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting. Clinical characteristics and pathological data for each patient were assessed, and progression-free survival (PFS) was evaluated. Bias due to patient background was minimized by application of inverse probability of treatment weighting (IPTW) analysis. Results: A total of 122 patients, 75 (61.5%) of whom were positive for TTF-1 immunostaining in tumor specimens, was included in this multicenter study. At the time of analysis, 89 (73.0%) patients had experienced progression events and 44 (36.1%) had died [median follow-up 14.6 months (range, 0.53-29.5 months)]. PFS was longer for TTF-1-positive patients than for TTF-1-negative patients [median, 12.2 vs. 6.0 months; hazard ratio (HR) =0.63 (95% CI: 0.37-1.06); log-rank P=0.028]. IPTW-adjusted PFS was significantly longer for TTF-1-positive than for TTF-1-negative patients [HR =0.62 (95% CI: 0.46-0.83); log-rank P=0.024]. Conclusions: TTF-1 expression in advanced non-squamous NSCLC can serve as a basis for prediction of PFS in patients treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting.

Case report: Pneumonia with clinical symptoms precedes imaging evidence after immune checkpoint inhibitors combined with radiotherapy in lung squamous cell cancer.

Immune-checkpoint inhibitors (ICI) targeting programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) have quickly changed the treatment landscape in advanced non-small cell lung cancer. However, any patient treated with an immune checkpoint inhibitor is at risk for immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is a rare but potentially severe pulmonary toxicity of immunotherapy. Since the imaging features and symptoms are not specific, the diagnosis of CIP is challenging. In addition, CIP may mimic other lung diseases. Due to these characteristics, proper patient management may be delayed. So, a comprehensive understanding of imaging features is essential for a prompt detection and correct management of these drug-induced lung diseases. We presented a patient with lung squamous cell cancer who has clinical symptoms preceding imaging evidence of pneumonitis after immunotherapy and radiotherapy. We also discussed the safety of immunotherapy, the complexity and management of immune pneumonitis.

Hypophysitis: A rare but noteworthy immune-related adverse event secondary to camrelizumab therapy.

The programmed cell death 1 (PD-1) inhibitor - camrelizumab - is a promising agent for the treatment of several malignancies. Secondary hypophysitis has been reported in patients treated with the other PD-1 inhibitors such as nivolumab and pembrolizumab. However, camrelizumab-related hypophysitis has not yet been described. Herein, we report three cases of hypophysitis secondary to camrelizumab therapy. Case 1 was a 60-year-old male patient with non-small-cell lung carcinoma, who was diagnosed with central adrenal insufficiency associated with hypophysitis after 11 cycles of camrelizumab treatment (200 mg every 2 weeks). Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a 68-year-old male patient with hepatocellular carcinoma who received ten cycles of camrelizumab (200 mg every 2 weeks) plus apatinib (250 mg daily), before the diagnosis of hypophysitis. Steroid therapy was also efficacious. Case 3 was a 69-year-old male patient diagnosed with renal carcinoma. After eight cycles of camrelizumab therapy (200 mg every 2 weeks) combined with oral apatinib (250 mg daily), the patient presented with hypophysitis, which responded well to glucocorticoid therapy. These results suggest a caution for hypophysitis in patients treated with camrelizumab.

Type 1 diabetes mellitus induced by PD-1 inhibitors in China: a report of two cases.

The immune-related adverse events associated with immunotherapy may affect endocrine glands and other tissues. Two Chinese patients with malignancies were treated with programmed cell death-1 (PD-1) inhibitors (nivolumab and pembrolizumab) and followed up with biochemical tests over 1 year. After PD-1 treatment for 6 to 10 months, the patients developed symptoms of diabetes, ketoacidosis, and insulin secretion failure. Type 1 diabetes mellitus was confirmed by the characteristic fluctuation of blood glucose that was controlled with multiple daily insulin injections. Neither patient's insulin depletion status was reversed in subsequent years. To decrease the life-threatening complications of diabetic hyperosmolar syndrome and ketoacidosis caused by type 1 diabetes mellitus, it is necessary to monitor the blood glucose and hemoglobin A1c levels. Islet ß-cell autoantibodies and human leukocyte antigen genes can provide additional information in select cases.