Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms

Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

<p>Abstract</p> <p>Background</p> <p>The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors.</p> <p>Methods</p> <p>We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity.</p> <p>Results</p> <p>Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (<it>p </it>< 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (<it>p </it>< 0.001, <it>p </it>< 0.001, <it>p </it>= 0.022, respectively) and normal skin (<it>p </it>< 0.001, <it>p </it>= 0.002, <it>p </it>= 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression.</p> <p>Conclusion</p> <p>Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.</p

Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another Metastatic Lesion in Malignant Melanoma Patients

Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the Food and Drug Administration as a treatment option for patients with unresectable melanoma without brain metastasis. In the literature, vemurafenib has been reported to be also effective against brain metastasis. We encountered 3 cases with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was clinically effective against metastatic lesions other than those in the brain. The brain lesions developed after the metastatic lesion had occurred. Therefore, we assume that the melanomas of the patients acquired resistance against vemurafenib. The brain metastases were treated with the cyberknife. Patients 1 and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH elevation died despite the treatment. We need to carefully follow patients on vemurafenib therapy because brain metastasis can suddenly occur even if the metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib against brain metastasis is poor in cases with LDH elevation

Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs). We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4). We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors