UNASSIGNED: The treatment of metastatic prostate cancer has been revolutionized with the advent of many targeted therapies, including immunotherapy. Pembrolizumab has demonstrated benefit in the treatment of certain patients with docetaxel-refractory metastatic castrate-resistant prostate cancer (mCRPC). However, extrapolation of these data to patients with HIV is limited, as these patients are conventionally excluded from therapeutic clinical trials. This study aims to develop a better understanding of the clinical outcomes of HIV positive patients with prostate cancer treated with immunotherapy. A review of the literature is conducted on the use of immunotherapy in HIV positive patients with prostate cancer, and a summary is presented of two clinical cases from a single institution.
UNASSIGNED: This is a retrospective case report of 2 patients diagnosed with prostate cancer and HIV who received treatment with pembrolizumab. Quantitative analysis was performed to summarize patient demographics, clinical history, and outcomes.
UNASSIGNED: Two patients with mCRPC and HIV on highly active antiretroviral therapy were identified. Both individuals had biochemical and radiographic response to treatment with pembrolizumab. The duration of response for individual 1 is >31 months and 14 months for individual 2. Neither patient had immune-related adverse events or decreased suppression of their HIV infection. One patient died from disease progression after 14 months of treatment and the other remains on treatment with pembrolizumab to date.
UNASSIGNED: In this small case series, pembrolizumab appears to be a safe and effective treatment option for HIV positive patients with metastatic prostate cancer.

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, but aggressive, type of B-cell lymphoma. Patients with relapsed refractory PMBCL (rrPMBCL) have limited therapeutic options and usually have a relatively poor outcome. Immune checkpoint blockade has become a potential treatment for this disease. We report here a case of a female patient with rrPMBCL who was treated with nivolumab plus gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. Complete remission was achieved after four cycles of combined therapy. With continued nivolumab maintenance monotherapy, she has remained in complete remission for longer than 28 months. This is the first report of nivolumab plus GDP chemotherapy inducing complete remission in patient with rrPMBCL. This case supplements the limited literature and provides implications for clinical trial designs regarding the potential use of nivolumab in the treatment of rrPMBCL.

Cancer cells utilize multiple mechanisms to evade and suppress anticancer immune responses creating a \"cold\" immunosuppressive tumor microenvironment. Oncolytic virotherapy is emerging as a promising approach to revert tumor immunosuppression and enhance the efficacy of other forms of immunotherapy. Growing evidence indicates that oncolytic viruses (OVs) act in a multimodal fashion, inducing immunogenic cell death and thereby eliciting robust anticancer immune responses. In this review, we summarize information about OV-mediated immune conversion of the tumor microenvironment. As a case study we focus on the rodent protoparvovirus H-1PV and its dual role as an oncolytic and immune modulatory agent. Potential strategies to improve H-1PV anticancer efficacy are also discussed.

Hemophagocytic Lymphohistiocytosis (HLH), a rare but potentially fatal syndrome of immune hyperactivation, may be an under-recognized immune-related adverse event (irAE). Unlike other irAEs, HLH triggered by immune checkpoint blockade is not well described; no particular diagnostic guidelines and treatment regimens exist. The HLH-2004 criteria remain as the common diagnostic guide. For the treatment of HLH, various combinations of chemotherapeutic, immunosuppressive and glucocorticoid agents are used.
We report a case of HLH in a 58-year-old metastatic melanoma patient who was undergoing immune checkpoint blockade with pembrolizumab, a programmed cell death-1 (PD-1) receptor inhibitor. The patient presented with fever, upper normal sized spleen, anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, reduced NK cell activity and elevated sCD163 levels, fulfilling the Histiocyte Society HLH-2004 diagnostic criteria. Our patient was successfully treated with oral prednisone (1 mg/kilogram/day), suggesting that HLH from immune checkpoint inhibitors may respond to steroids alone.
Early diagnosis and treatment of HLH are critical to avoid progressive tissue damage, organ failure and possibly death. HLH should be suspected in clinical presentations with fever, cytopenias and hyperinflammatory markers. HLH in the setting of immune checkpoint blockade may be treated with steroids only but further evidence is required.

BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response.
METHODS: Case #1: A 43-year-old Caucasian male with Stage III melanoma of the left knee had subsequent nodal, hepatic and osseous metastases and was started on ipilimumab/nivolumab. He developed an intractable headache one week later. MRI revealed new enhancing and hemorrhagic brain metastases. After 6 weeks of immunotherapy, there was interval hemorrhage of a dominant intracranial lesion but substantial improvement in systemic metastatic disease. Durable, near complete intracranial and systemic response was achieved after completion of both induction and maintenance immunotherapy. Case #2: A 58-year old Caucasian woman with stage II melanoma of the right index finger developed cutaneous, pulmonary and hepatic metastases within 4 months of adjuvant radiation. Although combined checkpoint blockade resulted in improvement in both cutaneous and systemic disease, brain MR performed for eye discomfort demonstrated new enhancing and hemorrhagic brain metastases. Serial MR imaging five months later revealed only a solitary focus of brain enhancement with continued improved systemic disease.
CONCLUSIONS: These cases raise the question of whether the initial immune activation and modulation of the blood brain barrier by Ipilimumab/Nivolumab somehow \"unmasks\" previously clinically silent metastatic disease, rather than representing new or progressive metastatic disease. An overview of currently available literature discussing the role of immune checkpoint blockade in the treatment of intracranial metastatic melanoma will be provided, as well as discussion highlighting the need for future work elucidating the response of brain metastases to anti-CTLA/PD-1 drugs and documentation of brain-specific adverse events.

BACKGROUND: Checkpoint blocking agents such as pembrolizumab or nivolumab may induce a diversity of mostly autoimmune-mediated side effects. These autoimmune phenomena mainly affect ductless glands such as the pituitary gland (hypophysitis), the thyroid gland (thyreoiditis), the skin (vitiligo and rash), the colon (colitis), and the lung (pneumonitis). Furthermore, many other organs or organ systems may be affected.
METHODS: This work describes a case of an immune thrombocytopenia that developed or rather became clinically significant shortly after initiation of a systemic therapy with first nivolumab and later pembrolizumab given due to metastatic melanoma. Platelet counts before this systemic therapy were slightly decreased with values around 110/nl (normal value 140-400/nl). Thrombocytopenia developed or became apparent rapidly within 10 days after the first intravenous application of nivolumab and worsened after changeover to pembrolizumab. Therapy had to be stopped due to disease progression and steady aggravation of thrombocytopenia. Immune hematology assays could prove an autoimmune mediated genesis of thrombocytopenia.
CONCLUSIONS: Checkpoint inhibitors may induce a multiplicity of mostly autoimmune-mediated side effects. In contrast to chemotherapy-induced cytopenia that results from bone marrow toxicity, thrombocytopenia in melanoma patients treated with checkpoint inhibiting substances seems to result from autoimmune-mediated side effects in the majority of the cases. Thorough laboratory controls during these therapies are therefore required. In case of thrombocytopenia, immune hematology testing to diagnose or rule out immune thrombocytopenia is indispensable.