Multiple Autoimmune Complications After a Single Dose of Pembrolizumab.

Pembrolizumab, a monoclonal antibody that inhibits programmed cell death protein-1 (PD-1), is an important treatment for various malignancies. Unfortunately, it has also been associated with a wide array of immune-related adverse events. We present a unique case of a patient who received a single dose of pembrolizumab and subsequently developed multiple immune-mediated complications, including dermatitis, hepatitis, myositis, myocarditis, and myasthenia gravis.

A Review of the Abscopal Effect in the Era of Immunotherapy.

The abscopal effect is a systemic immune response mediated by the effects of radiation on the immune system. This effect has been observed in a number of cancer types in addition to lung cancer, including but not limited to renal cell carcinoma, hepatocellular carcinoma, lymphoma, and melanoma. The combination of radiation therapy and immune checkpoint inhibition (ICI) acts at several stages of the antitumor response, suggesting a mechanism of synergy between the two modalities. This review focuses on recent advances in the understanding of the effect of radiation and immunotherapy in the context of the abscopal effect.

De-novo acute myeloid leukemia in a BRCA positive female with locally treated ductal carcinoma In Situ.

Acute myeloid leukemia (AML) is primarily a disease of older adults and can arise de novo, in relation to previous treatment or in the setting of underlying hematological disease. While it is known to arise from chemoradiation in the setting of breast cancer, little is known about the association between BRCA carriers and AML. We report a case of a young female BRCA carrier who develops de novo AML without prior chemoradiation treatment, and examine if there is a link between BRCA and developing leukemia.

High-Risk Mantle Cell Lymphoma in the Era of Novel Agents.

PURPOSE OF REVIEW: Mantle cell lymphoma (MCL) is a heterogenous disease with a variety of morphologic and genetic features, some of which are associated with high risk disease. Here we critically analyze the current state of the understanding of MCL's biology and its implications in therapy, with a focus on chemotherapy-free and targeted therapy regimens. RECENT FINDINGS: Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma, defined by a hallmark chromosomal translocation t(11;14) which leads to constitutive expression of cyclin D1. Recent discoveries in the biology of MCL have identified a number of factors, including TP53 mutations and complex karyotype, that lead to unresponsiveness to traditional chemoimmunotherapy and poor outcomes. Bruton tyrosine kinase inhibitors, BH3-mimetics and other novel agents thwart survival of the neoplastic B-cells in a manner independent of high-risk mutations and have shown promising activity in relapsed/refractory MCL. These therapies are being investigated in the frontline setting, while optimal responses to chemotherapy-free regimens, particularly in high-risk disease, might require combination approaches. High-risk MCL does not respond well to chemoimmunotherapy. Targeted agents are highly active in the relapsed refractory setting and show promise in high-risk disease. Novel approaches may soon replace the current standard of care in both relapsed and frontline settings.

DA-REPOCH Versus R-CHOP for the Treatment of Activated B-Cell Subtype Diffuse Large B-Cell Lymphoma: A Community Center Experience.

Diffuse large B-cell lymphoma (DLBCL) represents around one quarter of non-Hodgkin lymphomas in both the United States and globally. The activated B-cell (ABC) subtype of DLBCL is associated with higher relapse rates and a worse prognosis when treated with standard regimens in comparison to other subtypes of DLBCL. Recent studies have demonstrated a potential benefit with combination of dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-REPOCH) in comparison to standard combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in ABC DLBCL patients. We aimed to see if there was any benefit on progression-free survival (PFS) and overall survival (OS) in a pooled patient population from a community oncology practice with the use of DA-REPOCH in ABC DLBCL. Our study did not reveal a statistically significant advantage in either PFS or OS with DA-REPOCH; however, a smaller percentage or patients progressed or relapsed when treated with DA-REPOCH. While the toxicity profile was similar, a higher percentage of patients receiving R-CHOP experienced grade 3 or higher toxicities. A prospective trial of R-CHOP versus DA-REPOCH in patients with the ABC subtype of DLBCL is warranted to further determine a potential benefit to DA-REPOCH in this patient population.

Intraductal Tubulopapillary Neoplasm of the Pancreas Presenting as a Localized Pancreatic Tumor in a 52-Year-Old Woman: Focusing on a Rare Pancreatic Malignancy and Contrasting to Intrapapillary Mucinous Neoplasm.

Intraductal tubulopapillary neoplasm (ITPN) is a distinctive type of pancreatic tumor first discovered more than three decades ago. ITPNs currently account for less than 1% of all pancreatic exocrine tumor cases recognized, and less than 5% of pancreatic intraductal tumors. A patient's presentation is often nonspecific in comparison to other intraductal pancreatic neoplasms. We discuss a 52-year-old female presenting with abdominal pain and weight loss with ITPN, and go on to define the typical presentation, clinical features, and pathology behind the tumor.

Highlighting Survival with Yttrium-90 Radioembolization Therapy in Unresectable Hepatocellular Carcinoma.

Unresectable hepatocellular carcinoma has several different therapeutic options, including targeted agents as well as locoregional therapy. Yttrium-90 (Y90) radioembolization therapy is an established treatment for unresectable disease and has been compared to other locoregional options as well as different targeted therapies. Newer case series are also reporting a potential benefit to the addition of immunotherapy to Y90 radioembolization. Here we report a case of prolonged survival in a patient whose treatment course included Y90 radioembolization along with sorafenib and nivolumab.

Acute Hypersensitivity Pneumonitis Associated With a High Ki-67 Proliferative Index.

Hypersensitivity pneumonitis (HSP) is an interstitial lung disease caused by exposure to a large range of environmental antigens. Inhaling aerosolized particles leads to a heightened immune response. HSP comes in acute, subacute, or chronic forms, all with their own potential clinical and radiographic findings. Mycobacterium avium complex (MAC) is the most common nontuberculous mycobacteria and is known to cause HSP with certain exposures. However, although certain histologic findings can be seen with HSP, a high ki-67 proliferation index is unusual and more commonly associated with malignancy. In this report, we discuss a case of MAC that had acute HSP associated with a high ki-67 proliferative index.

Cell Death Pathways in Lymphoid Malignancies.

PURPOSE OF REVIEW: This review highlights the importance of the Bcl-2 family members in lymphoma cell survival and discusses the approaches to modulate their function, directly or indirectly, to advance lymphoma therapeutics. RECENT FINDINGS: The balance of cell death versus survival is ultimately leveraged at the mitochondria. Mitochondrial outer membrane permeabilization (MOMP) is the critical event that governs the release of pro-apoptotic molecules from the intermembrane mitochondrial space. MOMP is achieved through the coordinated actions of pro- and anti-apoptotic Bcl-2 family member proteins. Recognition of functional alterations among the Bcl-2 family member proteins led to identification of tractable targets to combat hematologic malignancies. A new class of drugs, termed BH3 mimetics, was introduced in the clinic. Venetoclax, a Bcl-2 inhibitor, received regulatory approvals in therapy of chronic lymphocytic leukemia and acute myeloid leukemia. Alternative pro-survival Bcl-2 family proteins, in particular Mcl-1, have been successfully targeted in preclinical studies using novel-specific BH3 mimetics. Finally, anti-apoptotic Bcl-2 family members may be targeted indirectly, via interference with the pro-survival signaling pathways, e.g., phosphoinotiside-3 kinase, B-cell receptor signaling, and NF-κB.