Rapidly Fatal Dissemination of Merkel Cell Carcinoma in a Patient Treated with Alemtuzumab for Chronic Lymphocytic Leukemia.

Alemtuzumab is FDA-approved for the treatment of chronic lymphocytic leukemia (CLL). Nonetheless, its use for this indication has fallen out of favor due to serious concerns for infectious complications and increased risks of second malignancies from the profound and lasting immunosuppression. We report here in a patient with a rapidly progressive metastatic Merkel cell carcinoma (MCC) who was previously treated with alemtuzumab and fludarabine for CLL. He developed profound lymphopenia and hypogammaglobulinemia. While the risk of MCC is increased in CLL, its rapid dissemination has not been previously reported with fludarabine alone. In light of the rapidly fatal outcome in our patient due to MCC, we advise caution with the use of alemtuzumab. In patients treated with alemtuzumab for nononcologic indications, aggressive surveillance for cutaneous malignancies should be implemented until its safety profile can be further characterized.

Omalizumab therapy for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) responds to a variety of immunosuppressive agents and usually controls, but does not cure, the disease. Omalizumab, Food and Drug Administration-approved for asthma, selectively suppresses the activity of IgE, an important immunoglobulin in the pathogenesis of BP. OBJECTIVE: We wished to determine if systemic omalizumab would have a therapeutic effect in patients with BP. METHODS: We treated 6 patients with BP using omalizumab and followed up their disease for up to 42 months. RESULTS: Although variable, 5 of the 6 patients with BP received therapeutic benefit from systemic omalizumab (the sixth terminated treatment because of intercurrent illness) with less use of other immunosuppressants, inhibition of new bullae, less pruritus, and dramatic decreases in eosinophil counts. None of the patients had untoward side effects from omalizumab. LIMITATIONS: This was an open, uncontrolled study. CONCLUSIONS: Omalizumab neutralizes the activity of IgE in patients with BP and improves the control of their disease activity.

Differential Molecular Expression Patterns Associated with Metastasis in Cutaneous Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

The majority of cutaneous squamous cell carcinomas are treated by surgical removal; however, approximately 4% of tumors will metastasize. Molecular expression testing may improve accuracy in estimating the prognosis and defining the mechanisms important in the disease progression, which may impact response to therapy. Using PubMed (MEDLINE) and EMBASE, a systematic review was performed to evaluate studies published from January 2005 to August 2019 reporting tumor protein or RNA expression along with either outcomes (metastasis or death) or a comparison of primary with metastatic tumor samples. Inclusion criteria were met by 45 studies containing 81 comparisons of 44 distinct proteins and 25 microRNAs. On meta-analysis of studies analyzing primary tumor samples in terms of later outcomes, high primary tumor expression of PD-L1 (OR = 2.34, 95% confidence interval = 1.09-5.02, P = 0.030), EGFR (OR = 2.57, 95% confidence interval = 1.24-5.33, P = 0.011), and podoplanin (OR = 2.33, 95% confidence interval = 1.00-5.41, P = 0.049) conferred increased odds for metastasis. In comparison, metastatic tissue was more likely to have a high expression of PD-L1 than primary tissue (OR = 3.13, 95% confidence interval = 1.00-9.75, P = 0.049). Further studies are needed to confirm whether testing for PD-L1, EGFR, and podoplanin expression aids in cutaneous squamous cell carcinomas prognostic estimation of metastasis or death or predicts response to therapy.

Use of mutated self-cleaving 2A peptides as a molecular rheostat to direct simultaneous formation of membrane and secreted anti-HIV immunoglobulins.

In nature, B cells produce surface immunoglobulin and secreted antibody from the same immunoglobulin gene via alternative splicing of the pre-messenger RNA. Here we present a novel system for genetically programming B cells to direct the simultaneous formation of membrane-bound and secreted immunoglobulins that we term a "Molecular Rheostat", based on the use of mutated "self-cleaving" 2A peptides. The Molecular Rheostat is designed so that the ratio of secreted to membrane-bound immunoglobulins can be controlled by selecting appropriate mutations in the 2A peptide. Lentiviral transgenesis of Molecular Rheostat constructs into B cell lines enables the simultaneous expression of functional b12-based IgM-like BCRs that signal to the cells and mediate the secretion of b12 IgG broadly neutralizing antibodies that can bind and neutralize HIV-1 pseudovirus. We show that these b12-based Molecular Rheostat constructs promote the maturation of EU12 B cells in an in vitro model of B lymphopoiesis. The Molecular Rheostat offers a novel tool for genetically manipulating B cell specificity for B-cell based gene therapy.