Clinical Development and Therapeutic Applications of Bispecific Antibodies for Hematologic Malignancies.

Bispecific antibodies are composed of two monoclonal antibodies that engage T cells with tumor cell antigens and lead to tumor cell lysis. The most common types fall into the category of bispecific T cell engagers, or BiTEs, that have the canonical CD3-CD19 bispecific construct. Blinatumomab is the first bispecific antibody that received FDA approval for relapsed refractory B cell precursor acute lymphoblastic leukemia. Blinatumomab has been shown to have robust clinical outcomes and is associated with adverse events such as cytokine release syndrome and neurotoxicity. Other bispecific antibodies are under clinical investigation for multiple myeloma and acute myeloid leukemia. Along with immune checkpoint inhibitors and chimeric antigen T cell receptor therapies, bispecific antibodies are considered a mainstay as a therapeutic option for cancer immunotherapies for Hematologic malignancies.

Clinical sequelae of the novel coronavirus: does COVID-19 infection predispose patients to cancer?

As cancer patients are clinically known to be predisposed to COVID-19 infection, a corollary question of whether COVID-19 infection predisposes to cancer is explored. This article seeks to establish an association between novel coronavirus sequelae and cancer. A literature review on COVID-19 mechanisms of action, molecular responses it elicits upon infection and tumorigenesis pathways is conducted to establish this association. Major signaling pathways implicated in aberrant cellular growth are activated, the ensuing cytokine storm weakens the immune system response to tumors, and patients may develop cancer as a result of superimposed mutagenic and/or carcinogenic events. Future work needs to be performed to support this hypothesis, both in in vitro models and preclinical studies. COVID-19 patients may need to be monitored post-infection for developing cancer.

Clinical care of chimeric antigen receptor T-cell patients and managing immune-related adverse effects in the ambulatory and hospitalized setting: a review.

Chimeric antigen receptor (CAR) T-cell therapies are increasingly providing options for care of oncology patients with advanced hematologic malignancies, which has led to two US FDA approvals. However, they are often associated with significant immune related adverse events that require prompt management. These toxicities are mainly cytokine release syndrome and neurotoxicity, and can be managed in an appropriate setting when presenting to nononcologists or internists. This paper discusses patient management for these toxicities. A management approach can be determined by the severity of the toxicity. Tocilizumab, a humanized monoclonal antibody, was FDA approved for the treatment of cytokine release syndrome, and corticosteroids may be used. Neurotoxicity is generally managed with supportive care and steroidal therapy.