Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma.

Relapsed/refractory (RR) multiple myeloma (MM) patients are a fragile population because of prolonged drug exposure and advanced age. Preserving a good quality of life is of high priority for these patients and the treatment of disease- and treatment-related complications plays a key role in their management. By preventing and limiting MM-induced complications, supportive care improves patients' outcome. Erythropoietin-stimulating agents and bisphosphonates are well-established supportive strategies, yet novel agents are under investigation, such as anabolic bone agents and activin receptor-like kinase (ALK) inhibitors. The recent dramatic changes in the treatment landscape of MM pose an additional challenge for the routine care of RRMM patients. Multidrug combinations in first and later lines increase the risk for long-lasting toxicities, including adverse cardiovascular and neurological events. Moreover, recently approved first-in-class drugs have unique side-effect profiles, such as ocular toxicity of belantamab mafodotin or gastrointestinal toxicity of selinexor. This review discusses current standards in supportive treatment of RRMM patients, including recommendations in light of the recent SARS-CoV-19 pandemic, and critically looks at the incidence and management of side effects of standard as well as next generation anti-MM agents.

Cytokine Release Syndrome Associated with T-Cell-Based Therapies for Hematological Malignancies: Pathophysiology, Clinical Presentation, and Treatment.

Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few decades, the development of therapeutic monoclonal antibodies and T-cell therapies has rapidly evolved, and CRS can be a serious adverse event related to these treatments. CRS is a set of toxic adverse events that can be observed during infection or following the administration of antibodies for therapeutic purposes and, more recently, during T-cell-engaging therapies. CRS is triggered by on-target effects induced by binding of chimeric antigen receptor (CAR) T cells or bispecific antibody to its antigen and by subsequent activation of bystander immune and non-immune cells. CRS is associated with high circulating concentrations of several pro-inflammatory cytokines, including interleukins, interferons, tumor necrosis factors, colony-stimulating factors, and transforming growth factors. Recently, considerable developments have been achieved with regard to preventing and controlling CRS, but it remains an unmet clinical need. This review comprehensively summarizes the pathophysiology, clinical presentation, and treatment of CRS caused by T-cell-engaging therapies utilized in the treatment of hematological malignancies.