Immune therapies in the treatment of multiple myeloma.

Abstract

This special issue of the American Journal of Hematology is devoted to immune therapies in the treatment of multiple myeloma. It was made possible by an unrestricted grant support from Janssen and by the tireless editorial leadership of Dr. Shaji Kumar, who served as Guest-Editor. This issue would not have been possible without the constant care and attention of Kurt Polesky, Health Science Sales Manager at Wiley. Five articles in these issues cover different fields and applications of immune-based therapies for multiple myeloma. Prof. Dhodapkar in “The immune system in multiple myeloma and precursor states: Lessons and implications for immunotherapy and interception”1 discussed how chronic B-cell activation is an essential component of the cellular environment associated with monoclonal gammopathy of undetermined significance (MGUS), the precursor phase of multiple myeloma. Even at this initial phase, MGUS cells may be sensitive to immune or preventative therapies. In multiple myeloma, tumor cells are sensitive to immune effectors, but there is a generalized immune suppression of both intrinsic and extrinsic T-cell functions, which has multiple determinants, including tumor-associated immune suppression, and host-related and environmental or therapy-associated factors, all resulting in impaired tumor- and pathogen-specific immune function. Ravi and Costa in “Bispecific T-cell engagers for treatment of multiple myeloma”2 discuss the defects in T cell and dendritic cell functions, which underly the therapeutic approach of recovering tumor antigen recognition and tumor killing activities with bispecific T cell engagers (TCEs). TCEs combine the capability of simultaneously engaging high affinity binding sites in antigens of the tumor cells and low-affinity binding to CD3. The combined interactions result in T cell receptor activation and ultimately lysis of the tumor cells. Leong et al. in “Antibody drug conjugates for the treatment of multiple myeloma”3 describe a new therapeutic approach based on the use of antibody drug conjugates (ADCs). ADCs are humanized or human monoclonal antibodies chemically linked to a payload consisting of drugs that bind to surface receptors of tumor cells and are cytotoxic when internalized by receptor-mediated endocytosis. Clinical trials results and associated toxicities are discussed for multiple members of this new class. Lancman et al. in “Trial designs and endpoints for immune therapies in multiple myeloma”4 highlight challenges in trial design, which include selection and consideration of specific patient characteristics (age and performance status, renal compromise, high risk/extramedullary disease, and prior immune therapies) and safety monitoring such as the proper identification and recognition of immune-related toxicities, and of infection and hypogammaglobulinemia. Relevant endpoints for this type of studies include not only the canonical ones such a progression-free-survival, overall survival, and minimal residual disease, but also depth of response and time to response and quality of life as well. Ludwig and Kumar in “Prevention of infections including vaccination strategies in multiple myeloma”5 discuss how the immune dysfunction associated with multiple myeloma confers extreme susceptibility to viral or bacterial infections. They provide a comprehensive review and discussion of both pharmacologic and immune (vaccine)-based prophylaxes with detailed recommendations for preventing infections in patients with multiple myeloma. I'm certain that the AJH readers will find these five articles both instructive and clinically relevant in their daily practice. The authors declare that there is no conflict of interest.