Novel T Cell Therapies for Multiple Myeloma

Special Article - Multiple Myeloma

Ann Hematol Oncol. 2016; 3(11): 1120.

Novel T Cell Therapies for Multiple Myeloma

Suen H1,2*, Bryant C1,3, Hart D3 and Joshua D1

¹Department of Haematology, Royal Prince Alfred Hospital, University of Sydney, Australia

²School of Life Sciences, University of Technology Sydney, Australia

³Dendritic Cell Research, ANZAC Research Institute, University of Sydney, Australia

*Corresponding author: Hayley Suen, Department of Haematology, Royal Prince Alfred Hospital, University of Sydney, Missenden Road, Camperdown, Sydney, NSW 2050, Australia

Received: September 30, 2016; Accepted: October 28, 2016; Published: October 31, 2016


Multiple myeloma is a cancer of malignant plasma cells in the bone marrow and treatment has vastly improved in the last decade with the introduction of novel agents such as immunomodulatory drugs and proteasome inhibitors. New therapies are however required to eradicate residual disease and convert remission into cure. An increased understanding of immune defects in patients with myeloma has allowed for the development of immunotherapies that aim to unleash host T cells from tumour suppression and reactivate host immunity. Such T cell therapies are currently being trialled in patients producing promising results. In this review, we will describe the dysfunctional T cell landscape in myeloma, summarise the recent advances in T cell therapies and discuss future possibilities for myeloma treatment.

Keywords: Multiple myeloma; Immunotherapy; T cell; CAR-T cells; Immune checkpoint blockade; Adoptive T cell therapy


Despite significant therapeutic gains due to the use of immunomodulatory drugs (IMiDs) and proteasome inhibitors in MM, all patients eventually relapse from persisting residual disease and MM remains incurable [1]. New therapies are required to eradicate residual disease and promote long term survival. Immunotherapy in conjunction with standard chemotherapy may be the avenue to long-term remissions and ultimately cures [2,3]. There is both direct and indirect evidence that immunological control of the malignant myeloma cells is possible. Allogeneic hematopoietic stem cell transplantation, the prototypic cellular immune therapy, can cure myeloma; however it is associated with high morbidity and mortality [4]. Indirect evidence for host anti-tumour activity includes the observation of pre-malignancy specific effector T cells in the bone marrow of patients with monoclonal gammopathy of undetermined significance (MGUS) [5], patients with disease in plateau phase, where a significant tumour load is detected but the disease remains stable and suggests a degree of host immune control [6] and the correlation between expanded CD8+ cytotoxic T cell clones and improved survival [7-10]. Whilst the immune system has the ability to target and eradicate MM tumour cells, this ability is hampered by widespread immune dysfunction in MM, which affects the T cell compartment, in particular cytotoxic T cells, which are the predominant type of effector cell involved in immune-mediated cancer destruction [11]. Tumour-induced mechanisms incapacitate immune cells, including tumour-specific cytotoxic T cells, thus permitting tumour evasion and consequent progression [12]. In this review, we will highlight the current abnormalities in the T cell landscape in MM and the development of T cell therapies for MM. In particular, we will review the use of IMiDs, checkpoint inhibitors, adoptive T cell therapy, dendritic cell (DC) vaccination and alternative approaches to MM treatment (Figure 1).

Citation:Suen H, Bryant C, Hart D and Joshua D. Novel T Cell Therapies for Multiple Myeloma. Ann Hematol Oncol. 2016; 3(11): 1120. ISSN : 2375-7965