CAR T-Cell Therapy for Multiple Myeloma (MM)

Introduction: Multiple myeloma (MM) is an incurable haematological malignancy characterised by clonal expansion of abnormal plasma cells in the bone marrow. MM affects around 384 people in Ireland each year, and the median age of diagnosis is 65 years. A diagnosis of MM is indicated by greater than 10% plasma cells in the bone marrow, and evidence of end-organ damage (hypercalcemia, renal insufficiency, anaemia and bone lesions). Typical treatment of MM comprises a combination of several drug classes, normally three or four, including proteasome inhibitors, immunomodulatory agents, monoclonal antibodies, alkylating agents and corticosteroids. Treatment aims to get the patient into deep remission, to achieve the best chance of progression free survival, as eventually all patients will relapse.

The current standard-of-care treatment approach is to treat MM continuously to maximise treatment response and achieve deeper remission, both at diagnosis and relapse. As a result, patients require many hospital visits, may experience continuous side effects, and additionally this has financial implications. Chimeric antigen receptor (CAR) T-cell therapy has changed this treatment paradigm approach. CAR T-cell therapy is administered as a single treatment and provided a patient responds, does not require continuous maintenance therapy. CAR T-cell therapy has emerged in recent years as a promising treatment strategy for many blood cancers. CARs are genetically engineered T-cell receptors designed to target a tumour-associated antigen and promote T-cell mediated death. CAR T-cell therapy is currently FDA approved for both early and later stages of MM.