Dr John Jones Senior Lecturer in Haemato-oncology, Consultant Haematologist and a member of LMRUK’s Research and Review Committee, breaks down what myeloma is and explores the treatment options currently available.
Multiple myeloma is a cancer of plasma cells, which are immune cells normally responsible for producing antibodies. In myeloma, abnormal plasma cells accumulate in the bone marrow and produce large amounts of ineffective antibodies, termed a ‘paraprotein’, or antibody fragments called ‘light chains’. The cancerous plasma cells and their products cause damage to the bones, reduce healthy blood production, impair kidney production and weaken the immune system.
The disease was once associated with very poor long-term survival, but treatment advances over the past two decades have transformed outcomes for most patients. Modern therapy now combines targeted drugs, immunotherapy, stem cell transplantation, and increasingly personalised treatment strategies.
Current treatment approaches depend on the stage of disease (newly diagnosed or relapsed), patient fitness, and genetic risk profile. Initial therapy often includes combinations of immunomodulatory drugs such as lenalidomide, proteasome inhibitors such as bortezomib, corticosteroids, and monoclonal antibodies including daratumumab. Eligible patients may also undergo autologous stem cell transplantation, which can deepen remission and prolong disease control.
Maintenance therapy, particularly with lenalidomide, is commonly used after transplantation to delay relapse. For relapsed disease, newer agents including carfilzomib, pomalidomide, and antibody-drug conjugates, such and belantamab offer additional options, but the most recent promising advances have come from immune-based therapies.
Bispecific antibodies, including elranatamab, teclistamab, and talquetamab, are now available for relapsed patients through the NHS. These drugs work by redirecting the immune system towards myeloma cells and can be administered “off-the-shelf,”.
Another approach is CAR-T cell therapy, which involves engineering a patient’s own T cells to target proteins such as BCMA on myeloma cells. Clinical trials have shown remarkably high response rates, even in heavily pre-treated patients. It is hoped that CAR-T therapy will be available through the NHS shortly.
Research underway today is changing the outlook for patients. Current studies are examining earlier use of CAR-T therapy, dual-target and trispecific antibodies, and treatments guided by minimal residual disease (MRD) testing to personalise therapy intensity. Researchers are also investigating new immune targets such as FcRH5 to overcome resistance after BCMA-directed treatment.
Novel oral CELMoD drugs, including mezigdomide, have shown encouraging trial results in relapsed disease. Some early studies are even exploring whether treating precursor conditions, such as MGUS and smouldering myeloma, before full myeloma develops may prevent progression entirely.
As a result of these advances survival rates for myeloma have improved dramatically. In the 1970s, median survival was less than three years. With the introduction of proteasome inhibitors, immunomodulatory agents, monoclonal antibodies, maintenance strategies and with multiple options at relapse, the average survival is beyond 10 years and considered more of a chronic condition for many patients.
Despite this, challenges remain, including side effects of treatments, infections and in patients who develop treatment resistance. However, the pace of innovation in myeloma research is exceptionally rapid. Many experts now believe that continued advances in immune-based therapy and precision medicine may eventually make long-term disease control, and functional cure for some patients, a realistic goal.
