The maladies of multiple myeloma

Dr Lucille Sarah Singh sheds lights on how multiple myeloma affects the body and why indefinite follow-ups are needed.

Mention breast or lung cancer and people generally know what it means: a cancer starting in the breast or in the lungs. However, mention multiple myeloma (MM) and most people have no frame of reference. Is there an organ or tissue called myeloma? 

MM is a cancer arising in plasma cells which reside in our bone marrow. These plasma cells are an important part of our immune system as they produce antibodies. Abnormal plasma cells can still produce antibodies, albeit non-functional antibodies, which are secreted into the blood. On laboratory tests, this dud antibody, termed M-protein, is often the first diagnostic clue that someone has MM. 

Abnormal plasma cells and M-proteins can be seen outside the setting of MM so the mere presence of an M-protein isn’t enough for diagnosis. Besides the M-protein in blood and proving malignant plasma cells on bone marrow biopsy, other changes are needed to support the diagnosis.

How multiple myeloma affects the body

The malignant plasma cells can give rise to lytic bone lesions which on scans look like moth eaten holes. It’s not surprising that bone pain is often the first symptom. Calcium leaches out of the bone and a high calcium level is detected on blood tests. The bones can become brittle and minimal trauma results in fractures. 

The bone marrow is the manufacturing centre for blood cells. Further increases in the plasma cell population will result in a fall in the other blood cell lines causing anaemia; this manifests as progressive fatigue. Patients with MM often require blood transfusions. Low platelets can result in easy bruising and bleeding. A low neutrophil count can result in infections. 

The antibody or parts thereof that the cancerous plasma cells produce can also cause problems. The kidneys have to work harder to clear the increased protein load and can fail, meaning some patients may require dialysis. Even with appropriate treatment, kidney damage is sometimes irreversible and patients require life-long dialysis. The antibody fragments can deposit in other tissues causing dysfunction e.g. heart, liver, peripheral nerves. 

Sometimes the malignant plasma cells can form a clump usually in association/next to bone, but can occur in any tissue and present as a lump. This is called a plasmacytoma. Biopsy of the mass will show malignant plasma cells. 

True to its name, MM causes multiple lesions in bone but also directly and indirectly affects multiple other tissues. When a cell that’s an integral part of your immune system goes rogue, it has implications on the ability to fight infections. Recurrent and serious infections are a real concern and patients may fail to mount an adequate response to vaccinations. 

High- and standard-risk

Patients often ask what stage of MM they have. MM can’t be staged like solid cancers since it lives in the bone marrow, and by definition all patients are Stage 4, if staging systems used in solid tumours are used. 

We rather group MM into high-risk and standard-risk disease based on genetic mutations found in the malignant plasma cells. This helps us to determine what the most appropriate form of treatment is. 

Treatment

Not all patients with MM get all of the disease complications listed and there is no one-size-fits-all treatment. A person’s age, concomitant diseases, frailty status, belief system, and cost of treatment can all influence treatment choices. 

Treatment is divided into an induction phase lasting four to eight months and usually consists of a steroid, bisphosphonate (strengthens bone) and two chemotherapeutic agents. The combination of drugs provides synergism and increased therapeutic efficacy. 

The induction phase aims to clear the abnormal plasma cells completely. Some patients may require radiation to large plasmacytomas.

After induction, most patients will receive high-dose intravenous chemotherapy to nuke any remaining plasma cells followed by an autologous haematopoietic stem cell transplant. 

The majority of patients will then go on to receive maintenance therapy. The aim of maintenance therapy is to keep any pockets of abnormal plasma cells in check and prevent them from transforming into myeloma once again. 

Supportive care

Some patients require additional care which may include physiotherapy and occupational therapy, orthopaedic procedures, pain management, psychosocial support and dietary support. We often recommend counselling sessions early in the course of their treatment. It’s also useful to connect with local patient support programmes in the area. 

Indefinite follow-ups 

There is no cure but treatment can slow the disease course and prevent permanent damage to organs and tissues thus improving quality of life. MM given enough time will recur and patients will need to be followed-up indefinitely. 

The development of new MM drugs over the last 20 years has changed the trajectory of the disease, shifting the life expectancy from one to three years to well over 10 years. The promise of new and emerging therapeutic combinations will hopefully improve upon this even further. 

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