Multiple Myeloma

Multiple Myeloma is a plasma cell cancer that affects the bone marrow. It causes the bones to develop plasmacytomas (tumors), and a large number of abnormal antibodies to be released into the body, leading to hypercalcemia (too much calcium) and osteolytic lesions (holes in the bone). It usually occurs in people over 40 years old and is relatively rare, with about 12,500 new cases every year.

This disease has a low cell proliferation rate and is resistant to a large number of chemotherapy drugs. Consequently, in most cases there is no cure, and treatment is aimed at relieving symptoms and neutralizing complications. Left alone, a patient with this disease would survive for an average of 7 months after diagnosis. Chemo- and radiation therapy treatment can extend the prognosis to 36-48 months.

The cancerous plasma cells that cause Multiple Myeloma begin their lives as stem cells, which are found in the bone marrow. These cells have the ability to differentiate into every type of blood cell found in the body, including B lymphocytes, the precursors to plasma cells. As these white blood cells become plasma cells, a mutation occurs and causes them to become cancerous. Untreated malignant cells can spread into all bone cavities in the body.

Symptoms of Multiple Myeloma include anemia (low numbers of red blood cells), heightened susceptibility to bacterial infections, bone pain in the spine or ribs, bones that are easily fractured, and renal failure (failure of kidneys to function properly).

This disease tends to affect men more often than women, and blacks more often than whites. It is the second most prevalent blood cancer, though was once mistaken for a type of bone cancer, because of its direct effect on the skeleton. Scientists have not reached a consensus on the cause of Multiple Myeloma, and attribute it to the combination of many different factors, including genetics, exposure to chemicals or radiation, and normal aging of the immune system.

An unusual characteristic of multiple myeloma is exactly which chemotherapy drugs it will respond to. The usual suspects, like bleomycin, carboplatin and cyclophosphamide are nearly useless. What is effective, though, is the steroid dexamethasone. Now, dexamethasone is used in many other chemotherapy regimens, like ABVD or AC+T, but there it's used as an antiemetic, or to enhance the effectiveness of other antiemetics like ondansetron or palonosetron. In multiple myeloma, however, it's used to directly kill off cancer cells. It's usually combined with thalidomide, and sometimes melphalan.

Treatment with dexamethasone, thalidomide and oral melphalan is very rarely curative, however. The only therapy that's curative with any significant rate of success is a bone marrow transplant, usually an allogenic one. This consists of first ablating, that is destroying, the patient's bone marrow with very high doses of chemotherapy. The drugs usually used are carmustine (or BCNU, its trade name), etoposide, cytarabine (also called ARA-C), and melphalan. When doing this, the melphalan is administered by IV at very high doses, rather than the small doses orally used in maintenance therapy. Bone marrow transplants carry severe risks. Once the BEAM chemotherapy has been administered, the immune system is almost completely obliterated, leaving the patient vulnerable to bacterial and fungal infections. Patients often receive amphotericin B or voriconazole and vancomyicn prophylactically, since any infection that develops could kill within hours if left unchecked. Since ARA-C also interferes with most viruses, viral infection is less of a risk, but potentially more serious if it does occur. Once the patient's blood counts drop to their nadir, the donor bone marrow is injected. Often shots of Neupogen or Neulasta are administered at this time to speed regeneration of the bone marrow. If all goes well, the donor bone marrow 'takes', and begins producing immune cells. These immune cells should attack any remaining cancer and destroy it, called the graft versus tumor effect.

Dangerous as that is, it's the best hope for long-term cancer-free survival for multiple myeloma patients. Work is being done on new drugs to treat it with less risk, though. Among these are bortezomib (or Velcade), and sunitinib (Sutent), which are tyrosine kinase inhibitors, and also monoclonal antibodies. Unfortunately, progress is slow, but the next ten years should bring significant improvements in multiple myeloma treatment. Hopefully, it will become as treatable as Hodgkin's Disease and testicular cancer, but that's a long way off.