What therapy options are there? Some patients with early or smouldering myeloma can be watched carefully without therapy and their long term survival will not be jeopardised if the careful watch policy is assiduously carried out such that disease progression is picked up early. The reason for this is that the usual types of chemotherapy for this disease are not curative and the life prolonging properties of chemotherapy are as useful at a time when the patient is symptomatic as early in the course of the disease – but see below.
In many patients a relatively simple chemotherapy regimen is chosen, which employs two drugs that active orally and are therefore given as tablets, viz. melphalan tablets and prednisolone tablets (the last of these two being a steroid).
Such a regimen is capable of achieving a good response in half of all patients treated and maintains this remission for almost two years, on average. The chemotherapy is continued until the paraprotein level stops falling in the serum and stabilise ( a state called ‘plateau phase’) and then the patient is watched (with serial blood tests and perhaps bone marrows) until the disease starts to become active again.
Combinations of drugs given intravenously has been the type of chemotherapy that has been most widely studied in the last decade, but the remarks concerning simpler oral chemotherapy remain relevant to many patients; indeed the controversy as to whether the more intense intravenous regimes are better for all patients continues to go on in medical meetings. The side effects of chemotherapy are the same as in other circumstances for its use.
In general, the more intense chemotherapy regimens, including one popular one called ‘VAD’, are reserved for younger and fitter patients who would be perceived to gain more from a possibly slightly better response rate and would tolerate the regime better.
Having achieved a remission, (not a complete remission, because the paraprotein usually remains detectable after such therapy), by either intense or gentler chemotherapy, it has been standard to observe the patients off all therapy until relapse. However, with the interest in high dose chemotherapy and bone marrow transplantation in the leukaemias and lymphomas there was an impetus to use this approach in myeloma.
Several groups have employed high dose chemotherapy and transplantation (either allogeneic – from another person – or auto - from themselves- being nowadays from their own blood peripheral stem cells, which have been mobilised into the circulating blood by use of growth factor stimulation).
Some excellent long term remissions - with no detectable paraprotein detectable on serum electrophoresis - have been reported and the subject of ‘curative’ chemotherapy together with a high dose phase and autograft using peripheral stem cell recovery will continue to much discussed in younger and fitter patients in the next decade.
After chemotherapy has been completed there are two newly recognised therapies that prolong any remission (or perhaps cure after high dose therapy). The first of these is the use of adjuvant alpha interferon, which the patient gives themselves by daily of thrice weekly injection for a minimum of six months. This immunomodulator has been shown in well structured clinical trials to prolong the mean remission time and therefore has established for itself a place in the maintenance therapy of myeloma. Languor is the commonest side effect of interferon therapy.
Another type of therapy has also been recently demonstrated to prolong remission if used in the maintenance period after the end of chemotherapy. This is the use of bisphosphonate therapy. The bisphosphonates are an interesting group of compounds, which attach to bone and make it less likely to be broken down by any disease process, particularly here the bony absorption by myeloma. It is now standard practice to give bisphosphonate therapy (either intravenous pamidronate or oral clodronate) in the maintenance period, and at the same time as the interferon.
Lastly it should be stated that local radiotherapy has a very important role in the therapy of multiple myeloma in controlling bony pain. The patient who comes with low back pain or limb pain because of destructive plasmacytoma in the particular bone, will be most quickly out of pain if he receives local radiotherapy to that bone.
