If you have smouldering myeloma, your treatment will simply consist of active surveillance, which means being watched closely. This is usually done with bone marrow biopsies, blood and urine tests, and imaging. Your doctor may recommend starting treatment if you are at risk of developing symptoms within 18 months to two years. Before that, if your bone density is relatively low and you have any indications of bone damage (osteoporosis or osteopenia), you may be prescribed bisphosphonates to slow it down.

If you have been diagnosed with MGUS (monoclonal gammopathy of unknown significance), you will also be monitored regularly for any health changes or progression.

The first step – known as first-line treatment or induction therapy – aims to control the myeloma quickly and relieve symptoms. It will involve treatment with a combination of drugs, including some which have been introduced in recent years and have drastically improved myeloma survival. Combinations of these have been found to be more effective than single drugs.  A typical combination will include:

• A chemotherapy drug to kill the myeloma cells (cyclophosphamide, melphalan or doxorubicin)
• A steroid to suppress inflammation (dexamethasone or prednisolone)
• One or more of the newer anti-myeloma treatments including thalidomide (Thalidomide) and lenalidomide (Revlimid) enhance the performance of the chemotherapy drugs by boosting the immune system and preventing myeloma cells from surviving. Bortezomib (Velcade) target cells actively producing proteins, principally the abnormal plasma cells. Daratumumab (Darzalex) mimics antibodies and targets myeloma cells.
• Pain relief as needed; usually non-steroidal anti-inflammatory drugs (NSAIDs).

 

If you are newly diagnosed and not eligible for a stem cell transplant, according to EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, combinations you might be prescribed are (note that not all of these combinations are available in every country. For see the MPE factsheets below or check the Medicines access portal in the MPE Myeloma Access Atlas):

• daratumumab (Darzalex) – lenalidomide (Revlimid) – dexamethasone (DaraRd)
• daratumumab – bortezomib (Velcade) – melphalan – prednisone (DaraVMP)
• bortezomib (Velcade) – lenalidomide (Revlimid) – dexamethasone (VRd)
• bortezomib (Velcade) – melphalan – prednisone (VMP)
• bortezomib (Revlimid) – dexamethasone (Rd)

 

If you are newly diagnosed and considered eligible for a stem cell transplant, combinations you might be prescribed for your initial or induction treatment before stem cell transplant are (note that not all of these combinations are available in every country. For see the MPE factsheets below or check the Medicines access portal in the MPE Myeloma Access Atlas):

• bortezomib (Velcade) – lenalidomide (Revlimid) – dexamethasone (VRd)
• daratumumab (Darzalex) – bortezomib (Velcade) – thalidomide – dexamethasone (DaraVTd)
• bortezomib (Velcade) – thalidomide – dexamethasone (VTd)
• bortezomib (Velcade) – cyclophosphamide – dexamethasone (VCd)

In some cases, induction therapy can remove all abnormal plasma cells, which is called a complete response or complete remission. However, treatment will need to be continued, as without it, the myeloma would return.

Treatment is usually taken for a few days or weeks at a time with a few days to a week off treatment, although these lengths can vary. This is known as a cycle and is usually repeated over 4-6 months depending on how you respond and what side-effects you may experience. Treatment in cycles allow time for the healthy cells, which may have been damaged by the chemotherapy, to recover. Not everyone will respond to any one combination of drugs, so you will be monitored and another combination can be chosen if the one you have started does not appear to be working or if you are unable to tolerate the treatment.

After the initial period of induction therapy, a decision will be made on what comes next.

If you are well and in complete remission, and myeloma is your only medical condition, the most likely course is a stem cell transplant with intensive chemotherapy. Consolidation therapy is usually given following a stem cell transplant once cancer can’t be detected. This works to kill any remaining cancer cells that may be left in the body. Maintenance therapy is usually given after a stem cell transplant or after stem cell transplant and consolidation therapy. The maintenance therapy drug is usually given in a low dose over a long time to reduce the risk of relapse in patients in remission.

If you are not very well, or aged over about 70, it is likely that you will not be given a transplant but instead will be offered continued consolidation drug therapy. Maintenance therapy might also be used after induction therapy.

As some combination drug treatments may not be effective for particular people, it may be necessary to try a different combination. All myeloma patients will experience this at some point in time, and likely several times throughout their disease course, where they undergo a period of remission (or complete removal of plasma cells) and then eventual worsening of their myeloma usually seen by an increase in paraprotein levels. You may also feel that your pain, tiredness, or myeloma symptoms become worse during a period of relapse.

It is understandably disappointing, but there is no reason why another treatment should not work better. It is also not a reason to be over-anxious, but it will probably mean a change to the medication you are taking. For some people, a treatment that worked well earlier can be repeated with good results. The same reasoning applies when a treatment that has been effective, no longer appears to work so well (known as refractory myeloma).

The first time a relapse happens, most people will receive another stem cell transplant, but if that is not possible then they will be given a combination treatment with bortezomib (Velcade). This is given by injection under the skin, once or twice a week. Bortezomib is usually given in combination with a steroid, such as dexamethasone or prednisone, along with other drugs such as doxorubicin (a chemotherapy), pomalidomide (Imnovid), or daratumumab (Darzalex). Other options for treatment at first relapse are treatments using lenalidomide (Revlimid) and dexamethasone in combination with drugs such as carfilzomib (Kyprolis), isatuximab, daratumumab (Revlimid), or elotuzumab (Empliciti).

In subsequent relapses, these are various combinations that have been approved in recent years for treatment. Treatment at subsequent relapses will usually depend on if your myeloma is considered refractory (meaning will not respond) to specific drugs. Some examples of approved treatment combinations used are:

• bortezomib (Velcade) – panobinostat (Farydak) – dexamethasone
• pomalidomide with or without isatuximab – dexamethasone
• daratumumab (Darzalex)
• elotuzumab (Empliciti) – pomalidomide – dexamethasone
• belantamab mafodotin (Blenrep)
• selinexor (Nexpovio)
• idecabtagene vicleucel (Abecma)

See MPE’s treatment factsheets for myeloma approved drugs below or clicking in this link:

Autologous transplants (ASCT)

If you are well and in complete remission after initial induction treatment, and myeloma is your only medical condition, the most likely course is a stem cell transplant using your own cells (called an autologous stem cell transplant or auto-SCT or ASCT). It involves the collection of stem cells from your bone marrow and is possible in eligible and fit patients.

The first step is drug treatment to stimulate the production of stem cells and their movement from the bone marrow into the blood. In the actual transplant, given in hospital, blood is passed through an apheresis machine, meaning the blood is separated into its different components. During apheresis stem cells are removed and all the other components are returned to the body. The stem cells are then frozen (or used fresh) and used in transplants – usually enough for two occasions can be saved and frozen.

A relatively high dose of the chemotherapy drug melphalan is then given, followed about two days later by the stem cells, which will move into the bone marrow and start to develop into new blood cells. The process can take several weeks, during which it is essential to avoid infection. It is common to feel unwell during this time, and several more weeks of recovery may be needed after you leave hospital. The great advantage of transplants is that patients usually respond very well and can achieve a long remission period.

 

 Allogenic transplants (Allo-SCT)

In relatively rare circumstances, younger, fit people can be offered a transplant of stem cells from other close relatives; usually a brother or sister. This is known as an allogenic transplant or Allo-SCT. It makes use of the donor’s stem cells to boost the immune response of the person with myeloma, by developing into specialised blood cells that can attack the abnormal plasma cells. This is believed to be the reason why allogenic transplants have a lower rate of relapse than autologous transplants.

There is a problem, though, as an allogenic transplant carries the risk of graft-versus-host disease (GVHD), in which the donated cells attack the patient’s healthy tissues as well as the abnormal plasma cells.