Multiple myeloma - information pack
Multiple myeloma, plasmacytoma
(myelo = marrow, -oma = tumour)
Also known as:
- Plasmacytoma
- MM
- Myeloma
- Plasma cell myeloma
- Myelomatosis
- Kahler’s disease
Contents
How rare is multiple myeloma?
In the UK and Europe the usual definition of a rare cancer is one that occurs in less than 6 people out of every 100,00 each year. Because there are around 200 rare cancers, this means that they make up about 24% (nearly a quarter) of all cancers.
Multiple myeloma affects around 24,00 people a year in the UK, making up around 15% of blood cancers and around 2% overall. The total cases are 4.5 -6 per 100,000, so it is classed as rare. Multiple myeloma mostly affects older people and is more common in men and black people.
What is multiple myeloma?
Overview:
Multiple myeloma is a type of blood cancer that can affect multiple areas of the body – hence the name. It starts in the bone marrow of the biggest bones where white blood cells are produced. Because it affects many areas of the body, there are many symptoms that will lead a doctor to a diagnosis. It might be picked up in a routine blood test or after symptoms such as bone pain, anaemia or kidney problems. The symptoms of myeloma are caused by the build up of large numbers of cancerous cells in the bone marrow and the proteins they release into the blood. It is generally thought of as incurable, but the disease can be managed. As most patients are over 70 treatments are often designed to improve the quality and length of life.
Biology of multiple myeloma:
The interior of our bones contains a spongy material, the marrow, where most of the cells that are needed for our immune system are made. There are many types of these white blood cells, but one is called a B-cell. Once these are made in the bone marrow they move to the lymph nodes to mature as plasma cells before being released into the circulation. Normally these cells play a vital role in the immune system, making molecules called antibodies (sometimes called immunoglobulins) that recognise infections and mark them for destruction.
Cancer occurs when the DNA in cells gets damaged by various means. When cells divide there is a chance that damage can occur to the DNA during division. The exact cause of the damage in MM is unknown. What we do know is that in multiple myeloma, when some new B-cells divide, certain genes for making antibodies acquire a powerful “on switch” that moves from other parts of your DNA. These are known as oncogenes – genes that promote cancer.
Once mature, affected B-cells become plasma cells that produce excessive amounts of whole or partial antibodies, called paraprotein. This makes the blood thicker (hyperviscosity) and can clog the narrow tubules in the kidneys. These cells then return to the bone marrow where they multiply and cause damage to the bone and the cells it normally produces. The affected bones are the ones where the bone marrow is producing new cells, including the bones of the spine, skull, pelvis, rib cage, and the long bones of the arms and legs and the areas around the shoulders and hips.
Bone damage is caused by the release of inflammatory cytokines, cellular messengers that trigger inflammation (especially one called IL-6). These increase the rate of bone breakdown leading to bone pain, increased fracture risk and kidney damage.
People with MM can also become anaemic and prone to infections because the high numbers of myeloma cells prevent the formation of normal red (oxygen carrying) and white (immune) blood cells.
These changes don’t necessarily lead to cancer. Some people have a similar, non cancerous condition called MGUS (monoclonal gammopathy of unknown significance). However about 1.5% of MGUS cases will become cancerous each year, so patients with MGUS are monitored carefully for any change.
What other diseases are related to MM?
There are several variants of multiple myeloma- for example plasma cell leukaemia, where the abnormal plasma cells circulate in large numbers in the blood: heavy chain diseases, where only part of the abnormal protein is produced; amyloidosis where abnormal proteins are deposited in organs such as the kidneys and plasmacytomas which are isolated nests of myeloma cells.
What are the current treatments options?
Myeloma is currently considered incurable. Treatments can bring about a remission, where there is no significant disease present, or a plateau where it is stable. Treatment will usually stop during a remission until there are signs of a relapse, when it will resume, usually with a different combination of therapies.
As most patients are elderly and may have other medical conditions, treatment can be aimed at controlling symptoms such as bone pain and fatigue.
This may include radiotherapy and the use of bisphosphonates (sodium clodronate (Bonefos®) zoledronic acid (Zometa®) or disodium pamidronate (Aredia®)) which slow down the rate of bone loss.
The precise treatment will vary according to the stage of the condition, particular problems it is causing, your age, health and preferences.
- Chemotherapy. These attack rapidly dividing cells and have been used for many years, but are very non-specific. They include cyclophosphamide and melphalan.
- Steroids, for example dexamethasone and prednisolone. These stop myeloma cells growing and relieve inflammation around nests of myeloma cells.
- Immunomodulatory drugs (IMiDs). As the name suggests these work by modifying the immune system. The first to demonstrate activity in myeloma was thalidomide. Newer forms are lenalidomide (Revlimed®) and pomalidomide (Imnovid®)
- Proteasome inhibitors. These affect the mechanisms in myeloma cells which are used to remove damaged and unwanted proteins. Examples include bortezomib (Velcade®) and carfilzomib (Kyprolis®)
- Monoclonal antibodies. These are molecules which recognise proteins on the surface of myeloma cells and flag them for destruction by the patient’s immune system. The only example in routine use at present is daratumumab (Darzalex®) which targets a protein on the surface of myeloma cells called CD38
- Histone deacetylase inhibitors (HDACs). These work by interfering with the way myeloma cells switch off genes which would control their growth. The only HDAC currently used to treat myeloma is panobinostat (Farydak®)
Treatments aimed at reducing the number of myeloma cells are usually given in combination, using drugs with complementary modes of action. Common combinations include:
- VTD: Velcade, thalidomide and dexamethasone
- MPT: Melphalan, prednisolone and thalidomide
- CTD: Cyclophosphamide, thalidomide and dexamethasone
Younger patients may be offered high-dose therapy and stem cell transplantation which aims to kill all the myeloma cells. This inevitably also destroys all the normal blood cells which are replaced with stem cells taken either from the patient before treatment (autologous transplantation) or from a matched donor. This is a highly intensive procedure and is therefore not suitable if the patient has other significant medical problems
What are the current clinical trials for multiple myeloma?
The notes on these studies include a lot of specialised language.
If you are asked to be involved in one of the clinical trials your medical team will explain the science to you if you want to know more.
Thirty-six trials were listed as open in sites in the UK on ClinicalTrials.gov as of 11/11/22. The 21 potential new medicines being tested are:
- Venetoclax: a BCL-2 inhibitor
- CAEL-101: a fibril reactive monoclonal antibody
- ANV419: a monoclonal fusion antibody which blocks the IL-2 receptor
- CC-92480: a drug which accelerates degradation of Ikaros and Aiolus leading to enhanced immunostimulatory and tumoricidal activity
- CID-103: an anti-CD38 antibody
- Bb2121: a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen
- Iberdomide (CC-20): a novel cereblon E3 ligase modulator
- CCS1477 (Inobrodib): targets twin acetyltransferases p300 and CBP
- Teclistamab: a T-cell–redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells.
- Belantamab mafodotin: an antibody-drug conjugate that contains belantamab linked to mcMMAF, a cytotoxic microtubule disrupting agent. The antibody has been designed to attach to a protein called B-cell maturation antigen (BCMA)
- RO7425781: a GPRC5D T-cell engaging bispecific antibody which causes T-cell activation and the killing of myeloma cells (the function of GPRC5D is unknown- in this case it is being used as a convenient tumour marker)
- S65487: a BCL-2 inhibitor
- Talquetamab: a GPRC5D T-cell engaging bispecific antibody which causes T-cell activation and the killing of myeloma cells (the function of GPRC5D is unknown- in this case it is being used as a convenient tumour marker)
- Teclistamab: A bispecific humanized monoclonal antibody against human CD3, a T-cell surface antigen, and human B-cell maturation antigen (BCMA; TNFRSF17), a tumor-associated antigen (TAA) expressed on plasma cells.
- Ciltacabtagene autoleucel (cilta-cel): a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies
- Elranatamab: a B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody
- REGN5458: an anti-BCMA x Anti-CD3 Bispecific Antibody
- Defactinib: blocks focal adhesion kinase (FAK)
- Isatuximab: a monoclonal antibody that binds to CD38
- Modakafusp alfa: an antibody–cytokine fusion protein (immunocytokine) consisting of two attenuated IFNα2b molecules genetically fused to the Fc portion of a humanized, anti-CD38, IgG4 monoclonal antibody
- Ixazomib: a proteasome inhibitor.
Where can I find multiple myeloma support groups?
Name
Website
Notes
Myeloma UK
Excellent source of useful information, including a very good trial finder and a very detailed information pack for new patients here.
Incidence data may not be complete.
Incidence per 100,000 – 12
UK incidence per 100,000 –
UK Prevalance –
Europe prevalance –
US prevalance (estimate based on assumption of ~5x UK population) –
Link to alternative data source – Cancer Research UK
Age range affected – more common under 40
Gender balance – predominantly women but does occur in men
Ethnicity data – more common in black women (https://www.breastcancer.org/types/triple-negative)
