Myeloma Made Simple: Drug Classes Made Simple | The Main Types of Drug Used to Treat Myeloma

Dr. Joseph Mikhael: Welcome to this episode of Myeloma Made Simple.  Today's topic is Drug Classes Made Simple. One of the reasons why patients are living  longer than ever with multiple myeloma is that we've developed so many new drugs to  fight this disease. This has been a result of incredible amounts of research all across the  world to develop these new drugs. We are going to review major drug classes in multiple myeloma.  I will review the basic mechanism of action for each class, along wi

th a brief overview of the  benefits and the risks of each. But of course, I cannot provide every detail, so this should  be discussed with your provider. Many of these drugs will be covered in much more depth in  future episodes of Multiple Myeloma Made Simple. Arguably, the oldest class of drugs we have in  multiple myeloma are called alkylators. This is a more traditional form of chemotherapy that has  been used in both low dose and in high dose forms. There are two key drugs in this class, 

melphalan and cyclophosphamide. There is also a third drug that is partly  an alkylator known as bendamustine, but that is not routinely used in  multiple myeloma. We will not address it. We use melphalan in very high dose when we give an  autologous stem cell transplant. We also use it in lower doses, either by pill or intravenously,  typically in patients not going to transplant. Cyclophosphamide is used either by pill or IV in  combination with other drugs to treat myeloma. Sometimes we use c

yclophosphamide to help mobilize  stem cells to collect them for transplant. These drugs have significant activity in  myeloma, both alone and in combinations, but they do, of course, come with risks.  They can cause nausea, as well as reduce blood counts as typical chemotherapies do.  This can increase the risk of infections, cause fatigue or bleeding. Furthermore, we  know that exposure to melphalan can increase a patient's risk of developing  another cancer, namely leukemia. The second major

class of drugs are called  proteasome inhibitors. These drugs work by inhibiting something in the cell called  the proteasome that is responsible for processing certain proteins in the cell. When it  is inhibited, those proteins accumulate and the cell will die. This is particularly important  in myeloma where the proteasome may be even increased in its activity, so inhibiting it  becomes critical to the death of the cell. The commonly known proteasome inhibitors that we  use include bortezomib,

also known as Velcade, ixazomib, also known as Ninlaro, and carfilzomib, also known as Kyprolis. These drugs are highly  effective and can be used as single agents, but also typically in combination with  immunomodulatory drugs, monoclonal antibodies, and literally all other drug classes. Bortezomib  can cause neuropathy, typically numbness and tingling in the feet or hands in. Ixazomib can  cause stomach problems like nausea and diarrhea. And carfilzomib can cause high blood pressure  or other

cardiac issues. All drugs in the class can drop blood counts and are associated with an  increased risk of shingles, so viral prevention is necessary. We use proteasome inhibitors in  all phases of treatment for multiple myeloma. The next class of drugs are known as  immunomodulatory drugs. As their name indicates, they not only directly affect myeloma cells,  but interact between those myeloma cells and its environment. They act on a molecule known as  cereblon, and can also be used either a s

ingle agent or in combination with other classes. The  three immunomodulatory drugs include thalidomide, lenalidomide known as Revlimid and pomalidomide,  also known as Pomalyst. These drugs are all given orally and have differing side effects.  We see primarily neuropathy, fatigue, and constipation with thalidomide. Whereas  with lenalidomide, we can see fatigue, low blood counts, diarrhea and muscle  cramping. Pomalidomide is very similar to lenalidomide in its side effect profile,  but we ten

d to see a little less diarrhea. All three drugs are known to be  associated with blood clotting, and so patients should be on something to  prevent blood clots such as aspirin or a specific anticoagulant. We use immunomodulatory drugs in  all phases of treatment for multiple myeloma. The next class of drugs are known as monoclonal  antibodies. This is really a form of immunotherapy where we can employ a patient's own immune  system to destroy their multiple myeloma. It is called monoclonal beca

use it has a target  and is an antibody because it acts much like our own inherent antibodies that are designed to  attack things that could cause harm to the body. Much like when you give a vaccination, your body  produces antibodies to that disease, we now create specific antibodies to target the myeloma cell.  These antibodies target something on the surface of the myeloma cell that it can hook onto and  then trigger the immune system to help destroy that cell. They're Y shaped so that the op

en part  of the Y can hook onto the cell and the other bottom part of the Y triggers that immune system  to help destroy the cell. Sometimes we call this targeted therapy as it is specific to the myeloma  cell and not to the healthy cells around it. The key targets we use in myeloma with  monoclonal antibodies include CD38 and SLAMF7. We have two monoclonal antibodies that  target CD38, daratumumab, also known as Darzalex, and isatuximab, also known as Sarclisa. We have  one monoclonal antibody

that targets SLAMF7, elotuzumab, also known as Empliciti. These  drugs can all be given intravenously, although now there is a subcutaneous form of  daratumumab. These drugs are generally well tolerated, where the greatest side effect is  during the first or second dose when patients can have a reaction to the administration of the  drug, sometimes called an infusion reaction for which patients are given medications before to  prevent them. They're caused by the immune system overreacting to the

presence of that antibody in  the system. They can also drop blood counts and can increase the risk of shingles, so antiviral  prophylaxis or prevention is given. These drugs are extensively used in all phases of myeloma  treatment, typically combined with other classes. One of the newer classes of drugs are called  XPO1 inhibitors, of which we have one drug, selinexor, also known as Xpovio. These  drugs inhibit a pathway out of the nucleus, the XPO1 pathway. We all have good anti-tumor  protei

ns in the nuclei of our cells that ensure that the cells don't become cancerous. One of the  ways cancers, and a particular myeloma can grow, is to expel these proteins out of  the nucleus through the XPO1 pathway, and selinexor blocks that pathway so that the cell  ultimately will die and will not become cancerous. Selinexor is given orally. Its side effects  include fatigue, nausea, and vomiting, as well as a drop in blood counts. We now typically  give this drug once weekly to reduce the side

effects and the drug can be given on its own or  in combination with other classes of drugs. And this really is just the beginning as many other  classes of drugs are being developed in myeloma.