Understanding the Difference Between Chemo and Immunotherapies in Myeloma with Dr. Scott Goldsmith

Understanding the different myeloma therapies available can be overwhelming. This is why we had Dr. Scott R. Goldsmith in our Newly Diagnosed Myeloma Patient Chapter explain the difference between immunotherapy and chemotherapy, what types of myeloma drugs are classified as chemotherapy and which as immunotherapy, the mechanisms behind them and the different combinations used for patients.

You can watch his presentation or read the highlights of this talk below. 

Fifty years ago, there were hardly any treatments for myeloma. Over the last few decades, and especially in recent years, we've seen continued development in drug therapies thanks to the contributions that patients have made through participating in clinical trials.

Myeloma therapies are built upon success. Approved clinical trials have brought about more effective therapies for myeloma patients, like how the recommended therapies for newly diagnosed myeloma patients moved from doublet to triplet and even now quadruplet therapies in order to be more successful. It was discovered that drugs work differently and synergize, meaning the result of them together is more efficacious than their separate effects. 

Different classes of drugs can be combined in myeloma therapy. Below we will describe the different classes of therapies that are prescribed to myeloma patients. 

Conventional Chemotherapy 

Chemotherapy works specifically by targeting cancer cells that are in the process of dividing. Cancer cells divide more frequently than normal cells, that's how they become cancerous, so they are targeted by two main mechanisms that will lead to cell death:

• Inhibiting division machinery 
• Damaging the DNA of the cancer 

The disadvantage is that this may also affect healthy cells that are more likely to divide. This causes unwanted side effects such as hair loss, digestive issues, and skin problems.

The most common use of conventional chemotherapy in myeloma is using melphalan to kill myeloma cells before a stem cell transplant. 

Novel Therapies 

Separate from chemotherapy are novel therapies. Novel therapies try to target things that are specific to myeloma cells themselves like target signals, pathways, or machinery that myeloma cells rely on to survive. This is one of the staple treatments for newly diagnosed multiple myeloma.  

• Proteasome inhibitors: this method of treatment inhibits (prevents) the breakdown of myeloma cell-produced proteins, causing the mutated antibodies to build up in the myeloma cell and cause it to die. It essentially blocks the myeloma cell from secreting its mutated proteins into the blood and the rest of the body. 

We have three approved proteasome inhibitors for myeloma therapy: 
- Velcade (bortezomib) - most commonly used 
- Kyprolis (carfilzomib)
- Ninlaro (ixazomib) 

• Immunomodulatory drugs: this method of treatment prevents blood vessels from forming in myeloma cells and disengages the myeloma cell's ability to communicate with other cells in the body. Their versatile purposes make them ideal for effective myeloma therapy combinations. They are sometimes referred to as chemotherapy but don't function in the same way because they are more specifically targeted and have different mechanisms. 

Three of these therapies include: 
- Revlimid (lenalidomide) - most commonly used
- Pomalyst (pomalidomide) 
- Thalomid (thalidomide) 

• Other novel therapy drugs:

-vFarydak (Panobinostat) - out of the market
-vXPOVIO (Selinexor) - is used in later lines of treatment. It plugs up the myeloma cell so that it explodes on itself. 

Immunotherapies 

Immunotherapy treatments take advantage of immune system cells that already exist in the patient's body and use the immune system to attack cancer.

Because myeloma cells survive by "hiding" within the body and blood, the immunotherapies work to reveal the myeloma within the immune system and then direct the immune cells against the myeloma cells. The immunotherapy drugs often work well combined with novel therapies. 

There are three main types of immunotherapies: 

• Monoclonal antibodies: this type of therapy binds surface targets on myeloma cells to identify and eliminate them. 

- Darzalex (daratumumab) 
- Sarclisa (isatuximab)
- Empliciti (elotuzumab)

• Antibody Drug Conjugate (ADC): Antibodies can be joined with toxicities to deliver treatment precisely to myeloma cells instead of circulating throughout the body. 

- BLENREP (belantamab mafodotin) 

• CAR T cells: (Chimeric Antigen Receptor): This therapy includes the collecting of a patient's immune system cells (called T-cells) and then sends them to a manufacturing plant where they're able to be genetically engineered to identify and eliminate myeloma cells. These re-programmed T-cells are then sent back to be reinfused into the patient. Though this process takes time, the initial results of this type of therapy have been very successful. 

- Abecma (ide-cel) 
- Carvykti (cilta-cel) 

• Bispecific antibodies: This therapy combines two different antibodies (immunoglobulins) so one arm of the antibody (shaped like a Y) connects to the surface of a patient's T-cell, and the other arm is able to connect to the myeloma cell to bring them close together to kill the myeloma cell.

Summary

Having all these options is amazing and also overwhelming even for those who are practicing it. Doctors need to understand patients’ values, their medical issues and their long-term goals. They also need to know if the treatments are going to compete with each other or if they're going to work together in order to select the best option for their patients. 

Patients who have participated in clinical trials have helped the myeloma treatment arsenal consistently improve. You can be an empowered patient by learning more about these therapies and having intelligent conversations with your doctor about what works best for you!