Multiple Myeloma Relapse–Decision Making About Treatment Combinations

The goal in relapsed myeloma is to use treatments that were not used after the initial diagnosis, or after a previous diagnosis. The logic behind this approach is that because myeloma cells survived the initial treatment, they are likely now resistant to any drugs used during it, so attacking the myeloma using a new drug may prove more effective.

Initially, people with newly diagnosed myeloma typically undergo a three-drug regimen, or triplet therapy, consisting of a combination of three drugs. According to Dr. Vincent Rajkumer, medical oncologist at the Mayo Clinic, patients with newly diagnosed myeloma that have been treated with a triplet regimen and subsequent stem cell transplant can expect to go four years before the disease comes back, or relapses.

Here are some of the drugs that may be used in combination therapies:

• Velcade (bortezomib), Kyprolis (carfilzomib), and Ninlaro (ixazomib): These are proteasome inhibitors. In other words, they disrupt the mechanism by which cancer cells break down proteins. This build-up of protein within the cell eventually causes the cells to die.
• Revlimid (lenalidomide) and Pomalyst (Pomalidomide): These are known as immunomodulatory drugs. In other words, they activate your immune system to target cancer cells and kill them like they would any other infection.
• Dexamethasone: This is a steroid drug that prevents inflammation and associated pain from myeloma, and it can even help kill myeloma cells at high doses.
• Dara (Daratumumab): This is known as an immunotherapy. More specifically, it is a monoclonal antibody that 'tags' cancer cells for recognition by the immune system.

Dr. Rajkumar says, "I would say that most of us would prefer a monoclonal antibody based combination for the first relapse." This combination is typically:

• Dara (daratumumab) + Revlimid (lenalidomide) + Dexamethasone

A treatment without a monoclonal antibody that your oncologist may recommended is:

• Kyprolis (carfilzomib) + Revlimid (lenalidomide) + Dexamethasone

If patient's myeloma is resistant to lenalidomide–perhaps from previous use–then your oncologist will recommend one of the following combinations:

• Kyprolis (carfilzomib) + Pomalyst (pomalidomide) + Dexamethasone
• Kyprolis (carfilzomib) + Revlimid (lenalidomide) + Dexamethasone

If patients prefer to only take oral medications, rather than infusions or injections, then they will take a combination of one of the following:

• If sensitive to lenalidomide: (Ninlaro) ixazomib, Revlimid (lenalidomide), and Dexamethasone
• If resistant to lenalidomide: (Ninlaro) ixazomib, Pomalyst (pomalidomide), and Dexamethasone

If your myeloma continues to relapse following these combinations, that’s when oncologists start to think about using drugs only approved in clinical trials, including:

• Selinexor: This is a fairly new class of drugs which stops the ability of myeloma cells to get rid of tumor suppressor proteins, the proteins inside cells, even cancerous cells, which are experts at preventing tumors.
• CAR T-Cell Therapy: Oncologists extract T-cells, killer cells of the immune system, from a patient's body, modify them to only target a protein uniquely expressed on the surface of myeloma cells, and then reinsert them back into the patient.

Ultimately, oncologist can differ in the treatments they recommend for relapsed myeloma, but you should be informed as to all of the options available before making a decision. Rajkumar explains that regardless of the treatment used, "You can expect at least two years [of response] on average with each regimen that we have."

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