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Because of a growing menu of effective treatments, people with multiple myeloma (MM) can now have longer disease-free periods. In many cases, though, the cancer returns (relapses) or begins to grow again during treatment (refracts). When that happens, doctors design a plan for treating relapsed/refractory multiple myeloma (RRMM). 

There Is No One-Size-Fits-All Treatment

Treatment of RRMM must be tailored to each person to be most effective. Creating your plan is a complicated process because your care team must take a lot of things into account. In most cases, the choice of treatment depends on:

  • Your response to previous treatments
  • Drugs you’ve already taken
  • Any bad side effects you had
  • Other health issues
  • Expected effectiveness of new treatment
  • How well your body might endure the new treatment

Why Should Treatment Plans Be Individually Tailored?

To treat RRMM effectively, your doctors must think about several factors.

What makes your case unique?

People with RRMM are not the same. Your case may be more or less aggressive than someone else’s, for example. They may receive different first-line treatments, respond differently to the same treatments, or respond for different periods of time.  

Some people with MM may have one or more additional health complications – like heart disease or kidney problems – that would limit or affect their ability to handle certain drugs or therapies. These risk factors need to be balanced against treatment goals and possible effectiveness.

You may need to have various tests to figure out your level of risk in connection to specific treatments. Your doctor also can consider possible emotional aspects of different treatments, including how you feel about going to the hospital or getting IV (intravenous) drug therapy often.

Variety of treatment options

In general, treating RRMM requires using a new drug or combination of drugs to get results. In recent years, the number of MM treatment options have greatly expanded, radically improving prospects for people with MM. So it’s easier to treat RRMM without using drugs that were part of your initial treatment. 

Some of the most effective treatment options today include:

  • Proteasome inhibitors (PIs), which prevent cancer cells from destroying “garbage” proteins, allowing for the cancer cell’s death. These include bortezomib, carfilzomib, and xazomib.
  • Immunomodulatory agents (IMiDs) – like lenalidomide, pomalidomide, and thalidomide – which help your immune system fight cancer
  • Anti-CD38 antibodies, which bind to the CD38 protein found on myeloma cells and block it to help the immune system kill cancer cells
  • Corticosteroids (as a very short-term kickstart treatment), typically used in combination with other drugs to boost response

Plus, a whole new generation of drugs have created to fight RRMM, such as:

  • XPO inhibitors or SINEs (selective inhibitor of nuclear export), which are anti-tumor drugs like selinexor
  • BCL-2 inhibitors, which disrupt the Bcl-2 protein in the cancer cell
  • Alkylators like melflufen, a peptide-drug conjugate (PDC) that targets tumor cells and can be effective if your MM no longer responds to bortezomib
  • Histone deacetylase (HDAC)inhibitors – like panobinostat and vorinostat – relatively new cancer drugs that stop the cell’s life cycle
  • Immunotherapy based on conjugated anti-BCMA antibodies and CAR-T cells:
    • Antibody drug conjugates (ADC), immunotherapy that works by combining chemotherapy with a monoclonal antibody
    • CAR T-cell therapy, a type of immunotherapy in which T cells are given new receptors that target proteins produced by cancer cells. CAR T-cell therapy is more effective when cells from healthy donors are used instead of patient cells; the cells are healthier and can be frozen for on-demand treatment.

In general, RRMM is treated with a triplet regimen that includes at least:

  • Two drug classes (other than steroids) that you took before, and
  • At least one drug from a class that hasn’t been used

The drugs included in this type of plan will vary depending on your first-line treatment and how you responded. For example, since most first-line MM treatment includes lenalidomide, many people are resistant when they first relapse. That said, if a certain drug was effective for a while initially, it may be effective if used again or in combination with a different drug. 

It's especially challenging to choose a treatment plan for a second relapse (third-line RRMM regimen) because, at that point, the MM likely won’t respond to the most commonly used drugs like bortezomib, carfilzomib, lenalidomide, and monoclonal antibodies.  

Limits of clinical research

With so many treatment advances, there’s not much data to go on. We don’t know that much about how certain RRMM treatments affect specific people. And many of those who have RRMM aren’t represented in clinical research studies. That makes it harder for your doctors to predict how effective a treatment might be. For example, older people and those with serious health conditions are not usually included in research studies.

What Are Some Other Considerations?

Side effects are another important factor. Some RRMM drugs and therapies have side effects including rash, nerve pain, diarrhea, or low platelet count in the blood.

Some drugs used to treat RRMM can aggravate health issues you might already have, like heart disease, kidney problems, diabetes, nerve damage, and blood clots. If these drugs are included in your treatment plan, your doctor will have to keep a close watch on those health issues:

  • Anthracyclines and carfilzomib – may cause heart damage
  • Lenalidomide and ixazomib – doses may be lowered if your kidneys don’t function well
  • Thalidomide, bortezomib, vincristine – may affect peripheral neuropathy (nerve damage)
  • Corticosteroids – may affect glucose intolerance (diabetes)
  • IMiDs – may affect thrombosis (blood clots)

Another important factor is timing. Some treatments appear to be most effective at certain times. For example, guidelines approved by the American Society of Blood and Marrow Transplantation (ASBMT) support a second round of stem cell transplants if the person’s initial remission (when signs of the cancer are greatly reduced or gone) lasted 18-24 months.

RRMM treatment is quickly changing. Ask your doctor about taking part in clinical trials.

Lastly, the most effective treatment plans for RRMM must take into account how far away you have to go for the treatment, its cost benefit, and your preferences when it comes to things like how often you get treatment or how complicated or involved the treatment is.

Show Sources

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Frontiers in Oncology: “Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma."

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Annals of Hematology: “Glucocorticoids in multiple myeloma: past, present, and future.” 

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