Wael Harb, MD, is a board-certified medical oncologist and vice president of medical management at Syneos Health in Newport Beach, California.
Multiple myeloma (MM) is a rare blood cancer that starts in your plasma cells, special white blood cells that help your immune system fight off infection. If these cells become cancerous and start growing out of control, they can crowd out other healthy cells in your bone marrow, the soft, inner tissues of your bones where all blood cells are made.
"Relapsed" and "refractory" are terms that are often lumped together, but they're not the same. Relapsed multiple myeloma means that your cancer improved with treatment, then later came back. The term "refractory" means that the multiple myeloma isn't responding to your most recent treatment.
We asked Wael Harb, MD, a board-certified medical oncologist at Syneos Health in Newport Beach, California, to explain recent findings about refractory multiple myeloma, including the progress doctors have made in treating it and why it's important to get involved with your care.
Who gets multiple myeloma?
We don't understand why multiple myeloma happens. There are some theories about environmental exposures – chemicals and pollution – that might trigger it. Typically, it's an acquired condition, not a genetic condition. There are rare situations where multiple family members have multiple myeloma, so there may be some genetic predisposition, but most of the time, it's sporadic.
How is refractory multiple myeloma diagnosed?
Often we monitor the patient closely, because they might not have symptoms. There are biomarkers in the blood or urine that we can detect. Imaging studies can help us detect relapse. Or the patient might have symptoms.
Multiple myeloma starts in the bone marrow, where white cells, red cells, and platelets form. It's like the factory for your blood. Bone marrow is the usual home for plasma cells, so when they become malignant, they can cause bone pain. Sometimes they cause eroding in the bones and what we call holes in the bones or lytic lesions. And they can cause fractures.
Of course, people can have pain for a lot of reasons and think, "Maybe it's musculoskeletal." So it's really important for somebody who has been diagnosed with relapsed/refractory multiple myeloma to be vigilant for symptoms like bone pain.
The second thing [myeloma cells can affect] is bone marrow function. We see these plasma cells take over and cause the bone marrow not to function, so we don't produce enough red cells. Patients may have anemia, fatigue, or get short of breath. It can also cause the whole immune system to be weak, so we see recurrent, severe infections.
You can also have a lot of nonspecific symptoms, which is why it's important to check blood tests, urine tests, and sometimes repeat a bone marrow biopsy.
What makes multiple myeloma resist treatment or return after treatment?
Multiple myeloma is still considered a disease that's not curable, but we've made huge progress over the last two decades. Now, patients can have a very long life span, more than a decade or even longer, and some people live close to a normal life.
But unfortunately, sometimes the multiple myeloma changes over time. As the disease progresses, it acquires new mutations that make it more aggressive. That can change its behavior. It can go from slow-growing and responsive to treatment to very aggressive and unresponsive to any treatment.
How can refractory multiple myeloma be treated?
Multiple myeloma is a complex disease. We have to understand the tempo of the disease, including what treatment has been received and what the response to the previous treatment was. The more treatment the patient receives, the less likely it will be to respond.
A patient who has had multiple treatments and hasn't responded to them is much harder to treat.
[But] we have a lot of good options, including proteasome inhibitors and immunomodulatory drugs. These are designed to block a signal inside malignant cancer cells. We also have older treatments like chemotherapy, but the newer targeted therapies have fewer side effects.
And we have more specialized therapies such as CAR T-cell therapy and bispecific therapies.
An autologous stem cell transplant uses stem cells from your own body. You get high-dose chemotherapy beforehand, which is the cancer treatment, then the stem cells "rescue" your bone marrow's ability to produce blood cells.
What do you consider when choosing a treatment plan?
First, we have to understand what the patient has already had in terms of treatment and how they've responded. If the patient had treatment and went into remission for longer than a year, then the previous treatment could work again. If their cancer didn't respond to that treatment, it doesn't make sense to go back.
Combination therapy, such as combining proteasome inhibitors with immunomodulators, can often work better than one drug. There are a lot of combinations to choose from.
And you have to look at the patient's health. We have to consider, can they tolerate multiple treatments together? We have to look at their heart and liver function. Did the previous treatment cause neuropathy? If so, we don't want to add to that. We also take into account how aggressive the cancer is. If it's more aggressive, we want to treat it with a more aggressive treatment. Slow-growing? We may choose a less aggressive treatment.
What can people do to help manage their symptoms or side effects from treatment?
Patients who are engaged in their own care do much better. Address issues as they come up. If you ignore symptoms of an infection, then it can get out of control and you may end up in the hospital. If you ignore bone pain, then you can end up with a fracture.
It's important to work closely with your medical team. I know it can be hard for patients – they wonder, Is this normal? Is this a new symptom? Is this a side effect I should be expecting? – but err on the side of caution.
Patients can also play a major role in improving their quality of life. For instance, pay attention to your diet. A lot of times, we recommend a nutritional consult. Not enough vitamin D or calcium can cause a deficiency because there are problems with bones being weak. … If you don't pay attention to how much protein you eat, you can lose muscle function and it may be easier to develop infections.
Hydration is also important. Being dehydrated can really affect kidney function.
There are only about 36,000 cases of multiple myeloma in the U.S. each year. If you have access in your area, see a specialist who treats multiple myeloma instead of someone who treats all cancers.
What are some concerns that people should always bring up with their doctor?
It's hard to get a diagnosis of cancer and hear that it's incurable. Hearing that it isn't responding to treatment is even scarier.
We really want patients to be part of the treatment process. We take into account the goal of treatment and how that aligns with their [personal] goals. It's important for them to understand what comes next if a current treatment doesn't work.
Definitely ask your doctor about joining a clinical trial. Without them, we'd have zero of the drugs that we have now. All medications being tested today are highly precise choices. And if they don't work, we can still fall back on the very good traditional treatments that we have.
Having refractory multiple myeloma doesn't mean you don't have options. You have a lot of reason to hope.
