Hutchins was first diagnosed in 2008 at age 47 with smoldering myeloma — an intermediate form of the disease — when he got suspicious blood test results from a routine physical. Now 55, Hutchins, who describes himself as a “typical guy who doesn’t go to the doctor,” was required to get a physical when Remedy Health Media, a digital health platform he founded in 1994, took on private equity.
For the next four years, from 2008 to 2012, Hutchins’ cancer did not progress. The only drug he took for his smoldering myeloma was the bone-building Zometa (zoledronic acid), because bone loss is a common complication of the disease. Even though Hutchins is in the healthcare field and was told to watch out for bone pain, he says he still felt as though everything was okay and that his back problems had nothing to do with his cancer. He’d been having regular specialized blood tests for myeloma, and they did not show active disease.
For an entire year, he continued pursuing athletic endeavors and stuck to his physical therapy routine like glue. “I hurt myself on a regular basis. I figured my back pain was related to playing hockey,” says Hutchins. “It sounds stupid now, but I was the most compliant person in physical therapy you could imagine. But I wasn’t getting better.”
Finally, in 2012, “a physical therapist said, ‘you’re our best customer. I would love for you to be here forever, but I think you should go get an MRI.’”
The MRI showed that Hutchins had collapsed vertebrae and bone lesions. His multiple myeloma had gone from smoldering to active. “I was obtuse, or in denial, or who knows,” he says.
His treatment started with what’s called triplet therapy, a combination of three different drugs that attack the blood cancer in three different ways. It can include a chemotherapy drug, which kills fast-growing cells (both healthy and cancerous); a targeted therapy, which zeroes in on abnormalities within a cancer cell; an immunotherapy drug, which harnesses the body’s immune system to attack myeloma cells; or a corticosteroid, which helps the immune system control inflammation in the body and fight cancer cells.
Hutchins’ triplet therapy included the immunotherapy drug Revlimid (lenalidomide), the targeted therapy Velcade (bortezomib), and the corticosteroid dexamethasone. That combination, along with a maintenance regimen involving low doses of Revlimid, put his multiple myeloma into remission, which means his disease was under control but still there.
Hutchins’ journey has been challenging. Three years after his initial triplet therapy, his disease relapsed. He’s been on several other treatments, including another triplet therapy involving the recently approved proteasome inhibitor Ninlaro (ixazomib), one of three new multiple myeloma treatments okayed by the FDA in 2015. It didn’t put him in remission. He’s had two bouts with shingles, a common problem in multiple myeloma patients. And he’s had several back surgeries to help shore up the damaged vertebrae in his spine; the multiple myeloma had attacked and weakened them. Radiation on the spots of bone where the cancer was growing didn’t work, so last March he had a laminectomy, a procedure in which surgeons shave the bone to remove as much of the cancer as possible — a procedure Hutchins calls his “big boy surgery.”
Hutchins’ experience shows how difficult this cancer can be to diagnose and treat. Multiple myeloma is a disease of antibody-forming white blood cells called plasma cells that fight infection. The disease takes hold in the bone marrow when plasma cells start making an abnormal protein. Myeloma can be detected with specific blood tests, but such tests are not part of routine physicals. Patients commonly come to the doctor with fatigue; initial blood tests show they’re severely anemic or perhaps they have kidney failure. Eventually, follow-up testing uncovers the myeloma, explains Kenneth Anderson, an oncologist at Dana-Farber Cancer Institute and the program director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics in Boston.
By the time bone pain or kidney failure cause patients to seek medical attention, the disease can already be far along. Damage to the skeleton is common in this disease. Bone loss from the myeloma cells attacking the skeleton releases calcium into the bloodstream. This excess calcium, along with high amounts of abnormal proteins, strains the kidneys, and can raise the risk of kidney failure. Low red blood cell counts cause anemia, with resulting fatigue.
While multiple myeloma is rare, representing 1 to 2 percent of cancers, it is difficult to cure. According to the American Cancer Society, more than 30,000 people in the U.S. will be diagnosed with multiple myeloma every year, and more than 12,000 patients are expected to die of the disease.
There aren’t many risk factors for multiple myeloma other than age — the disease is most commonly diagnosed after age 65. African-Americans are twice as likely to get the disease as Caucasians, but no one knows why. Exposure to radiation can increase risk. Although there are no known inherited gene mutations that predispose individuals to multiple myeloma, having a parent or sibling with the disease makes a person four times more likely to develop it. However, most patients do not have a relative with the disease.
Myeloma starts with a condition called monoclonal gammopathy of undetermined significance (MGUS), in which an abnormal protein is found in the blood in small amounts. At this stage, people don’t have clinical blood, calcium, kidney, or bone problems. MGUS occurs in about 3 percent of people by age 50. While the frequency of MGUS increases with age, only about 1 percent of those people per year go on to develop multiple myeloma. “The majority grow old and die of something else,” says Anderson.
The 1 percent annually who do progress are sometimes first diagnosed with smoldering multiple myeloma. “Patients with smoldering multiple myeloma have lower levels of protein and bone marrow plasma cells and no hypercalcemia, anemia, renal dysfunction, or bone disease, and progress to active myeloma over years. Clinical trials of novel targeted and immune therapies are now attempting to delay and someday prevent them from developing active disease requiring therapy,” says Anderson.
In some cases, says Anderson, patients can go on for eight to 10 years in this stage, but in most cases, the smoldering myeloma will eventually develop into active disease.
Doctors will take many factors into account when deciding which treatment combination is best for their myeloma patients, including, for example, their general health, whether their disease is smoldering or active, and whether they are deemed high risk.
Treatment for myeloma has come a long way since the 1960s, when therapy consisted of melphalan, a high-dose chemotherapy, and the corticosteroid prednisone. “From the late 1990s to the present, there have been 18 different FDA-approved drugs that work in different ways, allowing them to be used in combination for more effective therapy,” says Anderson, who adds that researchers understand more about the biology of the disease, the microenvironment in the bone marrow, and the importance of targeting tumor cells directly.
Darzalex (daratumumab) and Empliciti (elotuzumab) are two of the newest drugs given the okay by the FDA to treat multiple myeloma. Called monoclonal antibodies, these drugs activate the immune system to help destroy cancer by targeting specific proteins on myeloma cells.
Other immune-stimulating therapies include Thalomid (thalidomide), Revlimid (lenalidomide), and Pomalyst (pomalidomide). These drugs kill myeloma cells while simultaneously activating the immune system to help clear the disease.
Another new type of treatment takes advantage of the cells’ proteasomes, a complex of enzymes that helps cells rid themselves of waste. The proteasome inhibitors — Ninlaro, Velcade, and Kyprolis (carfilzomib) — clog up the cancer cell’s “garbage disposal system,” which causes it to fill up with its own refuse and die.
Similarly, yet another new drug, Farydak (panobino-stat), inhibits the activities of enzymes known as histone deacetylases. This class of drug causes changes in the gene expression of myeloma cells, which can modify the behavior of cancer cells, making them more or less likely to grow, multiply, and/or die when exposed to other forms of anti-myeloma therapy. (See “Common Drugs for Multiple Myeloma,” page 60.)
“With all of this progress, the median survival has been extended [by at least] seven to 10 years and likely a lot longer,” says Anderson. In fact, he says, these therapies are so effective that doctors are using them earlier, so that more patients can benefit. In the past, he adds, doctors waited to treat the disease until patients developed high blood calcium, kidney disease, or bone disease. Now, doctors are intervening even before patients show symptoms.
“Your best shot [at a] cure is the first shot,” says Amit Verma, an oncologist and the director of hematologic malignancies at the Montefiore Einstein Center for Cancer Care in New York. “When the disease comes back, it comes in a worse form. Patients have more mutations, and they have acquired resistance to chemotherapy. My own feeling is when you have a really effective therapy, use it upfront.”
In addition to drug therapies, doctors also use stem cell transplantation from the patient’s own cells, either from bone marrow or, now more commonly, from their autologous peripheral blood lymphocytes.
“Drugs are still the preferred therapy — transplants are not a cure,” says Melissa Alsina, an oncologist at Moffitt Cancer Center in Tampa, Florida. But transplants can extend survival. “Several studies show that stem cell transplants improve the complete response rate, progression-free survival, and overall survival,” she says.
A complete response means that all signs of cancer have disappeared, even though it doesn’t necessarily mean the cancer is cured. Progression-free survival is a term oncologists use to describe how long a person lives with multiple myeloma without it becoming worse. Overall survival means the length of time a person remains alive after either the initial diagnosis or the start of treatment.
Several trials are under way examining the timing of stem cell transplants. For example the DETERMINATION trial is looking at whether transplants are more effective if done early.
For the transplant procedure, patients first undergo induction therapy, which means doctors treat the patient with either chemotherapy or one of the targeted therapies to get the patient into remission so that the transplant has the best chance of success. Verma says that today it’s more common to use triplet combinations of the targeted therapies to get patients into remission for stem cell transplants. “Advances have shown that you can put patients into remission even without [traditional] chemotherapy,” he says.
A few months ago, Hutchins’ outlook improved dramatically. His cancer went into remission, which meant he could move forward with a stem cell transplant. The induction therapy that worked for Hutchins did not involve traditional chemotherapy. He received a combination of the immunomodulatory agent Revlimid, the proteasome inhibitor Kyprolis, and the corticosteroid dexamethasone.
In July 2016, Hutchins received a transplant as an in-patient procedure at Mount Sinai in New York City, about a 45-minute train ride from his Connecticut home. In the hospital, Hutchins took melphalan, a chemotherapy drug that wipes out all dividing cells, both cancerous and normal. Eighteen hours later, his own stem cells, collected during an earlier remission, were transfused back into his body to help re-populate the bone marrow with healthy stem cells. A side result of the melphalan brought on “substances coming out of both ends,” which Hutchins describes as “expected and unpleasant.” He adds that he isn’t sure whether these side effects are worse than a three-week hospital stay.
Because most people receive a multiple myeloma diagnosis after age 65, Alsina says doctors take into account the patients’ general health, rather than age, in deciding whether they might be good candidates for the procedure.
Multiple myeloma carries many genetic changes, which puts some patients at increased risk of the cancer returning sooner. (See “A New Route,” page 58.) One of the challenges doctors face is identifying these genetic changes and figuring out which patients are at high risk of early relapse. About 15 percent have a high risk of the disease coming back early, says Bart Barlogie, professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York.
“As treatment has become more effective, patients often develop disease outside of the bone marrow, most commonly in the liver,” says Barlogie. This form of multiple myeloma is called extramedullary disease and becomes a progressive problem with each relapse. It is often difficult to treat. Barlogie has used Darzalex, one of the recently approved monoclonal antibodies, to help some patients achieve remission.
While at the University of Arkansas for Medical Sciences, Barlogie and his colleagues developed a gene test to identify the high-risk group. Now commercially available, MyPRS (Myeloma Prognostic Signature) looks at 70 genes and can discriminate between patients who are at high- versus low-risk for early relapses. Alsina uses this test in her practice and has been evaluating the gene test along with the myeloma group at Moffitt.
“Testing is done to inform patients and physicians about disease prognosis, which helps individualize therapy,” says Alsina. “It’s actually very powerful in discriminating progression-free survival in these patients, regardless of the stage of treatment.”
Meanwhile, Hutchins says that nothing about this disease is going to slow him down. As an advocate for the Multiple Myeloma Research Foundation, he still welcomes calls from patients newly diagnosed with multiple myeloma. He is happy for the opportunity to share what he has learned.
“You will rise to the challenge and will be resilient and move through this,” he says. “Really, what are your choices? You can mope around — I certainly did for a while — but it’s not a good strategy, and it’s not effective. Advocacy is the better way to go — take what you’ve learned and pass it on,” he says.