From Bleak to Bright

Winship Cancer Institute leads the way in treating multiple myeloma

By Paige Parvin 96G

Myeloma

Ann Borden

leading the way: Sagar Lonial has built Winship's multiple myeloma program into one of the best and most sought-after in the country, with a focus on promising Phase I clinical trials.

Seven years ago, Tamara Mobley was so busy, active, and energetic that if she were a cartoon, she'd be a blur. The dedicated mother of two young boys, a loving wife, and a full-time employee in a good job, she didn't get much downtime. As she looks back in a 2014 video interview for Emory’s Winship Cancer Institute, her positive energy fairly radiates.

“I think I was just busy, like any other typical mom,” Mobley says. “You know, just doing things to take care of the house, my family, and doing my best to be a valued employee. That was my life before, just ripping and running."

Then Mobley, who was 33, got tired. Not just garden-variety, too-little-sleep, I’ve-been-doing-too-much sort of tired, but bone tired, from the moment she woke up each morning. Then there was the severe back pain. And then, the passing out. Against all odds, she was getting sick, and it was happening fast. For a young, vibrant, working wife and mother, that was terrifying.

A trip to the emergency room led to a rapid diagnosis of multiple myeloma—a cancer of the blood—and an equally rapid recommendation from her doctor that she seek treatment at Emory and Winship. Mobley was so ill that she was brought to Emory University Hospital in an ambulance. And that’s when all the ripping and running slowed way, way down—at least for a while.

mobley

New Day: Tamara Mobley, shown here with her family, is one of hundreds of mutiple myeloma patients who have turned to Emory's Winship Cancer Institute.

NO OTHER STORY LIKE THIS IN CANCER

As cancer goes, multiple myeloma is a bit of a misfit.

For one thing, it’s rare. The American Cancer Society estimates that about 30,000 new cases of myeloma will be diagnosed this year, trailing far behind the most common cancers—breast and lung—each of which will derail more than 220,000 lives. That’s stiff competition for research funding and awareness.

For another, it’s mysterious. Multiple myeloma begins in the bone marrow with plasma cells going haywire, but experts aren’t entirely sure how that process starts or what the key risk factors are. They do know that the disease is most common in people over 65, that men are slightly more vulnerable, and that African Americans are more than twice as likely as white Americans to get it, but they don’t know why.

But probably the most notable difference between multiple myeloma and pretty much all other types of cancer is that the life expectancy for myeloma patients has doubled in the past decade, largely thanks to treatments developed and tested at Emory’s Winship Cancer Institute. Last November, the US Food and Drug Administration (FDA) approved the fourth new myeloma drug to be green-lighted within one year—three of those within one month—and all four were tested in clinical trials at Winship.

“There’s no other story like that in cancer,” says Sagar Lonial, Winship’s chief medical officer and chair of the Department of Hematology and Medical Oncology in the School of Medicine.

Since his arrival at Emory and Winship in 1997, Lonial has quietly built the multiple myeloma program into one of the best and most sought-after in the country, led by a team of experts who specialize in the disease. As Georgia’s only National Cancer Institute–designated cancer center and one of just 69 in the US, Winship offers patients the chance to be treated in the same building where research is taking place, with three floors dedicated to basic science and three to clinical care.

“That marriage of research and patient care is very powerful,” Lonial says. “Our scientists see cancer patients every day.”

One of those is Mobley, who has been in treatment at Winship since that devastating ambulance ride in 2009. Once her condition was stabilized, she began the standard protocol, which consists of a three-pronged attack: Chemotherapy to blast away the cancerous cells, stem cell harvesting and transplantation to regenerate healthy bone marrow cells, and a regimen of multiple medications calibrated to keep the cancer at bay and ideally send it into remission for a very, very long time.

It’s that last phase that has put Winship’s approach ahead of other myeloma treatment centers. Instead of a one-by-one, trial-and-error approach to drug therapy, Lonial has advocated a full court press, hitting the residual cancer with a simultaneous three-drug combination. Mobley was put on an aggressive course of therapy made up of lenolidamide (Revlimid), an immune modulator; bortezomib (Velcade), a proteasome inhibitor; and dexamethasone, a corticosteroid.

“That concept of combination therapy is one that our center is really focused on and one that really benefited her early on,” Lonial says.

According to myeloma researcher Lawrence Boise, Georgia Cancer Coalition Distinguished Cancer Scholar and coleader of the Cancer Cell Biology Program at Winship, scientists are finding that there are a number of reasons for this—but the most compelling is that it works. “Dr. Lonial doesn’t leave any bullets in the chamber,” Boise says. “In all the trials, all the data, all the comparisons show that three drugs are better than two.”

When Lonial joined Emory’s hematology and oncology department nearly two decades ago, other researchers might have seen a department struggling with turnover and inadequate resources. With the encouragement of a mentor—Kenneth Anderson, probably the best-known myeloma specialist in the world—Lonial saw an opportunity to build a program, literally, from the ground up. The bottom floor of Winship houses the Clinical Trials Unit, the key to the multiple myeloma program’s growth and success. Within a few years, Lonial had recruited top scientists and clinicians, including Boise, and was testing new classes of drugs in Phase I clinical trials. They proved to be game changers.

Multiple myeloma is a cancer of the blood that develops when normal, antibody-producing plasma cells become malignant and their growth spirals out of control, building up in the bone marrow until they crowd out healthy blood cells. They can form lesions and tumors in multiple bones, hence the condition’s name. But the cancerous cells also secrete protein and, like normal cells, they’re engineered to do this in a particular way—the protein assembled and folded just so. When that assembly goes awry, as it does in myeloma cells, the malformed proteins are broken down by proteasomes—protein complexes whose job it is to get rid of problem proteins by degrading them—and that opens up the pipeline for more myeloma cell production.

About ten years ago, scientists discovered that if you interfere with the proteasome’s work—allowing the abnormal proteins to accumulate—the cancerous cells, which in a sense are trying to function normally, will self-destruct. Rapidly.

“Proteasome is part of quality control, so if you inhibit that, and all these mid-folded proteins build up, that causes stress, and the cell kills itself,” Boise explains.

Winship conducted trials of a promising proteasome inhibitor, bortezomib (Velcade), in 2002. One of the first patients to receive it went into remission very quickly. “If there was a moment when the light went on, it was then. I remember running upstairs to the director’s office with the graph of this patient’s counts,” Lonial says. “That treatment is now the standard of care.”

HOPE FOR A BRIGHT FUTURE

Cathy Mooney didn’t need a wake-up call.

In 2002, at 48 years old, “I felt like I was at the top of my game,” she says. “I was exercising regularly, walking four miles five days a week. I was following a great diet. I had really never been in better health.”

But a routine physical exam turned up some troubling results, and a long series of visits to specialists and tests followed. After a frustrating three months, Mooney heard two words she never knew before: multiple myeloma.

"I was told the survival rate was three to five years," she says. "We were devastated. I felt wonderful; I did not feel sick.”

Mooney was advised to travel from her home in Thomasville, Georgia, to Little Rock, Arkansas, where there was a center specializing in myeloma. She received treatment there—including chemotherapy, autologous stem cell transplantation, and maintenance medications—for several years. But although her cancer could be coaxed into remission, it kept coming back.

In 2008, Mooney and her husband flew north to visit myeloma specialists at Sloan Kettering and the Dana-Farber Cancer Institute. The latter was Ken Anderson, who had been following Lonial’s progress at Winship. Both told Mooney that she could get the best, most current treatment in her home state of Georgia.

"When we went to Emory and met with Dr. Lonial and his team, we found him to be a truly compassionate person who really cared and was passionate about finding a cure for multiple myeloma," Mooney says. “He’s such a highly respected doctor in this field, one of the top in leading research and a rising star.”

Since Mooney’s diagnosis, her twin daughter and son have married and had children of their own. Her five grandchildren are a constant delight.

“This June will be 14 years since my diagnosis, which is a lot more than I hoped for,” she says. “I’m feeling great. The cancer has given me an opportunity to reassess my life and set new priorities. And Winship gives me hope for a bright future.”

Mooney

Living the good life: Myeloma patient Cathy Mooney travels to Winship once a month for routine checkups, treatment as needed, and visits with her grandchildren.

FAST TRACK TO NEW TREATMENTS

When Cathy Mooney was first diagnosed, the myeloma program at Winship was just beginning to take off. Now the center sees 400 to 500 new patients a year, with about 1,600 multiple myeloma patients overall. More than 200 Winship patients participate in the Phase I Clinical Trials Unit directed by Donald Harvey.

“That’s a huge group that we are able to see in one city,” says Ajay Nooka, assistant professor of hematology and medical oncology and part of the hematology care team at Winship. In addition to caring for patients, Nooka, who specializes in cancer epidemiology, structures and oversees many of Winship’s clinical trials and assesses their outcomes. The large patient population and high rate of clinical trial enrollment is a gold mine of data for researchers.

“The ultimate goal is to see where we stand in terms of treatment progress and what changes we can make to further improvements in patient outcomes," Nooka says.

Another advantage for Winship’s multiple myeloma team is Atlanta’s large population of African Americans, who are twice as likely as whites to be diagnosed with the disease.

“The difference between us and other centers is that a lot of our patients are our neighbors,” Lonial says. “A lot of the game in clinical trials is not just, are you able to do them, but do you have the patients? The growth for us has really stemmed from access to new drugs and access to patients. That’s a big reason why we had four drugs approved last year.”

In November, the FDA approved elotuzumab as part of an innovative immune-based therapy treatment for patients with relapsed multiple myeloma. That was the third myeloma drug approved by the FDA within the previous month and the fourth approved within the last year.

That’s good news for patients like Quincy Washington, who was 42 when he was diagnosed with multiple myeloma in 2007. At first his doctor suspected rheumatoid arthritis, but then sent Washington to an oncologist, where he learned about myeloma for the first time. The disease typically strikes African American men at a younger age than any other patient group.

“The doctor said, you have multiple myeloma. I said, okay. What do we do next?” Washington remembers. “She looked at my wife and said, is he in shock? And my wife said no, that’s pretty much his personality. I don’t really do the whole gloom-and-doom perspective.”

Washington happened to have a friend who specializes in oncology at Winship, and that’s how he discovered that he could get the most leading-edge care within miles of his home in Lithonia. He began treatment immediately, including enrollment in a clinical trial.

Now in long-term remission, Washington says, “My plan is to be cured. At some point, my numbers will be zero. When it comes to age, I’m a triple-digit kind of guy.”

Washington

What Do We Do Next? Diagnosed at 42, Quincy Washington—shown with his two daughters—had never heard of multiple myeloma. With successful treatment at Winship, he says his plan is simple: to be cured.

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