Home » Publications » Winship Cancer » Fall 2011 » Feature

A time of hope

By Quinn Eastman, Illustrations by Brian Stauffer

Treatments once were limited for multiple myeloma. Winship has changed that. 

Rudolph Byrd has built a career teaching students about literature, race and the civil rights movement.  For the past decade, he’s been teaching in a different way: informing researchers about cancer – in his own body. Through his participation in several clinical trials at Winship Cancer Institute, he’s helped doctors such as Sagar Lonial, MD, identify drugs that now have become part of a standard regimen for people battling multiple myeloma.

Survival rates for multiple myeloma, a blood cell cancer, have traditionally been grim. Effects of multiple myeloma’s malignant growth can include bone breakdown, kidney failure and anemia. Twenty years ago, most patients died within two or three years after diagnosis.

In the past decade, several new drugs have been developed and approved for use in multiple myeloma, including bortezomib, thalidomide and its cousin lenalidomide. Lonial has been integrally involved in many of the studies that led to the approval of these new drugs, and he currently is leading a nationwide trial on the use of lenalidomide to treat smoldering myeloma, or myeloma that is asymptomatic at diagnosis.

Together with traditional chemotherapy and stem cell transplantation, new therapies have doubled average survival times. The greatest benefit is seen in patients younger than 60, though these new drugs are helping all ages now, Lonial says.

Byrd’s experience illustrates these trends. He was diagnosed with multiple myeloma in 2000 while on sabbatical in Boston. Then 47, he decided to return home for treatment. His internist advised him to contact Lonial, then a new faculty member at Winship. Lonial says a mentor in Boston, Ken Anderson, MD, had urged him to begin testing a promising drug against multiple myeloma.

“I’ve been honored to be an adviser and watch Sagar Lonial develop a world-class multiple myeloma program at Winship,” says Anderson, who heads Dana-Farber Cancer Institute’s multiple myeloma program. “He recognized from the earliest days that bortezomib, for example, had the potential to be qualitatively different than conventional treatments and was instrumental in the clinical trials leading to its approval.”

Byrd, a professor of African American studies and founding director of the James Weldon Johnson Institute at Emory, underwent what would be the first of three stem cell transplants the following spring. Under Lonial’s care, Byrd was one of the first people in Georgia with multiple myeloma to receive bortezomib (Velcade), then an experimental drug. In the summer of 2011, he was embarking on his eighth clinical trial.

Participating in clinical trials made sense to Byrd as a historian and researcher. His core beliefs instructed him: “If you can choose to be helpful to others, you make that choice.”

In turn, Lonial has helped him, he says. “Each time there is a relapse, it’s a new disease with its own personality: aggressive, intent on its own survival,” Byrd says. “All this means he [Lonial] has had to be extremely creative. I wouldn’t have survived all these years without his efforts.”

“Every successful drug in myeloma, he’s gotten them before they were approved,” Lonial says. “It also really shows the importance of clinical trials in providing a foundation for scientific advances.”

Although Byrd received bortezomib and lenalidomide as well as other drugs after his stem cell transplant, they are now standard as initial treatment for most patients.

This transformation of the field means that patients like Kate Groover, embarking on a course of treatment for multiple myeloma in the summer of 2011, will receive a panel of effective therapies without having a stem cell transplant scheduled, perhaps for years.

During the time Lonial was conducting clinical trials in Atlanta and studying the effects of bortezomib, another young researcher in Miami was investigating how cells make decisions to live and die in response to stress and had begun to focus on multiple myeloma.

Lawrence Boise, PhD, joined Winship in 2009 so he could work side by side with clinicians like Lonial to better understand multiple myeloma with the hope of developing more effective therapeutic strategies.

“Larry’s arrival has been a turbo boost for our program,” Lonial says. “He’s a phenomenal scientist who’s tuned in to the problems we face in multiple myeloma.”

Much of researchers’ understanding of how bortezomib works against multiple myeloma did not come to light until after the drug’s approval, says Boise, professor of hematology and medical oncology and Georgia Cancer Coalition Distinguished Scholar.

It turns out that multiple myeloma cells’ vulnerability to bortezomib may have a link to the healthy cells the cancerous cells arise from: plasma cells. Plasma cells are part of the immune system and live in the bone marrow. Their job is to produce antibodies, proteins that fight invaders like bacteria or viruses.

“If you look at both plasma cells and multiple myeloma cells, they are chock full of the machinery cells use to pump out proteins,” Boise says.

He and his co-workers have shown that multiple myeloma cells are more sensitive to drugs that perturb their ability to clean up the waste byproducts of all that protein production. This may explain the effectiveness of bortezomib, which inhibits proteasomes, cellular machines that act as garbage disposals.

Part of Boise’s lab’s research is oriented toward exploiting this vulnerability, by finding ways to heighten the stress on myeloma cells. If proteasomes, one way for cancer cells to clean up, are shut down, they might escape by directing waste down a second path. Drugs have been identified that could specifically interfere with this second path, called aggresomes.

Based on these insights, Lonial and another colleague, Jonathan Kaufman, MD, assistant professor of hematology and oncology, have designed a clinical study, in which an add-on drug to the standard regimen, vorinostat, might further interfere with cancer cells’ trash cleanup. Lonial and R. Donald Harvey, PharmD and director of Winship’s phase I clinical trials program, are testing a new drug against multiple myeloma, ACY-1215, with the same rationale. 

“Our objective isn’t to improve response rates, because response rates to the standard treatment panel are already quite high,” Lonial says. Rather, his aim is to purge myeloma cells so effectively from the body that sensitive laboratory assays can’t detect them for months or years – what he gingerly calls “closer to a cure.”