With new treatments transforming multiple myeloma into a chronic condition and additional therapies on the horizon, some experts believe a cure is within view.
Dana Davis, a 56-year-old school administrator in suburban Atlanta, remembers the rib pain first.
“I had an excuse for everything,” Davis says with a laugh. “But finally, my wife said I couldn’t ignore it any longer. She insisted that I go to the doctor. Pretty quickly, they found that I had anemia. Then they diagnosed multiple myeloma.”
That was 15 years ago. Davis has already survived three times longer than patients with even the best prognosis could have expected in the 20th century. The father of a son and two daughters when he was diagnosed, he has been able to watch those children grow up, take in a foster son, who is now 11, and see his first grandchild born.
And Davis is now part of a clinical trial of a targeted monoclonal antibody, daratumumab, that researchers hope will be a game changer in the treatment of myeloma. Even more amazing, Davis’ story is becoming more and more common.
A multiple myeloma diagnosis used to mean that a patient could only expect to survive three to five years — with only chemotherapy agents available for treatment. Today, that landscape has changed so much that it’s almost unrecognizable, with average survival nearly tripled and additional advances on the horizon with a sophisticated array of therapeutic options.
Doctors are trying established drugs in new combinations, doses and formulations that seem to cut down on the side effects of treatment, and also to lengthen stretches of progression-free survival (PFS). Some drugs in the clinical trial pipeline enlist the body’s own immune system to fight the disease, while others target cells with specific genetic mutations, or never-before-targeted systems that control cell processes. The fact that oral drugs are in development means that patients don’t have to travel to an infusion center every few weeks to keep their cancer under control.
Multiple myeloma remains an incurable disease, but it is becoming more manageable. Doctors are beginning to talk of it as a “chronic disease.” Some are optimistic enough to even say that a cure may be possible.
“It’s a massive convergence of our understanding of biology, the technology becoming available to understand myeloma cells and how they respond, the genetic subtypes of myeloma, the ability to engage both the patient community and researcher, to transfer data and information,” says Walter Capone, president and CEO of the Multiple Myeloma Research Foundation. “It’s truly a renaissance in our ability to make treatment of myeloma more precise and accelerate breakthroughs for patients.”
Approximately 22,000 Americans receive a multiple myeloma diagnosis each year. Myeloma is the second most common blood cancer, after lymphoma. It tends to strike African-Americans more often, and those older than 65.
Myeloma starts in the plasma cells of the bone marrow, white blood cells that, when healthy, are specialized immune cells, specifically B-cell lymphocytes that make antibodies. As the myeloma kindles, the plasma cells stop doing what they’re supposed to do and start making large amounts of an abnormal, non-functional antibody called “M protein.” These proteins and cells can clump together, forming hole-like cysts in the bone. If more than one cyst has formed, the diagnosis is “multiple” myeloma. M proteins and other substances made by myeloma cells also can etch away bone tissue, causing pain and breaks. They may thicken the blood, interfering with the normal function of kidneys, bone marrow, nerves and the immune system. And they can lead to high levels of blood calcium, causing dehydration and kidney problems or failure, or make patients susceptible to infection.
Myeloma is expensive. The incidence of lung cancer is 11 times greater than the incidence of multiple myeloma, but the annual costs associated with multiple myeloma are $100-plus million more than the costs associated with patients with lung cancer that has spread to the bones. The costs of the new drugs for a single patient range from $98,000 to $276,000 per year.
From Standard Treatment to New Territory
In recent years, the standard treatment has been a course of traditional, high-dose chemotherapy drugs like melphalan or cyclophosphamide, considered an “induction” phase of treatment meant to induce remission of the cancer prior to a stem cell transplant. Next, the patient receives a stem cell transplant. This grueling, months-long procedure replaces the diseased bone marrow with healthy marrow from a donor. The side effects of myeloma treatment can be harrowing: drops in blood counts, crushing fatigue, diarrhea, severe bone pain, relentless infections, nausea, heart damage.
After the war, Vietnam veteran Steve Dudich joined the Salvation Army as a lieutenant where he served impoverished neighborhoods in the Bay Area.
"Were you in Vietnam?"
That’s a haunting question Steve Dudich, of Arroyo Grande, has heard more times than he cares to remember.
Doctors asked when they detected his daughter had a rare cancer of the forehead, when his wife miscarried a child and when he developed ischemic heart disease, forcing his heart to beat 250 beats per minute, more than twice as fast as it should be beating.
A Serbian whose family fled to America, Dudich joined the Marines at 16 years old (his father, he said, forged his mother’s signature on the recruitment paperwork). As soon as he caught wind that the Russians were transporting missiles to Cuba, he vowed he would do whatever he could to fight communism.
He never imagined it would lead him into battle against his own government.
“I’ve been an Agent Orange warrior ever since I was first in (the) country. I was burned bad by that stuff,” Dudich said. “Agent Orange has destroyed my life. It has harmed my children, it has harmed my first wife … what they have done to us and put us through when we came home, there’s no excuse for what this government did.”
U.S. forces sprayed more than 19 million gallons of the herbicide throughout Vietnam between 1961 and 1972, using the powerful acid to cut down dense foliage enemies used for cover.
Dudich sprinted through a barrage of bamboo doused in Agent Orange. The splinters penetrated his skin, injecting the herbicide into his body hundreds of times. The pain became overwhelming. He stripped down to his skivvies.
“People thought I’d gone crazy. I looked like I’d been dipped in a vat of acid,” Dudich said. “That’s where I think I got my worst contamination.”
The effects are lasting.
He developed outbreaks of rashes and blisters throughout his body, repulsing his young daughters.
“They were scared of me," Dudich said. "My eyes would have blisters, my face would have blisters. I’d stay in my room and not come out.”
His daughters harbor resentment, Dudich said. Although not physically visible, they sustain secondary exposure to Agent Orange.
One of his daughters said she considers herself “tweaked.”
Dudich has spent his life advocating for veterans rights.
Before his exposure to the herbicide, Dudich was a brash soldier. He carried a Ruger Blackhawk 357 revolver and quick drew it like a cowboy. He would wear a white T-shirt instead of Army camouflage and a soft cover instead of hard helmet.
The bright target would flush out snipers, and as soon as Dudich found out where they were firing from, he’d call in an airstrike.
“I had every attitude at my young age that I could have. I’m ghetto born and bred, man.”
Years after the war, Dudich’s commanding officers offered to promote him to captain with retroactive pay, and award him the Navy Cross. He turned them down.
“What’s that do for me?” Dudich asked.
Eventually, Dudich would be commissioned as an officer, however. He joined the Salvation Army as a lieutenant where he served impoverished neighborhoods in the Bay Area.
“Never have I regretted going into the service,” Dudich said. “I learned so much through the war. Going forward, I can see the things other people just can’t see.”
Glyphosate – the main ingredient in Monsanto’s widely used herbicide Roundup – is a colorless, odorless chemical and might seem innocuous to those who spray it on crops. But in the past few months the truth has come out: This chemical can be dangerous to farmers who are exposed to it and to people living close to farming areas.
In fact, glyphosate has been found to double the risk of one blood cancer, non-Hodgkin’s lymphoma, and increase the risk of a related cancer, multiple myeloma. (Multiple myeloma was recently classified as a sub-type of non-Hodgkin’s lymphoma, but they used to be considered distinct diseases.)
In a report released in late July, the world’s leading cancer experts at the International Agency for Research on Cancer shed new light on the cancer-causing properties of glyphosate. The report, which took an in-depth look at the latest research, concluded that glyphosate is definitely carcinogenic to animals in laboratory studies and that human exposure is linked to a higher risk of developing blood cancers such as non-Hodgkin’s lymphoma.
The report confirmed the findings of the Agency’s previous meta-analysis, which combined the results of several studies and concluded that occupational exposure to glyphosate doubles the risk of developing non-Hodgkin’s lymphoma. The more recent report also highlighted studies that found that farm workers’ glyphosate exposure increases their risk of multiple myeloma by 70 to 100 percent.
It’s no wonder, then, that two farmers have filed lawsuits against Monsanto charging that they had been exposed them to a chemical that is “unreasonably dangerous.” Bottles of Roundup carry no warning that it is a probable human carcinogen.
In response to the International Agency’s recent findings, California has moved to add glyphosate to the state’s list of known carcinogens. This would require that Roundup bottles come with some sort of label warning of its dangers.
And farm workers aren’t the only ones exposed to the herbicide. Researchers have found glyphosate residues in food as well. The cancer research agency points out that a 2007 study found glyphosate residues on six of eight tofu samples made from Brazilian soybeans. Soybeans are the largest genetically modified crop produced globally and account for about half of the total area dedicated to growing GMO crops.
It’s time to label genetically modified food and let consumers decide whether they want to support an agricultural system that exposes farmers – and potentially themselves – to unreasonable risks.
After stem cell transplants for blood cancers, patients — with help from their caregivers — must be careful to avoid infections.
Nikki Mann knows first-hand that it takes patience, diligence and teamwork to help a loved one recover from a stem-cell transplant following a blood cancer diagnosis.
Her husband, Bill Mann, successfully underwent a stem-cell transplant in 2004, four years after he was diagnosed with multiple myeloma at the age of 45.
Although the transplant was uncharted territory for the Manns, Nikki’s role as caregiver had already been cemented through their initial years of his cancer saga. This time, they both had to be mindful of the heightened risk for infection in the ensuing days and weeks, because a stem-cell recipient’s immune system is weakened for a period of time after a transplant.
From an infection standpoint, the main risks are viral and fungal infections, but some bacterial infection risk is present too, particularly for patients whose treatment regimen relies on intravenous catheters that stay implanted for months at a time, says medical oncologist Ravi Vij, a specialist in bone marrow/stem cell transplants at the Siteman Cancer Center at the Washington University School of Medicine in St. Louis, Mo.
Vietnam veterans who were exposed to Agent Orange appear to have an increased risk for developing monoclonal gammopathy of undetermined significance, a precursor to multiple myeloma, according to results of a prospective study.
Researchers evaluated stored blood samples from U.S. Air Force personnel and found those who conducted Vietnam War missions that involved ‘Agent Orange’ herbicide had a more than twofold greater risk for developing monoclonal gammopathy of undetermined significance (MGUS).
“Multiple myeloma has been classified as exhibiting ‘limited or suggestive evidence’ of an association with herbicides in Vietnam War veterans,” Ola Landgren, MD, PhD, chief of myeloma service at Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote. “Occupational studies have shown that other pesticides (insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state MGUS; however, to our knowledge, no [previous] studies have uncovered such an association in Vietnam War veterans.”
Landgren and colleagues conducted this prospective cohort study to determine the prevalence of MGUS among Operation Ranch Hand veterans compared to a control population and to assess the risk of MGUS in relation to the Agent Orange contaminant and human carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Operation Ranch Hand was part of a U.S. military strategy from 1962 to 1971 that involved spraying approximately 20 million gallons of herbicides over rural areas of South Vietnam in an attempt to deprive the Viet Cong of food and vegetation cover.
Researchers evaluated data from the Air Force Health Study, which collected and stored serum samples and relevant exposure data. A follow-up examination of the Air Force Health Study was performed in 2002.
Landgren and colleagues tested all of the specimens in 2013 without knowledge of the exposure status. Their analysis included data from 958 male veterans, 479 of whom were part of Operation Ranch Hand and 479 comparison veterans who did not fly on those missions. All cases and controls had similar demographics, medical histories and lifestyle characteristics.
The prevalence of MGUS was 7.1% in Ranch Hand veterans compared with 3.1% in the control group. This equated to a 2.4-fold increased risk for MGUS in the Ranch Hand veterans after adjusting for age, race, BMI and the time of blood draw for TCDD measurement in 2002 compared to the control cohort (adjusted OR = 2.37; 95% CI, 1.27-4.44).
Further, the risk for MGUS was significantly greater among veterans aged younger than 70 years (OR = 3.4; 95% CI, 1.46-8.13).
The researchers acknowledged several study limitations. There were no objective measurements of exposure to phenoxy herbicides, so researchers used cohort status as a surrogate. Also, the first TCDD measures weren’t taken until 1987 and — with 25 years between exposure and measurement — the researchers could not account for individual variations in the whole-body elimination of TCDD.
A bias may also have been introduced because a greater proportion of Ranch Hand veterans had a TCDD level measured in 1987 than controls (86.6% vs. 74.1%).
Celebrating 29 years of marriage in December '17. After over 7 years of remission, Dom's Multiple Myeloma (Cancer of the blood plasma cells- attributed to Agent Orange Exposure while Dom served in Vietnam) has returned. Much of this blog concentrates on our adventure leading up to a Stem Cell Transplant, his remission, and our new adventure.