Hodgkin Lymphoma: In Search of the Sweet Spot

   

A new study aims to reduce long-term effects of Hodgkin lymphoma treatment.

By Jane Langille; Photos by Seth Dixon

 

Staying sharp during treatment: Tyler Kingsbury, the first patient to enroll in a new Hodgkin lymphoma clinical trial at St. Jude, practices soccer moves during a break from treatment.

 
 

As the goalkeeper for a competitive soccer team, Tyler Kingsbury knows how to strike the ball on the sweet spot to send it exactly where he wants it to go.

Last November, the 16-year-old found an unexpected yellow-card warning — a little lump under his armpit. It was an inflamed lymph node that flagged a need for further tests.

Shortly after Thanksgiving, a pediatrician in Florida diagnosed Hodgkin lymphoma. The cancer was in his chest and a lymph node in his neck.

“A friend and mom of another player on Tyler’s team strongly recommended St. Jude Children’s Research Hospital. Her daughter participated in a clinical trial for Hodgkin lymphoma at St. Jude four years ago and is still cancer-free and doing well,” says Tyler’s mom, Kimberlee Kingsbury. “Everyone we spoke to said that if it were their child, they would go to St. Jude. But the final decision was Tyler’s.”

Tyler chose St. Jude and also volunteered to be patient No. 1 in a new clinical trial for children, adolescents and young adults with Hodgkin lymphoma.

“Three months at St. Jude for chemotherapy and an additional month for radiation, only if needed, sounded better than four to six months of treatment in Tampa,” Tyler says.

The new study builds on strong evidence from previous trials that have focused on hitting the sweet spot – maintaining high survival rates while minimizing the long-term problems that can show up decades later with conventional therapy.

“The reason for this trial is to keep moving the field forward with less therapy for those with an adequate response.”

Jamie Flerlage, MD

 

Team of experts

Hodgkin lymphoma is a cancer that begins in the lymph system. Abnormal cells called Reed Sternberg cells multiply, causing the lymph nodes to get larger. The disease can spread to the lungs, spleen, liver or bone marrow.

In the United States, up to 8,500 individuals are diagnosed with Hodgkin lymphoma each year. The disease mostly affects children over the age of 15 and young adults up to the age of 39 years, with another peak occurring in older adults.

Because of advances in chemotherapy and radiation techniques, five-year survival rates for children with Hodgkin lymphoma are very good — between 90 and 95% for early diagnoses and close to 90% if the disease has spread. But here’s the catch: treatment carries an increased risk of cardiovascular and lung problems, and a significant risk of secondary cancers due to historically extended radiation fields. Prolonged treatment with steroids puts patients at risk for bone fractures because of low bone density, high blood pressure, obesity and secondary diabetes.

In 1990, researchers from St. Jude, Stanford University Medical Center and Dana-Farber Cancer Institute formed a consortium to find a way to keep cure rates high while limiting the late effects of treatment.

St. Jude oncologist Jamie Flerlage, MD, is the primary investigator for the newest consortium study, called cHOD17. The trial locations include St. Jude, Dana-Farber, Stanford, Massachusetts General Hospital and two of the hospital’s affiliates — the St. Jude Affiliate Clinic at Novant Health Hemby Children’s Hospital in Charlotte, North Carolina; and the Jim and Trudy Maloof St. Jude Midwest Affiliate Clinic in Peoria, Illinois.

“Our main objective is to test whether we can reduce radiation and steroids for patients who respond very well to the initial two cycles of chemotherapy while keeping survival rates the same,” Flerlage says.

Jamie Flerlage, MD, with Tyler

Saving lives with fewer side effects

“Our main objective is to test whether we can reduce radiation and steroids for patients who respond very well to the initial two cycles of chemotherapy while keeping survival rates the same,” says Tyler’s oncologist, Jamie Flerlage, MD.

Eye on the ball

Similar to previous studies, children in the new trial receive risk-adapted therapy. That means they’re placed into one of three risk groups depending on the extent of their disease. They receive radiation therapy depending on how their cancer responds.

All patients receive two cycles of chemotherapy that includes steroids. Those in low- and intermediate-risk groups receive a proven combination of five drugs known as the Stanford V regimen, but with bendamustine substituted for mechlorethamine, which is no longer available.

“This is the first time bendamustine will be tested in front-line therapy in children. We expect it will work well, because it works beautifully and is very well tolerated in both adult and pediatric patients who have relapsed,” Flerlage explains.

Another plus: Bendamustine is widely available, while the other drug is not. Results from this study may provide support for other countries around the world to adopt the protocol.

Patients with high-risk disease receive a different chemo-therapy combination tailored to their larger extent of disease, following promising results from a trial that ended last year.

Tyler is in the intermediate-risk group. Between weekly appointments in the first cycle of chemotherapy, he is attending virtual classes online.

“Tyler is living a very normal life during treatment,” says his dad, Jeff Kingsbury. “One of the researchers put us in touch with a local soccer club in Memphis, so he can keep training.”

The new study builds on strong evidence from previous trials that have focused on hitting the sweet spot – maintaining high survival rates while minimizing the long-term problems that can show up decades later with conventional therapy.

 

Early game strategy

The cHOD17 trial is one of the first studies in pediatrics to rely solely on an early PET scan after the initial cycles of chemotherapy to determine the next step of treatment. The scan allows doctors to check how many active lymphoma cells remain in the body.

If no active cells are found, patients forgo radiation therapy. Patients in the intermediate-risk and high-risk groups who must receive more chemotherapy after that scan will no longer receive steroids with treatment. Although steroids work well to decrease cancer cells, these drugs are now being removed from further cycles for patients whose active cancer cells are gone. By reducing steroid exposure, clinicians help children avoid problems such as obesity and joint issues.

If active cancer cells are present after two cycles, further treatment involves targeted radiation to the specific lymph nodes. Low-risk patients receive radiation therapy, while those in the intermediate and high-risk groups receive more chemotherapy, with steroids, and then complete their radiation treatment.

Goalkeeping

“The reason for this trial is to keep moving the field forward with less therapy for those with an adequate response,” Flerlage says. “We assume we are over-treating groups of patients because so few patients relapse. We need to find the sweet spot.”

Flerlage says most patients who relapse can be cured with more chemotherapy and radiation therapy.

The cHOD17 study is also the first to screen patients before treatment and two years later for side effects that may affect their quality of life, such as attention, memory and sleep problems.

“We hope to identify when the issues begin so that we can make adjustments to therapy and help more patients avoid them in the future,” Flerlage says.

Tyler is itching to get back to goalkeeping in Florida once he finishes cancer treatment. After high school, he has his sights set on college and wants to see how far he can go with soccer.

He seems relaxed about being the first patient in a study that may help children with Hodgkin lymphoma achieve cures with fewer late effects. “It’s probably the best cancer center in the world for kids with cancer,” he explains.

Nick Dustman with bike

Historically, children with Hodgkin lymphoma received the same cancer treatment as adults. Back in 1985, when he was 16 years old, Nick Dustman discovered that a lump under his ear was actually Hodgkin lymphoma. Doctors at St. Jude found cancer in his neck and performed a major abdominal operation to assess whether it had spread to other lymph nodes and organs.

His nodes were all negative for cancer. He received radiation to a broad area of his body from the bottom of his rib cage to his neck. This form of radiation is rarely used today but back then, it successfully boosted cure rates for Hodgkin lymphoma.

After treatment, Nick returned to his life. When he grew up, he became a national sales director for a pharmaceutical company and an avid biker. Then at age 41, Dustman began having trouble breathing after biking a couple of miles.

He enrolled in St. Jude LIFE, a research study that brings long-term childhood cancer survivors back to St. Jude for regular health screenings. St. Jude doctors discovered he had serious heart problems and immediately referred him to a cardiologist.

“My cardiologist found that my left main artery was almost 100% blocked. He was surprised I could make it up a flight of stairs, let alone ride a bike,” Dustman says. “I had a six-way bypass procedure.”

Nick has also managed other late effects from his childhood cancer treatment, including esophageal stricture, thyroid problems and hearing issues.

Today, at age 50, he bikes an average of 20 miles per day and 45 miles on Saturdays.

“I’m extremely fortunate,” he says. “St. Jude saved my life twice.”

 
 

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