Immunotherapy Helps Survivor Continue Her Winning Fight Against Cancer
“How do you feel?” asked Sameek Roychowdhury, MD, PhD.
“Good, really good,” answered Rhonda Ball with a smile as she sat in the examining room.
“No, I’m eating well… I’m eating too much!” Ball said.
Not long ago, Ball wasn’t feeling well at all. She was constantly sick to her stomach, couldn’t eat, had no energy and was having some balance issues. Her cancer kept coming back, each time to a different location in her body. She had what is known as cancer of unknown origin — cancer that is present in the body, but the location where it started is not known — which is difficult to treat.
“My husband thought I was going to die,” she said.
Fortunately, Ball was being treated by Dr. Roychowdhury, an assistant professor in the Division of Medical Oncology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). The Roychowdhury Lab and his clinic (where he sees patients) use genomic testing to find the genetic abnormalities of the cancer cells of patients who haven’t responded to their initial treatment in order to get a clearer look at the causes of the disease. They then use this information to administer one or a combination of “smart drugs” to treat the specific mutation. This is known as precision cancer medicine.
Ball was first diagnosed with early-stage breast cancer in 2009. She was diagnosed with endometrial (uterine) cancer in 2012 and underwent surgery, followed by chemotherapy at the OSUCCC – James. Her right hip started hurting in 2014, and several exams later, her doctors discovered her cancer was back. The small tumor in her hip was followed by a tumor on the back of her neck and one on her stomach. The tumors on her hip and neck were removed.
“I couldn’t eat,” Ball said, adding that she lost 50 pounds and felt too weak to do much of anything. “I’d try and have a small bowl of cereal in the morning and most of the time I couldn’t keep that down. The rest of the day I’d have some flat ginger ale and some rainbow sherbet.”
Ball began feeling better after doctors detected and removed a small, cancerous blockage in her bowel, but the mystery of the recurring tumors remained, as did the tumor on her stomach.
Were they connected?
“Not the pre-cancerous breast cancer and the uterine cancer, not that I know of,” Dr. Roychowdhury said, adding that the cancers in Ball’s hip, neck, stomach and bowel did seem to have a common denominator.
“A genetic test revealed she had a KRAS gene mutation,” Dr. Roychowdhury said. “This has proven to be difficult to develop therapies for, and none were available.”
The lab dug deeper in to the genetic code of Ball’s tumors and discovered something else: The microsatellite instability marker, or MSI-H marker, which is often found in inherited cancer syndromes such as colon and endometrial cancers.
Ball’s most-recent cancer did not appear to have started in her colon or uterine. Nevertheless, Dr. Roychowdhury enrolled her in a clinical trial in which she received pembrolizumab (marketed as Keytruda), a new immunotherapy drug approved by the Food and Drug Administration (FDA) for the treatment of head and neck cancers.
According to the FDA, “Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells.” This is known as immunotherapy.
The clinical trial worked for Ball.
“The tumor on my stomach was getting bigger and was starting to break the skin. The first day I took the (Keytruda), it felt like my tumor was burning, like it was on fire. In a week, it wasn’t gone, but I could already tell it was a lot smaller. Now, all that’s left is a little scar tissue.”
On August 10, Ball and her husband, Buzz, renewed their wedding vows, something they do every year. The FDA granted “accelerated approval” on May 23 for the use of Keytruda in any patient with the MSI-H marker.
“This is the first approval for the use of a drug based on the genetic marker, independent of the tumor type,” Dr. Roychowdhury said. “And Rhonda was a participant on one of the five trials that helped get the drug approved.”
The Roychowdhury Lab’s battle against MSI-H is just beginning. The members are working on several related projects that involve diagnosis, enhanced treatment and the discovery of a new, related genetic marker to attack.
The lab analyzed 39 types of cancer and found the MSI-H marker in 3.8 percent of the cases. This has led Dr. Roychowdhury to believe that every cancer patient should be tested for the marker. However, this is a complicated and expensive test.
“We used big-genetics data to develop a new algorithm to detect MSI-H,” Dr. Roychowdhury said. “And then we developed the framework for a new diagnostics test for MSI-H that can be used for any type of cancer and is a lot easier to administer. It’s called MSIDx (the Dx is for diagnostics).”
In some cases, the cancer cells in a patient’s body eventually figure out how to trick or evade immunotherapy drugs.
“We always have to be mindful of that,” Dr. Roychowdhury said.
He and his team are quite mindful of this possibility, and are working with a pharmaceutical company to “increase the response rate and longevity of Keytruda by combining it with a second – and new – drug we’re developing,” Dr. Roychowdhury said. The combination has proven quite potent in the lab and Dr. Roychowdhury is optimistic that a clinical trial will start soon.
“Let me tell you about another grant, a Pelotonia Idea Grant we’re applying for, that started with you,” he told Ball during her recent visit. “It’s a new marker that we think will prove very helpful in diagnosing genetic mutations. It’s called methylation.”
While the MSI-H genetic mutation can change a letter in the genetic code, methylation can change “something on the letter without changing the entire letter,” Dr. Roychowdhury explained, adding that he and his lab began this new line of research as they dug deeper into Ball’s genetic code. “Instead of changing a G to a C in the genetic code, it’s like it’s putting an apostrophe above the G.”
Dr. Roychowdhury and his lab are working on a new diagnostic test to detect methylation.
“What if there are other genes that get methylated and this leads to MSI-H and then cancer,” he told Ball, adding that identifying methylation could enhance the ability to prescribe even smarter, more targeted immunotherapy drugs to patients and lead to better outcomes.
“We’ve found something that we hope will help people, so I’m pretty excited,” Dr. Roychowdhury said, and Ball nodded in agreement.
Ball has been through a lot the past several years. But determination, a great attitude, the support and caregiving help of Buzz and the state-of-the-art immunotherapy treatment from Dr. Roychowdhury and his team in her clinical trial have helped her turn the corner. Ball is now feeling “better than I’ve felt in years,” and is optimistic about the future.
“It has changed me,” she said of cancer. “I appreciate everything and everyone a lot more now. But I know my cancer could pop back up again.”
And this, she said, is why the work of the Roychowdhury Lab and the scores of other labs at the OSUCCC – James, and at comprehensive cancer centers around the country, is so important.
“Research is everything,” Ball said. “I wouldn’t be sitting here today if it wasn’t for research. I feel so lucky that this first-class, amazing place is less than 30 minutes from my house, that I have such a wonderful doctor and my clinical trial is working and I don’t have any side effects. I just wish every cancer patient everywhere had this same opportunity.”