He had 2 months to live. Cancer research "that seemed like science fiction" saved his life.
Michael Wolff spent 18 months undergoing intensive treatment for follicular lymphoma, a slow-growing blood cancer. Despite the strict regimen, he was only getting sicker.
Wolff's oncologist didn't understand it and sent the then 54-year-old to Dr. Mrinal Gounder at Memorial Sloan Kettering Cancer Center. Wolff underwent another biopsy.
The test found that Wolff had an extremely rare, aggressive blood cancer called histiocytic sarcoma. Only about 300 patients are diagnosed with the condition each year in the U.S. Gounder, an oncologist who focuses on treating sarcomas, said the lymphoma that Wolff was being treated for earlier may have led to the development of the riskier cancer.
Wolff said that Gounder told him he had only treated about 10 cases of the disease before. Wolff didn't want to ask what had happened to those patients. Soon, he was given his prognosis: Gounder estimated Wolff had two months to live.
That was 10 years ago. Now, Wolff is considered cured after technology that he said "seemed like science fiction" was used to find an effective treatment for the rare cancer.
Using genetic sequencing to find treatment options
Genetic sequencing is a process where the DNA that makes up a cancer tumor is analyzed for unique genetic mutations. Those changes can point researchers in the direction of possible treatments, said Dr. Shridar Ganesan, the director of NYU Langone's molecular oncology program and a physician–scientist who was not involved in Wolff's care.
"For a long while, the classification of cancer was kind of dominated by anatomy, by where the lump is, and how it looks like under the microscope," Ganesan said. "But we realize now that in addition to kind of rise and lumps, we have to also take into account the exact changes that make the cancer cells different than normal cells, because that, in many ways, is the clue to both telling us why these cells are misbehaving, and can give us insights into how to then specifically target the growth of these abnormal cells."
Wolff was at the "edge of a cliff," Gounder said. So he put Wolff on another course of intensive chemotherapy, then began analyzing the sarcoma. The process took about six weeks. Wolff said the chemotherapy left him unable to sleep and beset with high fevers. Gounder said the treatment didn't do much to help. But by the time the chemotherapy course was complete, the genetic sequencing results had come back.
The results showed "six or seven potential roads" that could have been used for treatment, Gounder said. He and others at Memorial Sloan Kettering looked at all the options, then settled on a pill called Mekinist, which is most often used to treat melanomas. Gounder believed a mutation found in Wolff's cancer made the pill a good option. There had never been a case where the drug had been used to treat histiocytic sarcoma.
"When he said 'I think I found something and I think we have a drug that can (treat you),' I said 'Well, what's the research?'" Wolff remembered. "He said 'You're the research.'"
"I'm just so thankful"
Wolff began taking the new regimen. He was skeptical that a medication that "looked like a little sugar pill" could help him when chemotherapy had failed. Within two days, the chemotherapy side effects he was experiencing were gone. Ten days into the treatment, Gounder did a PET scan.
The exam found an 80% reduction in Wolff's tumors. Wolff said he considered the results "a miracle."
"I was totally blown away that this thing could have any effect," he said.
Gounder said Wolff's improvement was a welcome surprise — and helped change the game for future patients. In 2018, he published Wolff's case in the New England Journal of Medicine. Mekenist is now used to treat histiocytic sarcomas, and in 2022, the Food and Drug Administration also approved the use of another medication, Cotellic. The outcomes for patients are "night and day," Gounder said.
Meanwhile, Wolff's cancer has not returned, 10 years after he was given just months to live. He was able to stop taking the medication, and last summer, Gounder told him he didn't need to return for annual checkups. He still sees a hematologist, an interventional radiologist and a dermatologist to treat side effects from the chemotherapy courses, but he's been able to return to his career as a renowned jazz musician.
"I've been able to record so much music and play so many concerts around the world," Wolff said. "Every time I do something like that, I'm just so thankful to be able to do it."
What's next for genetic sequencing?
Wolff's case was 10 years ago, when genetic sequencing of cancers was in the early stages. Now, scientists can analyze a tumor's whole genome in a matter of days, Gounder said.
Ganesan said the technology is being used more widely now, particularly in patients with advanced-stage cancers. In some cases, like Wolff's, doctors find a new use for an existing drug. In others, knowing the specific makeup of a cancer allows doctors to develop new treatment options.
As genetic sequencing is used more widely, scientists are also learning more about the "enormous diversity of cancers," Ganesan said. He hopes that eventually, many cancers can be treated or cured using options discovered by genetic sequencing.
"Two people with the same organ-based cancer diagnosis may have very different diseases. This is giving us a chance to understand that, and also to understand the very specific treatments," Ganesan said. "In the old days, we used to give a therapy and say 'Oh, 30% respond, I wonder why?' Now, it starts to tease apart why patients respond to some therapies and not to others, and also define, build and craft specific treatments for individual patients."
