
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.
Michael Wolff attends the 2011 WBGO-FM Champions of Jazz benefit at Jazz at Lincoln Center on November 2, 2011 in New York City.
Charles Eshelman
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.
Memorial Sloan Kettering Cancer Center- David H. Koch Center.
HVEPhoto / Getty Images
"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."
Musician Michael Wolff performs at the 2011 WBGO-FM Champions of Jazz benefit at Jazz at Lincoln Center on November 2, 2011 in New York City.
Stephen Lovekin / Getty Images
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."
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The MATTERHORN population 'looks like patients in the clinic,' and the similarity in patient dispositions between the study groups was important, said Klempner. 'To me, this says that academic and community oncologists and our surgical colleagues can feel confident that adding durvalumab to FLOT does not impact our ability to complete neoadjuvant FLOT, get to surgery, achieve our zero resection, or complete adjuvant therapy,' he said. 'I also want to stake the claim for D-FLOT as the name for this new standard regimen,' he added to loud applause in the session. 'This is a pivotal trial in upper GI cancer patients in a space that's really been taking center stage in recent years with many recent advances,' Pamela Kunz MD, PhD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center in New Haven, Connecticut, said at a press conference before the presentation. 'This is going to change the standard of care for this patient population.' She added that physicians must carefully select patients for durvalumab plus FLOT treatment. 'Can all patients tolerate a four-drug treatment?' Kunz asked. 'The study demonstrated it was reasonably well tolerated, but in terms of the patients in front of us, we need to think about them.' This study was funded by AstraZeneca. Janjigian reported disclosed financial relationships with AbbVie, AmerisourceBergen, Arcus Biosciences, Ask-Gene Pharma, Astellas Pharma, AstraZeneca, Basilea Pharmaceutica, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Clinical Care Options, Daiichi Sankyo, eChinaHealth, ED MedResources, EISAI, Eli Lilly and Co., Genentech, Geneos Therapeutics, GlaxoSmithKline, Guardant Health, H.C. Wainwright & Co., Imedex, Imugene, Inspirna, Lynx Health, Merck, Merck Serono, Mersana Therapeutics, Pfizer, Sanofi Genzyme, Seagen, Silverback Therapeutics, Transcenta, and Zymeworks. Klempner reported relationships with Nuvalent, Merck Serano, Amgen, Astellas Pharma, AstraZeneca, BeiGene, Bristol Myers Squibb, Daiichi Sankyo UCB Japan, Eisai, Elevation Oncology, Gilead Sciences, I-Mab, Merck, Novartis, SERVIER, Taiho Oncology, Arcus Biosciences, Leap Therapeutics, and Mersana. Disclosures for Kunz were not available at press time.