Fixing one wrong note: How MSK precision diagnostics saved a musician with a rare cancer

For renowned composer and pianist Michael Wolff, jazz is life. It’s been his profession for a half-century. It’s also a metaphor for the cancer treatment that saved him. In fact, his remarkable case has led to a new way to treat other patients around the world.

Michael recently celebrated it all in a spectacular moment with his sons, musicians Nat and Alex Wolff, when they opened for Billie Eilish at Madison Square Garden. They called their dad to join them onstage for a song they’d written about his experience with cancer. On looking out at the crowd of 20,000 people, Michael says, “I felt like the luckiest man in the world.”

Michael came to Memorial Sloan Kettering Cancer Center (MSK) in 2015 in bad condition. He had recently completed treatment for lymphoma at another hospital, but his symptoms — high fevers, violent shaking, and severe weakness — were unrelenting.

“I was in horrible shape,” he remembers. “I couldn’t get out of bed.” 

His wife, actress Polly Draper, insisted he get a second opinion at MSK. The initial test results were grim. MSK’s expert pathologists discovered Michael had an entirely different type of cancer — histiocytic sarcoma, a blood cancer so rare it affects only 300 people in the United States every year. It had spread throughout his body.

Michael was not optimistic when he went to see sarcoma medical oncologist and early drug development specialist Mrinal Gounder, MD.  

“I told Michael there was no standard treatment for this very rare cancer, but that I was waiting for genomic test results from our pathologists,” Dr. Gounder recalls. “I hoped it would lead us to a therapy that we could use.”

Treating Cancers Based on Molecular Findings 

That genomic test would take Michael on a journey where no one had gone before but many have followed since. 

“We were improvising on the fly,” Dr. Gounder says. “His whole treatment was very much like jazz music.”  

That improvisation was an early demonstration of how testing a tumor’s molecular makeup can lead to a more precise diagnosis. It showed how these test results can point toward targeted drugs that are able to attack a cancer based on its genetic mutations rather than its location in the body. This approach has since changed the way many cancers are treated, especially rare cancers. 

Precision Diagnostics: How One Wrong Note Can Cause Cancer

When Michael came to MSK in 2015, the diagnostic test called MSK-IMPACT^® had just been launched. It would later become the first molecular test authorized by the U.S. Food and Drug Administration to look for mutations across a range of cancers. Developed by the Henry and Marie-Josée Kravis Center for Molecular Oncology (CMO), this test has led to new drugs for many tumor types. In the decade since the center’s founding, MSK-IMPACT has been updated several times: Today, it identifies more than 500 cancer-causing genetic mutations. The test is usually covered by insurance and is available to all MSK patients whose cancer has spread. 

The precision of MSK-IMPACT is extraordinary. It can detect cancer-causing gene mutations down to a single misplaced A, T, G, or C — the four “base pairs” that make up the DNA code. 

In Michael’s case, the test revealed mutations in several genes. One was in a gene called MAP2K1. A seemingly miniscule error set the cancer in motion: A T had been mistakenly substituted with an A, initiating a cascade of damaging effects.

One wrong note had thrown his entire body into disharmony. 

When Dr. Gounder saw Michael’s test results, the MAP2K1 mutation stood out right away. A recent publication in Clinical Cancer Research from MSK pathologist Maria Arcila, MD, and colleagues had shown how MAP2K1 led to a subset of lung cancers.

Michael later wrote in his memoir about the day when, sitting in Dr. Gounder’s office shivering in misery, he got the results. “Dr. Gounder came striding in with a crazy-big smile on his face and told me to give him a high five. ‘Mr. Wolff,’ he practically shouted, ‘I have some good news to share! A mutation has shown up in your genomic test.’ ”

Blocking the MAP2K1 Mutation With Trametinib

Even more exciting, Dr. Gounder’s research had uncovered a treatment that might work. It was a tiny pill called trametinib (Mekinist^®). The drug had been approved to treat melanomas with certain mutations, based on clinical trials led by an MSK doctor. Because Michael’s rare cancer had a similar genetic vulnerability, they decided to give it a try.

Michael was the first person ever to take trametinib for histiocytic sarcoma. Dr. Gounder helped make sure that his insurance would cover the expensive experimental treatment.  

Michael was hopeful but skeptical. “When I saw these little pills, I thought, ‘If all that chemo didn’t help, this is definitely not going to do anything,’ ” he says. “But after only two days, all my symptoms went away.”  

At his next appointment with Dr. Gounder, Michael told him he had no more sweats, no more chills, and no more shaking. 

“Dr. Gounder was a consummate professional, but upon receiving this news, he couldn’t contain himself,” Michael wrote. “ ‘Look at my arm! Look at my arm!’ he shouted. ‘The hair on my arm is actually standing up! This is why I get up in the morning. This is what I live for! High five, high five, high five!’ ”

A PET scan performed 10 days after Michael started taking trametinib confirmed what he was feeling: His tumors had already shrunk by 80%. “I had chills when I saw the results,” Dr. Gounder says. “It was clear we were on to something big.” 

Indeed, they were. Three years later, after several scans in a row had shown Michael was free of disease, Dr. Gounder said he could stop taking the drug.  

Histiocytosis Research Pioneered at MSK Now Benefits Patients Everywhere  

Michael’s response to the tiny pill for the rare cancer was so extraordinary that Dr. Gounder and his colleagues published a case study about him in the New England Journal of Medicine.

“After we published that case, I started getting calls from patients and doctors all over the world,” Dr. Gounder says.

The insight gained from Michael’s case mirrored research being done at MSK for other subtypes of histiocytosis as well. Thanks to studies led by neuro-oncologist and early drug development specialist Eli Diamond, MD, patients with these rare cancers now have options for targeted therapies that are based on their particular mutations. These treatments offer better outcomes than traditional chemotherapy.

At MSK, patients with histiocytic sarcoma are now treated by leukemia specialist Raajit Rampal, MD, PhD, Director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program.

MSK’s Multidisciplinary Team of Specialists 

Bringing Michael’s cancer under control was not the only challenge for his care team. Although it wasn’t nearly as hard on Michael’s body as chemotherapy, trametinib caused severe rashes, among other side effects. 

Additionally, the steroids and chemotherapy he previously received had devastated his immune system, resulting in a rare, life-threatening fungal infection. MSK infectious disease specialist Susan Seo, MD, found the right medication to treat it. The fungal infection also exacerbated a condition called hereditary angioedema, which was causing Michael’s blood vessels to swell and close. To treat it, he has now had more than 20 procedures under the care of MSK’s interventional radiologists, including Stephen Solomon, MD, and Etay Ziv, MD, PhD.  

“The treatment I’ve gotten from all the doctors I’ve seen at MSK has been amazing,” Michael says. “For a while, I was going there so often that everyone knew me. Everybody chipped in to care for me.”  

Jazz Is Life  

Today, Michael, now 72, is considered cured. He has resumed composing and performing music. He recently released an album, Memoir, following his book, On That Note: A Memoir of Jazz, Tics, and Survival. 

For Michael, there is an unmistakable connection between jazz and discovery. It has led to epiphanies in music, in medical care, and most importantly, in his life with his family. 

In his book, he wrote about moments spent in New York City’s Washington Square Park while he was recovering from cancer, and the realization that he had changed.

“I had endless time to think, and as my head cleared from the disease and the drugs, I kept thinking about my family and how they’d saved me. As much as I love music, I know now that the people in my life are the most important thing.”  

He is also eternally grateful to Dr. Gounder, whom he calls a hero and a friend. 

“Both fortunately and unfortunately, I rarely get to see Michael anymore,” Dr. Gounder says. “I try to go to his shows when I can, and I always enjoy seeing him and the rest of his family.” 

Dr. Gounder says Michael’s successful treatment is a remarkable demonstration of team science, adding, “His experience could not have happened anywhere but MSK.”