Fixing a wrong note: How MSK Precision Diagnostics saved a musician with a rare cancer

For renowned composer and pianist Michael Wolff, jazz is life. It has been his profession for half a century. It is also a metaphor for the cancer treatment that saved him. In fact, his remarkable case 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 father to join them on stage for a song they wrote about his experience with cancer. Looking out at the crowd of 20,000, Michael says, “I felt like the luckiest man in the world.”

Michael came to Memorial Sloan Kettering Cancer Center (MSK) in 2015 in poor condition. He recently finished treatment for lymphoma at another hospital, but his symptoms – high fever, violent shaking and severe weakness – were relentless.

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

His wife, actress Polly Draper, insisted on getting a second opinion at MSK. Initial test results were bleak. MSK pathologists discovered that Michael had an entirely different type of cancer—histiocytic sarcoma, a blood cancer so rare that it affects only 300 people in the United States each year. It had spread throughout his body.

Michael wasn’t optimistic when he went to sarcoma oncologist and early-stage drug development specialist Mrinal Gounder, MD.

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

“I was improvising on the fly,” says Dr. Gounder. “His whole treatment was very similar to jazz music.”

That improvisation was an early demonstration of how testing the molecular makeup of a tumor can lead to a more accurate diagnosis. He showed how these test results can point to 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 a wrong note can cause cancer

When Michael came to MSK in 2015, the diagnostic test was called MSK-IMPACT^® it had just been released. It would later become the first molecular test cleared by the US Food and Drug Administration to look for mutations in 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 was established, MSK-IMPACT has been updated several times: today, it identifies more than 500 genetic mutations that cause cancer. The test is usually covered by insurance and is available to all MSK patients whose cancer has spread.

The accuracy of the MSK-IMPACT is extraordinary. It can detect cancer-causing genetic mutations down to a single wrong position A, T, Gor 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. An apparently tiny error set cancer in motion: A T had been mistakenly replaced by a Atriggering a cascade of harmful effects.

One wrong note had thrown his whole body into disharmony.

When Dr. Gounder saw Michael’s test results, he MAP2K1 the mutation was immediately noticeable. A recent publication in Clinical cancer research from MSK pathologist Maria Arcila, MD, and colleagues showed how MAP2K1 led to a subset of lung cancers.

Michael later wrote in his memoirs about the day when, sitting in Dr. Gounder’s office shaking with misery, he got the results. “Dr. Gounder walked in with a crazy smile on his face and told me to high five him. ‘Mr. Wolff, he practically shouts, I have some good news to share! A mutation showed up in your genomic test. “

Blockade of MAP2K1 Mutation with Trametinib

Even more interestingly, Dr. Gounder’s research has uncovered a treatment that might work. It was a small pill called trametinib (Mekinist^®). The drug had been approved to treat melanomas with certain mutations, based on clinical trials led by an MSK doctor. Since 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 ensure 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 chemotherapy didn’t help, this surely won’t,'” he says. “But after just two days, all my symptoms were gone.”

At his next appointment with Dr. Gounder, Michael told him that he no longer had sweats, chills, or tremors.

“Dr. Gounder was a consummate professional, but after 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! That’s why I get up in the morning. This is what I live for! High five, high five, high five!’ “

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

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

Histiocytosis research, pioneered at MSK, is now benefiting patients everywhere

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

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

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

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

MSK’s multidisciplinary team of specialists

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

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

“The treatment I received from all the doctors I saw at MSK was amazing,” says Michael. “For a while, I used to go there so often that everyone knew me. Everyone stepped in to take care of me.”

Jazz is life

Today, Michael, now 72, is considered cured. He resumed composing and performing music. He recently released an album, statementfollowing his book, On that note: A memoir about jazz, tics, and survival.

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

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

“I had endless time to think, and as my mind cleared of the illness and medication, I kept thinking about my family and how they 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 friend.

“Fortunately and unfortunately, I rarely see Michael anymore,” says Dr. Gounder. “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 the team’s science, adding: “His experience could not have happened anywhere but MSK.”