There Is Hope

Grand Rounds

How immunotherapy offered a new lease on life

By Jim Schnabel

Hope Hughes (right) at home in Hurley, N.Y., with wife, Kathy Kayes.

I was one of those people who never gets sick,” she remembers.

But one day in the spring of 2017, Hope Hughes noticed a spot of blood in her urine. The busy 64-year-old, who worked as a management consulting executive in Manhattan, mentioned it two weeks later during a routine checkup with her OB-GYN, who ordered an ultrasound. The radiologist, looking over the ultrasound images, noticed something suspicious: a mass in Hughes’s bladder.

Hughes’s primary care physician, a graduate of Weill Cornell Medicine, referred her to the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. There, CT scans and other tests confirmed stage 3 bladder cancer, including some spread to local lymph nodes. With the traditional treatment, surgery plus chemotherapy, the five-year survival rate for bladder cancer this advanced was well below 50 percent.

“It was a shock,” Hughes says. She and her wife, Kathy, had two children, 11 and 13, and she wondered if she would live to see them grow up. “I didn’t want to leave them.”

“I’m grateful for every day — grateful for every breath.”

Hope Hughes

Medically speaking, Hughes was in the best of hands. Cancer surgeon Dr. Douglas Scherr, professor of urology and clinical director of urologic oncology at Weill Cornell Medicine, removed her tumor-filled bladder. Oncologist Dr. David Nanus, the Mark W. Pasmantier Professor of Hematology and Oncology in Medicine, then oversaw her treatment with four rounds of a three-drug chemotherapy regimen. When the last round was done, her cancer appeared to be in remission.

But after months of complications, including bowel obstructions and infections, a surgery in August 2018 revealed multiple small metastatic tumors in her abdomen.

Traditionally, care options at this point were limited. More chemo was one, though it usually didn’t buy much time, and her doctors worried that Hughes might be too weak to withstand treatment. The other option was palliative care, to help with pain.

But Dr. Nanus had recently begun treating some patients with a new, much less harsh non-chemotherapy treatment, pembrolizumab (Keytruda™), which the Food and Drug Administration had just approved for use as second-line therapy against certain advanced cancers, including bladder cancer.

Pembrolizumab belonged to a promising new class of treatments called immune checkpoint inhibitors. The immune system has built-in checkpoints it uses to keep its activity within healthy limits, and tumors typically find ways to exploit these off switches to blunt the immune response against them. Pembrolizumab was designed to prevent tumors from hitting one of the most important off switches, the PD-1 receptor, and thereby allow the immune system to mount a more effective attack. Clinical trials, including pioneering trials led by Dr. Jedd Wolchok, appointed in 2022 as Meyer Director of the Meyer Cancer Center, had shown that checkpoint inhibitors could sometimes bring dramatic and durable remissions in patients with advanced cancer.

Studies also had found that checkpoint inhibitors, like other immunotherapies, tended to be more effective against highly mutated tumors. When Dr. Nanus sequenced Hughes’s biopsied tumor tissue, he found that it had a high mutation burden.

A blonde-haired middle aged white woman, wearing a black long sleeved shirt, hugs an older white woman, wearing a blue sweater, photographed with their 17-year-old son, who is wearing a forest green sweater with gray slacks.

Hughes and Kayes with their 17-year-old son, Justin Kayes-Hughes. Their daughter, Ashley, was away at college at the time this photo was taken.

Clinical trials had shown that checkpoint inhibitors could sometimes bring dramatic and durable remissions in patients with advanced cancer.

“We’re not giving up,’” Dr. Nanus told Hughes. And so, while in the hospital from surgery and other complications of her cancer, Hughes received the first of the more than 30 intravenous infusions of pembrolizumab she would have over two years.

Initially, she remained ill from cancer complications, with no outward sign of the therapy working. However, two months after her first dose, CT scans showed a response — a modest but perceptible shrinkage of her tumors and swollen lymph nodes.

By this time, Hughes felt better and had gone home from the hospital. Her infusions continued every three weeks, with her scans showing increased reductions in her tumors. After about two years, the maximum recommended duration of treatment, Hughes stopped taking pembrolizumab and simply went in for scans every few months.

Immunotherapies like pembrolizumab do not bring long-term remissions in all cancer patients treated with them; for advanced bladder cancer, the overall response rate is 20 to 30 percent. But under Dr. Wolchok’s leadership, the Meyer Cancer Center increasingly uses these immune-boosting therapies to treat some forms of advanced cancer — and, just as importantly, to investigate why some patients fail to respond, while others, like Hughes, gain a new lease on life.

As of early 2023, she has been off treatment for two and a half years, without signs of recurrence.

“I’ve gotten to see my daughter graduate high school, and my son’s now about to graduate. I’m playing golf four days a week,” Hughes says. “I’m grateful for every day — grateful for every breath.”

Photos: Julia Xanthos Liddy

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