Immunotherapy After Surgery Helps Prevent Cancer Recurrence in MMRd Patients With ctDNA, MSK Study Shows

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Man posing with his wife, son, and daughter.

Jon Desjardins, far left, is happy to be around for his family, thanks to successful treatment with immunotherapy after surgery for colorectal cancer. He joined a clinical trial led by Dr. Yelena Janjigian testing the effectiveness of this treatment in people who have circulating tumor DNA in their blood.

A small pilot study led by researchers at Memorial Sloan Kettering Cancer Center (MSK) has found that a simple blood test can help doctors identify which patients are most likely to benefit from immunotherapy after cancer surgery to remove tumors — potentially preventing the disease from coming back.

The phase 1 trial, presented by physician-scientist Yelena Janjigian, MD, at the 2025 American Association for Cancer Research (AACR) Annual Meeting, focused on patients whose tumors had a specific genetic feature called mismatch repair deficiency (MMRd). This abnormality, found in about 6% of solid tumors, makes it harder for cells to fix mistakes in their DNA. It also makes the tumors more likely to respond to immunotherapy.

MSK medical oncologist Yelena Janjigian

Dr. Yelena Janjigian

In this trial, patients had their MMRd tumors surgically removed and then underwent a blood test known as a liquid biopsy. This test looks for tiny fragments of tumor DNA — known as circulating tumor DNA or ctDNA — that may still be present in the bloodstream after surgery. Patients who tested positive for ctDNA were given a checkpoint inhibitor, a type of immunotherapy drug.

“This is the first time we’ve shown that finding ctDNA after surgery — and acting on it quickly — can actually prevent cancer from coming back,” Dr. Janjigian says. “The results exceeded our expectations and highlight how ctDNA can guide smarter, more personalized cancer care.”

Who the Study Helped — and Why It Matters

Doctors have long struggled with whether to give additional treatments like chemotherapy or immunotherapy after surgery, especially when imaging scans don’t show any visible signs of disease. Giving too much treatment can be harmful, but giving too little can leave behind cancer cells that eventually cause recurrence.

That’s where ctDNA comes in. Previous research has shown that people with detectable ctDNA after surgery are at very high risk for recurrence. More than 90% of people with ctDNA will see their cancer return if nothing is done.

This is the first time we've shown that finding ctDNA after surgery — and acting on it quickly — can actually prevent cancer from coming back.
Yelena Y. Janjigian physician-scientist

In this study, patients with MMRd tumors and positive ctDNA were given immunotherapy, a checkpoint inhibitor called pembrolizumab (Keytruda®). The results were encouraging:

  • 85% of patients had complete clearance of ctDNA after treatment
  • 64% were free of recurrence two years later
  • 92% were still alive at two years

“This gives us proof of concept that acting early — when there’s molecular evidence of cancer, but no visible disease — can improve outcomes,” Dr. Janjigian says. “It’s a step toward using real-time genetic information to tailor treatment, not just for who needs more therapy, but also for who doesn’t.”

Immunotherapy Succeeds in Patient After Other Treatments Fail

The trial proved to be a lifeline for Jon Desjardins, owner of a fire protection company. In 2022, he was diagnosed with colon cancer at age 50, despite being healthy and active with no family history of the disease. A surgeon at a Long Island hospital removed the tumor, along with a foot of his colon, and said he needed aggressive follow-up treatment.

Jon decided to come to MSK, where medical oncologist Avni Desai, MD, recommended four rounds of two chemotherapy drugs given in combination — the standard of care for his situation. Unfortunately, after completing the treatment, a blood test showed he still had ctDNA. But there was hopeful news: the opportunity for Jon to join the clinical trial. His tumor was MMRd, which suggested immunotherapy could be effective.

“She said they had gotten good results with Keytruda,” Jon recalls. “I was thinking, ‘I have to do this.’ My son was a sophomore in high school and my daughter was in eighth grade and I needed to be around. I didn’t have a choice if I wanted to stay alive.”

Starting in March 2023, Jon received nine rounds of pembrolizumab over the next six months. He was able to get treatment at MSK Commack, a 15-minute drive from his home in East Northport.

As Jon’s immune system activated to fight the cancer, it also caused arthritis. But Jon says that side effect is worth it.

“The pain in my knees and hips and hands has a huge plus side, in that I’m alive,” he says. “I’ll take the side effects any day.”

Since finishing treatment in September 2023, his blood has been tested for ctDNA every six months and come back clear every time. Dr. Desai has told them that if the next test — in September 2025 — comes back clean, the chances of the cancer returning are almost zero.

“I’m alive because of this trial, and I think it’s a miracle drug,” Jon says, who continues to serve as a volunteer firefighter. “I have the inflammation in my joints, but as my wife says, ‘There will be good days and bad days, but we can deal with the pain. You’re here and you’re breathing.’ ”

What Comes Next for Preventing Cancer Recurrence After Surgery

Meanwhile, the research continues. Dr. Janjigian and colleagues plan to confirm the phase 1 findings in a larger, randomized study and hopes the approach could be expanded to more types of cancer — even those without mismatch repair deficiency.

“This could change how we think about treating early-stage cancers,” Dr. Janjigian added. “We’re not just trying to treat what we can see. We’re trying to intercept the disease before it has a chance to grow.”

The study was a collaboration with the laboratory of MSK’s Luis Diaz Jr., MD, and included more than 30 investigators across oncology, surgery, pathology, and molecular diagnostics.

 

Additional MSK researchers involved in the study include:

Michael B. Foote, Melissa Lumish, Marinela Capanu, Joanne Chou, Julio Garcia-Aguilar, Martin Weiser, Jason Konner, Vivian Strong, Elizabeth Jewell, Jennifer Mueller, Steven Maron, Ping Gu, Rona Yaeger, Sree Chalasani, Andrea Cercek, Jia Li, Maliha Nusrat, Ryan Sugarman, David Jones, Daniela Molena, David Solit, Brian Loomis, Marc Ladanyi, and Michael Berger.

The study was supported by MSK’s precision interception and prevention program and Cycle for Survival. Pembrolizumab was provided by Merck.

For author disclosures, see study abstract.