Patients Are Cancer-Free After Experimental Treatment

All participants in a clinical trial for rectal cancer conducted by Memorial Sloan Kettering Cancer Center (MSK) seem cancer-free.

The participants had rectal cancer with a particular mutation. “In every case, the rectal cancer disappeared after immunotherapy - without the need for the standard treatments of radiation, surgery, or chemotherapy - and the cancer has not returned in any of the patients, who have been cancer-free for up to two years,” states an article published by MSK.

“The immunotherapy shrank the tumors much faster than I expected,” says research co-leader Andrea Cercek. “Patients came to my office after just two or three treatments and said, ‘This is incredible. I feel normal again.’”

A paper is published in New England Journal of Medicine. It reports that a monoclonal antibody called dostarlimab was administered every 3 weeks for 6 months in 12 patients with a certain type of rectal adenocarcinoma. All patients had a clinical complete response, with no evidence of cancer in all tests. No cases of progression or recurrence have been found.

New York Times has a story about the first patient, who has been cancer-free for two years.

Dostarlimab is sold under the brand name Jemperli. Dostarlimab “costs about $11,000 per dose,” New York Times reports. “It unmasks cancer cells, allowing the immune system to identify and destroy them.”

Research co-leader Luis Diaz knows of no other study in which a treatment completely obliterated a cancer in every patient. “I believe this is the first time this has happened in the history of cancer,” Diaz said.

The patients who participated in the study had tumors with a specific genetic makeup known as mismatch repair-deficient (MMRd). These tumors respond especially well to immunotherapy.

“An MMRd tumor develops a defect in its ability to repair certain types of mutations that occur in cells,'' explained Diaz. “When those mutations accumulate in the tumor, they stimulate the immune system, which attacks the mutation-ridden cancer cells.”

But cancer fights back by exploiting a safeguard called a checkpoint, which prevents immune cells from attacking normal cells. In other words, cancer cells put a brake on immune cells by pretending to be normal cells. An immunotherapy agent called a checkpoint inhibitor releases the brake on an immune cell, freeing it to recognize and attack cancer cells.

“When the brakes are taken off the immune cells, MMRd cells look especially strange because they have so many mutations. So the immune cells attack with much more force,” explained Cercek.

This is “the tip of the iceberg,” said Diaz. “We are investigating if this same method may help other cancers where the treatments are often life-altering and tumors can be MMRd. We are currently enrolling patients with gastric (stomach), prostate, and pancreatic cancers.”

Using “immunotherapy to replace surgery, chemotherapy, and radiation to remove cancer … might sound futuristic - but in this trial, we have a clinical example where that happened,” concluded Diaz.

The example is limited to MMRd cancers. But it seems plausible that the techniques developed by the MSK researchers could eventually find applications to other cancers as well.