It began eight years ago, when a newly published scientific paper caught Dr. Denise Galloway’s eye.
The paper described the discovery of a new virus, Merkel cell polyomavirus, that drives the majority of cases of Merkel cell carcinoma, a rare but aggressive skin cancer.
Within days of that publication, the Fred Hutchinson Cancer Research Center virologist was on the phone to her colleague, University of Washington and Seattle Cancer Care Alliance Dr. Paul Nghiem, a specialist in Merkel cell carcinoma. Nghiem is also a researcher at Fred Hutch.
Galloway wanted to know how the human immune system reacts to that virus. It was a purely curiosity-driven project at first, she said. But within just a few years of that conversation, the discoveries she, Nghiem and their colleagues made would take another turn, and lead to the development of an inexpensive blood test for Merkel cell carcinoma recurrence.
In a study published last week in the journal Cancer, Nghiem, Galloway and their colleagues report their findings on 219 Merkel cell carcinoma patients whose cancer was followed over time using the blood test. For about half of those patients — those who produce a certain type of immune protein —the test is able to accurately predict if their cancer is coming back, the researchers found.
Galloway said she initially just wanted to know whether people with this cancer made any of these immune proteins, known as antibodies, to the cancer-causing virus.
“We didn’t know what the answer was,” she said. “A lot of research is like that — it turns out to be clinically useful, but in the beginning you don’t know whether it will be or not.”
The test signals the presence of antibodies specific to one viral protein. Among those patients who produce those antibodies, it can quickly and inexpensively signal to clinicians whether a patient’s Merkel cell carcinoma is recurring in the body — in some cases even earlier than traditional imaging tests such as CT scans. That specific antibody is found in about half of patients with the cancer, but curiously doesn’t occur in healthy people, even though nearly all of us carry the polyomavirus on our skin.
For the half of Merkel cell carcinoma patients who produce these antibodies, the rise and fall of that protein in their blood can be a powerful predictive tool, the researchers found. In their study, they showed that 98 percent of patients with decreasing levels of antibody in their blood over time had no recurrence of their cancer, while 88 percent of those with rising amounts of antibody did have their cancer return soon after the test.
The blood test is already in routine use for all Merkel cell carcinoma patients at Seattle Cancer Care Alliance, where Nghiem treats patients with the carcinoma and other skin cancers. Physicians from other institutes around the U.S. have begun ordering it for their patients as well, Nghiem said, and he hopes the team’s recent publication will spur more doctors and patients to adopt the test.
That’s important because Merkel cell carcinoma, though rare, is a very aggressive cancer. Only about 2,000 new cases of the cancer are diagnosed every year in the U.S. — but more than 40 percent of those with the cancer will have a recurrence after their initial treatment, and close to a third will die of their disease. The cancer is about three times deadlier than the more well-known rare skin cancer melanoma.
But there’s hope, especially if the recurrence is caught early. Nghiem and his colleagues published a study earlier this year showing that the immunotherapy drug pembrolizumab, or Keytruda, shows promise in keeping metastatic Merkel cell carcinoma in check — about half of the patients treated on their trial had lasting remissions. Historically, only 10 percent of patients with metastatic Merkel cell carcinoma treated with chemotherapy had lengthy remissions.
Evidence from other cancers indicates that the earlier a recurrence is caught, the better immunotherapies such as pembrolizumab will work.
“We really think it’s better to treat a grape-sized tumor instead of a grapefruit-sized tumor for lots of reasons, including that the larger cancer gets, the more tricks it has figured out to evade bodily controls, including the immune system,” Nghiem said. “We want to find it early and yet we don’t want to expose people to too many unnecessary scans.”
If the test signals cancer’s recurrence, it’s important for clinicians to follow up with imaging tests to pinpoint and assess the new tumor and decide how to proceed with treatment, Nghiem said. And the approximately 50 percent of patients who don’t produce the antibody still need to be followed with traditional imaging. In their study, the researchers found that those who don’t produce the antibodies are more likely to have their cancer recur, meaning they should be followed with even more careful screening tests. But for those patients whose tests show falling antibody levels, they may be spared the exposure to radiation and expense of traditional CT scans.
In some cases in their study and in Nghiem’s practice at SCCA, the newly-developed blood test signaled a recurrence that imaging tests had yet to capture, meaning that it could herald cancer’s return earlier than conventional scans.
Rachel Tompa is a staff writer at Fred Hutchinson Cancer Research Center