A simple blood draw could soon tell doctors within weeks whether lung cancer patients are responding to immunotherapy — potentially saving months of ineffective treatment.
Researchers at Johns Hopkins in Baltimore have developed a liquid biopsy test that detects genetic fragments of tumors floating in the blood, known as circulating tumor DNA (ctDNA). Their study, published in Clinical Cancer Research, found that a single blood test taken 3 to 9 weeks after starting immunotherapy could predict whether patients with advanced non-small cell lung cancer would benefit from treatment.
The difference was striking. Patients whose tumor DNA became undetectable during that early window remained progression-free for a median of 26.6 months, compared with just 3.4 months for those whose tumor DNA stayed detectable. They also lived dramatically longer — a median overall survival of 46.9 months versus 11.4 months.
"This is a potential game-changer for how we monitor immunotherapy," said Dr. Valsamo "Elsa" Anagnostou, co-director of the Lung Cancer Precision Medicine Center of Excellence at Johns Hopkins and senior author of the study. "Our findings show that a single blood draw, collected very early on, can identify patients who are benefiting from immunotherapy and, just as important, those who may need a different treatment strategy."
Unlike chemotherapy, immunotherapy often produces confusing results on standard imaging scans. Tumors may swell before shrinking, a phenomenon called pseudoprogression, and some patients show mixed responses that leave doctors uncertain. With current methods, it can take months to know whether treatment is working.
The new approach tackles this problem by measuring molecular signs of response directly in the blood, giving physicians objective data weeks before scans would otherwise provide clear answers.
One key innovation: the test doesn't require a sample of tumor tissue, which can be difficult to obtain in advanced cancer. Instead, researchers simultaneously analyzed DNA from patients' white blood cells to filter out age-related genetic changes that could cloud results, a condition called clonal hematopoiesis. This "tumor-naive" approach makes the test more practical for everyday cancer care.
"For real-world adoption, that matters," Anagnostou noted. "It removes the need for tumor tissue and reduces costs and logistical burden, making the test more deployable in routine oncology settings rather than only in specialized centers."
The study included 109 patients with advanced non-small cell lung cancer, the most common form of the disease. Researchers analyzed 328 blood samples collected throughout treatment.
If the findings hold up in wider testing, the blood test could help spare patients from months of toxic, costly treatment that isn't working — and quickly connect them with alternatives that might. It could also offer early reassurance that a current regimen is succeeding.
"One of the biggest challenges with immunotherapy is that it can take months before scans clearly show whether treatment is working," Anagnostou said. "Our study shows we can do better."