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A blood test following CAR T-cell therapy for relapsed/refractory mantle cell lymphoma (MCL) appears to do a better job than PET-CT scans at predicting which patients have poor prognoses, a small, retrospective, real-world study finds.
In 15 of 18 patients who relapsed, the blood test identified relapse a median of 6.5 months before PET/CT did.
“The data from our study supports utilizing this blood test to detect minimal residual disease, and it adds value to PET scans,” said lead author Matthew J. Frank, MD, PhD, in an interview with Medscape Medical News. “We see molecular relapse below the threshold of what a PET-CT scan can show. In some cases, it might even replace the need for a PET scan in select patients.”
CAR T-cell therapy has dramatically changed survival rates in MCL, but the study notes that the disease progresses in more than 40% of patients within the first year after treatment begins. Imaging strategies such as PET-CT, the authors write, “have limitations in sensitivity and specificity for detecting treatment response and early relapse.”
“We wanted to see if we could use circulating tumor cells as an additional biomarker that would add value to help discern who will do well and who won’t,” said Frank, who is an assistant professor of medicine at Stanford University.
Study Methodology and Results
The researchers analyzed 37 patients with relapsed/refractory MCL who were treated with brexucabtagene autoleucel (brexu-cel) at Stanford University from October 2020 to January 2024 (median age 61; median of four prior lines of therapy; 36% high risk, 22% high-intermediate risk, 11% low-intermediate risk, and 28% low risk).
The patients underwent at least one blood test for MRD over a median follow-up of 35 months, and 18 experienced relapse. Two others died, one from therapy-related causes. Median PFS was 38.9 months, and overall survival was 51.5 months.
In 37 patients at 28 days following infusion, those whose blood tests showed measurable residual disease (MRD) had worse progression-free survival (PFS) compared with those with undetectable MRD (10.9 vs. 51.5 months, respectively; hazard ratio [HR] 3.99; P = .002), reported Frank and colleagues in the American Journal of Hematology.
In contrast, PET-CT scan results at 28 days didn’t predict progression.
While the 28-day blood tests were predictive of outcomes, PET-CT results at 28 days were not: Patients achieving complete response vs partial response per PET-CT showed no statistically significant difference in PFS.
Those with blood tests showing MRD also had worse overall survival vs those who didn’t (22.8 vs 51.5 months, respectively). In patients with PET-CT scans, OS was 51 months in those with noncomplete response and was not reached in those with complete response, Frank said. He provided the PET-CT OS data, which was not initially included in the study, upon request.
According to Frank, the blood test is simple compared to the PET-CT scans, which are inconvenient and expose patients to radiation. Blood test results return in about a week, he said, and “if you don't have any detectable tumor in the blood sample, it’s highly concordant to having a clean PET scan.”
Why the Blood Tests Are Helpful
The blood tests detect not just relapse but its speed, Frank said, allowing clinicians to consider further therapy when the cancer is returning quickly.
He noted that “MRD is already used to guide treatment in MCL.” For example, he said, research suggests that patients who are MRD-negative may not benefit from pursuing an autologous stem cell transplant, while there might be a benefit for MRD-positive patients.
Frank said Stanford has embraced the tests as standard practice, and the study says MRD testing there is conducted every 3 months through the first 2 years and then every 6 months. However, the study cautions that its findings are not highly powered enough to prove that the tests should replace routine PET-CT scans.
Insurers cover the tests, Frank said. He added that the expense seems to be similar to the cost of PET-CT scans but takes much less time.
Study Limitations and Next Steps
Limitations of the study include its small size and retrospective nature, Frank said.
Julie M. Vose, MD, who didn’t take part in the research, characterized the study as “very well run and organized” in an interview with Medscape Medical News.
Vose, a hematologist/oncologist at the University of Nebraska Medical Center, Omaha, said the blood test is “a useful adjunct to standard testing methods” but “does not necessarily show that identifying a relapse earlier makes a difference in the outcome for the individual patient with MCL.”
Frank noted that researchers have launched a prospective study to compare the value of testing for cancer cells vs testing for cancer DNA.
No funding was reported. Frank reports relationships with Kite Pharma-Gilead, Adaptive Biotechnologies, ADC, Cargo, Allogene, PeproMene, and Fate. Vose has no disclosures.
Adaptive Biotechnologies provided diagnostic testing and statistical support, and some authors work for the company. Some of the other authors reported several disclosures.
