‘Shocking’ results reveal imaging can detect early response to immunotherapy for melanoma
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Key takeaways:
- FDG PET/CT imaging detected metabolic changes in patients with advanced melanoma beginning immunotherapy in the first week.
- Detection of metabolic changes correlated with longer PFS.
Metabolic changes can be identified in patients with advanced melanoma by imaging tumors within 1 week of beginning immunotherapy, according to a study published in Clinical Cancer Research.
Patients who had metabolic changes detected with an 18F-fluorodeoxyglucose (FDG) PET/CT had a 100% overall response rate compared with 38% for those that did not, and a median PFS nearly 3 years longer.
“The shocking thing was how big these changes were,” Michael D. Farwell, MD, associate professor at Penn Medicine, told Healio.
“In imaging — even in biomarkers — people will say we saw a 15% increase in this cohort vs. this cohort, and this is not 15%. We were seeing 100%-plus increases,” he added. “These are not subtle.”
Patients receiving immunotherapy usually undergo imaging 3 months after starting treatment, although recent trials have explored benefits of performing those scans in the first 3 to 6 weeks, according to background information provided by the American Association for Cancer Research (AACR).
“The field didn’t appreciate how quickly the immunotherapy response happens,” Farwell said. “One of the guiding pieces of data for us was that in our neoadjuvant trial, we were seeing complete pathologic responses of tumors at 3 weeks. It was like, wow, this is happening really fast. If we’re imaging at 3 weeks, we’re imaging too late.”
Detecting response earlier could identify which patients should stay on therapy or de-escalate, and which patients should change treatments.
FDG PET/CT has been used to detect “metabolically active tumor cells,” researchers wrote in the study, but can sometimes cause problems too.
“A patient had a COVID vaccine, and all their lymph nodes light up,” Farwell explained. “They’re really hot, and usually in the clinic we complain about it because we say it gets in the way of trying to find the cancer. But what we’re basically doing is trying to take advantage of that. Can we see this increase in FDG activity within tumor sites when patients respond to immunotherapy?”
Farwell and colleagues believed an FDG PET/CT shortly after starting immunotherapy could identify a metabolic flare (MF), “increased tumor FDG activity due to infiltration by activated immune cells,” and a metabolic response (MR), a decrease in activity due to tumor death, which could predict a patient’s response to treatment, they wrote.
To be eligible for the single-center study, adults with advanced melanoma had to have been scheduled to begin treatment with the PD-1 inhibitor pembrolizumab (Keytruda, Merck) between November 2016 and November 2019, and could not have received previous treatment with anti-PD-1 or anti-PD-L1 therapy.
The study cohort comprised 19 patients (median age, 71 years; 74% men; 68% with stage 4 melanoma; 84% with no treatment history).
FDG PET/CT imaging occurred within 4 weeks prior to pembrolizumab treatment and about 1 week after.
Complete or partial responses occurred in 11 patients, six of whom had detectable MF or MR. Patients who had no clinical response to immunotherapy did not have detectable MF or MR in their scan.
Study participants with evidence of MF or MR had a median PFS of greater than 38 months (median not reached) vs. 2.8 months (95% CI, 0.3-5.2) for those that did not.
“The most convincing data are the responding patients,” Farwell said. “Even as the data stands now, we can identify them with a high degree of confidence, and we can actually act on that.
However, each patient is unique, Farwell added.
“We saw a big metabolic flare in one patient on day 6, and then other patients on days 7 and 8, we saw a metabolic response,” he said.
A pair of patients benefited from early scanning as imaging detected new lesions on each patient. One had a brain metastasis and received directed therapy. The other had a splenic lesion, and identifying it early allowed study investigators to confidently classify it as pseudoprogression.
“If you’re having a metabolic flare, everything’s getting hotter,” Farwell said. “The lesions that you didn’t realize were there suddenly become more visible. It’s basically giving you a better, more accurate picture of what the disease looks like in that patient.”
The study’s limitations included the small cohort, and it only explored PD-1 monotherapy, but Farwell believes that should not change the outcome.
“All immunotherapies are motivating immune cells to infiltrate tumors, and FDG is a pan-immune marker,” he said.
Additionally, researchers need to determine whether a patient has stable metabolism because the patient is not responding or because they are between an MF and MR.
“We’ve shown that the blood-based biomarkers have some correlation with the imaging,” Farwell said. “One could layer on some companion diagnostics to get a better window on that. You could also do another scan.”
Future trials could examine how tumors react over time with multiple scans or how other cancers react to imaging. The group at Penn plans to look using this approach for non-small cell lung cancer for its next trial, according to Farwell.
“It has a potential to be applied across all immunotherapies and cancers that are being treated with immunotherapy,” he said. “This even includes not just checkpoint blockade, but vaccines, cell-based therapies — all these therapies where you end up generating activated immune cells that are going to be FDG avid. The challenge is going to be validating it in those settings, and then a question is how much validation do you need to do before you roll it out across different diseases.”
References:
- Anderson TM, et al. Clin Cancer Res. 2024;doi:10.1158/1078-0432.CCR-23-2390.
- FDG PET/CT imaging after just one week may predict treatment response in patients with advanced melanoma (press release). Available at: https://www.aacr.org/about-the-aacr/newsroom/news-releases/patients-with-metastatic-colorectal-cancer-may-continue-benefitting-from-immunotherapy-after-treatment-discontinuation/. Posted Jan. 24, 2024. Accessed Jan. 24, 2024.
For more information:
Michael D. Farwell, MD, can be reached at michael.farwell@pennmedicine.upenn.edu.
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