RT Journal Article
SR Electronic
T1 Evaluation of the anti-PD-1 Flare Response in Patients with Advanced Melanoma Using FDG PET/CT Imaging and Hematologic Biomarkers
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1270
OP 1270
VO 60
IS supplement 1
A1 Bryan Chang
A1 Alexander Huang
A1 Catherine Shang
A1 Karen Palmer
A1 Erin Schubert
A1 Wei Xu
A1 Ravi Amaravadi
A1 Lynn Schuchter
A1 Tara Mitchell
A1 E. Wherry
A1 Michael Farwell
YR 2019
UL http://jnm.snmjournals.org/content/60/supplement_1/1270.abstract
AB 1270Purpose: Immunologic response to anti-PD-1 therapy can occur rapidly with previous reports showing T cell responses detectable in as little as several weeks. Given that activated lymphocytes are known to be FDG avid, we hypothesized that FDG PET/CT could be used to visualize an early “flare” response to immunotherapy, in which FDG activity within tumors increases due to infiltration by activated lymphocytes, and that this flare response would predict treatment response. Thus, a prospective clinical trial was initiated for patients with advanced melanoma using 18F-FDG PET/CT scans and blood biomarkers obtained before and ~1 week after a single dose of anti-PD-1 therapy. Materials and Methods: This IRB-approved study prospectively investigated 16 patients (10 males and 6 females, mean age 66 ± 16y) with metastatic melanoma after receiving 1 dose of anti-PD-1 therapy (pembrolizumab). FDG PET/CT imaging was performed at baseline (mean 12 ± 10 days before treatment), and after treatment (mean 8 ± 4 days after treatment) in all patients. Pembrolizumab was continued per standard clinical care. FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). A “flare” was defined as >100% increase in tumor SUVmax between baseline and post-therapy scans. Blood samples were collected prior to treatment, and at multiple time points (7 days and 3, 6, 9, and 12 weeks) post-treatment, for analysis of immune biomarkers. Response was determined using RECIST 1.1 criteria, with a median follow-up of 19 months. Results: 7 patients had a complete response (CR) to anti-PD-1 therapy, 3 patients had a partial response (PR), and 6 patients had progressive disease (PD). 13% of patients (2/16) demonstrated a flare on FDG PET/CT (acquired 6-7 days post-therapy), with dramatic increases in tumor SUVmax (range: 130% - 281%), without change in tumor size. Both patients with flare responses achieved CR, with no evidence of disease after at least 10 months of follow-up. The remaining 5 patients with CR that did not have a flare were imaged at 7-8 days post-therapy, and all 5 patients demonstrated a drop in SUVmax (mean: -17.3 ± 37.7%) or a decrease in size (mean: -4.7 ± 3.8%), or both, suggesting that they may have been imaged after their immune response had already peaked. Even though patients were imaged at early post-therapy time points, small but measurable decreases in lesion size were seen in responding patients (mean change in size: -2.7 ± 4.0%), and increases in lesion size were seen in nonresponding patients (mean change in size: 13.8 ± 2.9%). Changes in SUVmax for patients that did not have a flare (range: -68% to 59%) were not predictive of response. Preliminary analysis of MTV and TLG did not provide additional benefit compared to SUVmax. Our FDG PET/CT flare observations correlated with flow cytometric evaluation of blood samples taken pre- and post-treatment, which identified a robust increase in responding Ki67+ CD8 T cells, with a peak at day 7 which was greater in magnitude compared to all of the other time points, including week 3. Conclusions: In patients with advanced melanoma, the immune response to anti-PD-1 therapy appears to occur early, with evidence of T cell reinvigoration in the blood at 1 week post-therapy; an associated flare response on FDG PET/CT imaging at 1 week post-therapy is predictive of a complete response to immunotherapy.