FLT PET/CT imaging of metastatic prostate cancer patients treated with pTVG-HP DNA vaccine and pembrolizumab.

Abstract

BACKGROUND:

Immunotherapy has demonstrated remarkable success in treating different cancers. Nonetheless, a large number of patients do not respond, many respond without immediate changes detectable with conventional imaging, and many have unusual immune-related adverse events that cannot be predicted in advance. In this exploratory study, we investigate how 3'-Deoxy-3'-18F-fluorothymidine (FLT) positron emission tomography (PET) measurements of tumor and immune cell proliferation might be utilized as biomarkers in immunotherapy.

METHODS:

Seventeen patients with metastatic castrate resistant prostate cancer were treated with combination pTVG-HP DNA vaccine and pembrolizumab. Patients underwent baseline and 12-week FLT PET/CT scans. FLT PET standardized uptake values (SUVs) were extracted from tumors, non-metastatic lymph nodes, spleen, bone marrow, pancreas, and thyroid to quantify cell proliferation in these tissues. Regional immune cell responses to pTVG-HP DNA vaccine were assessed by comparing FLT uptake changes in vaccine draining and non-draining lymph nodes. Cox proportional hazards regression was utilized to relate FLT uptake and other clinical markers (PSA and tumor size) to progression-free survival. Area under receiver operating characteristic (AUC) curves and concordance indices were used to assess the predictive capabilities of FLT uptake.

RESULTS:

Changes in FLT uptake in vaccine draining lymph nodes were significantly greater than changes in non-draining lymph nodes (P = 0.02), suggesting a regional immune response to vaccination. However, the changes in FLT uptake in lymph nodes were not significantly predictive of progression-free survival. Increases in tumor FLT uptake were significantly predictive of shorter progression-free survival (concordance index = 0.83, P < 0.01). Baseline FLT uptake in the thyroid was significantly predictive of whether or not a patient would subsequently experience a thyroid-related adverse event (AUC = 0.97, P < 0.01).

CONCLUSIONS:

FLT PET uptake was significantly predictive of progression-free survival and the occurrence of adverse events relating to thyroid function. The results suggest FLT PET imaging has potential as a biomarker in immunotherapy, providing a marker of tumor and immune responses, and as a possible means of anticipating specific immune-related adverse events.

TRIAL REGISTRATION:

NCT02499835 .

• Authors: Matthew Scarpelli, Christopher Zahm, Scott Perlman, Douglas G McNeel, Robert Jeraj, Glenn Liu
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 7 Issue 1 Pg. 23 (01 30 2019) ISSN: 2051-1426 [Electronic] England
• PMID: 30700328 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• Dideoxynucleosides
• Vaccines, DNA
• pembrolizumab
• alovudine

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents, Immunological (therapeutic use)
• Dideoxynucleosides
• Humans
• Male
• Positron Emission Tomography Computed Tomography
• Prostatic Neoplasms, Castration-Resistant (diagnostic imaging, therapy)
• Vaccines, DNA (therapeutic use)