Programmed death ligand-1 PET imaging in patients with melanoma: a pilot study

Abstract

Programmed death ligand-1 (PD-L1) is an inducible protein heterogeneously expressed in melanoma. Assessment of PD-L1 expression is challenging and standard immunohistochemistry (IHC) requires biopsies and cannot capture heterogeneity of expression. Noninvasive imaging methods provide evaluation of expression across lesions in the body. We conducted a prospective pilot trial with PD-L1 PET imaging with [ 18 F]-BMS-986229 as a noninvasive approach to assess PD-L1 expression across lesions, in 10 patients with advanced melanoma, longitudinally during treatment with nivolumab and ipilimumab. PET imaging was performed at baseline and at 6 weeks after initiation of treatment. We examined the relationship of PD-L1 PET uptake to radiographic clinical response. [ 18 F]-BMS-986229 uptake was variably seen across lesions in patients at baseline. All patients showed positive uptake in lesions at baseline PET with a median SUV max of 3.6 (range: 1.7-8.6). PD-L1 PET SUV max decreased in all but two lesions 6 weeks after treatment initiation. Four of five patients had a mean (SUV max ) greater than or equal to 3.00 in Response Evaluation Criteria in Solid Tumors (RECIST) evaluable lesions at baseline, and all had a RECIST response while all progressors ( n = 3) had baseline PD-L1 mean SUV max less than or equal to 2.60. A higher lesional baseline SUV max was associated with greater individual lesion reduction during treatment. The PD-L1 uptake in lesions showed a low correlation with baseline PD-L1 by IHC. In this small pilot study, PD-L1 PET imaging using [ 18 F]-BMS-986229 showed feasibility in noninvasively assessing lesion uptake and PD-L1 heterogeneity in patients receiving combination immunotherapy. Future exploration of this tracer in larger patient cohorts is necessary to delineate its use in managing immunotherapy treatments.

Trial registration: ClinicalTrials.gov NCT03122522.

Keywords: PD-L1; immunoPET; immunotherapy; melanoma.

Fig. 1

High PD-L1 PET uptake in responding patients. Patient with metastatic melanoma with soft tissue disease in the right arm, right axillary node, left shoulder cutaneous lesion, and left pelvic implants on baseline FDG PET (arrows) showing uptake on baseline PD-L1 PET imaging (arrows), which decreased on the week 6 PD-L1 PET. Some nodes in the subpectoral region (lower panel) show more prominent uptake on baseline PD-L1 PET than baseline FDG PET (white arrow). The patient had PR at 3 and 6 months follow-up. Diffuse uptake noted in the lung was not related to disease (not shown). Scale bars for FDG (left) and PD-L1 PET (right) are for all corresponding images. CT, computed tomography; FDG, fluorodeoxyglucose; PD-L1, programmed death ligand-1; PR, partial response.

Fig. 2

Patient- and lesion-based PD-L1 PET uptake and patient response. RECIST response per patient and baseline maxSUV_max of all measurable lesions within a patient (a) and meanSUV_max for all measurable lesions within a patient (b). Change in individual lesion size from baseline to week 6 by RECIST versus baseline individual lesion SUV_max (c) and change in PD-L1 PET individual lesion SUV_max from baseline to week 6 (d). Patients and lesions are missing from the plots because of missing follow-up CT scan (one patient and one lesion) and missing follow-up PD-L1 PET scan (three patientsand four lesions). Baseline target lesion PD-L1 PET uptake (e). Lines identify SUV_max range for patients with multiple lesions. CT, computed tomography; PD-L1, programmed death ligand-1; RECIST, Response Evaluation Criteria in Solid Tumors; SUV, standard uptake value.

Fig. 3

High PD-L1 PET uptake in responding patients. Patient with metastatic melanoma with soft tissue lesions in right arm (red arrows) and right axillary node (blue arrow) showing uptake on both baseline FDG and PD-L1 PET. This patient had decreased PD-L1 PET uptake in the right axillary node at week 6 and resolved uptake in the right arm lesions. The patient had PR at 3 and 6 months follow-up. Scale bars for FDG (left) and PD-L1 PET (right) are for all corresponding images. FDG, fluorodeoxyglucose; PD-L1, programmed death ligand-1; PR, partial response.

Fig. 4

No PD-L1 PET uptake in nonresponding patients. Patient with metastatic melanoma with a right lung and a rib/intercostal muscle lesion seen on FDG PET (left top row) and CT scan (center top row). PD-L1 PET (right) imaging showed no uptake in the lung and rib/intercostal muscle lesions. Other FDG-avid lesions in bones (left middle row), liver (thicker arrow), and left adrenal (thin blue arrow, lowest row) also did not show uptake on PD-L1 PET. The patient had a progression of disease. Scale bars for FDG (left) and PD-L1 PET (right) are for all corresponding images. Lung uptake is noted in the posterior aspect; no corresponding CT abnormality was noted (second panel). CT, computed tomography; FDG, fluorodeoxyglucose; PD-L1, programmed death ligand-1.

Fig. 5

Heterogeneous baseline PD-L1 uptake among lesions. Patient with metastatic melanoma with left lung, right adrenal, and multiple soft tissue/subcutaneous nodules noted on FDG PET (arrows, fused images). On PD-L1 PET, these lesions showed heterogeneous uptake: the right adrenal lesion (4.3 cm) showing uptake on the baseline with decreased uptake in the follow-up scan (upper panel), lesion in the left lung (2.2 cm) (middle panel) showing no uptake, and left back subcutaneous nodule (1.6 cm) showing uptake (lower panel). The left back lesion showed resolution of uptake in follow-up imaging (right most fused image in the lower panel) and the right adrenal lesion shows decrease in uptake on follow-up PD-L1 imaging (the most right image in the top panel). This patient had PR radiographically at 3 and 6 months. FDG, fluorodeoxyglucose; PD-L1, programmed death ligand-1; PR, partial response.