Short-interval, low-dose (SILD) Lu-177 DOTAiTATE therapy to overcome resistance to immunotherapy with PD-1 checkpoint inhibitors: Proof of concept to induce remission in patients with metastatic Merkel cell carcinoma and melanoma

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Introduction: Immunotherapy with PD-1 immune checkpoint inhibitors (ICI) in Merkel cell carcinoma (MCC) or melanoma have proven efficacy.

Aim(s): To test the hypothesis that short-interval, low-dose (SILD) Lu- 177 DOTAiTATE peptide receptor radionuclide therapy (PRRT) may overcome resistance to immunotherapy with PD-1 immune checkpoint inhibitors (ICI) in MCC or melanoma patients.

Materials and methods: 6 patients (1 female, 5 males) with relapsed metastatic MCC (MCC, n=3) or melanoma (n=3) refractory to PD-1 ICI were imaged with Somatostatin Receptor (SSTR) PET/CT. PRRT was offered to patients after interdisciplinary tumor board consensus and presence of low to moderate SSTR expression on target lesions. PRRT was employed in lower doses (average 3 GBq per cycle) provided in shorter intervals (3 – 6 weeks) than conventional PRRT to remodel the tumor microenvironment to restore responsiveness to concurrent immunotherapy with the PD-1 antibody pembrolizumab.

Conference: 18th Annual ENETS Concerence (2021)

Presenting Author: Prasad V

Authors: Aicher A, Sindrilaru A, Beer A, Prasad V,

Keywords: PRRT, SILD, ICI, Merkel cell carcinoma, melanoma, tumor microenvironment remodelling,