Abstract
Medullary thyroid cancer (MTC) accounts for ~4% of all thyroid malignancies. MTC derives from the neural crest and secretes calcitonin (CTN) and carcinoembryonic antigen (CEA). Unlike differentiated thyroid cancer, MTC does not uptake iodine and I-131 RAI (radioactive iodine) treatment is ineffective. Patients with metastatic disease are candidates for FDA-approved agents with either vandetanib or cabozantinib; however, adverse effects limit their use. There are ongoing trials exploring the role of less toxic immunotherapies in patients with MTC. We present a 61-year-old male with the diagnosis of MTC and persistent local recurrence despite multiple surgeries. He was started on sunitinib, but ultimately its use was limited by toxicity. He then presented to the National Cancer Institute (NCI) and was enrolled on a clinical trial with heat-killed yeast-CEA vaccine (NCT01856920) and his calcitonin doubling time improved in 3 months. He then came off vaccine for elective surgery. After surgery, his calcitonin was rising and he enrolled on a phase I trial of avelumab, a programmed death-ligand 1 (PD-L1) inhibitor (NCT01772004). Thereafter, his calcitonin decreased > 40% on 5 consecutive evaluations. His tumor was subsequently found to express PD-L1. CEA-specific T cells were increased following vaccination, and a number of potential immune-enhancing changes were noted in the peripheral immunome over the course of sequential immunotherapy treatment. Although calcitonin declines do not always directly correlate with clinical responses, this response is noteworthy and highlights the potential for immunotherapy or sequential immunotherapy in metastatic or unresectable MTC.
Highlights
Medullary thyroid cancer (MTC) accounts for ∼4% of all thyroid malignancies
The growth rate of MTC is estimated by using RECIST v.1.1 (Response Evaluation Criteria in Solid Tumors); it can be determined by measuring serum levels of CTN and carcinoembryonic antigen (CEA) over multiple time points to determine doubling time, which play an important role in the follow-up and management of MTC
3 months after surgery, his calcitonin had risen to 9,765 pg/ml and CEA 17.1 ng/mL and the patient was enrolled on a phase I trial of avelumab, a programmed death-ligand 1 (PD-L1) inhibitor (phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological, and clinical activity of avelumab (MSB0010718C), a monoclonal anti-PD-L1 antibody, in subjects with metastatic or locally advanced solid tumors (NCT01772004)) [14]
Summary
Medullary thyroid cancer (MTC) accounts for ∼4% of all thyroid malignancies. It is a neuroendocrine tumor deriving from the neural crest-derived parafollicular or C cells of the thyroid gland [1]. On follow-up imaging studies, there was no evidence of distant metastases and he presented to the NCI with disease involving his thyroid bed and cervical nodes, most of which were not amenable to resection He enrolled on a clinical trial with yeast-based therapeutic cancer vaccine targeting CEA (a phase 2 study of GI-6207 in patients with recurrent medullary thyroid cancer; NCT01856920) [8, 13]. 3 months after surgery, his calcitonin had risen to 9,765 pg/ml and CEA 17.1 ng/mL and the patient was enrolled on a phase I trial of avelumab, a PD-L1 inhibitor (phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological, and clinical activity of avelumab (MSB0010718C), a monoclonal anti-PD-L1 antibody, in subjects with metastatic or locally advanced solid tumors (NCT01772004)) [14] He had five consecutive declines in his calcitonin to 5,732 pg/ml and CEA levels remained overall stable at 22.0 ng/mL while on the immune checkpoint inhibitor avelumab, a > 40% decline not previously seen in his NCI clinical course (Figure 1A). There were no alterations in the CD4+, CD8+, natural killer (NK) or NK-T compartments noted at any time point examined
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