Hyperprogression In Follicular Thyroid Cancer Treated With Combination Immunotherapy.

Abstract Hyperprogression is a severe adverse event usually reported in immunogenic cancers such as non-small cell lung cancer (NSCLC) and melanoma after immunotherapy. Currently, there are no reported cases of hyperprogression seen in thyroid cancer. Here, we present the first case of follicular thyroid cancer patient with PDL-1 <1% who developed hyperprogression when treated with nivolumab and ipilimumab combination immunotherapy. A 53-year old male with stage IV follicular thyroid cancer with multiple skeletal metastases, including left fifth rib, T1, T4, T5 vertebral body, was treated with Lenvatinib on 1/2018 and held on 12/2018 due to esophagus dilation. No targetable mutations were detected with molecular studies and PD-L1 was not expressed on the tumor. The patient received 1 cycle of nivolumab (3mg/kg) and ipilimumab (1mg/kg) on 7/27/2020, but could not continue the treatment due to neurologic deterioration and progression on follow-up CT. We defined hyperprogression per the criteria proposed by Lo Russo et al (2018), which defined it as meeting at least 3 out of 5 following criteria: TTF<2months, increase ≥50% in the sum of target lesions major diameters, the appearance of at least two new lesions in an organ already involved, the spread of the disease to a new organ, ECOG performance status worse than two during the first two months. CT scan results and the patient's symptoms were evaluated before and after initiation of immunotherapy. The sum of target lesions major diameters was calculated per RECIST 1.1 criteria. Before the initiation of immunotherapy, a CT chest scan revealed no target lesion, thus the sum of target lesions major diameters reported as 0. At baseline, the patient complained of numbness and tingling in the upper extremities. Follow-up imaging studies three weeks after the initiation of immunotherapy showed a 24.4 x 18.4 mm right hilar lymph node metastasis and a 6.7 x 4.2 cm right shoulder heterogeneous mass was reported on CT chest scan and scapula MRI, respectively. Along with progression of the disease, the patient developed rapid neurologic deteriorations including diminished bilateral hand grip and positive Romberg's test. The sum of target lesion major diameters was 85.4 mm, TTF<2months, and ECOG Performance Status 2. Per definition by Lo Russo et al. (2018), the patient met the criteria for hyperprogression. The patient's rapid deterioration in symptoms correlated with hyperprogression. This is the first case report of hyperprogression in follicular thyroid cancer, which is less immunogenic compared to NSCLC and melanoma. The underlying mechanism of hyperprogression and its association with immunotherapy remains unclear. Further research on potential risks of hyperprogression in less immunogenic cancer such as thyroid cancer is warranted. Citation Format: Yeun Ho Lee, Leeseul Kim, Myungwoo Nam, William Cheng, Won Kyung Hur, Jin Young Hwang, Yoonhee Choi, William H Bae, Eugene Kim, Heayoon Shauna Cho, Emma Yu, Chan Mi Jung, Christmann Low, Elena Vagia, Young Kwang Chae. Hyperprogression in follicular thyroid cancer treated with combination immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 519.