Abstract A018: Onset of dysthyroidism during treatment with immune checkpoint inhibitors is increased in responder patients

Abstract

Abstract Background: Immune checkpoints inhibitors (ICI) are characterized by a high therapeutic index; among toxicities, immune-related thyroiditis has been reported. The aim of this study is to evaluate either the grade and severity of thyroiditis or its frequency in responder patients. Material and Methods: We retrospectively evaluated 104 metastatic solid tumor patients treated at our Institute with ICI from 2010. We defined thyroid toxicity according to CTCAE version 4.0 and the disease control rate (DCR: CR, PR, SD) as efficacy endpoint. Correlation between dysthyroidism and DCR was assessed by Fisher's exact test. Results: Of 104 patients, 32 (30.8%) were treated by anti PD-1, 32 (30.8%) by anti PDL-1, 34 (32.7%) by anti CTLA-4 and 6 (5.7%) by combo (anti PD-1+anti CTLA-4). Population was heterogeneous, ranging from the first to the 8th line of therapy, and affected by the following cancers: 42 (40.4%) lung (38 NSCLC, 4 SCLC), 40 (38.5%) melanoma, 9 (8.6%) RCC, 7 (6.7%) gastric, 2 (1.9%) bladder and one each for colon, salivary glands, thyroid and uterine leiomiosarcoma. Best responses were: 3 CR, 14 PR, 33 SD and 54 PD; 50 (48%) of patients achieved DCR, 18 (37.5%) treated by anti PD-1, 16 (33.3%) by anti PDL-1, 12 (25%) by anti CTLA-2 (4.2%) by combo. Overall, 29 patients developed dysthyroidism (subclinic, G1, G2 hypo/hyperthyroidism): 2/34 (6%) in anti CTLA-4, 10/32 (31%) in anti PD-1, 13/32 (41%) in anti PDL-1, 4/6 (67%) in combo group, respectively; 19/29 (65.5%) of these patients achieved DCR. Of 75 patients who did not develop dysthyroidism, only 29 (38.6%) achieved DCR. The onset of dysthyroidism statistically significant correlated with DCR (65.5% vs 40.0%, p= 0.016); no correlation was detected between toxicity grade (subclinic and G1 from oneside, G2 from the other side) and DCR (p= 1.0). Conclusions: In responding patients, we found a statistically significant increase of thyroiditis during treatment with ICI. Thyroid function evaluation should be recommended routinely during ICI therapy, in particular with anti PD-1 and anti PDL-1 agents. Finally, the role of thyroiditis in predicting response to ICI must be confirmed in a large and homogeneous series of patients. Note:This abstract was not presented at the conference. Citation Format: Diego Signorelli, Michele Del Vecchio, Marina Garassino, Alice Intini, Maria Silvia Cona, Michele Magni, Ettore Seregni, Massimo Di Nicola, Filippo De Braud. Onset of dysthyroidism during treatment with immune checkpoint inhibitors is increased in responder patients. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A018.