3836 - Thyroid toxicity and anti-thyroid antibodies as predictive markers for patients treated with anti-PD1 checkpoint therapy

Background

Thyroid dysfunction is one of the most common adverse effects during anti-PD-1 therapy, and alongside elevated anti-thyroid antibodies (ATAb) it is correlated with overall (OS) and progression free survival (PFS). The objective and novelty of our study was the simultaneous investigation of thyroid dysfunction and ATAbs on survival.

Methods

We included 168 patients with non-small cell lung carcinoma (n = 93), renal cell carcinoma (n = 12), and advanced and metastatic melanoma (n = 63) treated with nivolumab or pembrolizumab. TSH and fT4 serum levels were measured prior to each anti-PD-1 infusion and ATAb titers in sera, i.e. anti-TPO and anti-Tg (cut-off: 3.05 IU/ml and 22.35 IU/ml, respectively; based on median value at baseline), at baseline, and after 2 months of treatment. Thyroid dysfunction was based on TSH and fT4 and classified as subclinical or overt. Tumor progression was classified according to RECIST v1.1 and was monitored until progression, death or withdrawal of the study. Cox regression was used with correction for tumor type.

Results

Patients who acquired overt thyroid toxicity during anti-PD-1 treatment had significantly higher OS (HR = 0.17 [95% CI: 0.04-0.74]; p = 0.018) and PFS (HR = 0.38 [0.15-0.98]; p = 0.05) than patients without thyroid toxicity with one-year OS rates of 95% vs 64% and one-year PFS rates of 65% vs 33%. Moreover, patients with positive ATAb status during treatment had higher OS (HR = 0.39 [0.21-0.72]; p = 0.003) and PFS (HR = 0.52 [0.33-0.81]; p = 0.004) than patients with negative ATAb status with one-year OS rates of 83% vs 49% and PFS rates of 54% vs 20%, respectively. For 84% of patients the ATAb status at baseline was the same as during treatment. Patients with persistent positive ATAb status (48%) had higher OS (HR = 0.41 [0.19-0.89], p = 0.03) and PFS (HR = 0.54 [0.31-0.95], p = 0.03) compared to patients with persistent negative ATAb status (36%).

Conclusions

Acquired overt thyroid toxicity and positive ATAb status during anti-PD-1 treatment are associated with improved PFS and OS. Moreover, our results indicate that ATAb status at baseline is of clinical relevance for PFS and OS. If validated, these parameters may serve as a novel positive predictive markers.

Clinical trial identification

Dutch trial register: MULTOMAB, NL6828.

Editorial acknowledgement

Legal entity responsible for the study

Erasmus Medical Center.

Funding

Erasmus Medical Center.

Disclosure

A.A.M. Van der Veldt: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme. R.H. Mathijssen: Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boekringer; Research grant / Funding (institution): Cristal Therapeutics; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (self): Servier. All other authors have declared no conflicts of interest.