Patterns of early 18F-FDG PET response to nivolumab (NIVO) and ipilimumab nivolumab (IPINIVO) in patients with metastatic renal cancer (MRC).

Abstract

374 Background: Immunotherapy with IPINIVO and NIVO is a standard treatment in MRC. This leads to recruitment and activation of immune cells. The ‘immune burst’ is seen at 1-4 weeks. Glycolysis leads to cellular 18F-FDG uptake. This can reflect malignancy. Sensitivity for renal tumours is poor, though high SUV suggests aggressive behaviour. Sensitivity for metastases can be 90% This study investigated 18F-FDG uptake in patients with MRC prior to treatment with immunotherapy. A scan was also performed at 2 weeks to assess a possible ‘flare’, due to glycolysis of the immune infiltrate, before significant standard radiological change was expected. Methods: Twenty six patients with MRC were enrolled. 8 patients had IPINIVO first line, and 18 had NIVO second line. Patients had a PET scan before and 2 weeks after treatment. Maximal standardised uptake values (SUV) were measured and corrected (COR) to the hepatic SUV. Results: All patients had some 18F-FDG avid metastases. SUVs varied within the same patient. For IPINIVO patients SUVmax was 17, mean 5.8 (3.7 and 2.5 COR respectively) and for NIVO patients SUV max was 25.1, mean 5.1. (7.6 and 2.3 COR respectively). There was no difference in mean SUV in the 2 groups (p=0.5). For NIVO patients there was a trend for patients who had a longer response to first line tyrosine kinase inhibitor, hence better prognosis, to have a lower SUV. (p=0.18) For NIVO there was a 12.4 % mean increase in SUV (p=0.06) In 8/16 patients there was a >20% increase in SUV in the measured metastases ( mean 50.4 % increase, range 22.2 – 142.9 ). Flare occurred at a range of tumour sites. Only metastases which were 18F-FDG avid had a flare. In 4 patients there was a >20% decrease in SUV. (Mean 41.2 Range -21.2% to -55.3%) For IPINIVO in 4/8 patients there was a >20% increase in SUV, mean 57.2 (Range 21- 134%) Flare only occurred in lymph nodes and an adrenal gland. In 2 patients there was a >20% decrease in SUV. (Mean - 50.7 Range -21.2% to -64%) Two patients had normal tissue flare: in thyroid, and mediastinal nodes. Conclusions: This is the first study to demonstrate tumour 18F-FDG flare in patients with MRC following immunotherapy, which may be due to influx and activation of glycolytic immune cells. There is a suggestion that tumour biology, and response to first line tyrosine kinase inhibitor is reflected in the SUV of metastases in patients having treatment with second line nivolumab.