Hyperprogression and hypercalcemia after nivolumab treatment in three cases with renal cell carcinoma

Hyperprogression is a specific type of response seen with immunotherapy that is observed in all malignancies with a frequency of 9% - 29%, characterized by a rapid increase in tumor burden. Many possible related factors and possible markers have been evaluated but a clinical or laboratory parameter associated with hyperprogression has not yet been established. For renal cell carcinoma, hypercalcemia is known to be a poor prognostic factor but it has not been linked to hyperprogression.

We retrospectively evaluated 52 patients diagnosed with renal cell carcinoma who had nivolumab treatment in any line. 3 of 9 patients who had hyperprogression were noticed to have hypercalcemia preceding hyperprogression. Here we present those 3 cases who developed hypercalcemia after nivolumab and had hyperprogression at follow-up.

All cases had less than 4 courses of nivolumab and showed hyperprogression in assessment. Nivolumab was discontinued. However, patients' survival was extremely poor, as expected.

The development of hypercalcemia may help predict hyperprogression in patients with renal cell carcinoma who receive immunotherapy. In such cases, early evaluation of progression and cessation of nivolumab may be considered.