Abstract
The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena in both tumor responses and toxicities. We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments. He was eventually started on nivolumab—the anti-programmed death receptor-1 monoclonal antibody approved for the treatment of advanced RCC. Clinical deterioration was observed soon after a 100 mg dose of nivolumab, with onset of acute renal failure and declining performance status. Radiologic progression was documented in multiple sites including worsening tumor infiltration of his residual kidney. The patient was on palliative treatment and visited by the home hospice team in an end-of-life situation. The patient unexpectedly improved and went on to achieve a durable tumor response. The case is illustrative of an extreme manifestation of pseudoprogression, and impels us to probe the assumptions and controversies surrounding this phenomenon.
Highlights
The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena related to both tumor response and toxicity
We report a case of metastatic renal cell carcinoma (RCC) that experienced ‘extreme pseudoprogression’ after a single dose of the anti-programmed death 1 monoclonal antibody nivolumab, with the emergence of a near-death situation soon after treatment
Pseudoprogression is a known phenomenon of immune checkpoint inhibitor therapy, and has been variably defined as a response after an initial increase of tumor burden, a reduction in tumor burden during or after the appearance of new lesions, or an increase in tumor burden not confirmed as progressive disease at the imaging assessment [7]
Summary
The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena related to both tumor response and toxicity. C Tumor progression 5 weeks after nivolumab: right hilar mass and lung (top), intramuscular (middle, white arrow), and liver metastases (bottom). In May 2015, after 4 months off anti-angiogenic therapy, there was global progression of disease with the right hilar node enlarging and new metastases appearing in multiple sites (lungs, muscle, bones). The recent 3 new skin metastases had resolved, a non-contrasted CT at 5 weeks post-nivolumab documented worsening tumor in multiple sites: skeletal muscles, liver, spleen, pancreas, peritoneal nodules, lungs, right hilar nodal mass and other soft tissue areas. At week 11, non-contrasted CT scan showed improvement in tumor status in most of the involved sites including a decreased size of the right kidney. CT imaging showed marginal increase in kidney size from baseline to the 5 week post-nivolumab scan, and subsequent decrease at the 11 week scan when the renal function had recovered. A contrast CT at 4 months as well as an US at 6 months post-nivolumab showed decreased renal size and near complete resolution of the renal metastases
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