Massive hyper-progression during anti-PD1 immunotherapy in a young patient with metastatic mucinous adenocarcinoma of the right colon: a case report and literature review

Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment landscape of both solid and hematological malignancies, including tumors historically considered “non-immunogenic”, such as colorectal cancer (CRC). The increasing use of immunotherapy brought to light novel patterns of response due to its intrinsic mechanism of action. Besides the “pseudo-progression”, another peculiar phenomenon linked to ICIs activity is the “hyper-progression” (HP), namely a paradoxical disease acceleration during immunotherapy. This event, which suggests potentially deleterious effects of immunotherapy, has not been yet completely understood and lacks strict definition criteria, pathogenetic characterization as well as predictive factors. In this report, we present a case of an atypical massive progression in a 40-years old man with metastatic mucinous right colon cancer harboring high microsatellites instability (MSI-H), occurring after 2 cycles of pembrolizumab as first line therapy. Unfortunately, he experienced a widespread cancer dissemination for massive bone colonization and both numerical and volumetric increase of pre-existing node metastasis associated with rapid clinical worsening, which were suggestive for HP. To our knowledge, this is one of the few cases of HP in metastatic CRC that has been reported, particularly with a so rapid clinical deterioration and massive skeletal involvement. Other experiences and further studies are warranted to better understand this phenomenon and anticipate its recognition