Hyperprogression after immunotherapy: A comprehensive review

Immune checkpoint inhibitors have revolutionized cancer treatment with patient improved survival, quality of life, and a longer response. However, up to 30% of patients experience paradoxical accelerated tumor progression early after immune-checkpoint blockade therapy. This phenomenon is also known as hyperprogression (HP). Unlike other responses, such as pseudoprogression or natural progression, HP causes worse survival outcomes in patients. Older age, higher metastatic burden, and previous radiation have been independently associated with HP. Even though the exact molecular mechanism underlying HP after immune-checkpoint blockade therapy remains unknown, oncogenic signaling activation including MDM2 amplification or EGFR alterations, the modification of tumor microenvironment by radiotherapy with immune checkpoint inhibitors, and alterations in immune landscape of tumors have been hypothesized as the biological mechanisms behind HP. Patients with HP have been presented with poor prognosis and increased deleterious mutations in cancer genes, along with alterations in the tumor microenvironment. As immune checkpoint inhibitors have been more widely accepted by oncologists, proper assessment of this unique tumor response remains challenging in clinical practice. This work documents the recent findings on epidemiology, biological and clinicopathological factors of HP after immunotherapy.