Biomarkers of Hyperprogression and Pseudoprogression with Immune Checkpoint Inhibitor Therapy

Abstract

Hyperprogression and pseudoprogression are two atypical responses to immune checkpoint inhibitor therapy that affect therapeutic decisions and prognosis. Identification of predictive biomarkers for atypical responses either before or during treatment remains a huge unmet need in cancer immunotherapy. Many studies have looked at potential biomarkers, including clinical factors and laboratory findings (e.g., peripheral blood counts, circulating tumor DNA, cytokine levels). The results of these studies have been inconsistent, possibly due to small sample sizes, different tumor types and heterogeneity of the definition of these atypical responses.

Pseudoprogression during Successful Rechallenge of Immune Checkpoint Inhibitor in a NSCLC Patient

“…To our best knowledge, this is the first case report describing a pseudoprogression developed in successful rechallenge of ICPI therapy for a recurrent NSCLC patient. Clinicopathological factors that predict the development of pseudoprogression, including clinical factors and laboratory findings (e.g., size of tumors, peripheral blood counts, circulating tumor DNA, cytokine levels) have been investigated [11,14]. However, these potential biomarkers have been inconsistent, probably due to small sample sizes, different tumor types, and heterogeneous definitions of these atypical responses [14].…”

“…Clinicopathological factors that predict the development of pseudoprogression, including clinical factors and laboratory findings (e.g., size of tumors, peripheral blood counts, circulating tumor DNA, cytokine levels) have been investigated [11,14]. However, these potential biomarkers have been inconsistent, probably due to small sample sizes, different tumor types, and heterogeneous definitions of these atypical responses [14]. Investigating the presence and activity of immune cells in the tumor area at the time of tumor growth by tumor biopsy might help assess tumor immunity, nevertheless, this has not yet been proven as a validated biomarker [14].…”

“…However, these potential biomarkers have been inconsistent, probably due to small sample sizes, different tumor types, and heterogeneous definitions of these atypical responses [14]. Investigating the presence and activity of immune cells in the tumor area at the time of tumor growth by tumor biopsy might help assess tumor immunity, nevertheless, this has not yet been proven as a validated biomarker [14]. Considering the frequency of pseudoprogression, it is not practical to perform a tumor biopsy when the tumor grows.…”

“…Lee et al [15] showed that circulating tumor DNA decreased in the presence of pseudoprogression, but this method has not reached the level of clinical application. Therefore, unfortunately, no reliable assessment has been reported to date to help clinicians decide between a potential pseudoprogression or a real progression [11,14].…”

Immune Checkpoint Blockade Therapy for Hepatocellular Carcinoma: Clinical Challenges and Considerations

“…Older age, higher metastatic burden, and previous radiation are found associated with HPD (68). Many studies have explored potential biomarkers from clinical, laboratory, and imaging angles (69). Unfortunately, there are no reliable ways to select patients with HCC who are risky for HPD before the treatment of ICIs.…”