3 research outputs found
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an
acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on
radiological evaluation present important technical limitations. No biomarkers have been identified
yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy
after progression to platinum-based therapy were prospectively studied. Samples from peripheral
blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood
mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified
by flow cytometry and correlated with HPD as identified with radiological criteria. A strong
expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and
second cycle of therapy was observed in HPD patients. After normalizing, the proportion of
posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the
rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD
progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cut-off value of 1.3
identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥
1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR)
was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients
(median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03,
p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first
cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in
clinical practice and complements radiological evaluation
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an
acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on
radiological evaluation present important technical limitations. No biomarkers have been identified
yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy
after progression to platinum-based therapy were prospectively studied. Samples from peripheral
blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood
mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified
by flow cytometry and correlated with HPD as identified with radiological criteria. A strong
expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and
second cycle of therapy was observed in HPD patients. After normalizing, the proportion of
posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the
rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD
progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cut-off value of 1.3
identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥
1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR)
was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients
(median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03,
p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first
cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in
clinical practice and complements radiological evaluation