PD-1/PD-L1 Monoclonal Antibody Use Is Effective in Young and Elderly Patients with NSCLC

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Targeted therapy with monoclonal antibodies has expanded treatment options for patients with non–small-cell lung cancer (NSCLC). Peripheral immune checkpoint blockade with inhibitors against PD-1 and PD-L1 alone or in combination with other anticancer therapies have proven effective but have been associated with serious immune-related adverse events (irAEs). In patients aged >75 years with metastatic NSCLC there is a lack of evidence regarding whether these treatments are as effective as when used in younger patients due to immunologic immune impairment associated with aging. Immunosenescence occurs naturally with age, leading to decreased adaptive immunity, an increase in autoimmunity risk, and a decrease in infection resistance.1 T-cell–mediated response is compromised due to immunosenescence, and questions remain if PD-1/PD-L1 inhibitors’ efficacy and safety may be compromised in this patient population due to both immunosenescence and chronic systemic inflammation.

To answer these questions, Nardone and colleagues performed a retrospective multicenter evaluation of 117 patients with metastatic chemotherapy-refractory NSCLC who were treated with PD-1 (nivolumab) or PD-L1 (atezolizumab) inhibitors for a median of 27 months. Patients who had active autoimmune disease (with the exception of diabetes and thyroiditis) and a solid organ transplant were excluded from the study. Patients were divided into 2 cohorts: 90 patients <75 years of age and 27 patients who were ≥75 years of age. Patients ranged from 44 to 85 years with a median age of 69 years.

Baseline inflammatory biomarkers were drawn for each study participant. Nivolumab was given via intravenous infusion of 3 mg/kg every 2 weeks to 84 patients. Atezolizumab was given via intravenous infusion of 1200 mg every 3 weeks to 33 patients. Both treatments were given until disease progression or severe adverse events occurred. Patients received a computed tomography scan every 3 months or if progressive disease was suspected. Blood counts and biochemistry were monitored prior to each treatment course, and an extensive testing for immune and inflammatory reactions was performed each month. When the 2 cohorts were evaluated for progression-free survival and overall survival, there were no differences noted between the 2 cohorts or in the 2 different monoclonal antibody treatments. Comparison between the 2 cohorts for inflammatory markers and irAEs also found no differences. Prolonged overall survival was associated with the occurrence of irAEs for both groups. For only the younger cohort was there a negative correlation between high baseline inflammatory markers and overall survival.

Source

Nardone V, Giannicola R, Giannarelli D, et al. Distinctive role of the systemic inflammatory profile in non-small-cell lung cancer younger and elderly patients treated with a PD-1 immune checkpoint blockade: a real-world retrospective multi-institutional analysis. Life (Basel). 2021;11:1235.

Reference

  1. Lian J, Yue Y, Yu W, Zhang Y. Immunosenescence: a key player in cancer development. J Hematol Oncol. 2020;13:151.

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