Early blood rise in auto‑antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic‑non‑small cell lung cancer patients treated with PD‑1 immune‑check point blockade by nivolumab

Abstract

Immune-checkpoint blockade by Nivolumab, a human monoclonal antibody to programmed cell death receptor-1, is an emerging treatment for metastatic non-small cell lung cancer (mNSCLC). In order to prolong patient survival, this treatment requires a continuous cross-priming of tumor derived-antigens to supply fresh tumor-specific immune-effectors; a phenomenon that may also trigger auto-immune-related adverse events (irAEs). The present study therefore investigated the prognostic value of multiple autoimmunity-associated parameters in patients with mNSCLC who were undergoing Nivolumab treatment. This retrospective study included 92 mNSCLC patients who received salvage therapy with Nivolumab (3 mg/kg, biweekly) between September 2015 and June 2018. Log-rank test, Mantel-Cox and McPherson analyses were conducted to correlate patient progression-free survival (PFS) and overall survival (OS) with different parameters including blood cell counts, serum inflammatory markers and auto-antibodies (AAbs). A median PFS and OS of 10 [inter-quartile range (IQR): 5.8-14.2] and 16 [IQR: 6.2-25.8] months, respectively, were recorded, which did not correlated with age, histology or the number of previous chemotherapy lines. Male gender, the type of therapeutic regimens received prior to Nivolumab, and the occurrence of irAEs were revealed to be positive predictors of prolonged survival (P<0.05). Early detection (within 30 days) of >1AAbs among anti-nuclear antigens (ANAs), extractable nuclear antigens (ENAs) and anti-smooth cell antigens (ASMAs) correlated with prolonged PFS [hazard ratio (HR)= 0.23; 95% confidence interval (

HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis

“…Patients who received the immunological treatment in our series were monitored for changes in blood cells, inflammatory markers, and aAbs. They reported a significant increase in ANA, ENA, and ASMA as described in previous studies by our group [ 15 ]. In total, 180 patients were voluntarily evaluated for germline expression of class I HLA A, B, C loci, and DRB1 for class II.…”

Radiomics predicts survival of patients with advanced non‑small cell lung cancer undergoing PD‑1 blockade using Nivolumab

“…The recent clinical development of immune-biological drugs such as PD-1/PDL1 inhibitor mAbs for the treatment of common malignancies has clearly risen an extraordinary challenge in terms of cost, adverse events and patients' monitoring. So far, no clear biomarkers are presently able to select patients who may benefit by treatment with Nivolumab in NSCLC, although some interesting preliminary results (37). Additionally, these drugs act by turning the immune-balance between tumour and immune system in favour of the latter, thus providing a clinical benefit and prolonging patients' survival even in the presence of an apparent radiological progression.…”

Classical Examples of the Concept of the ASIA Syndrome

“…Further, during the therapy autoantibodies appear in many patients, and often there is no association with particular organ affection. In some cases, the appearance of autoantibodies is associated with a good prognosis [ 115 , 116 ]. Some researchers managed to find organ-specific autoantibodies, but this is more likely due to the development of a chronic disease.…”