Pretreatment hemoglobin level as a predictor to evaluate the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer

Abstract

Background: Targeting immune checkpoints represents an immense breakthrough in cancer therapeutics. The prognostic value of hemoglobin (Hb) has been investigated in many malignancies including non-small cell lung cancer (NSCLC). However, the prognostic impact of pretreatment Hb count for immune checkpoint inhibitors (ICIs) in advanced NSCLC patients remains unclear. Methods: A total of 310 late-stage NSCLC patients who received ICI therapies between January 2015 and March 2019 were prospectively enrolled. We used a propensity score-matched cohort analysis for this study. Patients’ clinicopathological characteristics and pretreatment Hb concentration were assessed against the progression-free survival (PFS) and overall survival (OS) using the Kaplan–Meier method and Cox proportional hazards regression. Results: A propensity score (PS)-matched cohort analysis was applied to adjust for potential bias and to create two comparable groups according to patients’ clinicopathological characteristics. The patients with normal baseline Hb levels (⩾110 g/L) had significantly longer PFS [median: 10.0 versus 4.0 months, hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46−0.86; p = 0.001] and OS [median: 17.6 versus 10.5 months, HR (95% CI): 0.56 (0.40−0.79); p < 0.001] than those with decreased Hb count (<110 g/L) in a PS-matched cohort ( n = 255). For patients with normal pretreatment Hb levels, ICI combination therapy was significantly associated with better PFS [median: 11.1 versus 8.0 months, HR (95% CI): 0.74 (0.50−1.06); p = 0.09] and OS [median: 26.0 versus 12.9 months, HR (95% CI): 0.56 (0.37−0.86); p = 0.008] than monotherapy, but there was no such trend for patients with decreased baseline Hb levels. Conclusion: Our findings showed that normal pretreatment Hb count served as a favorable prognostic marker in advanced NSCLC patients treated with ICIs, representing an economical biomarker with readily measuring performance among all reported ones.

The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy

“…Patients with normal Hb level receiving PD-1 inhibitor were shown to have prolonged long term benefit of 14.4months and progression time of 7.8m (p<0.05). This was in line with previous studies of NSCLC treated with ICI ( 29 , 30 ). Hypoxia is a potent barrier to effective immunotherapy in cancer treatment ( 31 ).…”

Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer

“…Other peripheral blood indexes have also been proposed to be potential predictors for the effect of ICIs treatment. A recent prospective cohort study showed that normal pre-treatment level of Hbis a favorable prognostic factor for ICIs treatment in patients with advanced NSCLC (7). Furthermore, previous studies have shown that baseline level of LDH, a biomarker related to tumor burden, was associated with the poor treatment outcomes in NSCLC patients, which can also predict the prognosis of the patients treated with ICIs (29)(30)(31).…”

“…In recent years, peripheral blood biomarkers representing tumor burden or inflammation have been increasingly studied for the purpose of predicting NSCLC treatment effect. The lower pre-treatment level or post-treatment declination of those biomarkers was previously shown to associate with the higher response rate and better prognosis in the patients (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, most studies were based on monotherapy, and the meaningfulness of baseline values remains controversial.…”

The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

“…This indicated that IFN-γ is a vital biomarker for NSCLC patients treated with anti-PD-1 therapy. 157 Other potential biomarkers Other potential biomarkers being investigated in anti-PD-1/PD-L1 immunotherapy on NSCLC include the pretreatment haemoglobin level, 158 serum vascular endothelial growth factor (VEGF) concentration, 159 serum lactate dehydrogenase level, 160 gut microbiome composition 116 and neoantigen load. 161 Challenges for anti-PD-1/PD-L1 treatment in advanced NSCLC Currently, there are still many unresolved problems associated with the clinical use of anti-PD-1/PD-L1 therapies (Figure 2).…”