Peripheral white blood cell profiles may predict response to checkpoint blockade

While some patients enjoy excellent and durable responses to treatment with checkpoint inhibits, most do not, and some even hyper-progress. Selecting patients who will benefit most has been challenging.

Researchers from Italy reported on a series of 54 patients with non-small cell lung cancer (52% squamous and 48% adenocarcinoma) who received nivolumab (Opdivo), most of whom (89%) had Stage IV disease. Twenty patients had a complete or partial response or stable disease and 34 progressed. Assessments were made at baseline (T0) and after two (T1) and four (T2) treatment cycles.

The following peripheral blood immune profiles were examined:

  1. CD3 – expressed on all T-cells
  2. CD4 – T helper cells
  3. CD8 – cytotoxic T-cells
  4. CD56 – NK cells
  5. FOXP3 – Treg cells
  6. MDSC – myeloid-derived suppressor cells, which suppress T cell responses

The characteristics of those who had good responses versus those who did not included:

  1. ECOG performance status of 0 – 76.9% vs 23.1% (P< .001)
  2. At least four months since prior chemotherapy – 61.9% vs 38.1% (P< .004)
  3. Higher baseline CD3+ count (P= .046) and higher NK cell count (P < .001)
  4. Lower neutrophil count (P= .002)
  5. Lower neutrophil-to-lymphocyte ratio (P< .001)

An analysis of 31 patients who underwent all three assessments revealed that  significant increases in NK cells and a significant decrease in the proportion of CD4 cells from T0 to T2 were associated with treatment response. Responders also had a greater number and concentration of CD8+ expressing PD-1.

This study was exploratory in nature and a larger, prospective, randomized study with multivariate analyses needs to be conducted to better determine the value of these (and other) potentially predictive markers.

The ability to predict response to checkpoint blockade from baseline and on-treatment peripheral blood analyses is very appealing and could benefit many patients, and improve therapeutic selection and efficiency.