Practice Update: Oncology

ELCC 2017 11

White blood cell count predicts response to immunotherapy for lung cancer

White blood cell counts can predict whether or not patients with lung cancer will benefit from immunotherapy, reports an assessment of the ability of white blood cell counts to predict whether lung cancer patients responded to nivolumab. M arcello Tiseo, MD, of the University Hospital of Parma, Italy, explained, “Immune checkpoint inhibitors such as nivolumab and pembroli- with response to nivolumab, as was an increase in the number of natural killer cells during treatment. Responders to nivolumab also harbored a greater number and concentration of CD8-positive T cells that expressed PD-1.

zumab improve overall survival significantly in some, but not all, patients with non-small-cell lung cancer. Researchers are seeking predictive biomarkers to select patients who will benefit from this treatment to avoid unnecessary toxicity and a waste of resources in patients who will not respond.” He continued, “Programmed death – ligand 1 (PD- L1) expression in a biopsy of tumor tissue is used to select patients but is not completely accurate, possi- bly because the biopsy sample does not reflect the evolving immune response. Biomarkers in the blood are easier to obtain and may be better indicators of immune response.” The study included 54 patients with non-small-cell lung cancer who received nivolumab at a dose of 3 mg per kilogram of body weight every 14 days. White blood cells were counted at baseline, after two nivolumab cycles, and after four nivolumab cycles. Researchers compared white blood cell counts between responders and nonresponders to nivolumab. White blood cell counts at baseline and during ther- apy predicted whether patients would respond to nivolumab treatment. A greater number and concen- tration of natural killer cells at baseline was associated

Dr Tiseo said, “The number and function of natu- ral killer cells and frequency of PD-1 expression in CD8-positive T cells could be predictive biomarkers for nivolumab treatment in advanced non-small-cell lung cancer. Identification of a panel of blood pre- dictive biomarkers would enable early identification of patients most likely to benefit from anti-PD-1 and anti-PD-L1 treatment.” Stefan Zimmermann, MD, of the Hôpital Cantonal, Fribourg, Switzerland, concluded, “In the era of pre- cision medicine and increasing healthcare costs we urgently need predictive biomarkers to select patients who will benefit from a specific therapy.” He continued, “This study found that baseline levels of certain white blood cells play a role in predict- ing response to immunotherapy in patients with lung cancer. These new factors should be investigated in future clinical trials, together with tumor PD-L1 expres- sion and other markers that constitute the cancer immunogram to predict whether or not patients will benefit from treatment.”

PracticeUpdate Editorial Team

and 53% of controls, and progressive dis- ease in 22% of cases vs 40% of controls. Multiple logistic regression showed that age, gender, number of prior chemotherapy reg- imens, tumor histology, smoking status, and different salvage chemotherapy regimens were not independently associated with the likelihood of achieving partial response. Dr Rothschild said, “At this point we can only speculate on reasons for the better response in patients pretreated with check- point inhibitors. Probably, activation of the immune system by checkpoint inhibition might render tumor cells more sensitive to chemotherapy. Or chemotherapy may help tumor-specific T-cells to enter the tumor microenvironment and exert their function.” Dr Rothschild said that investigations are ongoing into the duration of response and toxicity, and he cautioned that this finding must be explored further in larger and pro- spective cohorts. Marina Garassino, MD, of the National

lung cancer, including adenocarcinoma (n=63), squamous cell carcinoma (n=18), and one case of large cell carcinoma were analyzed. Sixty-seven patients had been treated previously with a PD-1/PD-L1 inhibi- tor, including 56 patients who received nivolumab; seven, pembrolizumab; and four, atezolizumab. The remaining 15 patients, who had not been treated with PD-1/PD-L1 inhibitors, served as controls. All patients had been pretreated with chemotherapy, with a mean of 2.37 prior regimens among cases and 1.93 in controls. Salvage chemotherapy included docetaxel (62%), pemetrexed (20%), paclitaxel (6%), and others (12%). Computed tomography scans performed within the first month and then every 6 weeks showed a significantly higher par- tial response rate in cases than in controls (27% vs 7%, odds ratio 0.3, P < 0.0001). Stable disease was seen in 51% of cases

Cancer Institute of Milan (Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori) was enthusi- astic about the potential implications. She said, “This was the first research to suggest that chemotherapy could poten- tially work better after immunotherapy. All of us treating patients with immunotherapy have had a feeling about this possibility because we’ve seen unexpected results with some patients.” She continued, “This was the first study to describe this phenomenon formally. Though the results were very preliminary, they suggested that immunotherapy can change the natural history of the disease and the tumor microenvironment, therefore rendering the tumor more sensitive to che- motherapy. This could potentially point to new areas of research and new sequences of treatment.”

PracticeUpdate Editorial Team

VOL. 1 • NO. 1 • 2017