Therapeutic radiation has conflicting immune effects: radiation (RT)-induced immunogenic cell death can contribute to immune response, but lymphocytes are also sensitive to RT. It is unknown whether palliative RT leads to lymphopenia in patients treated with immune checkpoint inhibitors (ICI) and whether this impacts outcomes. As such, we sought to assess the impact of palliative RT on circulating lymphocyte count and neutrophil-lymphocyte-ratio (NTL) in patients being treated with PD-1 directed ICI and associations with survival.
We identified patients from five radiation oncology centers, treated with palliative RT and either pembrolizumab or nivolumab with non-small cell lung cancer (NSCLC), metastatic melanoma (MM), and renal cell carcinoma (RCC). Patients who received intervening cytotoxic chemotherapy were excluded. We recorded absolute lymphocyte count (ALC) and neutrophil to lymphocyte ratio (NTL) before and after palliative RT, and at the start of ICI. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models.
One hundred ten patients received 225 courses of palliative RT. Median change in ALC (dALC) after RT was -161 cells/mL. Decreases in ALC were greater with RT to the spine, lung/mediastinum, and chest wall compared with the brain, extremity, or abdomen/pelvis (p=0.002), and after courses >5 fractions (p=0.003). Extracranial and >5 fraction radiation was associated with increased odds of severe lymphopenia (ALC<500) at the end of RT (OR 3.7, p=0.001, and OR 3.9 p=0.001, respectively). Patients who developed RT-induced severe lymphopenia were more likely to have severe lymphopenia when ICI was initiated (OR 6.4, p=0.0001), particularly when RT was administered in the previous 3 months (OR 189, p<0.0001). Severe lymphopenia at onset of ICI therapy was associated with increased mortality on multivariable analysis (HR 2.1, p=0.03).
Extracranial or prolonged courses of RT increase the risk of severe lymphopenia, which is associated with poorer survival in patients treated with ICI.
International journal of radiation oncology, biology, physics. 2018 Sep 15 [Epub ahead of print]
Luke R G Pike, Andrew Bang, Brandon A Mahal, Allison Taylor, Monica Krishnan, Alexander Spektor, Daniel N Cagney, Ayal A Aizer, Brian M Alexander, Osama Rahma, Tracy Balboni, Patrick A Ott, F Stephen Hodi, Jonathan D Schoenfeld
Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center, Boston, Massachusetts; Harvard Radiation Oncology program, Massachusetts General Hospital, Boston, MA. Electronic address: ., Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center, Boston, Massachusetts; Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center, Boston, Massachusetts; Harvard Radiation Oncology program, Massachusetts General Hospital, Boston, MA., Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center, Boston, Massachusetts.