Research to elucidate predictive factors of the abscopal effect is an essential first step toward potentially modifying these factors to increase the incidence of systemic anti-tumor effects. This study, utilizing data from three institutional phase I/II trials, examined the predictive capacity of recorded parameters in patients undergoing combined radiotherapy (RT) and immunotherapy and explored outcomes based on those predictive factors.
All patients underwent combined immunotherapy and RT and had at least one nonirradiated noncontiguous lesion to evaluate out-of-field (abscopal) responses, defined as the best RECIST response.
Altogether, 153 patients met the study criteria, and the median follow-up was 21.1 months. The most common cancer types were NSCLC (n=62), SCLC (n=25), head/neck cancers (n=16), and renal cell carcinoma (n=13). Immunotherapies included ipilimumab (n=98) or pembrolizumab (n=55). Multivariable linear regression indicated that post-RT ALC, when analyzed as a continuous variable, correlated with abscopal responses (p<0.001). For post-RT absolute lymphocyte count (ALC), the abscopal response rate was 34.2% in the cohort with ALC higher than the median value, compared to 3.9% in patients with ALC lower than the median (P<0.0001). Corresponding figures for pre-RT ALC were 30.3% vs. 7.8%, respectively (P=0.0004). Cox multivariate analysis confirmed that lower post-RT ALC also associated with poorer PFS (p=0.009) and OS (p=0.026).
Lymphopenia, measured as the continuous variable of post-RT ALC, may impact the occurrence of abscopal responses and thus influence prognosis in patients treated with RT and immunotherapy. Although this hypothesis-generating finding requires corroboration by additional data, it suggests the importance of ALC monitoring and the potential of therapeutic manipulation of this parameter to induce abscopal effects.

Copyright © 2020. Published by Elsevier Inc.