Absolute Lymphocyte Count Predicts Abscopal Responses and Outcomes in Patients Receiving Combined Immunotherapy and Radiation Therapy: Analysis of 3 Phase 1/2 Trials

Purpose: 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 antitumor effects. This study, using data from 3 institutional phase 1/2 trials, examined the predictive capacity of recorded parameters in patients undergoing combined radiation therapy (RT) and immunotherapy and explored outcomes based on those predictive factors. Methods and Materials: All patients underwent combined immunotherapy and RT and had at least 1 nonirradiated noncontiguous lesion to evaluate out-of-field (abscopal) responses, defined as the best Response Evaluation Criteria in Solid Tumors response. Results: Altogether, 153 patients met study criteria, and the median follow-up was 21.1 months. The most common cancer types were non-small cell lung carcinoma (n = 62), small cell lung carcinoma (n = 25), head and neck cancers (n = 16), and renal cell carcinoma (n = 13). Immunotherapies included ipilimumab (n = 98) and pembrolizumab (n = 55). Multivariable linear regression indicated that post-RT absolute lymphocyte count (ALC), when analyzed as a continuous variable, correlated with abscopal responses (P <.001). For post-RT ALC, the abscopal response rate was 34.2% in the cohort with ALC higher than the median value, compared with 3.9% in patients with ALC lower than the median (P <.0001). Corresponding figures for pre-RT ALC were 30.3% versus 7.8%, respectively (P =.0004). Cox multivariate analysis confirmed that lower post-RT ALC also associated with poorer progression-free survival (P =.009) and overall survival (P =.026). Conclusions: Lymphopenia, measured as the continuous variable of post-RT ALC, may affect 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.