3392 - Phase II Trial of Autologous Lymphocyte Infusions after Radiotherapy to Mitigate Radiation Induced Lymphopenia and Enhance Immune Reconstitution in Patients with Solid Tumor Malignancies
Presenter(s)
E. Chang1, M. S. Ning2, J. K. Bronk2, S. Gandhi2, A. B. Chen2, Q. N. Nguyen2, M. S. O'Reilly2, J. Y. Chang2, Z. Liao2, R. Bassett Jr.3, M. V. Negrao4, C. M. Gay4, X. Le4, D. L. Gibbons4, J. J. Li5, M. Blum Murphy5, J. A. Ajani5, C. Hosing6, G. Al-Atrash6, and S. H. Lin2; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Thoracic-Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
Radiation induced lymphopenia (RIL) commonly occurs when highly radiosensitive lymphocytes are irradiated in the blood, heart, and secondary lymphoid organs. High grade RIL is associated with worse oncologic outcomes, including impaired efficacy of consolidative immunotherapy following definitive chemoradiation (CRT) for patients with locally advanced non-small cell lung cancer (NSCLC). We hypothesized that autologous lymphocyte infusions (ALI) following thoracic chemoradiation (CRT) would be feasible, safe, and facilitate immune reconstitution.Materials/Methods:
This is a phase II single arm trial including patients with NSCLC or esophageal cancer receiving definitive CRT. Patients with a history of prior thoracic RT or planned additional systemic therapy after CRT aside from standard of care immunotherapy were excluded. Autologous lymphocyte collection was performed prior to CRT. ALI occurred the day after CRT completion. Adverse events (AE) were assessed within 30 days after ALI. Complete blood count (CBC) with differential was assessed at baseline prior to CRT, weekly during CRT, and 6 weeks after ALI. Primary objectives were to assess absolute lymphocyte count (ALC) change and immune reconstitution, defined as achieving ALC =1000 cells/uL, 6 weeks after ALI. Secondary objectives included assessment of feasibility and safety. Statistical significance was assessed with the Wilcoxon signed-rank test.Results:
Nineteen patients completed pre-CRT apheresis. Fifteen patients completed post-CRT ALI. Three patients withdrew prior to ALI. One patient developed disease progression and did not undergo ALI. Median age was 59 years (range 45-84). Eleven patients were male, 4 were female, 11 had esophageal cancer, 4 had NSCLC, 9 were treated with protons, 5 were treated with photons, 1 was treated with both. No ALI-related AEs were observed. Lymphocyte reconstitution was observed in 5 of 11 (45%) patients with evaluable CBC 6 weeks after ALI. Median ALC at baseline was 1260 cells/uL (range 430-2140). Median ALC at 6 weeks after ALI was 800 cells/uL (range 350-1580). Median change in ALC from baseline to 6 weeks after ALI was -460 cells/uL compared to a historical change of -620 cells/uL, representing a 26% improvement (p=0.147).Conclusion:
ALI is safe and feasible after definitive CRT for patients with thoracic cancers. Future studies are needed to assess the quality of immune reconstitution and to characterize lymphocyte clonal populations after ALI. This study establishes a framework for future investigations exploring engineered cell therapy and immunomodulatory infusions after CRT in the solid tumor setting.