Radiation Biology

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SU_38_2387 - Impact of palliative radiation on lymphocyte count and neutrophil-to-lymphocyte ratio in patients receiving PD-1 inhibitors

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Impact of palliative radiation on lymphocyte count and neutrophil-to-lymphocyte ratio in patients receiving PD-1 inhibitors
L. R. G. Pike1, A. Bang2,3, A. Taylor2, M. S. Krishnan4, A. Spektor4, D. N. Cagney2, A. A. Aizer2, B. Alexander2, O. Rahma5, T. A. Balboni2, P. Ott5, F. S. Hodi5, and J. D. Schoenfeld2; 1Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, MA, 2Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, 3Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada, 4Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, 5Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center, Boston, MA

Purpose/Objective(s): Immune checkpoint inhibitors (ICI) are increasingly used in patients receiving palliative radiation (RT). However, studies suggest that RT, and particularly protracted RT courses, may decrease circulating lymphocytes, which could adversely impact ICI efficacy. We therefore evaluated circulating lymphocytes in a contemporary cohort of melanoma, non-small cell lung cancer and renal cell carcinoma patients treated with ICI and radiation.

Materials/Methods: We reviewed consecutive patients treated with palliative RT and ICI. We recorded absolute lymphocyte count (ALC), neutrophil count, and neutrophil to lymphocyte ratio (NTL) before and after palliative RT, and start of ICI. Patients who received other intervening systemic therapy were excluded. Survival was analyzed using the Kaplan-Meier method and log-rank tests. Chi-squared and non-parametric tests evaluated differences between groups.

Results: We identified 110 patients treated with PD-1 inhibitors; 38 also received CTLA-4 inhibitors (23 sequentially, 15 concurrently). The most common site irradiated was the brain (71 patients, 120 courses, 40% SRS). Among all patients, median change in ALC (dALC) and NTL (dNTL) after RT was -161 and 0.8, respectively. Changes were more pronounced after extracranial RT (dALC -384 vs. -48 for brain-directed RT p=0.01, dNTL 0.2 vs. 2.5, p=0.001), RT to the spine, lung, or chest wall vs. brain, extremity, or abdomen/pelvis (dALC -438, -384 or -470 vs. 252, 204, or -7, p=0.002, dNTL 11.6, 15.8 or 10.8 vs. 0.2, 1.2, or 3.4, p=0.05) or RT courses >5 fractions (dALC -328 vs. -11 p=0.003, dNTL 1.6 vs. 0.05, p=0.02). The association of dALC with >5 fractions RT remained significant after excluding brain-directed RT (dALC -443 vs. -26, p=0.01, dNTL 2.7 vs. 0.03, p=0.09), but not in brain-directed RT patients (dALC -128 vs 11, p=0.5, dNTL 0.5 vs 0.1, p=0.97). There was no association between timing of RT in relation to ICI on dALC and dNTL. Median survival (MS) was 319 days from PD-1 therapy onset. ALC<500 and NTL>4 at PD-1 therapy onset was associated with decreased MS (359 vs. 100 days, p<.0001, and 472 vs 250 days, p=0.01, respectively). In a MVA correcting for performance status and serum albumin, this association of ALC with survival persisted (HR 2.3, p=0.01). RT before PD-1 therapy onset was associated with ALC<500 or NTL>4 at onset when RT was extracranial (OR 3.9, p=0.0008 and 2.4, p=0.02) or >5 fractions (OR 2.9, p=0.01 and 2.3, p=0.03). There was no such association with RT performed after initiation of PD-1 therapy. Among RT patients treated <30d prior to PD-1 therapy, dALC after RT was associated with decreased MS (p=0.009).

Conclusion: In a contemporary cohort of patients treated with palliative RT and PD-1 inhibitors, we confirm that RT can decrease ALC and increase NTL, particularly extracranial RT and more protracted regimens. These parameters are associated with worse outcomes following treatment with ICI, suggesting the need for further optimization of combined RT/ICI regimens.

Author Disclosure: L.R. Pike: None. A. Bang: None. M.S. Krishnan: None. A. Spektor: Employee; Boston University. Honoraria; Bayer Pharmaceuticals, Astellas Pharma, Inc. D.N. Cagney: None. A.A. Aizer: Research Grant; Varian. B. Alexander: Consultant; Bristol Myers Squibb, Abbvie, Schlesinger Associates, Precision Health Economics. O. Rahma: None. T.A. Balboni: Employee; Dana-Farber Cancer Institute. Research Grant; Templeton Foundation. Steering Committee Member; ASCO Palliative Care Steering Committee Member. P. Ott: Research Grant; ARMO BioSciences, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celldex, Merck & Co. Honoraria; Celldex, CytomX Therapeutics. Consultant; Alexion Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genentech, Neon Therapeutics. F. Hodi: Research Grant; Bristol Myers Squibb. Consultant; Bristol Myers Squibb, Merck, Genentech, Amgen, Novartis, EMD Serono, Celldex. J.D. Schoenfeld: Research Grant; Merck, BMS. Consultant; Tilos. Advisory Board; AstraZeneca, Nanobiotix, Debiopharm, BMS. Travel Expenses; BMS. Translational PI; NCI Match Subprotocol Z1D.

Luke Pike, MD, DPhil

Luke R.G. Pike, MD DPhil (Harvard Radiation Oncology Program, Massachusetts General Hospital) completed a bachelor of science with joint honors in biochemistry and chemistry at Memorial University in Newfoundland, Canada. He went on to read for a Doctorate in Philosophy in Medical Oncology on the Rhodes Scholarship at St. John's College, Oxford University. He completed a Medical Doctorate at Yale University and an internship in internal medicine at Massachusetts General Hospital and is due to complete residency training in radiation oncology at the Harvard combined program (MGH/DFCI/BWH/Boston Children's/BIDMC) in 2020. His research focusses on cancer immunotherapy and innovation and entrepreneurship in health care.


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