Abstract 213P
Background
Lymphocytes are responsible for adaptive immunity and therefore are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count in a contemporary cohort of patients with metastatic renal cell carcinoma (mRCC).
Methods
Using the IMDC, patients with mRCC who received first-line IO-based regimens (ie, IO/IO doublet or IO/tyrosine kinase inhibitor combination) were analyzed. Baseline patient characteristics, disease control rate (DCR; defined as the percentage of complete/partial response or stable disease as per RECIST 1.1), time to next treatment (TTNT), and overall survival (OS) were compared with the presence of baseline lymphopenia (defined as absolute lymphocyte count below lower limit of normal).
Results
A total of 966 patients were included, of whom 195 (20%) had lymphopenia at systemic therapy initiation. Lymphopenia was associated with higher proportions of brain metastases (11% vs. 6.6%; P = 0.041) and bone metastases (54% vs. 31%; P < 0.001) and with lower proportions of previous nephrectomy (51% vs. 65%; P < 0.001) and the IMDC favourable-risk category (11% vs. 20%; P = 0.012). Patients with lymphopenia had lower DCR (70% vs. 80%; P = 0.034), shorter TTNT (10 months vs. 24 months; P < 0.001), and shorter OS (30 months vs. 48 months; P < 0.001). On multivariable analysis for OS, lymphopenia remained an independent prognostic factor (HR 1.68 95% CI 1.27–2.23; P < 0.001) after adjustment for the IMDC risk factors. Incorporation of lymphopenia into the IMDC criteria (ie, 6 factors vs. 7 factors) increased the C-index for OS prediction from 0.688 to 0.707. Table: 213P
Multivariable analysis for OS
HR | (95% CI) | P | |
KPS < 80% | 2.35 | (1.75–3.16) | < 0.001 |
Time from diagnosis to treatment < 1 year | 1.57 | (1.17–2.09) | 0.003 |
Hemoglobin < LLN | 1.26 | (0.96–1.66) | 0.099 |
Neutrophils > ULN | 1.82 | (1.30–2.54) | < 0.001 |
Lymphocytes < LLN | 1.68 | (1.27–2.23) | < 0.001 |
Platelets > ULN | 1.01 | (0.72–1.41) | > 0.9 |
Corrected calcium > ULN | 1.13 | (0.79–1.60) | 0.5 |
KPS, Karnofsky performance status; LLN, lower limit of normal; ULN, upper limit of normal.
Conclusions
Baseline lymphopenia may serve as an indicator of lower DCR, shorter TTNT, and shorter OS in the IO era. Prospective validation is required as we develop new prognostic tools for IO therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
D.Y.C. Heng.
Funding
Has not received any funding.
Disclosure
K. Takemura: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ono Pharmaceutical. T. Yuasa: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Ono Pharmaceutical. N.S. Basappa: Financial Interests, Personal, Advisory Board: Ipsen, Eisai, Pfizer, AstraZeneca, Janssen Inc, EMD Serono, Astellas, Bayer, BMS, Seagen, Takeda; Financial Interests, Institutional, Research Grant, Research Grant: Ipsen; Other, Personal, Other, Travel grant/support: Ipsen; Other, Personal, Other, Travel Grant/support: Eisai. L.A. Wood: Financial Interests, Personal, Research Funding: AstraZeneca, Bristol Myers Squibb, Merck, Pfizer, Roche Canada. S.K. Pal: Financial Interests, Institutional, Local PI: Eisai, Genentech, Roche, Exelixis, Pfizer, CRISPR Therapeutics, Allogene Therapeutics; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Leadership Role: SWOG; Other, Personal, Other, Travel reimbursement: CRISPR, Roche. B. Beuselinck: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Ipsen, Merck KGaA, Pfizer; Financial Interests, Personal, Research Funding: Bristol Myers Squibb. B.E. Szabados: Financial Interests, Personal, Other, travel funding: Roche/Genentech; Financial Interests, Personal, Invited Speaker: MSD, Pfizer; Financial Interests, Personal, Advisory Board: Ellipses, Merck kga, Ipsen. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca, Roche, Pfizer, MSD, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Seattle Genetics, Ipsen, Merck, MSD, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai, Novartis. R.R. McKay: Financial Interests, Personal, Advisory Board: Aveo, AstraZeneca, Bayer, Calithera, Dendreon, Exelixis, JNJ, Merck, Pfizer, Sanofi, Tempus, BMS, Lilly, Sanofi, SeaGen, Telix, Sorrento Therapeutics, Eisai; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Financial Interests, Personal, Steering Committee Member: Aveo, Merck, Eli Lilly; Financial Interests, Personal, Local PI: JNJ, SeaGen, Calibr, Poseida, Oncternal, Scholar Rock, Merck, Xencor, Genentech, Eli Lilly, BMS; Financial Interests, Personal, Trial Chair: Bayer, AstraZeneca; Financial Interests, Institutional, Local PI: Exelixis. N. Agarwal: Financial Interests, Personal, Advisory Board, In the last two calendar years, I participated in the scientific advisory board of these pharma companies between February 2021 to April 2021. None after that.: Merck, Aveo, Gilead, Lilly, Exelixis, Foundation Medicine; Financial Interests, Personal, Trial Chair, I am involved in the following phase 3 trials as the trial co-chair: TALAPRO-2, TALAPRO-3 (both Pfizer), and CONTACT-2 (Exelxis).: Pfizer, Exelixis; Financial Interests, Institutional, Other, I serve in the leadership of my cancer center (Huntsman Cancer Institute, University of Utah. Salt Lake City, UT, USA). There are multiple research projects sponsored by these companies which pay money to my institution.: Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GSK, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon.; Financial Interests, Personal, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharmas with no personal honorarium.: AstraZeneca, Calithera, Clovis, Crispr, Eisai, Eli Lilly, Exelixis, Immunomedics, Janssen; Financial Interests, Personal, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharma companies with no personal honorarium.: Merck, Nektar, New Link Genetics, Oric, Pfizer, Prometheus, Rexahn, Takeda, and Tracon. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: Research To Practice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; Financial Interests, Personal, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Other, Study section reviewer. $200.00 per day for 1 day: National Cancer Institute; Financial Interests, Personal, Other, Cancer Center Grand Rounds: Cleveland Clinic; Financial Interests, Personal, Advisory Board, Advisory Board/month: CURESPONSE; Financial Interests, Personal, Advisory Board: Tempest, Precede Bio (not publicly traded)); Financial Interests, Personal, Member of Board of Directors, unpaidhttps://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Member of Board of Directors, Unpaidhttps://kidneycan.org: KidneyCan; Financial Interests, Personal, Other, External Advisory Board Member: Gustave Roussy; Financial Interests, Personal, Stocks/Shares, advisor: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Precede Bio (not publicly traded)), CURESPONSE (not publicly traded), Inndura; Financial Interests, Personal, Stocks/Shares: Primium; Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, AstraZeneca, Takeda, Tracon; Financial Interests, Institutional, Local PI, National Chair: Roche; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Local PI: Surface Oncology, GSK; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Local PI, leads trials as PI: Nikang; Non-Financial Interests, Personal, Leadership Role, Co-Chair of the meeting, 2019- current and BOD member (unpaid): Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Personal, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author.: Medical Communication; Non-Financial Interests, Personal, Member: ASCO, AACR; Non-Financial Interests, Personal, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter.: General US Politics; Other, Personal, Other, Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Personal, Other, the institution filed patents related to biomarkers of immune checkpoint blockers, and circulating tumor DNA. No money made and some patents were abandoned.: Filed patents; Other, Personal, Other, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS). D.Y.C. Heng: Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, Ipsen, Novartis, AstraZeneca, Roche; Financial Interests, Personal, Steering Committee Member: Exilexis; Financial Interests, Institutional, Local PI: BMS, Pfizer, Ipsen. All other authors have declared no conflicts of interest.
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