213P - Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma treated with first-line combination immunotherapies: Results from the International metastatic renal cell carcinoma database consortium (IMDC)

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

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. 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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.