1838P - Prognostic value of neutrophil-to-lymphocyte ratio and lymphopenia in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-PSMA-617: VISION post hoc analysis

Background

The prognostic value of neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) in patients with mCRPC treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has not been studied. Here, we assessed the association of NLR and ALC with [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) treatment outcomes in patients from the VISION study.

Methods

Adults with PSMA-positive mCRPC received ¹⁷⁷Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤ 6 cycles) + standard of care (SoC), or SoC alone. In this post hoc analysis, patients were categorized by NLR < 3 vs ≥ 3 and ALC < 1.0 × 10³/μl vs ≥ 1.0 × 10³/μl at baseline. Associations with overall survival (OS) and radiographic progression-free survival (rPFS) were assessed using the Kaplan–Meier method. Hazard ratios (HR) were estimated using Cox proportional hazards models.

Results

NLR and ALC data were available for a subset of patients (Table). Baseline characteristics were well balanced across subgroups. At baseline, median NLR was 3.8 vs 4.0 and median ALC was 1.06 × 10³/μl and 1.0 × 10³/μl, for ¹⁷⁷Lu-PSMA-617 + SoC vs SoC alone, respectively. Shorter OS and rPFS were observed with higher NLR and lower ALC in each treatment arm (Table). ¹⁷⁷Lu-PSMA-617 + SoC prolonged OS and rPFS vs SoC alone in all subgroups (Table). More patients with baseline NLR ≥ 3 reported serious adverse events (¹⁷⁷Lu-PSMA-617 + SoC, 41.0%; SoC, 28.7%) than those with NLR < 3 (30.7%; 24.1%).

Table: 1838P

OS and rPFS by baseline NLR and ALC

CI, confidence interval

Conclusions

NLR ≥ 3 and ALC < 1.0 × 10³/μl at baseline are prognostic for poor efficacy outcomes in patients with mCRPC in VISION. Treatment with ¹⁷⁷Lu-PSMA-617 improved OS and rPFS vs SoC alone regardless of baseline NLR/ALC. Additional analyses including change in NLR and ALC during treatment, associations with prostate-specific antigen and biochemical and objective response rates will be presented.

Clinical trial identification

EudraCT 2018-000459-41.

Editorial acknowledgement

Under direction of the authors, Shufei Song, PhD, of Oxford PharmaGenesis, Oxford, UK provided medical writing support, which was funded by Novartis, in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

X.X. Wei: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Coordinating PI: BMS. K.N.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas. J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Menarini Silicon Biosystems, ImCheck Therapeutics, Crescendo; Financial Interests, Institutional, Advisory Board: Harpoon; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Cellcentric, Daiichi Sankyo, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals, Crescendo Biologics, Menarini Silicon Biosystems; Non-Financial Interests, Principal Investigator: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Crescendo, ImCheck Therapeutics; Non-Financial Interests, Institutional, Product Samples: Daiichi Sankyo, Bayer, Merck Serono, AstraZeneca, Harpoon, Pfizer, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GSK. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. B. Krause: Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: Terumo, Novartis, PSI CRO, ITM, Astellas, Janssen; Financial Interests, Personal, Advisory Board: ITM, Bayer Vital, Janssen, Novartis, Terumo. K. Herrmann: Financial Interests, Personal, Advisory Board: Bayer, Adacap/Novartis, Curium, Boston Scientific, GE Healthcare, AstraZeneca; Financial Interests, Personal, Invited Speaker: Sirtex, Siemens Healthineers, Monrol; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, DMSB: ymabs; Financial Interests, Personal, Advisory Board, Scientific Advisor: AdvanceCell; Financial Interests, Personal, Advisory Board, Advisor, Consultant: Janssen; Financial Interests, Personal, Advisory Board, Consultant: Eco1R; Financial Interests, Personal, Member of Board of Directors: Sofie Biosciences, Theragnostics, Pharma 15; Financial Interests, Personal, Ownership Interest: Sofie Biosciences; Financial Interests, Personal, Stocks/Shares: Aktis Oncology; Non-Financial Interests, Leadership Role, Chair Oncology&Theragnostics Committee: EANM. K. Rahbar: Financial Interests, Personal and Institutional, Advisory Role: ABX, Bayer; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: AAA; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Janseen Cilag, Amgen; Financial Interests, Personal, Advisory Role: ABX CRO, Pharmatrace. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: EMD Serono, Telix Pharma, Blue Earth Diagnostics, POINT Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity, Merck, Myovant, EMD Serono; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Local PI: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen; Financial Interests, Institutional, Steering Committee Member: Gilead, Novartis, POINT Biopharma, Clarity, Ambrx, Promontory. M.J. 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Meisel: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Amgen, Astellas, Boehringer Ingelheim, Celgene, Janssen, Gerresheimer, GSK, Merck, MSD, Novartis, Roche, Regeneron, Sanofi, Servier, Takeda, Vifor, Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Funding: Bayer, Merck & Cie; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Funding: Amgen, Astellas, Boehringer Ingelheim, Janssen, Merck, Roche, Sanofi, Servier, Takeda; Financial Interests, Personal, Licencing Fees or royalty for IP: Merck. G. Holder: Financial Interests, Personal, Stocks or ownership: Novartis, Aclon, Santhera; Financial Interests, Personal, Full or part-time Employment: Advanced Accelerator Applications, Novartis. J. Wu: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. O. Sartor: Financial Interests, Personal, Speaker, Consultant, Advisor: Advanced Accelerator Applications, Amgen, ArtBio, Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity, Clovis, Constellation, Convergent, Dendreon, EMD Serono, Foundation Medicine, Fusion, Hengrui, Isotopen Technologien Meunchen, Janssen, Merck, Morphimmune, Myovant, Myriad, NorthStar, Novartis, PointBiopharma, Pfizer, RATIO, Sanofi, TELIX, Theragnoscics; Financial Interests, Institutional, Research Grant: Advanced Accelerator Applications, Amgen, Bayer, Constellation, Janssen, Merck; Non-Financial Interests, Institutional, Research Grant: Endocyte, Invitae, Progenics, Tenebio; Non-Financial Interests, Personal, Speaker, Consultant, Advisor: Genzyme, Noria Therapeutics, Inc, Noxopharm, Progenics, Tenebio, Tessa, Z-alpha; Financial Interests, Personal, Stocks/Shares: RATIO; Financial Interests, Institutional, Stocks/Shares: TELIX. All other authors have declared no conflicts of interest.