I-O Connect
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1w
PD-1/PD-L1 checkpoint inhibition: predictive biomarkers, combination strategies, and overcoming resistance across tumor types

PD-1/PD-L1 checkpoint inhibitors have produced durable responses across multiple solid tumor types, yet primary and acquired resistance remains a substantial challenge. Predictive biomarker identification beyond PD-L1 tumor proportion score (TPS) and tumor mutational burden (TMB) continues to evolve.

PD-L1 TPS shows variable predictive utility across histologies, and TMB-high status does not uniformly confer benefit across tumor types. Emerging multiparameter approaches, incorporating tumor microenvironment profiling, T-cell inflamed gene expression, and circulating tumor DNA dynamics, are under prospective evaluation. Combination strategies with anti-CTLA-4, anti-LAG-3, anti-TIGIT, and VEGF/VEGFR inhibitors have expanded across indications; LAG-3 co-inhibition demonstrated improved progression-free survival in advanced melanoma versus PD-1 blockade alone. Immune-related adverse events, including colitis, pneumonitis, and endocrinopathies, require multidisciplinary management and careful rechallenge decision-making.

Medical oncologists, tumor immunologists, and immuno-oncology specialists managing diverse solid tumors will benefit from discussion on biomarker-driven patient selection, rational combination design, irAE management, and resistance strategies.

How do you incorporate multiparameter biomarker data, beyond PD-L1 TPS, into your checkpoint inhibitor selection and combination strategy decisions across tumor types? What is your approach to checkpoint inhibitor rechallenge following a significant immune-related adverse event, and what factors most influence this decision?

  • 1w
    Beyond PD-L1 TPS, the two other FDA-validated, clinically actionable biomarkers are MSI-H/dMMR and TMB-high (≥10 mut/Mb), both of which support tumor-agnostic pembrolizumab and dostarlimab (dMMR only) use, but all three Show More
  • 2w
    I use PD-L1, TMB, tumor type, molecular profile, and clinical factors together rather than relying on a single biomarker, with combination strategies such as CTLA-4 or VEGF/VEGFR inhibition considered when Show More

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1mo

When key predictive biomarkers are low or absent, what most influences your decision to still use immunotherapy?

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7mo
Updates from ASH 2025: Treating Older Adults with AML and Managing CAR T–Related Neurotoxicity

This ASH 2025 conference video features expert perspectives on newly published ASH guidelines for the treatment of newly diagnosed older adults with acute myeloid leukemia (AML). Discussion focuses on individualized treatment selection, molecular risk–informed decision-making, assessment of transplant eligibility, and the role of supportive and end-of-life care.

The video also reviews real-world evidence evaluating anti-inflammatory approaches for the management of immune effector cell–associated neurotoxicity syndrome (ICANS) following CAR T-cell therapy, highlighting evolving strategies to address this challenging toxicity in clinical practice.

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