I-O Connect
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Yesterday
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A 2026 review found PD-L1 and TMB have limited predictive utility in NSCLC. Multi-omic signatures with ctDNA and immune profiling improve ICI selection; AI-based digital immune twin frameworks guide personalized immunotherapy in advanced NSCLC.

Discover multi-omic ICI biomarker data 

  • Yesterday
    Of note, AI is great but that and radiomics are very hard to standardize so as to be able to apply to diverse populations across the world.
  • 6d
    This review highlights the limitations of relying on PD-L1 and TMB alone to predict response to immunotherapy in NSCLC. Combining ctDNA, immune profiling, and other multi-omic data may provide a Show More

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1w

Did you know? Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have produced durable, long-term survival in a subset of patients across multiple solid tumor types. A pooled analysis of 5-year overall survival data from landmark trials in melanoma, NSCLC, and renal cell carcinoma found that patients achieving a response to checkpoint inhibition had estimated 5-year survival rates of 34–48% — compared to under 5% historically in these metastatic settings. Predictive biomarkers including PD-L1 expression, tumor mutational burden, and microsatellite instability status continue to refine patient selection.

In your practice, how are you integrating multiple predictive biomarkers — PD-L1 CPS, TMB, and MSI status — to guide immunotherapy selection and sequencing, particularly in tumor types with overlapping biomarker indications?

NCCN Guidelines

In your practice, how are you integrating multiple predictive biomarkers — PD-L1 CPS, TMB, and MSI status — to guide immunotherapy selection and sequencing, particularly in tumor types with overlapping biomarker indications?

  • 1w
    Usually depends on the given indication, for instance PDL1 is important in mTNBC but then for CRC we really more on MSI. I hardly consider TMB aside from trying Show More
  • 2w
    I use these biomarkers complementarily rather than hierarchically. PD-L1 CPS remains the most tumor-specific guide when the indication is CPS-driven, while MSI-H/dMMR is a strong tumor-agnostic marker that can support Show More

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2w
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?

  • 2w
    Reviewing the NGS results for other alterations eg presence of KEAP1 and STK11 in NSCLC would push me towards dual IO rather than mono IO. An EGFR mutation would Show More
  • 1mo
    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

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3mo

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

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8mo
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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