26 maart 2021: Bron: Annals of oncology

Uit ervaringen en eerder onderzoek bij longkanker, melanomen en blaaskanker - urineleiderkanker wordt ervan uitgegaan dat als een kankerpatiënt een zogeheten hoge tumormutatiebelasting (TMB-H) heeft dat immuuntherapie met een anti-PD medicijn - checkpointremmer dan de meeste kans geeft op goede resultaten. 

Uit een groot onderzoek bij meer dan 10.000 kankerpatiënten met ook andere vormen van kanker waaronder borstkanker, prostaatkanker en hersentumoren van het type glioblastoma blijkt dat een hoge tumormutatiebelasting nauwelijks betere resultaten geeft in de praktijk voor aanslaan van immuuntherapie met anti-PD medicijnen dan bij patiënten met een lage tumormutatiebelasting. 

Ook de overall overleving (OS) gaf weinig verschil verschil te zien tussen hoge en lage tumormutatiebelasting. 

Belangrijkste punt uit deze studie:

Hoge tumormutatiebelasting (TMB-H) kon geen verbeterde of klinisch relevante respons op immuuntherapie met checkpointremmers - anti-PD medicijnen voorspellen bij alle vormen van kanker.​
Vormen van kanker waarbij TMB-H geen respons voorspelt, vertonen over het algemeen geen verband tussen tumor neoantigen belasting en CD8 T-celinfiltratie.​
Verdere studies moeten worden uitgevoerd voordat TMB-H wordt toegepast als biomarker voor ICB bij alle kankertypes.

Het studieverslag van deze studie is in PDF vorm te downloaden
Hier het abstract van de studie:

High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types


  • TMB-H failed to predict improved or clinically relevant response to ICB in all cancer types.
  • Cancer types where TMB-H does not predict response generally show no relationship between tumor neoantigen load and CD8 T-cell infiltration.
  • Further studies should be carried out before application of TMB-H as a biomarker for ICB in all cancer types.


High tumor mutation burden (TMB-H) has been proposed as a predictive biomarker for response to immune checkpoint blockade (ICB), largely due to the potential for tumor mutations to generate immunogenic neoantigens. Despite recent pan-cancer approval of ICB treatment for any TMB-H tumor, as assessed by the targeted FoundationOne CDx assay in nine tumor types, the utility of this biomarker has not been fully demonstrated across all cancers.

Patients and methods

Data from over 10 000 patient tumors included in The Cancer Genome Atlas were used to compare approaches to determine TMB and identify the correlation between predicted neoantigen load and CD8 T cells. Association of TMB with ICB treatment outcomes was analyzed by both objective response rates (ORRs, N = 1551) and overall survival (OS, N = 1936).


In cancer types where CD8 T-cell levels positively correlated with neoantigen load, such as melanoma, lung, and bladder cancers, TMB-H tumors exhibited a 39.8% ORR to ICB [95% confidence interval (CI) 34.9-44.8], which was significantly higher than that observed in low TMB (TMB-L) tumors [odds ratio (OR) = 4.1, 95% CI 2.9-5.8, P < 2 × 10−16]. In cancer types that showed no relationship between CD8 T-cell levels and neoantigen load, such as breast cancer, prostate cancer, and glioma, TMB-H tumors failed to achieve a 20% ORR (ORR = 15.3%, 95% CI 9.2-23.4, P = 0.95), and exhibited a significantly lower ORR relative to TMB-L tumors (OR = 0.46, 95% CI 0.24-0.88, P = 0.02). Bulk ORRs were not significantly different between the two categories of tumors (P = 0.10) for patient cohorts assessed. Equivalent results were obtained by analyzing OS and by treating TMB as a continuous variable.


Our analysis failed to support application of TMB-H as a biomarker for treatment with ICB in all solid cancer types. Further tumor type-specific studies are warranted.


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