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Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Dung T Le1,2,3, Jennifer N Durham1,2,3, Kellie N Smith1,3

  • 1Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.

Science (New York, N.Y.)
|June 10, 2017
PubMed

Insights

Mismatch repair deficient cancers, with many mutations, show high response rates to programmed death receptor-1 (PD-1) blockade. This immunotherapy approach is effective across various cancer types, offering durable patient benefits.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Cancers with mismatch repair deficiency exhibit a high mutation burden.
  • Previous studies indicated sensitivity of mismatch repair deficient colorectal cancers to PD-1 blockade.

Purpose of the Study:

  • To evaluate the efficacy of programmed death receptor-1 (PD-1) blockade in patients with advanced mismatch repair-deficient cancers across diverse tumor types.

Main Methods:

  • Expanded a proof-of-concept study on PD-1 blockade efficacy.
  • Included patients with advanced mismatch repair-deficient cancers from 12 tumor types.
  • Assessed radiographic responses, progression-free survival, and overall survival.

Main Results:

  • Objective radiographic responses observed in 53% of patients.
  • Complete responses achieved in 21% of patients.
  • Responses were durable, with median progression-free and overall survival not reached.

Conclusions:

  • Mismatch repair-deficient cancers are sensitive to PD-1 blockade, irrespective of tumor origin.
  • High neoantigen load in these cancers likely drives sensitivity to immune checkpoint blockade.
  • PD-1 blockade represents a promising therapeutic strategy for mismatch repair-deficient cancers.

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