Margherita Ambrosini: Rare and important subgroup of POLE/D1 proofreading deficient (pd) mCRC treated with ICIs across Europe, USA and Israel

Margherita Ambrosini, Medical Oncology resident at University of Milan, shared on X/Twitter:

“Excited and honored to can finally share our work about the rare and important subgroup of POLE/D1 proofreading deficient (pd) mCRC treated with ICIs across Europe, USA and Israel.

POLE/D1pd define a small (~1%) subgroup of ultramutated mCRC with excellent immune-sensitivity.

89% ORR
2y PFS 88% – 2y OS 86%.

Even higher than dMMR/MSI-H mCRC treated with ICIs – even after adjustment for baseline prognostic factors.

Who?
male sex
young age
POLD1 right sided, POLE right and left sided
atypical RAS mutations
exceptionally high TMB.

Possible cohexistence with dMMR/MSI-H status.

Source: Margherita Ambrosini/X