Dostarlimab in dMMR Rectal Cancer: 100% Complete Response at Memorial Sloan Kettering
A neoadjuvant PD-1 inhibitor trial at Memorial Sloan Kettering produced complete responses in every mismatch-repair-deficient rectal cancer patient treated, sustained across five years — but the result applies only to the 5-10% of rectal cancers with this genetic subtype.
Dostarlimab (brand name Jemperli) is a PD-1 inhibitor that blocks the PD-1 checkpoint on T cells, releasing the brakes that tumors use to evade immune attack. At Memorial Sloan Kettering, oncologists Andrea Cercek and Luis Diaz Jr. administered the drug neoadjuvantly — before any surgery, radiation, or chemotherapy — to patients with mismatch repair deficient (dMMR) or microsatellite instability high (MSI-high) rectal cancer. The original 2022 NEJM report described 12 of 12 patients reaching clinical complete response. The 2025 AACR and NEJM updates expanded this to 49 rectal-cancer patients, all with 100% complete response at a median 30.2 months of follow-up. A broader cohort of 103 patients across multiple dMMR solid tumor types showed an 82% complete response rate, with 92% disease-free at two years. Four of the original twelve remain cancer-free at five years. The mechanism works because dMMR tumors accumulate enormous numbers of mutations, generating abundant neoantigens that an unleashed immune system can recognize and destroy. The clinical implication: patients diagnosed with colorectal cancer should request MMR or MSI status testing, because those who qualify can potentially skip surgery and its life-altering side effects (colostomy, incontinence, sexual dysfunction). The major caveat is scope. Fewer than 10% of rectal cancer cases are dMMR or MSI-high, and results from a single elite academic center do not yet guarantee identical outcomes in community practice. For the roughly 90% of colorectal cancers that are mismatch-repair proficient, no comparable immunotherapy result exists.