RT Journal Article
SR Electronic
T1 Circulating tumor DNA (ctDNA) serial analysis during progression on PD-1 blockade and later CTLA-4 rescue in patients with mismatch repair deficient metastatic colorectal cancer
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e003312
DO 10.1136/jitc-2021-003312
VO 10
IS 1
A1 Pashtoon Murtaza Kasi
A1 Griffin Budde
A1 Michael Krainock
A1 Vasily N Aushev
A1 Allyson Koyen Malashevich
A1 Meenakshi Malhotra
A1 Perry Olshan
A1 Paul R Billings
A1 Alexey Aleshin
YR 2022
UL http://jitc.bmj.com/content/10/1/e003312.abstract
AB Immune checkpoint inhibitors have shown great promise in treating patients with mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). Although single-agent pembrolizumab has been approved for first-line treatment of dMMR/MSI-H metastatic CRC, combination therapy with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibition (ipilimumab/nivolumab) has reported higher response rates. It is unclear whether patients who progress on PD-1 inhibition will respond to CTLA-4 blockade. Here, we report a case series of three patients with dMMR/MSI-H mCRC, where a durable and ongoing response to nivolumab with ipilimumab was achieved after initial progression with pembrolizumab monotherapy. Blood-based biomarkers such as carcinoembryonic antigen and CA 19-9 were employed to assess treatment response and monitor disease progression along with circulating tumor DNA (ctDNA). Our findings indicate ctDNA’s potential to accurately monitor response to therapy and detect disease progression, as validated by standard imaging. This case series demonstrates that CTLA-4 rescue is worthy of additional investigation as a treatment strategy after progression on PD-1 blockade in patients with dMMR/MSI-high mCRC. Our data support the utilization and expansion of clinical studies with combination therapies and using ctDNA kinetics as early dynamic marker for therapy response assessment.