Mayo Clinic, Rochester, MN
Sakti Chakrabarti , Lucas J. Huebner , Heidi Diann Finnes , Andrea Muranyi , Shalini Singh , June Clements , Robert R. McWilliams , Joleen Marie Hubbard , Kandavel Shanmugam , Frank A. Sinicrope
Background: Colorectal cancer with dMMR display heterogeneity in the extent of intratumoral T-cell infiltration which may explain their variable responsiveness to PD-1 blockade. We examined the association of intratumoral CD3+ and CD8+ T-cell densities (TCD) with objective response rate (ORR) and response duration in patients with dMMR mCRCs receiving pembrolizumab (PEM). Methods: Record review was performed on 12 patients with dMMR mCRC treated with PEM (200 mg intravenously every 3 weeks) after failure of prior chemotherapy [median no. of regimens was 1 (range 1-4)] between 01/2015 and 12/2017. CD3+ and CD8+ TCDs were analyzed in the primary tumor core (CT) and at the invasive margin (IM) by immunohistochemistry and automated image analysis to determine density score (0 to 100) for each T-cell subtype and compartment (Ventana Medical Systems, Inc.). Patients were categorized as 1) responders [CR (complete response) + PR (partial response)] vs. non responders [SD (stable disease) + PD (progressive disease)] per RECIST version 1.1, and 2) by duration of response (< or > 12 months). Results: Median follow-up post PEM was 19.5 (9-41) months. Responders included 2 CR and 5 PR; non-responders included 4 SD and 1 PD. The ORR and median time to response were 58.3% (7/12) and 12 weeks (range 9-40), respectively. CD3+ and CD8+ TCD scores were higher in responders vs. in non-responders as well as in patients who had disease control for > 12 months; differences were greatest for CD8+ CT (Table). Conclusions: Among patients treated with PEM, data suggest higher intratumoral CD3+ and CD8+ TCDs in responders versus non-responders and in those with a longer duration of disease control. If confirmed, TCDs may potentially predict responsiveness to PD-1 blockade in dMMR mCRCs.
TCD | Responders (n= 7) | Non-responders (n= 5) | Disease control >12 mo., n= 8 | Disease control <12 mo., n= 4 |
---|---|---|---|---|
CD3+ IM, median(range) | 54 (15-100) | 46 (9-96) | 59(9-96) | 39 (18-51) |
CD3+ CT, median(range) | 74 (34-98) | 52 (7-100) | 79 (8-98) | 54 (34-83) |
CD8+ IM, median(range) | 47 (13-89) | 37 (11-83) | 60 (11-89) | 29 (15-54) |
CD8+ CT, median(range) | 88 (31-100) | 37 (10-94) | 88 (10-100) | 36 (31-66) |
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