TY - JOUR
T1 - Baseline tumor-infiltrating lymphocyte patterns and response to immune checkpoint inhibition in metastatic cutaneous melanoma
AU - van Duin, Isabella A.J.
AU - Schuiveling, Mark
AU - ter Maat, Laurens S.
AU - van Amsterdam, Wouter A.C.
AU - van den Berkmortel, Franchette
AU - Boers-Sonderen, Marye
AU - de Groot, Jan Willem B.
AU - Hospers, Geke A.P.
AU - Kapiteijn, Ellen
AU - Labots, Mariette
AU - Piersma, Djura
AU - Schrader, Anne M.R.
AU - Vreugdenhil, Gerard
AU - Westgeest, Hans
AU - Veta, Mitko
AU - Blokx, Willeke A.M.
AU - van Diest, Paul J.
AU - Suijkerbuijk, Karijn P.M.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/9
Y1 - 2024/9
N2 - Introduction: The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors. Methods: In this multicenter cohort study, patients who received first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were identified. TILs were scored on hematoxylin and eosin (H&E) slides of primary melanoma and pre-treatment metastases using the validated TILs-WG, Clark and MIA score. The primary outcome was objective response rate (ORR), with progression free survival and overall survival being secondary outcomes. Univariable and multivariable logistic regression and Cox proportional hazard were performed, adjusting for known clinical predictors. Results: Metastatic melanoma specimens were available for 650 patients and primary specimens for 565 patients. No association was found in primary melanoma specimens. In metastatic specimens, a 10-point increase in the TILs-WG score was associated with a higher probability of response (aOR 1.17, 95 % CI 1.07–1.28), increased PFS (HR 0.93, 95 % CI 0.87–0.996), and OS (HR 0.94, 95 % CI 0.89–0.99). When categorized, patients in the highest tertile TILs-WG score (15–100 %) compared to the lowest tertile (0 %) had a longer median PFS (13.1 vs. 7.3 months, p = 0.04) and OS (49.4 vs. 19.5 months, p = 0.003). Similar results were noted using the MIA and Clark scores. Conclusion: In advanced melanoma patients, TIL patterns on H&E slides of pre-treatment metastases, regardless of measurement method, are independently associated with ICI response. TILs are easily scored on readily available H&Es, facilitating the use of this biomarker in clinical practice.
AB - Introduction: The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors. Methods: In this multicenter cohort study, patients who received first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were identified. TILs were scored on hematoxylin and eosin (H&E) slides of primary melanoma and pre-treatment metastases using the validated TILs-WG, Clark and MIA score. The primary outcome was objective response rate (ORR), with progression free survival and overall survival being secondary outcomes. Univariable and multivariable logistic regression and Cox proportional hazard were performed, adjusting for known clinical predictors. Results: Metastatic melanoma specimens were available for 650 patients and primary specimens for 565 patients. No association was found in primary melanoma specimens. In metastatic specimens, a 10-point increase in the TILs-WG score was associated with a higher probability of response (aOR 1.17, 95 % CI 1.07–1.28), increased PFS (HR 0.93, 95 % CI 0.87–0.996), and OS (HR 0.94, 95 % CI 0.89–0.99). When categorized, patients in the highest tertile TILs-WG score (15–100 %) compared to the lowest tertile (0 %) had a longer median PFS (13.1 vs. 7.3 months, p = 0.04) and OS (49.4 vs. 19.5 months, p = 0.003). Similar results were noted using the MIA and Clark scores. Conclusion: In advanced melanoma patients, TIL patterns on H&E slides of pre-treatment metastases, regardless of measurement method, are independently associated with ICI response. TILs are easily scored on readily available H&Es, facilitating the use of this biomarker in clinical practice.
KW - Immune checkpoint inhibition
KW - Melanoma
KW - Response
KW - Tumor-infiltrating lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=85197751906&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2024.114190
DO - 10.1016/j.ejca.2024.114190
M3 - Article
C2 - 38991284
AN - SCOPUS:85197751906
SN - 0959-8049
VL - 208
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 114190
ER -