TY - JOUR
T1 - Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma
AU - Campbell, Matthew T.
AU - Matin, Surena F.
AU - Tam, Alda L.
AU - Sheth, Rahul A.
AU - Ahrar, Kamran
AU - Tidwell, Rebecca S.
AU - Rao, Priya
AU - Karam, Jose A.
AU - Wood, Christopher G.
AU - Tannir, Nizar M.
AU - Jonasch, Eric
AU - Gao, Jianjun
AU - Zurita, Amado J.
AU - Shah, Amishi Y.
AU - Jindal, Sonali
AU - Duan, Fei
AU - Basu, Sreyashi
AU - Chen, Hong
AU - Espejo, Alexsandra B.
AU - Allison, James P.
AU - Yadav, Shalini S.
AU - Sharma, Padmanee
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology.
AB - Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology.
UR - http://www.scopus.com/inward/record.url?scp=85118611998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118611998&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26415-4
DO - 10.1038/s41467-021-26415-4
M3 - Article
C2 - 34737281
AN - SCOPUS:85118611998
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6375
ER -