Journal Article

Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma

Sharma, Padmanee, Espejo, Alexsandra B., Matin, Surena F., Tannir, Nizar M., Jindal, Sonali, Zurita, Amado J., Chen, Hong, Allison, James P., Tam, Alda L., Jonasch, Eric, Yadav, Shalini S., Ahrar, Kamran, Tidwell, Rebecca S., Shah, Amishi Y., Sheth, Rahul A., Karam, Jose A., Wood, Christopher G., Basu, Sreyashi, Campbell, Matthew T., Rao, Priya, Duan, Fei, Gao, Jianjun

2021

Overview

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. Anti-CTLA4 therapy has not been comprehensively explored for the treatment of metastatic renal cell carcinoma (mRCC). Here, in a pilot study of anti-CTLA4 therapy with or without cryoablation in mRCC, the authors report that the combination is feasible and enhances immune infiltration in patients with metastatic clear cell histology.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/51 / 38/39 / 38/90 / 631/67/589/1588/1351 / 692/4028/67/580 / 692/4028/67/589/1588/1351 / Adult / Adverse events / Aged / Aged, 80 and over / Antibodies, Monoclonal, Humanized - administration & dosage / Antineoplastic Agents, Immunological - administration & dosage / Carcinoma, Renal Cell - drug therapy / Carcinoma, Renal Cell - metabolism / Carcinoma, Renal Cell - pathology / Carcinoma, Renal Cell - surgery / Colitis / Combined Modality Therapy / Cryosurgery - methods / Cryotherapy / CTLA-4 Antigen - antagonists & inhibitors / CTLA-4 protein / Diarrhea / Female / Glomerulonephritis / Hepatitis / Histology / Humanities and Social Sciences / Humans / Immune checkpoint / Immune response / Immune system / Immunotherapy / Infiltration / Kidney cancer / Kidney Neoplasms - drug therapy / Kidney Neoplasms - metabolism / Kidney Neoplasms - pathology / Kidney Neoplasms - surgery / Male / Metastases / Metastasis / Microenvironments / Middle Aged / Monitoring / Monoclonal antibodies / multidisciplinary / Neoplasm Metastasis / Patient Safety / Patients / Pilot Projects / Pneumonitis / Renal cell carcinoma / Safety / Science / Science (multidisciplinary) / Survival / Survival Rate / Targeted cancer therapy / Telemedicine / Therapy / Toxicity / Treatment Outcome / Tumors / Young Adult