Cryoablation combined with transarterial infusion of pembrolizumab (CATAP) for liver metastases of melanoma: an ambispective, proof-of-concept cohort study

Abstract

Background The presence of liver metastasis correlates with poor therapeutic response of PD-1 blockade therapy in melanoma. A novel treatment protocol by combining cryoablation with transarterial infusion of pembrolizumab (CATAP) was proposed, and its feasibility and safety was assessed among this group of patients. Methods This registered ambispective cohort study enrolled fifteen melanoma patients with multiple hepatic metastases who received planned two-stage CATAP therapy: in the combined stage, subtotal cryoablation on day 1, in which one to two intrahepatic lesions were ablated completely with other lesions left untreated, sequentially combined transarterial infusion of pembrolizumab on day 3, every three weeks, for at least one cycle; in the infusion stage, arterial infusion of pembrolizumab was recommended at three-week interval until disease progression. The primary endpoint was objective response rate by RECIST (version 1.1); secondary end points included progression-free survival (PFS) and safety; exploratory endpoints were changes of cytokines and immune cell compositions in peripheral blood samples. Results Of the 15 patients enrolled, no grade 3-4 adverse events or major complications were observed. One patient (6.7%) achieved complete response, and 3 (20.0%) achieved partial response. The overall response rates of CATAP for the entire cohort and patients with cutaneous melanoma were 26.7% (95% confidence interval (CI) 4.3-49.0%) and 33.3% (95% CI 2.5-64.1%), respectively. Clinical response was observed in a proportion of patients (2/6; 33.3%) who failed first-line intravenous pembrolizumab treatment. The median overall PFS time and hepatic PFS time were 4.0 (95% CI 2.5-5.5) and 5.73 (95% CI 1.1-10.4) months, respectively. A significant increase in CD3-CD16 + CD56 + cells (natural killer cells; P = 0.0124) and a marginally significant decrease in CD4 + CD25 + cells (regulatory T cells; P = 0.0546) were observed three weeks after the first cycle of treatment in the combined stage. Conclusions The CATAP therapy demonstrated positive clinical activity and a favorable safety profile for melanoma patients with liver metastasis.

Successful secondary radical operation on unretractable metastatic platinum-sensitive recurrent ovarian cancer by immunotherapy: a case report

“…Notably, the transarterial infusion of a pembrolizumab interval combined with the intravenous use of doxorubicin and carboplatin was effective in addressing immune resistance when disease progression occurred again after nearly 9 months of pembrolizumab monotherapy. According to previous studies of arterial infusion chemotherapy for ovarian cancer (29) and transarterial infusion of pembrolizumab for liver metastases of melanoma (30), the intra-arterial administration of pembrolizumab offers a much higher local drug concentration than the intravenous administration. Additionally, the immunostimulatory effects of chemotherapeutic drugs have already been proven to activate effector cells and/or inhibit immunosuppressive cells or enhance immunogenicity and improve the infiltration of lymphocytes (31).…”

Survival in Metastatic Renal Cell Carcinoma Patients Treated With Sunitinib With or Without Cryoablation

“…In a number of malignancies, decreasing tumor burden through cytoreductive cryoablation can have positive effect on survival. In particular, studies have demonstrated that cryoablation leads to better survival in patients with metastatic hepatocellular carcinoma ( 22 ), lung cancer ( 23 ), and melanoma ( 24 ), on top of strengthening tumor response to systemic therapy. Several studies have reported synergies between cryoablation and immune response.…”

ROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities

“…In a recent study, cryoablation combined with a transarterial infusion of pembrolizumab has shown promising clinical activity in managing melanoma liver metastasis. However, the efficacy of the therapy needs to be confirmed with a controlled trial in the future [ 186 ]. ROS production can be anticipated with this destructive modality, but the therapeutic relevance for cryoablation-related ROS in melanoma remains limited as of now.…”