Immune checkpoint inhibitor (anti-CTLA-4, anti-PD-1) therapy alone versus immune checkpoint inhibitor (anti-CTLA-4, anti-PD-1) therapy in combination with anti-RANKL denosumuab in malignant melanoma: a retrospective analysis at a tertiary care center. Issue 4 (August 2018)

• Record Type: Journal Article
• Authors: Afzal, Muhammad Z.; Shirai, Keisuke
• Is Part Of: Melanoma research. Volume 28:Issue 4(2018)
• Publication Date: 2018-08
• Subjects: anti-RANKL -- denosumab -- immune checkpoint inhibitors -- ipilimumab -- malignant melanoma -- nivolumab -- pembrolizumab; Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000459
• Languages: English
• ISSNs: 0960-8931

Abstract

Abstract : Denosumab is a monoclonal antibody against RANK ligand with a role in the prevention of skeletal-related events and is also known to possess antitumor properties. In this retrospective review, we aim to evaluate the synergist effect of a combination therapy with immune checkpoint inhibitors and denosumab in malignant melanoma patients. Patients of 18 years of age or older with a diagnosis of malignant melanoma who have received immune checkpoint inhibitors and denosumab between June 2015 and May 2017 were divided into two cohorts: cohort A (immune checkpoint inhibitors only) and cohort B (immune checkpoint inhibitors and denosumab). Overall survival, progression-free survival, objective response rate, and safety analysis were performed. Stratified analysis based on metastatic (M) status was performed as well. Eleven (29.72%) out of 37 patients received immune checkpoint inhibitors and denosumab combination. Median overall survival in cohort B was 57 months compared with 22.8 months in cohort A and 22 months in M1c patients from cohort A. Median progression-free survival was 4.15 months in cohort B compared with 11.6 months in cohort A and 5.12 months in M1c patients from cohort A. The mean number of distant sites involved in metastasis were significantly higher in cohort B (3.54 vs. 2.23, P =0.0015). Cohort B also had more patients with more than two distant metastatic sites (90.9 vs. 30.8%, P =0.001). A combination therapy with denosumab and immune checkpoint inhibitors may have a beneficial effect on survival and progression as in our study; the patients receiving combination therapy did not behave poorly despite having poor prognostic features.