Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases.

Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases.

Publication date: Jun 11, 2019

PD-1 inhibition (PD-1i) is the standard of care in melanoma and other malignancies. In patients with bone metastases of solid tumors, the monoclonal antibody denosumab directed against RANKL is approved for the prevention of skeletal-related events. However, RANKL is not only relevant in osteoclastogenesis, but also has immunological effects. Hence, we aimed at investigating, whether the combination of PD-1i and denosumab produces synergistic effects in metastatic melanoma treatment.

We retrospectively collected and analyzed clinical data of metastatic melanoma patients with bone metastases, who received PD-1i and denosumab therapy.

29 patients were identified with a median age of 60.7 years: 20 were male and 9 were female. 20 patients (69%) were in stage IV M1c and 9 (31%) in stage IV M1d; 52% had an increased serum LDH. 24 patients (83%) received PD-1i as first-line therapy and five patients (17%) as second- or third-line therapy. 13 patients received the triple combination nivolumab, ipilimumab and denosumab (N + I+D), 16 patients received PD-1i and denosumab (PD-1i + D). Within a median follow-up time of 19.8 months, 17 patients progressed with a median time to progression of 6 months. The objective response rate was 54% in the N + I + D group and 50% in the PD-1i + D group. Recalcification of bone metastases was radiologically observed in 18 (62%) patients. No unexpected treatment-related adverse events emerged.

The combination therapy of metastatic melanoma with PD-1i and denosumab was feasible without unexpected safety issues and showed a promising efficacy signal. Further investigation in prospective studies is needed.

Angela, Y., Haferkamp, S., Weishaupt, C., Ugurel, S., Becker, J.C., Obernd”orfer, F., , Alar, , Satzger, and Gutzmer, R. Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases. 22944. 2019 Cancer Immunol Immunother.

Concepts Keywords
Combination Therapy Melanoma treatment
Ipilimumab Synergistic metastatic melanoma
LDH Immunotherapy
Malignancies Organ systems
Melanoma Medicine
Monoclonal Antibody Clinical medicine
RANKL Monoclonal antibodies
Serum Bristol-Myers Squibb
Synergistic Immune system
Antineoplastic drugs
Breakthrough therapy
RANKL
Denosumab
Ipilimumab
Melanoma

Semantics

Type Source Name
gene UNIPROT TNFRSF11A
disease MESH N+I+D
drug DRUGBANK L-Aspartic Acid
drug DRUGBANK Ipilimumab
drug DRUGBANK Nivolumab
gene UNIPROT TNFSF11
disease MESH malignancies
gene UNIPROT PDCD1
gene UNIPROT RPL17
disease MESH metastases
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
drug DRUGBANK Denosumab

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