Angela, Yenny and Haferkamp, Sebastian and Weishaupt, Carsten and Ugurel, Selma and Becker, Juergen C. and Oberndoerfer, Florian and Alar, Vesna and Satzger, Imke and Gutzmer, Ralf (2019) Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases. CANCER IMMUNOLOGY IMMUNOTHERAPY, 68 (7). pp. 1187-1194. ISSN 0340-7004, 1432-0851
Full text not available from this repository. (Request a copy)Abstract
BackgroundPD-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.MethodsWe retrospectively collected and analyzed clinical data of metastatic melanoma patients with bone metastases, who received PD-1i and denosumab therapy.Results29 patients were identified with a median age of 60.7years: 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 19.8months, 17 patients progressed with a median time to progression of 6months. 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.ConclusionsThe 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; SOLID TUMORS; RANKL; IPILIMUMAB; NIVOLUMAB; DIAGNOSIS; SURVIVAL; RECEPTOR; Melanoma; Immunotherapy; RANK; RANKL; Bone metastasis; Adverse events |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 06:49 |
| Last Modified: | 06 Apr 2020 06:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26778 |
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