Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination

Abstract

A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4.3) were compared between patients receiving concurrent RT (IR) or no irradiation (NIR). Fifty-nine patients received anti-PD-1 immunotherapy [pembrolizumab (n=28) or nivolumab (n=31)] between August 2014 and December 2015 at our institution. Among these, 29% (n=17) received palliative RT for a total of 21 sites, with a mean dose of 30 Gy delivered in 10 fractions. Acute and late toxicity profiles were similar in the two groups. After a 10-month median follow-up, the objective response rate (complete or partial response) was significantly higher in the IR group versus the NIR group (64.7 vs. 33.3%, P=0.02) and one complete responder after RT was compatible with an abscopal effect. The 6-month disease-free survival and overall survival rates for the NIR group versus the IR group were 49.7 versus 64.7% (P=0.32) and 58.8 versus 76.4% (P=0.42), respectively. We report here that the combination of RT and anti-PD-1 immunotherapy is well tolerated and leads to a significant higher tumor response rate within and outside the irradiated field, which is emphasized by the first reported case of an abscopal effect in solid tumors.

Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

“…Outcomes of some retrospective studies using that combination with intra-or extracranial palliative irradiation, mostly to treat melanomas, indicated no excessive anti-PD-1 or radiotherapy toxicity. 13,15,16 Clinical trials testing the combination of irradiation and PD-1/PD-L1 inhibition have been initiated, but the results are not yet available.…”

Local and disease control for nasal melanoma treated with radiation and concomitant anti‐programmed death 1 antibody

“…The efficacy of immunotherapy (anti‐programmed death 1 [PD‐1] monoclonal antibody and/or anti‐cytotoxic T‐lymphocyte‐associated antigen 4 [CTLA‐4] monoclonal antibody) on mucosal melanoma is lower in comparison with cutaneous melanoma, as there are critical genetic differences that have not yet been fully explored, and mucosal melanoma rarely has BRAF mutations . Thus, the combination of radiotherapy (RT) and concomitant anti‐PD‐1 antibody therapy is often applied as the first‐line treatment for mucosal melanoma of the nasal cavity in our institute because preclinical data have shown that combinations of immune checkpoint inhibitors (ICI) and RT improved the response of these patients …”

Extracranial abscopal effect induced by combining immunotherapy with brain radiotherapy in a patient with lung adenocarcinoma: A case report and literature review

“…Immunotherapy can liberate and activate CD8+ T cells from an immunosuppressed state, thereby increasing the probability of abscopal effects . Reports of abscopal effects have increased along with the development of combined radiotherapy and immunotherapy, but these have mainly occurred in patients with highly immunogenic melanomas …”