Summary of immunotherapy efficacy ordered in accordance with drug reimbursement program in melanoma patients

Abstract

Nivolumab and pembrolizumab are monoclonal antibodies of the IgG4 class, which target the cell death receptor (PD-1) found on T cells. The binding of the anti-PD-1 drug to the receptor therefore prevents the inhibition of these T cells and increases the immune response against melanoma cells. Pembrolizumab and nivolumab monotherapy has similar efficacy, including PFS and OS. Nivolumab and pembrolizumab immunotherapy are effective regardless of the BRAF mutation status. Currently, the choice between nivolumab and pembrolizumab is primarily dependent on to the frequency of infusions (every 3 weeks for pembrolizumab vs. every 2 weeks for nivolumab or every 6 weeks vs. every 4 weeks). Based on the available data, it can be concluded that autoimmune disease is not an absolute contraindication to the use of immunotherapy, but close clinical monitoring of these patients and specialist consultations (e.g. rheumatologist, dermatologist) must be provided. Patients with severe autoimmune disease who are treated with biologicals or have a history of life-threatening autoimmune disease complications (e.g. severe Crohn's disease) should not be qualified for immunotherapy, as opposed to patients with minimally symptomatic autoimmune disease (e.g., mild dermal psoriasis).

An update on the safety of nivolumab for the treatment of advanced melanoma

“…Safety of nivolumab in patients with advanced melanoma routinely treated was shown to be consistent with previously published data from clinical trials [21,22], but in every day practice higher number of rheumatoid irAEs is reported than in the trials. This may be due to preexisting conditions and higher age of patients treated outside randomized clinical trials [22,23]. As expected the toxicity of nivolumab-ipilimumab combination, also in real-world data, is higher and any grade irAEs are experienced by 88% of patients, while grade 3 or 4 by more than 50% [24].…”

“…At the same time hydroxychloroquine activity block the late stages of autophagic proteolysis and does not alter the antitumor T cell response [81]. Multidisciplinary (MDT), treatment with close monitoring is absolutely required in these cases and rheumatologist or dermatologist should be enrolled into such MDT [23]. It should be remembered that autoimmune disease also differ by background that is GBS is classically B cell-mediated disease, while rheumatoid arthritis or Sjogren's syndrome result from chronic inflammation with PD-1 positive T cell infiltrates in the tissues [82].…”