1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Real World Outcomes of Ipilimumab and Nivolumab in Patients with Metastatic Melanoma

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Immunotherapy has drastically changed the outlook for melanoma patients over the past decade. Specifically, the dual blockade of immune checkpoints using ipilimumab and nivolumab has shown unprecedented response rates and survival outcomes. This immense achievement, though, is at the cost of toxicity, with 60% of the patients experiencing high-grade adverse events (AEs). Our study aims to report the efficacy and toxicity outcomes of an out-of-trial, real-life population. Methods: Data on metastatic melanoma patients treated with ipilimumab and nivolumab were retrieved from our melanoma database—a single-center prospectively updated, medical-records based oncologic registry. Data included demographics, clinical and pathological information, as well as tumor responses and survival. Associations between patient or treatment characteristics and outcomes were also evaluated. Results: We identified 172 metastatic melanoma patients, of whom 64% were treatment-naïve. The median follow-up was 12 months. The response rates for treatment-naïve and previously-treated patients were 61% and 25%, respectively; median progression-free survival (PFS) were 12.2 and 2.6 months, and median overall survival (OS) were not-reached (NR) and 6.1 months, respectively. The estimated three-year OS for treatment-naïve patients was 58% (95% CI 42–65). At data cutoff, 22% were still on-treatment. Grade 3–4 adverse events (AEs) were reported in 60% of the patients, almost all of whom were exposed to steroid treatments (59%); AEs were fatal in 4 patients, and led to permanent treatment discontinuation in 31%. Factors significantly associated with outcome were cutaneous histology, low lactate dehydrogenase (LDH), low number of metastatic sites, performance status, first line of treatment and number of combinations administered during the induction phase. Conclusions: Despite the profoundly different baseline patient characteristics, the combination of ipilimumab and nivolumab is as effective in the real-world population as it was in clinical trials, including long-term outcomes. In addition to confirming the significance of baseline prognostic factors, our study reveals that the number of combinations effectively administered may also be correlated with good outcome.

          Related collections

          Most cited references 27

          • Record: found
          • Abstract: found
          • Article: not found

          PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors.

          Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. Adding alphaPD-L1 to this regimen results in rejection of 65% of preimplanted tumors vs. 10% with CTLA-4 blockade alone. Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. Combination blockade also synergistically increases Teff-to-myeloid-derived suppressor cell ratios within B16 melanomas. IFN-gamma production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-gamma/TNF-alpha double-producing CD8(+) T cells within the tumor. These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.

            Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study

              Nivolumab monotherapy and combination nivolumab plus ipilimumab increase proportions of patients achieving a response and survival versus ipilimumab in patients with metastatic melanoma; however, efficacy in active brain metastases is unknown. We aimed to establish the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with active melanoma brain metastases.
                Bookmark

                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                18 August 2020
                August 2020
                : 12
                : 8
                Affiliations
                [1 ]Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan 52621, Israel; Guy.Ben-Betzalel@ 123456sheba.health.gov.il (G.B.-B.); Shaked.LevAri@ 123456sheba.health.gov.il (S.L.-A.); Ronnie.Shapira@ 123456sheba.health.gov.il (R.S.-F.); Yael.Steinberg@ 123456sheba.health.gov.il (Y.S.-S.); netagochman@ 123456gmail.com (N.G.); jacob.schachter@ 123456sheba.health.gov.il (J.S.); tomermrsn@ 123456gmail.com (T.M.)
                [2 ]Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
                [3 ]Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1589, Israel
                [4 ]The Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
                Author notes
                [* ]Correspondence: Nethanel.asher@ 123456sheba.health.gov.il (N.A.); Gal.markel@ 123456sheba.health.gov.il (G.M.); Tel.: +972-526669283 (N.A.); Fax: +972-35304934 (N.A.)
                Article
                cancers-12-02329
                10.3390/cancers12082329
                7464656
                32824780
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Comments

                Comment on this article