4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Pixantrone demonstrates significant in vitro activity against multiple myeloma and plasma cell leukemia

      research-article

      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

          Treatment results for multiple myeloma and plasma cell leukemia have considerably improved, but cure remains elusive and establishing new therapeutic approaches constitutes a major unmet clinical need. We analyzed the anti-myeloma properties of the aza-anthracenedione pixantrone which has been successfully used in a phase III study for the treatment of patients with aggressive non-Hodgkin’s lymphoma as monotherapy as well as in combination regimes in vitro and in an adapted in vivo model (ex ovo chicken chorioallantoic membrane (CAM) assay). Pixantrone significantly inhibited proliferation and metabolic activity of all investigated myeloma cell lines. Importantly, anti-myeloma effects were more pronounced in tumor cell lines than in stromal cells, mesenchymal stem cells, and peripheral blood mononuclear cells of healthy controls. Apoptosis of myeloma cell lines was observed only after a 7-day incubation period, indicating a fast cytostatic and a slower cytotoxic effect of this drug. Pixantrone reduced the viability of primary plasma cells of patients and induced downregulation of myeloma-cell growth in the CAM assay. Additionally, we demonstrate in vitro synergism between pixantrone and the histone deacetylase inhibitor panobinostat with respect to its anti-proliferative features. From these data, we conclude that systematic investigations of the clinical usefulness of pixantrone in the framework of controlled clinical trials are clearly indicated (e.g., in penta-refractory patients).

          Electronic supplementary material

          The online version of this article (10.1007/s00277-019-03797-6) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references21

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

          Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death.

          To construct and validate among patients with multiple myeloma (MM) who were treated with intensive therapy a prognostic index of early MM progression-related death.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial.

            Pixantrone dimaleate (pixantrone)--a novel aza-anthracenedione--was synthesised to reduce anthracycline-related cardiotoxicity without compromising antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone versus an investigator's choice of a single-agent therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma.

              Bendamustine with bortezomib and dexamethasone was evaluated in 79 patients with relapsed/refractory multiple myeloma. Median age was 64 years, and patients had a median of 2 prior treatment lines (range, 1 to 6 lines). Bendamustine 70 mg/m(2) days 1 and 4; bortezomib 1.3 mg/m(2) intravenously days 1, 4, 8, and 11; and dexamethasone 20 mg days 1, 4, 8, and 11 once every 28 days was given for up to 8 cycles. Primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival, time to response, and toxicity. ORR was 60.8%, and when minor responses were included, 75.9%. Median time to response was 31 days. ORR rate was similar in patients previously exposed to bortezomib, lenalidomide, and bortezomib plus lenalidomide. PFS was 9.7 and OS was 25.6 months. Multivariate analysis showed high lactate dehydrogenase, ≥3 prior treatment lines, and low platelet counts correlating with short survival. Grade 3/4 thrombocytopenia was noted in 38%, and grade 3/4/5 infections were noted in 23%. Grade ≤2 polyneuropathy increased from 19% at baseline to 52% at cycle 8 and grade 4, from 0% to 7%. Bendamustine-bortezomib-dexamethasone is active and well tolerated in patients with relapsed/refractory myeloma. This trial was registered in the EudraCT database as No. 2008-006421-13.
                Bookmark

                Author and article information

                Contributors
                0043 50 504 82142 , Brigitte.Kircher@i-med.ac.at
                Journal
                Ann Hematol
                Ann. Hematol
                Annals of Hematology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0939-5555
                1432-0584
                18 October 2019
                18 October 2019
                2019
                : 98
                : 11
                : 2569-2578
                Affiliations
                [1 ]GRID grid.5361.1, ISNI 0000 0000 8853 2677, Internal Medicine V (Hematology & Oncology), , Medical University of Innsbruck, ; Anichstr. 35, 6020 Innsbruck, Austria
                [2 ]GRID grid.420164.5, Tyrolean Cancer Research Institute, ; Innsbruck, Austria
                [3 ]Oncotyrol, Center for Personalized Cancer Medicine, Innsbruck, Austria
                [4 ]GRID grid.21604.31, ISNI 0000 0004 0523 5263, Department of Internal Medicine III, Laboratory for Immunological and Molecular Cancer Research, , Paracelsus Medical University Salzburg, ; Salzburg, Austria
                Author information
                http://orcid.org/0000-0003-1624-2664
                Article
                3797
                10.1007/s00277-019-03797-6
                6848044
                31628518
                33276ba4-41a4-44cb-b130-712e4884b070
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 8 February 2019
                : 8 September 2019
                Funding
                Funded by: FPT7/2007-2013
                Award ID: 278570
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Hematology
                multiple myeloma,plasma cell leukemia,pixantrone,anti-myeloma activity,drug screening
                Hematology
                multiple myeloma, plasma cell leukemia, pixantrone, anti-myeloma activity, drug screening

                Comments

                Comment on this article