Skip to main content
Home
Zeitschriften
Zeitungen
Podcast
Gesundheitspolitik
Praxis
Allerlei
Jobs
Fachgebiete
Allgemeinmedizin Anästhesiologie & Intensivmedizin Apotheke Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kinder & Jugendheilkunde Neurologie & Psychiatrie Orthopädie & Unfallchirurgie Pflege Urologie Zahnmedizin
Subfächer Innere Medizin
Diabetologie Gastroenterologie Infektiologie Kardiologie Onkologie und Hämatologie Pneumologie Rheumatologie
Fortbildungen
Überblick Fortbildungen DFP-Literaturstudium-Artikel DFP-Webcast Fortbildungen DFP-Podcasts
Erweiterte Suche
Anmelden
nach oben
memo - Magazine of European Medical Oncology
Erschienen in:

18.07.2017 | case report

Activity of panobinostat in combination with bortezomib and dexamethasone in advanced, proteasome inhibitor refractory multiple myeloma

verfasst von: Branka Petricevic, Wolfgang Hilbe, Niklas Zojer

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Summary

The patient described here presented with relapsed multiple myeloma progressing after therapy with immunomodulatory agents (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib and carfilzomib). Eventually, the patient achieved an excellent response to the combination of panobinostat, bortezomib and dexamethasone, overcoming resistance to proteasome inhibitors and achieving a sustained VGPR (very good partial remission), which was consolidated with high-dose melphalan and autologous stem-cell transplantation.
Vorheriger Artikel Renal insufficiency in patients with multiple myeloma
Nächster Artikel Prognostic significance of aberrant expression of CD markers in acute lymphoblastic leukemia
Literatur
1.
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.CrossRefPubMedPubMedCentral
2.
Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376(9758):2075–85.CrossRefPubMed
3.
Mateos M‑V, Oriol A, Martínez-López J, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010;11(10):934–41.CrossRefPubMed
4.
5.
Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Mye ́lome. Blood. 2007;109(8):3489–95.CrossRefPubMed
6.
Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stemcell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119(4):940–8.CrossRefPubMed
7.
Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol. 2012;30(24):2946–55.CrossRefPubMed
8.
Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide, thalidomide, and dexametha-sone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011;118(5):1231–8.CrossRefPubMedPubMedCentral
9.
Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter International Myeloma Working Group study. Leukemia. 2012;26:149–57.CrossRefPubMed
10.
Laubach JP, Voorhees PM, Hassoun H, Jakubowiak A, Lonial S, Richardson PG. Current strategies for treatment of relapsed/refractory multiple myeloma. Expert Rev Hematol. 2014;7:97–111.CrossRefPubMed
11.
Hideshima T, Richardson PG, Anderson KC. Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Mol Cancer Ther. 2011;10(11):2034–42.CrossRefPubMedPubMedCentral
12.
Atadja P. Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett. 2009;280:233–41.CrossRefPubMed
13.
Wolf JL, Siegel D, Goldschmidt H, et al. A phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma. Leuk Lymphoma. 2012;53:1820–3.CrossRefPubMed
14.
Ocio EM, Vilanova D, Atadja P, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica. 2010;95:794–803.CrossRefPubMed
15.
Catley L, Weisberg E, Kiziltepe T, et al. Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood. 2006;108:3441–9.CrossRefPubMedPubMedCentral
16.
San-Miguel JF, Richardson PG, Gunther A, et al. Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma. J Clin Oncol. 2013;31:3696–703.CrossRefPubMed
17.
Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122:2331–7.CrossRefPubMed
18.
San-Miguel JF, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014;15(11):1195–206.CrossRefPubMed
19.
ASPIRE Investigators, Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142–52.CrossRef
20.
Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120(14):2817–25.CrossRefPubMedPubMedCentral
21.
San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055–66.CrossRef
22.
Richardson PG, Siegel DS, Vij R, et al. Pomalidomide alone or in combination with low- dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014;123(12):1826–32.CrossRefPubMedPubMedCentral
23.
Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008;14:2775–84.CrossRefPubMedPubMedCentral
24.
Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.CrossRefPubMed
25.
Deaglio S, Vaisitti T, Billington R, et al. CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. 2007;109:5390–8.CrossRefPubMed
26.
Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482–8.CrossRefPubMed
27.
Santonocito AM, Consoli U, Bagnato S, et al. Flow cytometric detection of aneuploid CD38(++) plasmacells and CD19(+) B‑lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients. Leuk Res. 2004;28:469–77.CrossRefPubMed
28.
de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840–8.CrossRefPubMed
29.
Overdijk MB, Verploegen S, Bögels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7:311–21.CrossRefPubMedPubMedCentral
30.
Lammerts van Bueren J, Jakobs D, Kaldenhoven N. et al. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79. Presented at the 56th ASH Annual Meeting and Exposition, San Francisco, 6.–9. Dec. 2014. abstract.
31.
Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016;128:37–44.CrossRefPubMedPubMedCentral
32.
Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.CrossRefPubMed
33.
Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–66.CrossRefPubMed
34.
Chanan-Khan AA, Giralt S. Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol. 2010;28(15):2612–24.CrossRefPubMed
35.
Harousseau JL, Dimopoulos MA, Wang M, et al. Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica. 2010;95(10):1738–44.CrossRefPubMedPubMedCentral
36.
Giver CR, Jaye DL, Waller EK, Kaufman JL, Lonial S. Rapid recovery from panobinostat (LBH589)-induced thrombocytopenia in mice involves a rebound effect of bone marrow megakaryocytes. Leukemia. 2011;25(2):362–5.CrossRefPubMed
37.
SUMMIT/CREST Investigators, Lonial S, Waller EK, Richardson PG, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood. 2005;106(12):3777–84.CrossRef
38.
Richardson PG, Vánia TM, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016;127(6):713–21.CrossRefPubMedPubMedCentral
39.
Kalff A, Mithraprabhu S, Khong TT, et al. A 2‑Stage Phase II Study of Panobinostat Consolidation in Multiple Myeloma (MM) Patients with 〈 CR Following Single High-Dose Chemotherapy (HDT) Conditioned Autologous Stem Cell Transplantation (ASCT) As Part of First Line Therapy. Blood. 2016;128:4515.
40.
Fermand JP, Ravaud P, Chevret S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998;92(9):3131–6.PubMed
41.
Facon T, Mary JY, Harousseau JL, et al. Front-line or rescue autologous bone marrow transplantation (ABMT) following a first course of high dose melphalan (HDM) in multiple myeloma (MM): preliminary results of a prospective random-ized trial (CIAM) protocol. Blood. 1996;88(suppl 1, pt 1):685a.
42.
Barlogie B, Kyle R, Anderson K, et al. Comparable survival in multiple myeloma (MM) with high dose therapy (HDT) employing MEL 140 mg/m2 þ TBI 12 Gy autotransplants versus standard dose therapy with VBMCP and no benefit from interferon (IFN) maintenance: results of Intergroup Trial S9321. Blood. 2003;102(11):42a.
43.
Attal M, Lauwers-Cances V, Hulin C, et al. Autologous transplantation for multiple myeloma in the era of new drugs: a phase III study of the Intergroupe Francophone Du Myelome (IFM/DFCI 2009 trial). Blood. 2015;126:391.
44.
Cavo M, Palumbo A, Zweegman S, et al. Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): A randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial). ASCO Annual Meeting. J Clin Oncol. 2016;34(suppl):abstr 8000.
45.
Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015;16(16):1617–29.CrossRefPubMed
46.
Palumbo A, Cavallo F, Gay F, Di Raimondo F, Yehuda BD, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905.CrossRefPubMed
47.
Gay F, Magarotto V, Spencer A. et al. Upfront or rescue transplant in young patients with newly diagnosed multiple myeloma: a pooled analysis of 529 patients. 22nd Congress of the EHA. 2016, p Abstract: S104.
48.
Sellner L, Heiss C, Benner A, Raab MS, Hillengass J, Hose D, Lehners N, Egerer G, Ho AD, Goldschmidt H, Neben K. Autologous retransplantation for patients with recurrent multiple myeloma: a single-center experience with 200 patients. Cancer. 2013;119:2438–46.CrossRefPubMed
49.
Cavo M, Rajkumar SV, Palumbo A, Moreau P, Orlowski R, Bladé J, Sezer O, Ludwig H, Dimopoulos MA, Attal M, Sonneveld P, Boccadoro M, Anderson KC, Richardson PG, Bensinger W, Johnsen HE, Kroeger N, Gahrton G, Bergsagel PL, Vesole DH, Einsele H, Jagannath S, Niesvizky R, Durie BG, San Miguel J, Lonial S. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011;117:6063–73.CrossRefPubMedPubMedCentral
50.
51.
Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L, Sengsayadeth S, Abidi M, Hari P, Mohty M, Chen YB, Koreth J, Landau H, Lazarus H, Leather H, Majhail N, Nath R, Osman K, Perales MA, Schriber J, Shaughnessy P, Vesole D, Vij R, Wingard J, Giralt S, Savani BN. Hematopoietic stem cell transplantation for multiple myeloma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21:1155–66.CrossRefPubMed
Metadaten
Titel
Activity of panobinostat in combination with bortezomib and dexamethasone in advanced, proteasome inhibitor refractory multiple myeloma
verfasst von
Branka Petricevic
Wolfgang Hilbe
Niklas Zojer
Publikationsdatum
18.07.2017
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 3/2017
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-017-0342-4

Weitere Artikel der Ausgabe 3/2017

New diagnostic tools for breast cancer

  • Open Access
  • short review

New chemotherapies in gastric adenocarcinoma

  • short review

Disease control with brentuximab vedotin in an aged patient with primary cutaneous anaplastic large-cell lymphoma

  • case report

Cross-over comparison and new chemotherapy regimens in metastatic pancreatic cancer

  • Open Access
  • short review

Local therapies for breast cancer

  • Open Access
  • short review

Renal insufficiency in patients with multiple myeloma

  • review