Treatment options for relapse after autograft in multiple myeloma – report from an EBMT educational meeting

References

• Oscio EM, Richardson PG, Rajkumar SV, et al. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG). Leukemia. 2014;28:525–542.
   PubMed Web of Science ®Google Scholar
• Laubach J, Garderet L, Mahindra A, et al. Management of relapsed multiple myeloma: recommendations of the international myeloma working group. Leukemia. 2016;30:1005–1017.
   PubMed Web of Science ®Google Scholar
• Holstein SA, Richardson PG, Laubach JP, et al. Management of relapsed multiple myeloma after autologous stem cell transplant. Biol Blood Marrow Transplant. 2015;21:793–798.
   PubMed Web of Science ®Google Scholar
• Giralt S, Garderet L, Durie B, et al. American Society of Blood and Marrow Transplant, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network and International Myeloma Working Group Consensus conference on salvage hematopoietic cell transplantation in patients with relapsed multiple myeloma. Biol Blood Marrow Transplant. 2015;21:2039–2051.
   PubMed Web of Science ®Google Scholar
• Bruno B, Auner HW, Gahrton G, et al. Stem cell transplantation in multiple myeloma and other plasma cell disorders (report from an EBMT preceptorship meeting). Leuk Lymphoma. 2016;6:1–13.
   Google Scholar
• Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565–1571.
   PubMed Web of Science ®Google Scholar
• von Lilienfeld-Toal M, Hahn-Ast C, Furkert K, et al. A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur J Haematol. 2008;81:247–252.
   PubMed Web of Science ®Google Scholar
• Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–2132.
   PubMed Web of Science ®Google Scholar
• Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–2142.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Siegel D, Baz R, et al. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood. 2013;121:1961–1967.
   PubMed Web of Science ®Google Scholar
• Leleu X, Attal M, Arnulf B, et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: intergroupe francophone du myélome 2009-02. Blood. 2013;121:1968–1975.
   PubMed Web of Science ®Google Scholar
• 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 randomized, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–1066.
   PubMed Web of Science ®Google Scholar
• Leleu X, Karlin L, Macro M, et al. Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results. Blood. 2015;125:1411–1417.
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Leleu X, Palumbo A, et al. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma. Leukemia. 2014;28:1573–1585.
   PubMed Web of Science ®Google Scholar
• Auner HW, Cenci S. Recent advances and future directions in targeting the secretory apparatus in multiple myeloma. Br J Haematol. 2015;168:14–25.
   PubMed Web of Science ®Google Scholar
• Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120:947–959.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609–2617.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–2498.
   PubMed Web of Science ®Google Scholar
• Sagaster V, Ludwig H, Kaufmann H, et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia. 2007;21:164–168.
   PubMed Web of Science ®Google Scholar
• Jagannath S, Richardson PG, Barlogie B, et al. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006;91:929–934.
   PubMed Web of Science ®Google Scholar
• Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383–6391.
   PubMed Web of Science ®Google Scholar
• 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;120:2817–2825.
   PubMed Web of Science ®Google Scholar
• Vij R, Wang M, Kaufman JL, et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012;119:5661–5670.
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomized, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27–38.
   PubMed Web of Science ®Google Scholar
• Kumar SK, LaPlant B, Roy V, et al. Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib. Blood Cancer J. 2015;5:e338.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Baz R, Wang M, et al. Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood. 2014;124:1038–1046.
   PubMed Web of Science ®Google Scholar
• Kumar SK, Bensinger WI, Zimmerman TM, et al. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood. 2014;124:1047–1055.
   PubMed Web of Science ®Google Scholar
• 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, randomized, double-blind phase 3 trial. Lancet Oncol. 2014;15:1195–1206.
   PubMed Web of Science ®Google Scholar
• Garderet L, Iacobelli S, Moreau P, et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012;30:2475–2482.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Xie W, Jagannath S, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014;123:1461–1469.
   PubMed Web of Science ®Google Scholar
• Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–152.
   PubMed Web of Science ®Google Scholar
• Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2016;374:1621–1634.
   PubMed Web of Science ®Google Scholar
• Baz R, Martin TG, Lin HY, et al. Randomized multicenter phase II study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016;127:2561–2568.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Craig Hofmeister C, Raje NS, et al. A phase 1, multicenter study of pomalidomide, bortezomib, and low-dose dexamethasone in patients with proteasome inhibitor exposed and lenalidomide-refractory myeloma (Trial MM-005). ASH annual meeting, 2015. Abst 3036.
   Google Scholar
• Lokhorst HM, Plesner T. Laubach, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373:1207–1219.
   PubMed Web of Science ®Google Scholar
• Martin K, Strickland S, Glenn M, et al. A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma. J Clin Oncol. 2014;32:8532.
   Web of Science ®Google Scholar
• Raab S, Goldschmidt H. Agis, et al. A phase 1/2a study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma. Haematologica. 2015;100:S789.
   Google Scholar
• Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–631.
   PubMed Web of Science ®Google Scholar
• van de Donk NW, Kamps S, Mutis T, et al. Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma. Leukemia. 2012;26:199–213.
   PubMed Web of Science ®Google Scholar
• Balasa B, Yun R, Belmar NA, et al. Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin-2 and TNF-alpha pathways. Cancer Immunol Immunother. 2015;64:61–73.
   PubMed Web of Science ®Google Scholar
• Overdijk MB, Verploegen S, Bogels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7:311–321.
   PubMed Web of Science ®Google Scholar
• Malavasi F, Funaro A, Roggero S, et al. Human CD38: a glycoprotein in search of a function. Immunol Today 1994;15:95–96.
   PubMedGoogle Scholar
• de Weers M, Tai YT. van der Veer, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840–1848.
   PubMed Web of Science ®Google Scholar
• Deaglio S, Mehta K, Malavasi F. Human CD38: a (r)evolutionary story of enzymes and receptors. Leukemia Res. 2001;25:1–12.
   PubMed Web of Science ®Google Scholar
• Krejcik J, Casneuf T, Nijhof I, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384–394.
   PubMed Web of Science ®Google Scholar
• Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomized, phase 2 trial. Lancet. 2016;387:1551–1560.
   PubMed Web of Science ®Google Scholar
• Usmani A, Weiss B, Bahlis NJ, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2015;126:29.
   Web of Science ®Google Scholar
• Collins SM, Bakan CE, Swartzel GD, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013;62:1841–1849.
   PubMed Web of Science ®Google Scholar
• van der Veer MS, de Weers M, van Kessel B, et al. Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica. 2011;96:284–290.
   PubMed Web of Science ®Google Scholar
• Endell J, Boxhammer R, Wurzenberger C, et al. The activity of MOR202, a fully human anti-CD38 antibody, is complemented by ADCP and is synergistically enhanced by lenalidomide in vitro and in vivo. Blood. 2012;120:4018.
   PubMed Web of Science ®Google Scholar
• Plesner T, Arkenau H, Gimsing P, et al. Daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: updated results of a phase 1/2 study (GEN503). Blood. 2015;126:507.
   Google Scholar
• Chari A, Lonial S, Suvannasankha A, et al. Open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma. Blood. 2015;126:508.
   PubMed Web of Science ®Google Scholar
• Lemieux E, Hulin C, Caillot D, et al. Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma. Biol Blood Marrow Transplant. 2013;19:445–449.
   PubMed Web of Science ®Google Scholar
• Jimenez-Zepeda VH, Mikhael J, Winter A, et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transplant. 2012;18:773–779.
   PubMed Web of Science ®Google Scholar
• Grovdal M, Nahi H, Gahrton G, et al. Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT. Bone Marrow Transplant. 2015;50:808–812.
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Kuroda J, Fuchida S, et al. The response to second-line induction with bortezomib and dexamethasone is predictive of long-term outcomes prior to high-dose chemotherapy with autologous stem cell transplantation for multiple myeloma. Intern Med. 2013;52:961–968.
   PubMed Web of Science ®Google Scholar
• Fenk R, Liese V, Neubauer F, et al. Predictive factors for successful salvage high-dose therapy in patients with multiple myeloma relapsing after autologous blood stem cell transplantation. Leuk Lymphoma. 2011;52:1455–1462.
   PubMed Web of Science ®Google Scholar
• Cook G, Williams C, Brown JM, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomized, open-label, phase 3 trial. Lancet Oncol. 2014;15:874–885.
   PubMed Web of Science ®Google Scholar
• Parrish C, Morris CT, Williams CD, et al. Stem cell harvesting after bortezomib-based re-induction for myeloma relapsing after autologous transplant: results from the BSBMT/UKMF myeloma X (Intensive) trial. Biol Blood Marrow Transplant. 2016;22:1009–1016.
   PubMed Web of Science ®Google Scholar
• Lokhorst H, Einsele H, Vesole D, et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol. 2010;28:4521–4530.
   PubMed Web of Science ®Google Scholar
• Festuccia M, Martino M, Ferrando F, et al. Allogeneic stem cell transplantation in multiple myeloma: immunotherapy and new drugs. Expert Opin Biol Ther. 2015;15:857–872.
   PubMed Web of Science ®Google Scholar
• Freytes CO, Vesole DH, LeRademacher L, et al. Second transplants for multiple myeloma relapsing after a previous autotransplant—reduced-intensity allogeneic vs autologous transplantation. Bone Marrow Transplant. 2014;49:416–421.
   PubMed Web of Science ®Google Scholar
• De Lavallade H, El-Cheikh J, Faucher C, et al. Reduced-intensity conditioning allogeneic SCT as salvage treatment for relapsed multiple myeloma. Bone Marrow Transplant. 2008;41:953–960.
   PubMed Web of Science ®Google Scholar
• Mehta J, Tricot G, Jagannath S, et al. Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft. Bone Marrow Transplant. 1998;21:887–892.
   PubMed Web of Science ®Google Scholar
• Qazilbash MH, Saliba R, De Lima M, et al. Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma. Cancer. 2006;106:1084–1089.
   PubMed Web of Science ®Google Scholar
• Wirk B, Byrne M, Dai Y, et al. Outcomes of salvage autologous versus allogeneic hematopoietic cell transplantation for relapsed multiple myeloma after initial autologous hematopoietic cell transplantation. J Clin Med Res. 2013;5:174–184.
   PubMedGoogle Scholar
• Patriarca F, Einsele H, Spina F, et al. Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant. 2012;18:617–626.
   PubMed Web of Science ®Google Scholar
• Patriarca F, Einsele H, Spina B, et al. Long term follow-up of a multicenter retrospective study based on donor availability in multiple myeloma patients relapsed after autotransplant. Hematologica. 2015;100:B 011.
   Google Scholar
• Giaccone L, Storer B, Patriarca F, et al. Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma. Blood. 2011;117:6721–6727.
   PubMed Web of Science ®Google Scholar
• Gahrton G, Iacobelli S, Bjorkstrand B, et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013;121:5055–5063.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015;33:2863–2869.
   PubMed Web of Science ®Google Scholar
• Bjorkstrand B, Iacobelli S, Hegenbart U, et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol] 2011;29:3016–3022.
   PubMed Web of Science ®Google Scholar
• Kröger N, Badbaran A, Zabelina T, et al. Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma. Biol Blood Marrow Transplant. 2013;19:398–404.
   PubMed Web of Science ®Google Scholar
• Kröger N, Shimoni A, Schilling G, et al. Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation. Br J Haematol. 2010;148:323–331.
   PubMed Web of Science ®Google Scholar