Management of relapsed multiple myeloma: Recommendations of the International Myeloma Working Group

Leukemia

Volumn 30, Issue 5, 2016, Pages 1005-1017

  Laubach, J ^a   Garderet, L ^b   Mahindra, A ^c   Gahrton, G ^d   Caers, J ^e   Sezer, O ^f   Voorhees, P ^g   Leleu, X ^h   Johnsen, H E ⁱ   Streetly, M ^j   Jurczyszyn, A ^k   Ludwig, H ^l   Mellqvist, U H ^m   Chng, W J ⁿ   Pilarski, L ^o   Einsele, H ^p   Hou, J ^q   Turesson, I ^r   Zamagni, E ^s   Chim, C S ^t   Mazumder, A ^u   Westin, J ^m   Lu, J ^v   Reiman, T ^w   Kristinsson, S ^d   Joshua, D ^x   Roussel, M ^y   O'Gorman, P ^z   Terpos, E ^aa   McCarthy, P ^ab   Dimopoulos, M ^aa   Moreau, P ^ac   Orlowski, R Z ^ad   Miguel, J S ^ae   Anderson, K C ^a   Palumbo, A ^af   Kumar, S ^ag   Rajkumar, V ^ag   Durie, B ^ah   Richardson, P G ^a   more..

^a DANA FARBER CANCER INSTITUTE   (United States)

^b HÔPITAL SAINT ANTOINE   (France)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^e UNIVERSITY OF LIÈGE   (Belgium)

^f MEMORIAL HOSPITAL   (Turkey)

^g UNIVERSITY OF NORTH CAROLINA   (United States)

^h LILLE UNIVERSITY HOSPITAL   (France)

ⁱ AALBORG UNIVERSITY HOSPITAL   (Denmark)

^j KING S COLLEGE HOSPITAL   (United Kingdom)

^k JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

^l WILHELMINEN HOSPITAL   (Austria)

^m SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

ⁿ NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^o UNIVERSITY OF ALBERTA   (Canada)

^p UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^q SECOND MILITARY MEDICAL UNIVERSITY   (China)

^r LUND UNIVERSITY HOSPITAL   (Sweden)

^s UNIVERSITY OF BOLOGNA   (Italy)

^t QUEEN MARY HOSPITAL   (Hong Kong)

^u NEW YORK UNIVERSITY   (United States)

^v PEKING UNIVERSITY PEOPLE S HOSPITAL   (China)

^w SAINT JOHN REGIONAL HOSPITAL   (Canada)

^x ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^y CHU PURPAN   (France)

^z DUBLIN CITY UNIVERSITY   (Ireland)

^aa UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^ab ROSWELL PARK CANCER INSTITUTE   (United States)

^ac HÔTEL DIEU   (France)

^ad UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^ae UNIVERSITY OF NAVARRA   (Spain)

^af UNIVERSITY OF TURIN   (Italy)

^ag MAYO CLINIC   (United States)

^ah CEDARS SINAI MEDICAL CENTER   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BENDAMUSTINE; BEVACIZUMAB; BHQ 880; BORTEZOMIB; BT 062; CARFILZOMIB; CISPLATIN; CYCLOPHOSPHAMIDE; DACETUZUMAB; DARATUMUMAB; DENOSUMAB; DEXAMETHASONE; DOXORUBICIN; ELOTUZUMAB; ETOPOSIDE; ISATUXIMAB; LENALIDOMIDE; LORVOTUZUMAB MERTANSINE; MELPHALAN; MILATUZUMAB; MONOCLONAL ANTIBODY; MOR 202; PANOBINOSTAT; POMALIDOMIDE; PREDNISONE; SILTUXIMAB; TABALUMAB; THALIDOMIDE; UNCLASSIFIED DRUG;

ALLOGENEIC STEM CELL TRANSPLANTATION; AUTOLOGOUS STEM CELL TRANSPLANTATION; BLOOD CELL COUNT; BONE MARROW EXAMINATION; CANCER COMBINATION CHEMOTHERAPY; CANCER PROGNOSIS; CHROMOSOME ABERRATION; CLINICAL FEATURE; CYTOPENIA; DRUG EFFICACY; DRUG SAFETY; FLUORESCENCE IN SITU HYBRIDIZATION; HUMAN; LACTATE DEHYDROGENASE BLOOD LEVEL; MONOTHERAPY; MULTICENTER STUDY (TOPIC); MULTIPLE MYELOMA; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PLASMA CELL; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN ELECTROPHORESIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENT DISEASE; REVIEW; SALVAGE THERAPY; DISEASE MANAGEMENT; HEMATOPOIETIC STEM CELL TRANSPLANTATION; PATHOLOGY; PRACTICE GUIDELINE; PROCEDURES;

ANTINEOPLASTIC AGENTS; DISEASE MANAGEMENT; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; MULTIPLE MYELOMA; PRACTICE GUIDELINES AS TOPIC; RECURRENCE; SALVAGE THERAPY;

EID: 84958074272     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2015.356     Document Type: Review

References (128)

1. Mckenna RWKR, Kuehl WM, Grogan TM, Harris NL, Coupland RW. Plasma cell neoplasms. In: Swerdlow SHCE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds). WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer: Lyon, 2008, pp 200-213.
2. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 2010; 11: 29-37.
3. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M 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: 2075-2085.
4. Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M et al. Bor-tezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010; 28: 4621-4629.
5. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008; 359: 906-917.
6. Rajkumar SV, Rosinol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008; 26: 2171-2177.
7. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91-97.
8. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875-1883.
9. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495-2502.
10. Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood 2012; 120: 9-19.
11. Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L et al. Major tumor shrinking and persistent molecular remissions after consolidation with borte-zomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 2010; 28: 2077-2084.
12. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516-2520.
13. Venner CP, Connors JM, Sutherland HJ, Shepherd JD, Hamata L, Mourad YA et al. Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (o12 months). Leuk Lymphoma 2011; 52: 34-41.
14. Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 2011; 117: 4691-4695.
15. Chim CS, Lie AK, Chan EY, Leung YY, Cheung SC, Chan SY et al. A staged approach with vincristine, adriamycin, and dexamethasone followed by bortezomib, thalidomide, and dexamethasone before autologous hematopoietic stem cell transplantation in the treatment of newly diagnosed multiple myeloma. Ann Hematol 2010; 89: 1019-1027.
16. Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J 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: 149-157.
17. Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia 2010; 24: 623-628.
18. Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia 2010; 24: 1769-1778.
19. Tovar N, de Larrea CF, Arostegui JI, Cibeira MT, Rosinol L, Rovira M et al. Natural history and prognostic impact of oligoclonal humoral response in patients with multiple myeloma after autologous stem cell transplantation: long-term results from a single institution. Haematologica 2013; 98: 1142-1146.
20. Conner TM, Doan QD, Walters IB, LeBlanc AL, Beveridge RA. An observational, retrospective analysis of retreatment with bortezomib for multiple myeloma. Clin Lymphoma Myeloma 2008; 8: 140-145.
21. Hrusovsky I, Emmerich B, von Rohr A, Voegeli J, Taverna C, Olie RA et al. Bortezomib retreatment in relapsed multiple myeloma-results from a retrospective multicentre survey in Germany and Switzerland. Oncology 2010; 79: 247-254.
22. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565-1571.
23. Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98: 492-494.
24. Dimopoulos MA, Anagnostopoulos A, Weber D. Treatment of plasma cell dyscrasias with thalidomide and its derivatives. J Clin Oncol 2003; 21: 4444-4454.
25. Glasmacher A, Hahn C, Hoffmann F, Naumann R, Goldschmidt H, von Lilienfeld-Toal M et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2006; 132: 584-593.
26. Kumar S, Gertz MA, Dispenzieri A, Lacy MQ, Geyer SM, Iturria NL et al. Response rate, durability of response, and survival after thalidomide therapy for relapsed multiple myeloma. Mayo Clin Proc 2003; 78: 34-39.
27. Richardson P, Schlossman R, Jagannath S, Alsina M, Desikan R, Blood E et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin Proc 2004; 79: 875-882.
28. Mileshkin L, Biagi JJ, Mitchell P, Underhill C, Grigg A, Bell R et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood 2003; 102: 69-77.
29. van Rhee F, Dhodapkar M, Shaughnessy Jr JD, Anaissie E, Siegel D, Hoering A et al. First thalidomide clinical trial in multiple myeloma: a decade. Blood 2008; 112: 1035-1038.
30. Grover JK, Uppal G, Raina V. The adverse effects of thalidomide in relapsed and refractory patients of multiple myeloma. Ann Oncol 2002; 13: 1636-1640.
31. Dimopoulos MA, Eleutherakis-Papaiakovou V. Adverse effects of thalidomide administration in patients with neoplastic diseases. Am J Med 2004; 117: 508-515.
32. von Lilienfeld-Toal M, Hahn-Ast C, Furkert K, Hoffmann F, Naumann R, Bargou R 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.
33. Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B et al. Prevention of thalidomide-and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22: 414-423.
34. Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 108: 3458-3464.
35. Richardson P, Jagannath S, Hussein M, Berenson J, Singhal S, Irwin D et al. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009; 114: 772-778.
36. Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357: 2123-2132.
37. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357: 2133-2142.
38. Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004; 22: 3269-3276.
39. Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J 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.
40. San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M 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: 1055-1066.
41. Leleu X, Karlin L, Macro M, Hulin C, Garderet L, Roussel M et al. Pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma (RRMM) with deletion (del)17p and/or translocation t(4;14). Blood 2013; 122: 689.
42. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609-2617.
43. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352: 2487-2498.
44. Sagaster V, Ludwig H, Kaufmann H, Odelga V, Zojer N, Ackermann J 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.
45. Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 2011; 12: 431-440.
46. Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D 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.
47. Mikhael JR, Belch AR, Prince HM, Lucio MN, Maiolino A, Corso A et al. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol 2009; 144: 169-175.
48. Dimopoulos MA, Beksac M, Benboubker L, Roddie H, Allietta N, Broer E et al. Phase II study of bortezomib-dexamethasone alone or with added cyclopho-sphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma. Haematologica 2013; 98: 1264-1272.
49. Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res 2007; 67: 6383-6391.
50. Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S 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.
51. Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK 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.
52. Knop S, Straka C, Haen M, Schwedes R, Hebart H, Einsele H. The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy. Haematologica 2005; 90: 1287-1288.
53. Damaj G, Malard F, Hulin C, Caillot D, Garidi R, Royer B et al. Efficacy of bend-amustine in relapsed/refractory myeloma patients: results from the French compassionate use program. Leuk Lymphoma 2012; 53: 632-634.
54. Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C et al. Time to event analyses in PANORAMA 2: a phase 2 study of panobinostat, bortezomib, and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma. Blood 2013; 122: 1970.
55. San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A 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: 1195-1206.
56. Offidani M, Corvatta L, Marconi M, Olivieri A, Catarini M, Mele A et al. Thalido-mide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma. Hematol J 2004; 5: 312-317.
57. Kyriakou C, Thomson K, D'Sa S, Flory A, Hanslip J, Goldstone AH et al. Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br J Haematol 2005; 129: 763-770.
58. Dimopoulos MA, Hamilos G, Zomas A, Gika D, Efstathiou E, Grigoraki V et al. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol J 2004; 5: 112-117.
59. Schey SA, Morgan GJ, Ramasamy K, Hazel B, Ladon D, Corderoy S et al. The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study. Br J Haematol 2010; 150: 326-333.
60. Morgan GJ, Schey SA, Wu P, Srikanth M, Phekoo KJ, Jenner M et al. Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients. Br J Haematol 2007; 137: 268-269.
61. van de Donk NW, Wittebol S, Minnema MC, Lokhorst HM. Lenalidomide (Revlimid) combined with continuous oral cyclophosphamide (endoxan) and prednisone (REP) is effective in lenalidomide/dexamethasone-refractory myeloma. Br J Haematol 2010; 148: 335-337.
62. Nijhof IS, Zweegman S, Levin M-D, Koene HR, Beeker A, Bloem AC et al. Phase 1/2 trial of lenalidomide in combination with cyclophosphamide and prednisone (REP) in patients with lenalidomide-refractory multiple myeloma (REPEAT-study). Blood 2013; 122: 287.
63. Palumbo A, Larocca A, Falco P, Sanpaolo G, Falcone AP, Federico V et al. Lenalidomide, melphalan, prednisone and thalidomide (RMPT) for relapsed/refractory multiple myeloma. Leukemia 2010; 24: 1037-1042.
64. Lentzsch S, O'Sullivan A, Kennedy RC, Abbas M, Dai L, Pregja SL et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 2012; 119: 4608-4613.
65. Ponisch W, Heyn S, Beck J, Wagner I, Mohren M, Hoffmann FA et al. Lenalidomide, bendamustine and prednisolone exhibits a favourable safety and efficacy profile in relapsed or refractory multiple myeloma: final results of a phase 1 clinical trial OSHO-#077. Br J Haematol 2013; 162: 202-209.
66. Baz R, Martin TG, Alsina M, Shain KH, Cho HJ, Wolf JL et al. Pomalidomide, cyclophosphamide, and dexamethasone is superior to pomalidomide and dexamethasone in relapsed and refractory myeloma: results of a multicenter randomized phase II study. Blood 2014; 124: 303-303.
67. Offidani M, Corvatta L, Marconi M, Visani G, Alesiani F, Brunori M et al. Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter, phase II study. Haematologica 2006; 91: 133-136.
68. Knop S, Gerecke C, Liebisch P, Topp MS, Platzbecker U, Sezer O et al. Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom). Blood 2009; 113: 4137-4143.
69. Reece DE, Rodriguez GP, Chen C, Trudel S, Kukreti V, Mikhael J et al. Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. J Clin Oncol 2008; 26: 4777-4783.
70. Offidani M, Corvatta L, Maracci L, Liberati AM, Ballanti S, Attolico I et al. Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study. Blood Cancer J 2013; 3: e162.
71. Rodon P, Hulin C, Pegourie B, Tiab M, Anglaret B, Benboubker L et al. Bendamustine, bortezomib and dexamethasone (BVD) in Elderly Patients with Multiple Myeloma in First Relapse: Updated Results of the Intergroupe Francophone Du Myelome (IFM) 2009-01 Trial. ASH Annual Meeting Abstracts, Vol. 120, 2012, p 4044.
72. Ludwig H, Kasparu H, Leitgeb C, Rauch E, Linkesch W, Zojer N et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 2014; 123: 985-991.
73. Palumbo A, Gay F, Bringhen S, Falcone A, Pescosta N, Callea V et al. Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma. Ann Oncol 2008; 19: 1160-1165.
74. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol 2007; 25: 3892-3901.
75. Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D 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.
76. Richardson PG, Weller E, Jagannath S, Avigan DE, Alsina M, Schlossman RL et al. Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. J Clin Oncol 2009; 27: 5713-5719.
77. Richardson PG, Jagannath S, Jakubowiak AJ, Lonial S, Raje N, Alsina M et al. Phase II Trial of Lenalidomide, Bortezomib, and Dexamethasone In Patients (pts) with Relapsed and Relapsed/Refractory Multiple Myeloma (MM): Updated Efficacy and Safety Data After 42 Years of Follow-up. ASH Annual Meeting Abstracts. Vol. 116, 2010, p. 3049.
78. Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E et al. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood 2013; 122: 3122-3128.
79. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015; 372: 142-152.
80. Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger W, Gasparetto C et al. Phase I/II dose expansion of a multi-center trial of carfilzomib and pomalidomide with dexamethasone (Car-Pom-d) in patients with relapsed/refractory multiple myeloma. Blood 2013; 122: 690.
81. Kim YK, Sohn SK, Lee JH, Yang DH, Moon JH, Ahn JS et al. Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study. Ann Hematol 2010; 89: 475-482.
82. Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J et al. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003; 21: 2732-2739.
83. Gerrie AS, Mikhael JR, Cheng L, Jiang H, Kukreti V, Panzarella T et al. D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma. Br J Haematol 2013; 161: 802-810.
84. Buda G, Orciuolo E, Galimberti S, Ghio F, Petrini M. VDTPACE as salvage therapy for heavily pretreated MM patients. Blood 2013; 122: 5377-5377.
85. Alvares CL, Davies FE, Horton C, Patel G, Powles R, Morgan GJ. The role of second autografts in the management of myeloma at first relapse. Haematologica 2006; 91: 141-142.
86. Olin RL, Vogl DT, Porter DL, Luger SM, Schuster SJ, Tsai DE et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant 2009; 43: 417-422.
87. Lemieux E, Hulin C, Caillot D, Tardy S, Dorvaux V, Michel J et al. Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 445-449.
88. Efebera YA, Qureshi SR, Cole SM, Saliba R, Pelosini M, Patel RM et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma. Biol Blood Marrow Transplant 2010; 16: 1122-1129.
89. Patriarca F, Einsele H, Spina F, Bruno B, Isola M, Nozzoli C 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.
90. de Lavallade H, El-Cheikh J, Faucher C, Furst S, Stoppa AM, Coso D et al. Reduced-intensity conditioning allogeneic SCT as salvage treatment for relapsed multiple myeloma. Bone Marrow Transplant 2008; 41: 953-960.
91. Shimoni A, Hardan I, Ayuk F, Schilling G, Atanackovic D, Zeller W et al. Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myeloma: long-term follow-up. Cancer 2010; 116: 3621-3630.
92. Kroger N, Shimoni A, Schilling G, Schwerdtfeger R, Bornhauser M, Nagler A 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.
93. Qazilbash MH, Saliba R, De Lima M, Hosing C, Couriel D, Aleman A et al. Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma. Cancer 2006; 106: 1084-1089.
94. Crawley C, Iacobelli S, Bjorkstrand B, Apperley JF, Niederwieser D, Gahrton G. Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007; 109: 3588-3594.
95. Gahrton G, Tura S, Ljungman P, Belanger C, Brandt L, Cavo M et al. Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation. N Engl J Med 1991; 325: 1267-1273.
96. Maloney DG, Molina AJ, Sahebi F, Stockerl-Goldstein KE, Sandmaier BM, Bensinger W et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003; 102: 3447-3454.
97. Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007; 356: 1110-1120.
98. Bjorkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L 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.
99. Ocio EM, Richardson PG, Rajkumar SV, Palumbo A, Mateos MV, Orlowski R 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.
100. Lonial S, Vij R, Harousseau JL, Facon T, Moreau P, Mazumder A et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 2012; 30: 1953-1959.
101. Plesner T, Lokhorst H, Gimsing P, Nahi H, Lisby S, Richardson PG Daratumumab, a CD38 Monoclonal Antibody in Patients with Multiple Myeloma-Data From a Dose-Escalation Phase I/II Study. ASH Annual Meeting Abstracts, Vol. 20, 2012, p 73.
102. Heffner LT, Jagannath S, Zimmerman TM, Lee KP, Rosenblatt J, Lonial S et al. BT062, an Antibody-Drug Conjugate Directed Against CD138, Given Weekly for 3 Weeks in Each 4 Week Cycle: Safety and Further Evidence of Clinical Activity. ASH Annual Meeting Abstracts. Vol. 120, 2012, p 4042.
103. Harrison SJ, Quach H, Link E, Seymour JF, Ritchie DS, Ruell S et al. A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma. Blood 2011; 118: 6274-6283.
104. Raje N, Hari PN, Vogl DT, Jagannath S, Orlowski RZ, Supko JG et al. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma: Preliminary Results From the First-in-Humans Phase I/II Study. ASH Annual Meeting Abstracts, Vol. 120, 2012, p 4061.
105. Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L et al. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk 2012; 12: 319-324.
106. Cea M, Cagnetta A, Gobbi M, Patrone F, Richardson PG, Hideshima T et al. New insights into the treatment of multiple myeloma with histone deacetylase inhibitors. Curr Pharm Des 2013; 19: 734-744.
107. Jakubowiak AJ, Richardson PG, Zimmerman T, Alsina M, Kaufman JL, Kandarpa M et al. Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study. Br J Haematol 2012; 158: 472-480.
108. Richardson PG, Wolf J, Jakubowiak A, Zonder J, Lonial S, Irwin D et al. Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial. J Clin Oncol 2011; 29: 4243-4249.
109. Shah JJ, Zonder JA, Cohen A, Bensinger W, Kaufman JL, Orlowski RZ et al. The Novel KSP Inhibitor ARRY-520 Is Active Both with and without Low-Dose Dexamethasone in Patients with Multiple Myeloma Refractory to Bortezomib and Lenalidomide: Results From a Phase 2 Study. ASH Annual Meeting Abstracts, 120, 2012, p 449.
110. Kumar SK, LaPlant BR, Chng WJ, Zonder JA, Callander N, Roy V et al. Phase 1/2 Trial of a Novel CDK Inhibitor Dinaciclib (SCH727965) in Patients with Relapsed Multiple Myeloma Demonstrates Encouraging Single Agent Activity. ASH Annual Meeting Abstracts, Vol. 120, 2012, p 76.
111. Raje N, Faber EA Jr., Richardson PG, Schiller GJ, Hohl RJ, Cohen AD et al. Phase 1 Study of Tabalumab, a Human Anti-BAFF Antibody and Bortezomib in Patients with Previously-Treated Multiple Myeloma. ASH Annual Meeting Abstracts Vol. 120, 2012, p 447.
112. Richardson PG, Mitsiades C, Schlossman R, Munshi N, Anderson K. New Drugs for Myeloma. The Oncologist 2007; 12: 664-689.
113. Lonial S, Mitsiades CS, Richardson PG. Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res 2011; 17: 1264-1277.
114. 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.
115. Smetana J, Berankova K, Zaoralova R, Nemec P, Greslikova H, Kupska R et al. Gain(1)(q21) is an unfavorable genetic prognostic factor for patients with relapsed multiple myeloma treated with thalidomide but not for those treated with bortezomib. Clin Lymphoma Myeloma Leuk 2013; 13: 123-130.
116. Jakubowiak AJ, Siegel DS, Martin T, Wang M, Vij R, Lonial S et al. Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study. Leukemia 2013; 27: 2351-2356.
117. Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood 2009; 114: 522-525.
118. Rasche L, Bernard C, Topp MS, Kapp M, Duell J, Wesemeier C et al. Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases. Ann Hematol 2012; 91: 1031-1037.
119. Papanikolaou X, Repousis P, Tzenou T, Maltezas D, Kotsopoulou M, Megalakaki K et al. Incidence, clinical features, laboratory findings and outcome of patients with multiple myeloma presenting with extramedullary relapse. Leuk Lymphoma 2013; 54: 1459-1464.
120. Sellner L, Heiss C, Benner A, Raab MS, Hillengass J, Hose D et al. Autologous retransplantation for patients with recurrent multiple myeloma: a single-center experience with 200 patients. Cancer 2013; 119: 2438-2446.
121. Jimenez-Zepeda VH, Mikhael J, Winter A, Franke N, Masih-Khan E, Trudel S 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.
122. Anagnostopoulos A, Hamilos G, Zorzou MP, Grigoraki V, Anagnostou D, Dimopoulos MA. Discordant response or progression in patients with myeloma treated with thalidomide-based regimens. Leuk Lymphoma 2004; 45: 113-116.
123. Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L et al. Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome. Blood 2014; 123: 3414-3419.
124. Ahn JS, Jung SH, Yang DH, Bae SY, Kim YK, Kim HJ et al. Patterns of relapse or progression after bortezomib-based salvage therapy in patients with relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk 2014; 14: 389-394.
125. Shah JJ, Orlowski RZ, Alexanian R, Wang M, Thomas S, Qazilbash MH et al. Phase I Trial of the Combination of Lenalidomide, Thalidomide and Dexamethasone In Relapsed/Refractory Multiple Myeloma. ASH Annual Meeting Abstracts 2010 Vol. 116, 2010, p1948.
126. Niesvizky R, Martin TG 3rd, Bensinger WI, Alsina M, Siegel DS, Kunkel LA et al. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Clin Cancer Res 2013; 19: 2248-2256.
127. Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 2004; 127: 165-172.
128. Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T et al. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol 2013; 14: 1129-1140.