A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma

Leukemia

Volumn 26, Issue 7, 2012, Pages 1675-1680

  Berenson, J R ^a,b,c   Yellin, O ^a   Kazamel, T ^a   Hilger, J D ^a   Chen, C S ^d   Cartmell, A ^e   Woliver, T ^f   Flam, M ^g   Bravin, E ^h   Nassir, Y ^b,i   Vescio, R ^j   Swift, R A ^b  

^a Oncotherapeutics   (United States)

^b MD Inc   (United States)

^c INSTITUTE FOR MYELOMA AND BONE CANCER RESEARCH   (United States)

^d LOMA LINDA UNIVERSITY HEALTH   (United States)

^e Comprehensive Blood and Cancer Center ^*  (United States)

^f Cancer Center of Santa Barbara   (United States)

^g Fresno Women's Medical Group   (United States)

^h Bassett Cancer Institute   (United States)

ⁱ Women's Cancer Research Institute   (United States)

^j CEDARS SINAI MEDICAL CENTER   (United States)

more..

Author keywords

bortezomib; clinical trial; lenalidomide; multiple myeloma; phase 2; relapsed refractory

Indexed keywords

ACETYLSALICYLIC ACID; BORTEZOMIB; CREATININE; DEXAMETHASONE; DOXORUBICIN; LENALIDOMIDE; M PROTEIN; WARFARIN;

ABDOMINAL PAIN; ADULT; AGED; ANEMIA; ARTICLE; BACKACHE; BALANCE DISORDER; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER RELAPSE; CELLULITIS; CLINICAL ARTICLE; CONFUSION; COUGHING; CREATININE BLOOD LEVEL; DIARRHEA; DISEASE SEVERITY; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DYSPHAGIA; DYSPNEA; EDEMA; FATIGUE; FEMALE; HUMAN; HYPOCALCEMIA; HYPOKALEMIA; LEUKOPENIA; LUNG EMBOLISM; MALE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; OPEN STUDY; PAIN; PELVIS PAIN SYNDROME; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROTEIN BLOOD LEVEL; PROTEIN URINE LEVEL; SYNCOPE; THROMBOCYTOPENIA; THROMBOPHLEBITIS; TREATMENT DURATION; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORONIC ACIDS; DEXAMETHASONE; DOXORUBICIN; DRUG RESISTANCE, NEOPLASM; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM GRADING; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; POLYETHYLENE GLYCOLS; PROGNOSIS; PROSPECTIVE STUDIES; PYRAZINES; SALVAGE THERAPY; SURVIVAL RATE; THALIDOMIDE;

EID: 84863775772     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2012.51     Document Type: Article

References (37)

1. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008; 111: 2521-2526.
2. Kumar SK, Rajkumar V, 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.
3. Kumar S, Flinn IW, Richardson PG, Hari P, Callander NS, Noga SJ et al. Novel threeand four-drug combination regimens of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for previously untreated multiple myeloma: results from the multi-center, randomized phase 2 EVOLUTION study. Blood 2010; 116, abstract 621.
4. Hideshima T, Mitsiades C, Akiyama M, Hayashi T, Chauhan D, Richardson P et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003; 101: 1530-1534.
5. Ma MH, Yang HH, Parker K, Manyak S, Friedman JM, Altamirano C et al. The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clin Cancer Res 2003; 9: 1136-1144.
6. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Fanourakis G, Gu X et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci USA 2002; 99: 14374-14379.
7. Weber D, Chen C, Niesvizky R, Belch A, Stadtmauer EA, Siegel D et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357: 2133-2142.
8. 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.
9. Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A. 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. Clin Oncol 2007; 25: 3892-3901.
10. Berenson JR, Yang HH, Vescio RA, Nassir Y, Mapes R, Lee SP et al. Safety and efficacy of bortezomib and melphalan combination in patients with relapsed or refractory multiple myeloma: updated results of a phase 1/2 study after longer follow-up. Ann Hematol 2008; 87: 623-631.
11. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K et al. Once-versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood 2010; 115: 3416-3417.
12. Jakubowiak AJ, Kendall T, Al-Zoubi A, Khaled Y, Mineishi S, Ahmed A et al. Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma. J Clin Oncol 2009; 27: 5015-5022.
13. Waterman GN, Yellin O, Swift RA, Mapes R, Eades B, Ackerman E et al. A modified regimen of pegylated liposomal doxorubicin, bortezomib, and dexamethasone is effective and well tolerated in the treatment of relapsed or refractory multiple myeloma. Ann Hematol 2011; 90: 193-200.
14. Hari M, Hector-Word Z, Lebovic D, Soengas M, Jakubowiak A. Pre-clinical evaluation of bortezomib, doxorubicin, dexamethasone, and lenalidomide in multiple myeloma (MM). J Clin Oncol 2008; 26 (15S), abstract 19513.
15. Jakubowiak AJ, Griffith KA, Reece DE, Hofmeister CC, Lonial S, Zimmerman TM et al. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial. Blood 2011; 118: 535-543.
16. Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina MA 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.
17. Palumbo A, Dimopoulos MA, Delforge M, Kropff M, Foa R, Yu Z et al. A phase III study to determine the efficacy and safety of lenalidomide in combination with melphalan and prednisone (MPR) in elderly patients with newly diagnosed multiple myeloma. Blood (ASH Annual Meeting Abstracts) 2009; 114: 613.
18. Richardson PG, Weller E, Jagannath S, Avigan DE, Alsina M, Schlossman RL. Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. J Clin Oncol 2009; 27: 5713-5719.
19. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010; 116: 679-686.
20. Kumar SK, Flinn I, Noga SJ, Hari P, Rifkin R, Callander N et al. Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase I results from the multicenter EVOLUTION study. Leukemia 2010; 24: 1350-1356.
21. 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.
22. Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 2008; 112: 4445-4451.
23. Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore Sr DF, Whittenberger BF. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (SO232). Blood 2010; 116: 5838-5841.
24. Knop S, Gerecke C, Liebisch P, Topp MS, Platzbecker U, Vollmuth C et al. Results of a phase III trial of deutsche studiengruppe multiples myeloma, showing efficacy and safety of RAD regimen (Revlimid00, Adriamycin'00 0, dexamethasone) in relapsed/refractory multiple myeloma [abstract]. Haematologica 2008; 93 (s1): 256 abstract 0637.
25. Wang M, Delasalle K, Giralt S, Alexanian R. Rapid control of previously untreated multiple myeloma with bortezomib-lenalidomide-dexamethasone (BLD). Hematology 2010; 15: 70-73.
26. Palumbo A, Falco P, Falcone A, Benevolo G, Canepa L, Gay F et al. Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. Clin Lymphoma Myeloma 2009; 9: 145-150.
27. 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 randomized controlled trial. Lancet Oncol 2010; 11: 29-37.
28. Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000; 96: 2943-2950.
29. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002; 99: 4525-4530.
30. Rajkumar SV, Gahrton G, Bergsagel PL. Approach to the treatment of multiple myeloma: a clash of philosophies. Blood 2011; 118: 3205-3211.
31. Gay F, Palumbo A. Multiple myeloma: management of adverse events. Med Oncol 2010; 27: 646-653.
32. Campbell RA, Manyak SJ, Yang HH, Sjak-Shie NN, Chen H, Gui D et al. LAGk-1: a clinically relevant drug resistant human multiple myeloma tumor murine model that enables rapid evaluation of treatments for multiple myeloma. Int J Oncol 2006; 28: 1409-1417.
33. Berenson JR, Yellin O, Chen CS, Patel R, Bessudo A, Boccia RV et al. A modified regimen of pegylated liposomal doxorubicin, bortezomib, and dexamethasone (DVD) is effective and well tolerated for previously untreated multiple myeloma patients. Br J Haematol 2011; 155: 580-587.
34. Durie BG. Staging and kinetics of multiple myeloma. Semin Oncol 1986; 13: 300-309.
35. Greipp PR, San Miguel J, Durie BGM, Crowley JJ, Barlogie B, Bladé J et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412-3420.
36. Bladé J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haematopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115-1123.
37. 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. Blood (ASH Annual Meeting Abstracts) 2010; 116, abstract 3049.