Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib

Blood

Volumn 128, Issue 20, 2016, Pages 2415-2422

  Kumar, Shaji K ^a   LaPlant, Betsy R ^a   Reeder, Craig B ^b   Roy, Vivek ^c   Halvorson, Alese E ^a   Buadi, Francis ^a   Gertz, Morie A ^a   Bergsagel, P Leif ^b   Dispenzieri, Angela ^a   Thompson, Melanie A ^a   Crawley, Jamie ^a   Kapoor, Prashant ^a   Mikhael, Joseph ^b   Stewart, Keith ^b   Hayman, Suzanne R ^a   Hwa, Yi L ^a   Gonsalves, Wilson ^a   Witzig, Thomas E ^a   Ailawadhi, Sikander ^c   Dingli, David ^a   Go, Ronald S ^a   Lin, Yi ^a   Rivera, Candido E ^c   Rajkumar, S Vincent ^a   Lacy, Martha Q ^a   more..

^a MAYO CLINIC   (United States)

^b MAYO CLINIC   (United States)

^c MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTIEMETIC AGENT; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; BORTEZOMIB; CARFILZOMIB; CREATININE; DEXAMETHASONE; IXAZOMIB CITRATE; LENALIDOMIDE; M PROTEIN; STEROID; ANTINEOPLASTIC AGENT; BORON DERIVATIVE; GLYCINE; IXAZOMIB;

ADULT; ADVERSE OUTCOME; AGED; ANEMIA; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER SURVIVAL; CLINICAL ASSESSMENT; COGNITIVE DEFECT; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DISEASE COURSE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EVENT FREE SURVIVAL; FATIGUE; FEMALE; HUMAN; LEUKOPENIA; LYMPHOCYTOPENIA; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NEUROPATHY; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL; POPULATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; SENSORY NEUROPATHY; SIDE EFFECT; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; VOMITING; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; DRUG EFFECTS; DRUG RESISTANCE; MIDDLE AGED; MORTALITY; PATHOLOGY; SURVIVAL ANALYSIS; TREATMENT OUTCOME; TUMOR RECURRENCE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORON COMPOUNDS; BORTEZOMIB; DEXAMETHASONE; DRUG RESISTANCE, NEOPLASM; FEMALE; GLYCINE; HUMANS; MALE; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM RECURRENCE, LOCAL; SURVIVAL ANALYSIS; TREATMENT OUTCOME;

EID: 85015367571     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2016-05-717769     Document Type: Article

References (26)

1. Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120(5):947-959.
2. Kumar SK, Mikhael JR, Buadi FK, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009; 84(12):1095-1110.
3. Adams J. Development of the proteasome inhibitor PS-341. Oncologist. 2002;7(1):9-16.
4. Orlowski RZ, Stinchcombe TE, Mitchell BS, et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol. 2002;20(22):4420-4427.
5. Richardson PG, Sonneveld P, Schuster M, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007;110(10):3557-3560.
6. Richardson PG, Sonneveld P, Schuster MW, et al; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005; 352(24):2487-2498.
7. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116(5): 679-686.
8. Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119(19):4375-4382.
9. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012;120(9):1801-1809.
10. Sonneveld P, Goldschmidt H, Rosiñol L, et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013;31(26):3279-3287.
11. Moreau P, Pylypenko H, Grosicki S, 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(5):431-440.
12. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010;116(23): 4745-4753.
13. Vij R, Siegel DS, Jagannath S, et al. An openlabel, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. Br J Haematol. 2012;158(6):739-748.
14. 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):2817-2825.
15. Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer [published corrections appears in Cancer Res. 2010;70(9):3853]. Cancer Res. 2010;70(5):1970-1980.
16. Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011;17(16):5311-5321.
17. Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res. 2011;17(23):7313-7323.
18. 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(7):1047-1055.
19. Kumar SK, Berdeja JG, Niesvizky R, et al. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol. 2014;15(13):1503-1512.
20. 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(7): 1038-1046.
21. Moreau P, Masszi T, Grzasko N, et al; TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17): 1621-1634.
22. Benboubker L, Dimopoulos MA, Dispenzieri A, et al; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10): 906-917.
23. 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.
24. Dimopoulos MA, Moreau P, Palumbo A, et al; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27-38.
25. Weber DM, Chen C, Niesvizky R, et al; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007; 357(21):2133-2142.
26. 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): 1055-1066.