1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Medicine
  4. Volume 70, 2019
  5. Article

Annual Review of Medicine

Volume 70, 2019

New Drugs in Multiple Myeloma

Abstract

Multiple myeloma is diagnosed in over 100,000 patients each year worldwide, has an increasing incidence and prevalence in many regions, and follows a relapsing course, making it a significant and growing healthcare challenge. Recent basic, translational, and clinical studies have expanded our therapeutic armamentarium, which now consists of alkylating agents, corticosteroids, deacetylase inhibitors, immunomodulatory agents, monoclonal antibodies, and proteasome inhibitors. New drugs in these categories, and additional agents, including both small and large molecules, as well as cellular therapies, are under development that promise to further expand our capabilities and bring us closer to the cure of this plasma cell dyscrasia.

Keyword(s): chimeric antigen receptor T cells, immunotherapy, monoclonal antibodies, multiple myeloma, novel agents
Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-112017-091045
2019-01-27
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/med/70/1/annurev-med-112017-091045.html?itemId=/content/journals/10.1146/annurev-med-112017-091045&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Orlowski RZ, Stinchcombe TE, Mitchell BS et al. 2002. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J. Clin. Oncol. 20:4420–27
     [Google Scholar]
  2. 2.  Richardson PG, Barlogie B, Berenson J et al. 2003. A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med. 348:2609–17
     [Google Scholar]
  3. 3.  Richardson PG, Sonneveld P, Schuster MW et al. 2005. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N. Engl. J. Med. 352:2487–98
     [Google Scholar]
  4. 4.  Manasanch EE, Orlowski RZ 2017. Proteasome inhibitors in cancer therapy. Nat. Rev. Clin. Oncol. 14:417–33
     [Google Scholar]
  5. 5.  Kuhn DJ, Chen Q, Voorhees PM et al. 2007. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood 110:3281–90
     [Google Scholar]
  6. 6.  O'Connor OA, Stewart AK, Vallone M et al. 2009. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin. Cancer Res. 15:7085–91
     [Google Scholar]
  7. 7.  Alsina M, Trudel S, Furman RR et al. 2012. A phase I single-agent study of twice-weekly consecutive-day dosing of the proteasome inhibitor carfilzomib in patients with relapsed or refractory multiple myeloma or lymphoma. Clin. Cancer Res. 18:4830–40
     [Google Scholar]
  8. 8.  Siegel DS, Martin T, Wang M et al. 2012. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 120:2817–25
     [Google Scholar]
  9. 9.  Stewart AK, Rajkumar SV, Dimopoulos MA et al. 2015. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N. Engl. J. Med. 372:142–52
     [Google Scholar]
  10. 10.  Dimopoulos M, Wang M, Maisnar V et al. 2018. Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study. J. Hematol. Oncol. 11:49
     [Google Scholar]
  11. 11.  Siegel DS, Dimopoulos MA, Ludwig H et al. 2018. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J. Clin. Oncol. 36:728–34
     [Google Scholar]
  12. 12.  Shah JJ, Stadtmauer EA, Abonour R et al. 2015. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood 126:2284–90
     [Google Scholar]
  13. 13.  Dimopoulos MA, Moreau P, Palumbo A et al. 2016. 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 17:27–38
     [Google Scholar]
  14. 14.  Dimopoulos MA, Goldschmidt H, Niesvizky R et al. 2017. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol 18:1327–37
     [Google Scholar]
  15. 15.  Facon T, Lee JH, Moreau P et al. 2017. Phase 3 study (CLARION) of carfilzomib, melphalan, prednisone (KMP) v bortezomib, melphalan, prednisone (VMP) in newly diagnosed multiple myeloma (NDMM). Clin. Lymphoma Myeloma Leukemia 17:e26–e27
     [Google Scholar]
  16. 16.  Moreau P, Mateos MV, Berenson JR et al. 2018. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol 19:953–64
     [Google Scholar]
  17. 17.  Shah C, Bishnoi R, Jain A et al. 2018. Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis. Leuk. Lymphoma. In press
  18. 18.  Richardson PG, Baz R, Wang M et al. 2014. Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood 124:1038–46
     [Google Scholar]
  19. 19.  Kumar SK, Bensinger WI, Zimmerman TM et al. 2014. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood 124:1047–55
     [Google Scholar]
  20. 20.  Kumar SK, Berdeja JG, Niesvizky R et al. 2014. 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 15:1503–12
     [Google Scholar]
  21. 21.  Moreau P, Masszi T, Grzasko N et al. 2016. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 374:1621–34
     [Google Scholar]
  22. 22.  Kumar SK, LaPlant BR, Reeder CB et al. 2016. Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib. Blood 128:2415–22
     [Google Scholar]
  23. 23.  Avet-Loiseau H, Bahlis NJ, Chng WJ et al. 2017. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood 130:2610–18
     [Google Scholar]
  24. 24.  Leleu X, Masszi T, Bahlis NJ et al. 2018. Patient-reported health-related quality of life from the phase III TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone versus placebo-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma. Am. J. Hematol. In press
  25. 25.  Orlowski RZ 2018. Letter—incorporating real-world evidence and patient value criteria into value-based frameworks for relapsed/refractory multiple myeloma. J. Manag. Care Spec. Pharm. 24:487
     [Google Scholar]
  26. 26.  Hari P, Lin HM, Zhu Y et al. 2018. Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma. J. Med. Econ. 21:793–98
     [Google Scholar]
  27. 27.  San Miguel J, Moreau P, Rajkumar V et al. 2015. Four phase 3 studies of the oral proteasome inhibitor (PI) ixazomib for multiple myeloma in the newly-diagnosed, relapsed/refractory, and maintenance settings: TOURMALINE-MM1, -MM2, -MM3, and -MM4. Clin. Lymphoma Myeloma Leuk. 15:e174
     [Google Scholar]
  28. 28.  Stuhmer T, Chatterjee M, Hildebrandt M et al. 2005. Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma. Blood 106:3609–17
     [Google Scholar]
  29. 29.  Ooi MG, Hayden PJ, Kotoula V et al. 2009. Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib. Clin. Cancer Res. 15:7153–60
     [Google Scholar]
  30. 30.  Jones RJ, Bjorklund CC, Baladandayuthapani V et al. 2012. Drug resistance to inhibitors of the human double minute-2 E3 ligase is mediated by point mutations of p53, but can be overcome with the p53 targeting agent RITA. Mol. Cancer Ther. 11:2243–53
     [Google Scholar]
  31. 31.  Sakamoto KM, Kim KB, Kumagai A et al. 2001. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. PNAS 98:8554–59
     [Google Scholar]
  32. 32.  Winter GE, Buckley DL, Paulk J et al. 2015. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348:1376–81
     [Google Scholar]
  33. 33.  Lu J, Qian Y, Altieri M et al. 2015. Hijacking the E3 ubiquitin ligase Cereblon to efficiently target BRD4. Chem. Biol. 22:755–63
     [Google Scholar]
  34. 34.  Zhang X, Lee HC, Shirazi F et al. 2018. Protein targeting chimeric molecules specific for bromodomain and extra-terminal motif family proteins are active against pre-clinical models of multiple myeloma. Leukemia 32:2224–39
     [Google Scholar]
  35. 35.  Singhal S, Mehta J, Desikan R et al. 1999. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341:1565–71 Erratum 2000. N. Engl. J. Med. 342:364
     [Google Scholar]
  36. 36.  Weber DM, Chen C, Niesvizky R et al. 2007. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N. Engl. J. Med. 357:2133–42
     [Google Scholar]
  37. 37.  Dimopoulos M, Spencer A, Attal M et al. 2007. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N. Engl. J. Med. 357:2123–32
     [Google Scholar]
  38. 38.  Ito T, Ando H, Suzuki T et al. 2010. Identification of a primary target of thalidomide teratogenicity. Science 327:1345–50
     [Google Scholar]
  39. 39.  Lu G, Middleton RE, Sun H et al. 2014. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343:305–9
     [Google Scholar]
  40. 40.  Gandhi AK, Kang J, Havens CG et al. 2014. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br. J. Haematol. 164:811–21
     [Google Scholar]
  41. 41.  Richardson PG, Siegel DS, Vij R et al. 2014. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood 123:1826–32
     [Google Scholar]
  42. 42.  Miguel JS, Weisel K, Moreau P et al. 2013. 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 14:1055–66
     [Google Scholar]
  43. 43.  Richardson PG, Rocafiguera AO, Beksac M et al. 2018. Pomalidomide (POM), bortezomib, and low‐dose dexamethasone (PVd) versus bortezomib and low-dose dexamethasone (Vd) in lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma (RRMM): Phase 3 OPTIMISMM trial. J. Clin. Oncol. 36:Suppl. Abstr 8001
     [Google Scholar]
  44. 44.  Matyskiela ME, Lu G, Ito T et al. 2016. A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase. Nature 535:252–57
     [Google Scholar]
  45. 45.  Matyskiela ME, Zhang W, Man HW et al. 2018. A cereblon modulator (CC-220) with improved degradation of Ikaros and Aiolos. J. Med. Chem. 61:535–42
     [Google Scholar]
  46. 46.  Richardson PG, Schlossman RL, Alsina M et al. 2013. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood 122:2331–37
     [Google Scholar]
  47. 47.  San-Miguel JF, Hungria VT, Yoon SS et al. 2014. 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 15:1195–206
     [Google Scholar]
  48. 48.  Wolf JL, Siegel D, Goldschmidt H et al. 2012. Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma. Leuk. Lymphoma 53:1820–23
     [Google Scholar]
  49. 49.  Berdeja JG, Hart LL, Mace JR et al. 2015. Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Haematologica 100:670–76
     [Google Scholar]
  50. 50.  Chari A, Cho HJ, Dhadwal A et al. 2017. A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma. Blood Adv 1:1575–83
     [Google Scholar]
  51. 51.  Laubach J, Tuchman SA, Rosenblatt J et al. 2016. Phase 1b study of panobinostat in combination with lenalidomide, bortezomib, and dexamethasone in relapsed refractory multiple myeloma. J. Clin. Oncol. 34:8014A
     [Google Scholar]
  52. 52.  Vogl DT, Raje N, Jagannath S et al. 2017. Ricolinostat, the first selective histone deacetylase 6 inhibitor, in combination with bortezomib and dexamethasone for relapsed or refractory multiple myeloma. Clin. Cancer Res. 23:3307–15
     [Google Scholar]
  53. 53.  Yee AJ, Bensinger WI, Supko JG et al. 2016. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol 17:1569–78
     [Google Scholar]
  54. 54.  Palumbo A, Sonneveld P 2015. Preclinical and clinical evaluation of elotuzumab, a SLAMF7-targeted humanized monoclonal antibody in development for multiple myeloma. Expert Rev. Hematol. 8:481–91
     [Google Scholar]
  55. 55.  Hsi ED, Steinle R, Balasa B et al. 2008. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin. Cancer Res. 14:2775–84
     [Google Scholar]
  56. 56.  Lonial S, Vij R, Harousseau JL et al. 2012. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J. Clin. Oncol. 30:1953–59
     [Google Scholar]
  57. 57.  Richardson PG, Jagannath S, Moreau P et al. 2015. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. Lancet Haematol 2:e516–27
     [Google Scholar]
  58. 58.  Lonial S, Dimopoulos M, Palumbo A et al. 2015. Elotuzumab therapy for relapsed or refractory multiple myeloma. N. Engl. J. Med. 373:621–31
     [Google Scholar]
  59. 59.  Dimopoulos MA, Lonial S, White D et al. 2017. Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth. Br. J. Haematol. 178:896–905
     [Google Scholar]
  60. 60.  Jakubowiak A, Offidani M, Pegourie B et al. 2016. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone versus bortezomib/dexamethasone for relapsed/refractory MM. Blood 127:2833–40
     [Google Scholar]
  61. 61.  Dimopoulos MA, Dytfeld D, Grosicki S et al. 2018. Elotuzumab plus pomalidomide/dexamethasone (EPd) versus Pd for treatment of relapsed/refractory multiple myeloma (RRMM): results from the phase 2, randomized open-label ELOQUENT-3 study. Haematologica Supplement:LB2606
     [Google Scholar]
  62. 62.  Usmani SZ, Nahi H, Mateos M-V et al. 2016. Open-label, multicenter, dose escalation phase 1b study to assess the subcutaneous delivery of daratumumab in patients (pts) with relapsed or refractory multiple myeloma (PAVO). Blood 128:1149 (Abstr.)
    [Google Scholar]
  63. 63.  Lokhorst HM, Plesner T, Laubach JP et al. 2015. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N. Engl. J. Med. 373:1207–19
     [Google Scholar]
  64. 64.  Lonial S, Weiss BM, Usmani SZ et al. 2016. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 387:1551–60
     [Google Scholar]
  65. 65.  Comenzo R, Moreau P, Mateos M-V et al. 2015. An open-label, multicenter, phase Ib study of daratumumab in combination with backbone regimens in patients with multiple myeloma. Cancer Res 75:CT320–CT
     [Google Scholar]
  66. 66.  Palumbo A, Chanan-Khan A, Weisel K et al. 2016. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N. Engl. J. Med. 375:754–66
     [Google Scholar]
  67. 67.  Dimopoulos MA, Oriol A, Nahi H et al. 2016. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 375:1319–31
     [Google Scholar]
  68. 68.  Avet-Loiseau H, Casneuf T, Chiu C et al. 2016. Evaluation of minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) patients treated with daratumumab in combination with lenalidomide plus dexamethasone or bortezomib plus dexamethasone. Blood 128:246 (Abstr.)
    [Google Scholar]
  69. 69.  Chari A, Suvannasankha A, Fay JW et al. 2017. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 130:974–81
     [Google Scholar]
  70. 70.  Deleted in proof
  71. 71.  Mateos M-V, Moreau P, Berenson JR et al. 2018. Once-weekly versus twice-weekly carfilzomib (K) dosing plus dexamethasone (d) in patients with relapsed and refractory multiple myeloma (RRMM): results of the randomized phase 3 study A.R.R.O.W. J. Clin. Oncol. 36:Suppl. Abstr 8000
     [Google Scholar]
  72. 72.  Richter JR, Martin TG, Vij R et al. 2016. Updated data from a phase II dose finding trial of single agent isatuximab (SAR650984, anti-CD38 mAb) in relapsed/refractory multiple myeloma (RRMM). J. Clin. Oncol. 34:8005 (Abstr.)
    [Google Scholar]
  73. 73.  Martin T, Baz R, Benson DM et al. 2017. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood 129:3294–303
     [Google Scholar]
  74. 74.  Richardson PG, Attal M, Campana F et al. 2018. Isatuximab plus pomalidomide/dexamethasone versus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma: ICARIA Phase III study design. Future Oncol 14:1035–47
     [Google Scholar]
  75. 75.  Tai YT, Mayes PA, Acharya C et al. 2014. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood 123:3128–38
     [Google Scholar]
  76. 76.  Trudel S, Lendvai N, Popat R et al. 2017. Deep and durable responses in patients (Pts) with relapsed/refractory multiple myeloma (MM) treated with monotherapy GSK2857916, an antibody drug conjugate against B-cell maturation antigen (BCMA): preliminary results from Part 2 of Study BMA117159. Blood 130:741 (Abstr.)
    [Google Scholar]
  77. 77.  Carpenter RO, Evbuomwan MO, Pittaluga S et al. 2013. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin. Cancer Res. 19:2048–60
     [Google Scholar]
  78. 78.  Ali SA, Shi V, Maric I et al. 2016. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 128:1688–700
     [Google Scholar]
  79. 79.  Raje N, Terpos E, Willenbacher W et al. 2018. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol 19:370–81
     [Google Scholar]
  80. 80.  Fan F, Zhao W, Liu J et al. 2017. Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma. J. Clin. Oncol. 35:LBA3001
     [Google Scholar]
  81. 81.  Rapoport AP, Stadtmauer EA, Binder-Scholl GK et al. 2015. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat. Med. 21:914–21
     [Google Scholar]
  82. 82.  Walker BA, Boyle EM, Wardell CP et al. 2015. Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma. J. Clin. Oncol. 33:3911–20
     [Google Scholar]
  83. 83.  Xu J, Pfarr N, Endris V et al. 2017. Molecular signaling in multiple myeloma: association of RAS/RAF mutations and MEK/ERK pathway activation. Oncogenesis 6:e337
     [Google Scholar]
  84. 84.  Andrulis M, Lehners N, Capper D et al. 2013. Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov 3:862–69
     [Google Scholar]
  85. 85.  Sharman JP, Chmielecki J, Morosini D et al. 2014. Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma. Clin. Lymphoma Myeloma Leuk. 14:e161–e163
     [Google Scholar]
  86. 86.  Mey UJM, Renner C, von Moos R 2017. Vemurafenib in combination with cobimetinib in relapsed and refractory extramedullary multiple myeloma harboring the BRAF V600E mutation. Hematol. Oncol. 35:890–93
     [Google Scholar]
  87. 87.  Holkova B, Zingone A, Kmieciak M et al. 2016. A phase II trial of AZD6244 (selumetinib, ARRY-142886), an oral MEK1/2 inhibitor, in relapsed/refractory multiple myeloma. Clin. Cancer Res. 22:1067–75
     [Google Scholar]
  88. 88.  Heuck CJ, Jethava Y, Khan R et al. 2016. Inhibiting MEK in MAPK pathway-activated myeloma. Leukemia 30:976–80
     [Google Scholar]
  89. 89.  Gomez J, Extremera S, Nieto A 2018. Overall survival (OS) results of randomized phase III study (ADMYRE trial) of plitidepsin and dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma (RRMM): evaluation of the crossover impact. J. Clin. Oncol. 36:Suppl. Abstr 8018
     [Google Scholar]
  90. 90.  Gupta AK, Li B, Cerniglia GJ et al. 2007. The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response. Neoplasia 9:271–78
     [Google Scholar]
  91. 91.  Ikezoe T, Saito T, Bandobashi K et al. 2004. HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2. Mol. Cancer Ther. 3:473–79
     [Google Scholar]
  92. 92.  Driessen C, Kraus M, Joerger M et al. 2016. Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein response and may overcome proteasome inhibitor resistance of multiple myeloma in combination with bortezomib: a phase I trial (SAKK 65/08). Haematologica 101:346–55
     [Google Scholar]
  93. 93.  Driessen C, Müller R, Novak U et al. 2016. The HIV protease inhibitor nelfinavir in combination with bortezomib and dexamethasone (NVd) has excellent activity in patients with advanced, proteasome inhibitor-refractory multiple myeloma: a multicenter phase II trial (SAKK 39/13). Blood 128:487 (Abstr.)
    [Google Scholar]
  94. 94.  Touzeau C, Dousset C, Le Gouill S et al. 2014. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia 28:210–12
     [Google Scholar]
  95. 95.  Kumar S, Kaufman JL, Gasparetto C et al. 2017. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood 130:2401–9
     [Google Scholar]
  96. 96.  Zhang Y, Zhou L, Leng Y et al. 2017. Positive transcription elongation factor b (P-TEFb) is a therapeutic target in human multiple myeloma. Oncotarget 8:59476–91
     [Google Scholar]
  97. 97.  Kumar SK, LaPlant B, Chng WJ et al. 2015. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood 125:443–48
     [Google Scholar]
  98. 98.  Chen C, Siegel D, Gutierrez M et al. 2018. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Blood 131:855–63
     [Google Scholar]
  99. 99.  Vogl DT, Dingli D, Cornell RF et al. 2018. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J. Clin. Oncol. 36:859–66
     [Google Scholar]
  100. 100.  Bahlis NJ, Kotb R, Sebag M et al. 2016. Selinexor in combination with bortezomib and dexamethasone (SdB) demonstrates significant activity in patients with refractory multiple myeloma (MM) including proteasome-inhibitor refractory patients: results of the phase I Stomp Trial. Blood 128:977 (Abstr.)
    [Google Scholar]
  101. 101.  Morgan GJ, Davies FE, Gregory WM et al. 2010. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 376:1989–99
     [Google Scholar]
  102. 102.  Orlowski RZ, Lonial S 2016. Integration of novel agents into the care of patients with multiple myeloma. Clin. Cancer Res. 22:5443–52
     [Google Scholar]
/content/journals/10.1146/annurev-med-112017-091045
Loading
New Drugs in Multiple Myeloma
Annual Review of Medicine 70, 521 (2019); https://doi.org/10.1146/annurev-med-112017-091045
/content/journals/10.1146/annurev-med-112017-091045
/content/journals/10.1146/annurev-med-112017-091045
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error