Skip to main content
Latest news
Browse specialties
Breast cancer Genitourinary cancers Lung & thoracic cancers
In focus
Next-generation sequencing: Emerging biomarkers in thyroid and NSCLCs ctDNA and bladder cancer: Current understanding and beyond ROS1 fusion-positive NSCLC NSCLC driver mutations: Discussing the importance of RET, ALK and ROS1 alterations in NSCLC Early-stage NSCLC management: Surgery, targeted treatment and immunotherapy ALK fusion-positive NSCLC: International approaches to management RET fusion-positive NSCLC: Informing on the use of pralsetinib for patients with RET fusion-positive, advanced NSCLC COVID-19 & cancer
Conferences
SABCS 2022 ESMO 2022 2022 ASCO Annual Meeting
About us
Medicine Matters Oncology
EXTENDED SEARCH
Top

27-09-2016 | Multiple myeloma | Article

The Role of Panobinostat Plus Bortezomib and Dexamethasone in Treating Relapsed or Relapsed and Refractory Multiple Myeloma: A European Perspective

Journal: Advances in Therapy

Authors: Jesus F. San-Miguel, Hermann Einsele, Philippe Moreau

Publisher: Springer Healthcare

Login to get access

Abstract

Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received ≥2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population. The authorization and recommendation were based on results from the pivotal phase 3 PANORAMA 1 (NCT01023308) clinical trial, which demonstrated an improvement in median progression-free survival of 7.8 months for the three-drug combination compared with placebo plus bortezomib and dexamethasone in this patient population. This review will discuss the current treatment landscape for relapsed/refractory MM, the mechanism of action of panobinostat, clinical data supporting the European authorization, concerns about safety and strategies for mitigating toxicity, and how panobinostat fits into the current MM landscape in Europe.
Funding: Editorial support, funded by Novartis Pharmaceuticals.
Literature
1.
Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–60.CrossRefPubMed
2.
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.CrossRefPubMed
3.
International Agency for Research on Cancer. Estimated cancer incidence, mortality, prevalence and disability-adjusted life years (DALYs) worldwide in 2012. GLOBOCAN. 2012. Accessed 25 Jan 2016.
4.
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRefPubMed
5.
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.CrossRefPubMedPubMedCentral
6.
Cornell RF, Kassim AA. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity. Bone Marrow Transpl. 2016;51:479–91.CrossRef
7.
Kumar SK, Lee JH, Lahuerta JJ, 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;26:149–57.CrossRefPubMed
8.
Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79:867–74.CrossRefPubMed
9.
Thalidomide (thalidomide capsules) [summary of product characteristics]. Uxbridge: Celgene Europe Limited; 2016.
10.
Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer. 2004;4:349–60.CrossRefPubMed
11.
Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr, Lee KP, Boise LH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107:4907–16.CrossRefPubMedPubMedCentral
12.
Kortuem KM, Stewart AK. Carfilzomib. Blood. 2013;121:893–7.CrossRefPubMed
13.
Hideshima T, Richardson PG, Anderson KC. Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Mol Cancer Ther. 2011;10:2034–42.CrossRefPubMed
14.
LeBlanc R, Catley LP, Hideshima T, et al. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res. 2002;62:4996–5000.PubMed
15.
Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–98.CrossRefPubMed
16.
Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383–91.CrossRefPubMed
17.
Meng L, Mohan R, Kwok BH, Elofsson M, Sin N, Crews CM. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci USA. 1999;96:10403–8.CrossRefPubMedPubMedCentral
18.
Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–52.CrossRefPubMed
19.
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 randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27–38.CrossRefPubMed
20.
Ludwig H, Masszi T, Petrucci M, et al. Carfilzomib (K) vs low-dose corticosteroids and optional cyclophosphamide (cy) in patients (pts) with relapsed and refractory multiple myeloma (RRMM): results from a phase 3 study (FOCUS). Ann Oncol. 2014;25 (abstract LBA28).
21.
Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118:4771–9.CrossRefPubMedPubMedCentral
22.
Lu G, Middleton RE, Sun H, et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2014;343:305–9.CrossRefPubMed
23.
Kronke J, Udeshi ND, Narla A, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343:301–5.CrossRefPubMed
24.
Richardson PG, Schlossman RL, Weller E, et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood. 2002;100:3063–7.CrossRefPubMed
25.
Richardson PG, Blood E, Mitsiades CS, et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006;108:3458–64.CrossRefPubMedPubMedCentral
26.
Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.CrossRefPubMed
27.
Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–32.CrossRefPubMed
28.
Revlimid (lenalidomide) [summary of product characteristics]. Uxbridge: Celgene Europe Limited; 2015.
29.
Dimopoulos MA, Chen C, Spencer A, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23:2147–52.CrossRefPubMed
30.
Imnovid (pomalidomide) [summary of product characteristics]. Uxbridge: Celgene Europe Limited; 2016.
31.
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;14:1055–66.CrossRefPubMed
32.
Dimopoulos MA, Weisel KC, Cavo M, et al. The STRATUS trial (MM010): a single-arm phase 3b study of pomalidomide plus low-dose dexamethasone (POM + LoDEX) in refractory or relapsed and refractory multiple myeloma. J Clin Oncol. 2014;32(suppl) (abstract TPS8625).
33.
Dimopoulos MA, Palumbo A, Corradini P, et al. An updated analysis of the STRATUS trial (MM-010): safety and efficacy of pomalidomide plus low-dose dexamethasone (POM + LoDEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Blood. 2015;126:4225.
34.
Baz RC, Martin TG 3rd, Lin HY, et al. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016;127:2561–8.CrossRefPubMed
35.
Richardson PG, Hofmeister C, Raje NS, et al. MM005: phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma. J Clin Oncol. 2014;32(suppl) (abstract 8589).
36.
Richardson PG, Bensmaine A, Doerr T, Wang J, Zaki MH, MM007 Study Investigators. MM007: a phase 3 trial comparing the efficacy and safety of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) versus BORT and LoDEX (VD) in subjects with relapsed or refractory multiple myeloma (RRMM). J Clin Oncol. 2015;33(suppl) (abstract TPS8610).
37.
Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008;14:2775–84.CrossRefPubMedPubMedCentral
38.
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;62:1841–9.CrossRefPubMedPubMedCentral
39.
Zonder JA, Mohrbacher AF, Singhal S, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood. 2012;120:552–9.CrossRefPubMedPubMedCentral
40.
Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.CrossRefPubMed
41.
Jakubowiak A, Offidani M, Pegourie B, et al. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016;127:2833–40.CrossRefPubMedPubMedCentral
42.
Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482–8.CrossRefPubMed
43.
de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840–8.CrossRefPubMed
44.
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;7:311–21.CrossRefPubMedPubMedCentral
45.
Jansen JHM, Boross P, Overdijk MB, van Bueren JJL, Parren PWHI, Leusen JHW. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012;120:2974.
46.
Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387:1551–60.CrossRefPubMed
47.
Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373:1207–19.CrossRefPubMed
48.
Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016;128:37–44.CrossRefPubMedPubMedCentral
49.
Plesner T, Arkenau HT, Lokhorst HM, et al. Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. Blood. 2014;124:84.CrossRef
50.
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.
51.
Dimopoulos MA, Oriol A, Nahi H, et al. An open-label, randomised phase 3 study of daratumumab, lenalidomide, and dexamethasone (DRD) versus lenalidomide and dexamethasone (RD) in relapsed or refractory multiple myeloma (RRMM): POLLUX. EHA Annual Meeting; June 9–12, 2016; Copenhagen, Denmark (abstract LB238).
52.
Palumbo A, Chanan-Khan A, Weisel K, et al. Phase 3 randomised controlled study of daratumumab, bortezomib and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: CASTOR. EHA Annual Meeting; June 9–12, 2016; Copenhagen, Denmark (abstract LB2236).
53.
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;17:7313–23.CrossRefPubMedPubMedCentral
54.
Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70:1970–80.CrossRefPubMed
55.
Moreau P, Masszi T, Grzasko N, et al. Ixazomib, an investigational oral proteasome inhibitor (PI), in combination with lenalidomide and dexamethasone (IRd), significantly extends progression-free survival (PFS) for patients (pts) with relapsed and/or refractory multiple myeloma (RRMM): the phase 3 TOURMALINE-MM1 study. Blood. 2015;126:727.CrossRef
56.
van de Donk NW, Janmaat ML, Mutis T, et al. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol Rev. 2016;270:95–112.CrossRefPubMedPubMedCentral
57.
Martin TG, Hsu K, Strickland SA, Glenn MJ, Mikhael J, Charpentier E. A phase 1 trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma. J Clin Oncol. 2014;32:5s(suppl) (abstract 8532).
58.
Martin T, Hsu K, Charpentier E, et al. A phase Ib dose escalation trial of SAR650984 (anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma. J Clin Oncol. 2014;32(5 suppl) (abstract 8512).
59.
Jiang H, Acharya C, An G, et al. SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide. Leukemia. 2016;30:399–408.CrossRefPubMed
60.
Wetzel M, Nicolazzi C, Vallée F, et al. SAR650984: characterization of a potent phase I humanized antiCD38 antibody for the treatment of multiple myeloma and other hematologic malignancies. Cancer Res. 2013;73:4735.CrossRef
61.
Smith EM, Boyd K, Davies FE. The potential role of epigenetic therapy in multiple myeloma. Br J Haematol. 2010;148:702–13.CrossRefPubMed
62.
Maes K, Menu E, Van Valckenborgh E, Van Riet I, Vanderkerken K, De Bruyne E. Epigenetic modulating agents as a new therapeutic approach in multiple myeloma. Cancers (Basel). 2013;5:430–61.CrossRefPubMedPubMedCentral
63.
Walker BA, Wardell CP, Chiecchio L, et al. Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. Blood. 2011;117:553–62.CrossRefPubMed
64.
Kalushkova A, Fryknas M, Lemaire M, et al. Polycomb target genes are silenced in multiple myeloma. PLoS ONE. 2010;5:e11483.CrossRefPubMedPubMedCentral
65.
Kaiser MF, Johnson DC, Wu P, et al. Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma. Blood. 2013;122:219–26.CrossRefPubMedPubMedCentral
66.
Mithraprabhu S, Kalff A, Chow A, Khong T, Spencer A. Dysregulated class I histone deacetylases are indicators of poor prognosis in multiple myeloma. Epigenetics. 2014;9:1511–20.CrossRefPubMedPubMedCentral
67.
Moreaux J, Reme T, Leonard W, et al. Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors. Br J Cancer. 2013;109:676–85.CrossRefPubMedPubMedCentral
68.
Mithraprabhu S, Khong T, Jones SS, Spencer A. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013;162:559–62.CrossRefPubMed
69.
Dimopoulos M, Siegel DS, Lonial S, 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;14:1129–40.CrossRefPubMed
70.
Raje N, Vogl D, Hari P, et al. ACY-1215, a selective histone deacetylase (HDAC) 6 inhibitor: interim results of combination therapy with bortezomib in patients with multiple myeloma (MM). Blood. 2013;122(21):759 (abstract 759).
71.
Yee AJ, Voorhees PM, Bensinger W, et al. Ricolinostat (ACY-1215), a selective HDAC6 inhibitor, in combination with lenalidomide and dexamethasone: results of a phase 1b trial in relapsed and relapsed refractory multiple myeloma. Blood. 2014;124:4772 (abstract 4772).CrossRef
72.
Raje N, Bensinger W, Lebovic D, et al. Ricolinostat (ACY-1215) the first selective HDAC6 inhibitor in combination with pomalidomide and dexamethasone in patients with relapsed & refractory multiple myeloma: phase 1b & early phase 2 results. Haematologica. 2015;100:86.
73.
Atadja P. Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett. 2009;280:233–41.CrossRefPubMed
74.
Ocio EM, Vilanova D, Atadja P, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica. 2010;95:794–803.CrossRefPubMed
75.
Chari A, Mazumder A, Jagannath S. Proteasome inhibition and its therapeutic potential in multiple myeloma. Biologics. 2010;4:273–87.PubMedPubMedCentral
76.
Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell. 2003;115:727–38.CrossRefPubMed
77.
Catley L, Weisberg E, Kiziltepe T, et al. Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood. 2006;108:3441–9.CrossRefPubMedPubMedCentral
78.
Kikuchi J, Wada T, Shimizu R, et al. Histone deacetylases are critical targets of bortezomib-induced cytotoxicity in multiple myeloma. Blood. 2010;116:406–17.CrossRefPubMed
79.
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, randomised, double-blind phase 3 trial. Lancet Oncol. 2014;15:1195–206.CrossRefPubMed
80.
Richardson PG, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone in relapsed/relapsed and refractory myeloma: outcomes by prior treatment. Blood. 2016;127:713–21.CrossRefPubMedPubMedCentral
81.
San Miguel JF, Hungria VT, Yoon SS, et al. Final analysis of overall survival from the phase 3 PANORAMA 1 trial of panobinostat plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2015;126:3026.
82.
Richardson PG, Hungria V, Yoon SS, et al. Patient reported outcomes (PROs) of multiple myeloma (MM) patients from the PANORAMA-1 study who have received at least two prior regimens including bortezomib and an immunomodulatory agent. Haematologica. 2016;101(s1):786.
83.
84.
National Institute for Health and Care Excellence. Panobinostat for treating multiple myeloma after at least 2 previous treatments. https://​www.​nice.​org.​uk/​guidance/​ta380. Accessed 11 July 2016.
85.
Bishton MJ, Harrison SJ, Martin BP, et al. Deciphering the molecular and biologic processes that mediate histone deacetylase inhibitor-induced thrombocytopenia. Blood. 2011;117:3658–68.CrossRefPubMed
86.
Giver CR, Jaye DL, Waller EK, Kaufman JL, Lonial S. Rapid recovery from panobinostat (LBH589)-induced thrombocytopenia in mice involves a rebound effect of bone marrow megakaryocytes. Leukemia. 2011;25:362–5.CrossRefPubMed
87.
Farydak (panobinostat) [summary of product characteristics]. Surrey: Novartis Pharmaceuticals UK Ltd; 2016.
88.
Dimopoulos MA, Richardson PG, Moreau P, Anderson KC. Current treatment landscape for relapsed and/or refractory multiple myeloma. Nat Rev Clin Oncol. 2015;12:42–54.CrossRefPubMed
89.
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;30:2475–82.CrossRefPubMed
90.
Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122:2331–7.CrossRefPubMed
91.
Richardson PG, Schlossman RL, Alsina M, 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(21) (abstract 1970).
92.
Lonial S, Anderson KC. Association of response endpoints with survival outcomes in multiple myeloma. Leukemia. 2014;28:258–68.CrossRefPubMed