895
Views
12
CrossRef citations to date
0
Altmetric
Review

Novel investigational drugs active as single agents in multiple myeloma

, , , &
Pages 699-711 | Received 17 Feb 2017, Accepted 25 Apr 2017, Published online: 08 May 2017

References

  • Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91:719–734.
  • Becker N. Epidemiology of multiple myeloma. Recent Results Cancer Res. 2011;183:25–35.
  • Altekruse SF, Kosary CL, Krapcho M, et al. editors. Seer cancer statistics review, 1975-2007. Bethesda (MD): National Cancer Institute; 2010. Available from. based on November 2009 SEER data submission, posted to the SEER web site: http://seer.cancer.gov/csr/1975_2007/
  • Turesson I, Velez R, Kristinsson SY, et al. Patterns of multiple myeloma during the past 5 decades: stable incidence rates for all age groups in the population but rapidly changing age distribution in the clinic. Mayo Clin Proc. 2010;85:225–230.
  • Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–1060.
  • Bianchi G, Munshi NC. Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood. 2015;125:3049–3058.
  • 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–e548.
  • Prideaux SM, Conway O’Brien E, Chevassut TJ. The genetic architecture of multiple myeloma. Adv Hematol. 2014;2014:864058.
  • Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015;33:2863–2869.
  • Larocca A, Palumbo A. How I treat fragile myeloma patients. Blood. 2015;126:2179–2185.
  • Palumbo A, Bringhen S, Mateos M-V, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125:2068–2074.
  • Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–1128.
  • Lipe B, Vukas R, Mikhael J. The role of maintenance therapy in multiple myeloma. Blood Cancer J. 2016;6:e485.
  • Strese S, Wickström M, Fuchs PF, et al. The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo. Biochem Pharmacol. 2013;86:888–895.
  • Ray A, Ravillah D, Das DS, et al. A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells. Br J Haematol. 2016;174:397–409.
  • Fenical W, Jensen PR, Palladino MA, et al. Discovery and development of the anticancer agent salinosporamide A (NPI-0052). Bioorg Med Chem. 2009;17:2175–2180.
  • Chauhan D, Catley L, Li G, et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell. 2005;8:407–419.
  • Chauhan D, Singh AV, Aujay M, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010;116:4906–4915.
  • Moreno L, Zabaleta A, Alignani D, et al. Critical analysis on the mechanism of action (MoA) of the anti-CD38 monoclonal antibody isatuximab in multiple myeloma (MM). San Diego (CA): ASH; 2016. p. 652. abstract 2105.
  • Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:311–322.
  • Martin MP, Olesen SH, Georg GI, et al. Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol. 2013;8:2360–2365.
  • Sarli V, Giannis A. Targeting the kinesin spindle protein: basic principles and clinical implications. Clin Cancer Res. 2008;14:7583–7587.
  • Gilmartin AG, Bleam MR, Groy A, et al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res. 2011;17:989–1000.
  • Wendel H-G, De Stanchina E, Fridman JS, et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature. 2004;428:332–337.
  • Kennedy SG, Kandel ES, Cross TK, et al. Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol. 1999;19:5800–5810.
  • Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857–868.
  • Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer. 2011;11:23–34.
  • Gullbo J, Wallinder C, Tullberg M, et al. Antitumor activity of the novel melphalan containing tripeptide J3 (L-prolyl-L-melphalanyl-p-L-fluorophenylalanine ethyl ester): comparison with its m-L-sarcolysin analogue P2. Mol Cancer Ther. 2003;2:1331–1339.
  • Wickström M, Johnsen JI, Ponthan F, et al. The novel melphalan prodrug J1 inhibits neuroblastoma growth in vitro and in vivo. Mol Cancer Ther. 2007;6:2409–2417.
  • 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;17:5311–5321.
  • Wickström M, Viktorsson K, Lundholm L, et al. The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan. Biochem Pharmacol. 2010;79:1281–1290.
  • Voorhees PM, Magarotto V, Sonneveld P, et al. Efficacy of melflufen, a peptidase targeted therapy, and dexamethasone in an ongoing open-label phase 2a study in patients with relapsed and relapsed-refractory multiple myeloma (RRMM) including an initial report on progression free survival. Blood. 2015;126:3029. abstr 126
  • Magarotto V, Sonneveld P, Voorhees P, et al. Encouraging preliminary data in ongoing open-label phASE 1/2 study. EHA Learning Center. Vienna:Magarotto V; Jun 12 2015. p.100535.
  • Safety and efficacy of melflufen and dexamethasone in relapsed and/or relapsed-refractory multiple myeloma patients - full text view - clinicaltrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT01897714?term=MELFLUFEN&rank=1
  • A study of melflufen in combination with dexamethasone in relapsed refractory multiple myeloma patients - full text view - clinicaltrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT02963493?term=MELFLUFEN&rank=2.
  • Harrison SJ, Mainwaring P, Price T, et al. Phase I clinical trial of marizomib (NPI-0052) in patients with advanced malignancies including multiple myeloma: study NPI-0052-102 final results. Clin Cancer Res. 2016;22:4559–4566.
  • Phase 1 clinical trial in patients with advanced malignancies - full text view - clinicalTrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT00629473?term=marizomib&rank=4.
  • Richardson PG, Zimmerman TM, Hofmeister CC, et al. Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma: NPI-0052-101 Part 1. Blood. 2016;127:2693–2700.
  • Vij R, Savona M, Siegel DS, et al. Clinical profile of single-agent oprozomib in patients (Pts) with multiple myeloma (MM): updated results from a multicenter, open-label, dose escalation phase 1b/2 study. Blood. 2014;124:34.
  • Open-label study of the safety and activity of oprozomib in patients with hematologic malignancies - full text view - clinicaltrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT01416428?term=onx-0912&rank=5.
  • Ghobrial IM, Savona MR, Vij R, et al. Final results from a multicenter, open-label, dose-escalation phase 1b/2 study of single-agent oprozomib in patients with hematologic malignancies. San Diego (CA): ASH; 2016. p. 653; 2110.
  • Martin TG, Hsu K, Strickland SA, et al. A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma. 2014 ASCO Annual Meeting |Abstracts |Meeting Library. Chicago. ASCO. 2014. p. 32:5s, (suppl; abstr 8532).
  • Phase 1/2 dose escalation and efficacy study of anti-cd38 monoclonal antibody in patients with selected cd38+ hematological malignancies - full text view - clinicaltrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/show/NCT01084252.
  • Richter JR, Martin TG, Vij R, et al. Updated data from a phase II dose finding trial of single agent isatuximab (SAR650984, anti-CD38 mAb) in relapsed/refractory multiple myeloma (RRMM). 2016 ASCO Annual Meeting |Abstracts |Meeting Library. Chicago. ASCO. 2016. p. 34, (suppl; abstr 8005).
  • Trial of Isatuximab (SAR650984) in patients with intermediate and high risk smoldering multiple myeloma - full text view - clinicaltrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT02960555?term=sar650984&rank=3.
  • Kumar S, Vij R, Kaufman JL, et al. Venetoclax monotherapy for relapsed/refractory multiple myeloma: safety and efficacy results from a phase i study. San Diego (CA): ASH; 2016. p. 635 abstract 488.
  • Kumar SK, LaPlant B, Chng WJ, et al. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015;125:443–448.
  • Lonial S, Shah J, Zonder J, et al. Prolonged survival and improved response rates with ARRY‐520 in relapsed/refractory multiple myeloma (RRMM) patients with low α‐1 acid glycoprotein (AAG) levels: results from a phase 2 study. Blood. 2013;122(abstract):285.
  • Heuck CJ, Jethava Y, Khan R, et al. Inhibiting MEK in MAPK pathway-activated myeloma. Leukemia. 2016;30:976–980.
  • Spencer A, Yoon -S-S, Harrison SJ, et al. The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014;124:2190–2195.
  • Ocio EM, Thomas SK, Günther A, et al. Phase 1 study of the novel pan-pim kinase inhibitor LGH447 in patients with relapsed/refractory multiple myeloma. Blood. 2013;122:3186.
  • Arrigo AP, Tanaka K, Goldberg AL, et al. Identity of the 19S “prosome” particle with the large multifunctional protease complex of mammalian cells (the proteasome). Nature. 1988;331:192–194.
  • Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999;59:2615–2622.
  • Carvalho P, Goder V, Rapoport TA. Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006;126:361–373.
  • Raasi S, Wolf DH. Ubiquitin receptors and ERAD: a network of pathways to the proteasome. Semin Cell Dev Biol. 2007;18:780–791.
  • Hideshima T, Richardson PG, Anderson KC. Targeting proteasome inhibition in hematologic malignancies. Rev Clin Exp Hematol. 2003;7:191–204.
  • Neri P, Ren L, Gratton K, et al. Bortezomib-induced “BRCAness” sensitizes multiple myeloma cells to PARP inhibitors. Blood. 2011;118:6368–6379.
  • Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621–1634.
  • Kortuem KM, Stewart AK. Carfilzomib. Blood. 2013;121:893–897.
  • 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.
  • 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;120:1801–1809.
  • Niewerth D, Jansen G, Riethoff LFV, et al. Antileukemic activity and mechanism of drug resistance to the marine Salinispora tropica proteasome inhibitor salinosporamide A (Marizomib). Mol Pharmacol. 2014;86:12–19.
  • Levin N, Spencer A, Harrison SJ, et al. Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients. Br J Haematol. 2016;174:711–720.
  • Reinherz EL, Kung PC, Goldstein G, et al. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980;77:1588–1592.
  • Lee HC. Structure and enzymatic functions of human CD38. Mol Med. 2006;12:317–323.
  • Chillemi A, Zaccarello G, Quarona V, et al. Anti-CD38 antibody therapy: windows of opportunity yielded by the functional characteristics of the target molecule. Mol Med. 2013;19:99–108.
  • Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–766.
  • 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;387:1551–1560.
  • Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–1331.
  • Ramsingh G, Mehan P, Luo J, et al. Primary plasma cell leukemia: a surveillance, epidemiology, and end results database analysis between 1973 and 2004. Cancer. 2009;115:5734–5739.
  • Deckert J, Wetzel M-C, Bartle LM, et al. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin Cancer Res. 2014;20:4574–4583.
  • Lonial S, Durie B, Palumbo A, et al. Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives. Leukemia. 2016;30:526–535.
  • Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 2016;6:1106–1117.
  • Touzeau C, Dousset C, Le Gouill S, et al. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia. 2014;28:210–212.
  • Matulis SM, Gupta VA, Nooka AK, et al. Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax. Leukemia. 2016;30:1086–1093.
  • Qin J-Z, Ziffra J, Stennett L, et al. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res. 2005;65:6282–6293.
  • Gomez-Bougie P, Wuillème-Toumi S, Ménoret E, et al. Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma. Cancer Res. 2007;67:5418–5424.
  • Punnoose EA, Leverson JD, Peale F, et al. Expression profile of BCL-2, BCL-XL, and MCL-1 predicts pharmacological response to the BCL-2 selective antagonist venetoclax in multiple myeloma models. Mol Cancer Ther. 2016;15:1132–1144.
  • Moreau P, Chanan-Khan AA, Roberts AW, et al. Venetoclax combined with bortezomib and dexamethasone for patients with relapsed/refractory multiple myeloma. San Diego (CA): ASH; 2016. p. 653. abstract 975.
  • Nemunaitis JJ, Small KA, Kirschmeier P, et al. A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies. J Transl Med. 2013;11:259.
  • Flynn JM, Jones JA, Andritsos L, et al. Update on the phase I study of the cyclin dependent kinase inhibitor dinaciclib (SCH 727965) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL): confirmation of clinical activity and feasibility of long-term administration. Blood. 2010;116:1396.
  • Nguyen TK, Grant S. Dinaciclib (SCH727965) inhibits the unfolded protein response through a CDK1- and 5-dependent mechanism. Mol Cancer Ther. 2014;13:662–674.
  • Obeng EA, Carlson LM, Gutman DM, et al. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107:4907–4916.
  • Zhu YX, Tiedemann R, Shi C-X, et al. RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5. Blood. 2011;117:3847–3857.
  • Tunquist BJ, Woessner RD, Walker DH. Mcl-1 stability determines mitotic cell fate of human multiple myeloma tumor cells treated with the kinesin spindle protein inhibitor ARRY-520. Mol Cancer Ther. 2010;9:2046–2056.
  • Hernández-García S, González-Méndez L, Misiewicz-Krzeminska I, et al. Filanesib primarily initiates the apoptotic program by activating bax through a calpain-dependent mechanism. Blood. 2015;126:5353.
  • LoRusso PM, Goncalves PH, Casetta L, et al. First-in-human phase 1 study of filanesib (ARRY-520), a kinesin spindle protein inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2015;33:440–449.
  • Shah JJ, Feng L, Thomas SK, et al. Phase 1 study of the novel kinesin spindle protein inhibitor filanesib + carfilzomib in patients with relapsed and/or refractory multiple myeloma (RRMM). Blood. 2015;126:376.
  • Chari A, Htut M, Zonder JA, et al. A phase 1 dose-escalation study of filanesib plus bortezomib and dexamethasone in patients with recurrent/refractory multiple myeloma. Cancer. 2016;122:3327–3335.
  • Ocio EM, Motlló C, Rodriguez-Otero P, et al. Safety and efficacy of filanesib in combination with pomalidomide and dexamethasone in refractory MM patients. Phase Ib/II pomdefil clinical trial conducted by the Spanish MM group. San Diego (CA): ASH; 2016. p. 653. abstract 4503.
  • fda, cder. Highlights of prescribing information.
  • Chapman MA, Lawrence MS, Keats JJ, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471:467–472.
  • Lohr JG, Stojanov P, Carter SL, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25:91–101.
  • Bolli N, Avet-Loiseau H, Wedge DC, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997.
  • Walker BA, Wardell CP, Melchor L, et al. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia. 2014;28:384–390.
  • Trudel S, Bahlis NJ, Venner CP, et al. Biomarker driven phase ii clinical trial of trametinib in relapsed/refractory multiple myeloma with sequential addition of the AKT inhibitor, GSK2141795 at time of disease progression to overcome treatment failure: a trial of the princess margaret phase II Consortium. Blood. 2016;128:4526. abstract 128
  • Dumble M, Crouthamel M-C, Zhang S-Y, et al. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. Agoulnik IU editor. Plos One. 2014;9:e100880.
  • Tolcher AW, Patnaik A, Papadopoulos KP, et al. Phase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma. Cancer Chemother Pharmacol. 2015;75:183–189.
  • Müller E, Bauer S, Stühmer T, et al. Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS. Leukemia. 2017;31:922–933.
  • Hsu J, Shi Y, Krajewski S, et al. The AKT kinase is activated in multiple myeloma tumor cells. Blood. 2001;98:2853–2855.
  • Ismail SI, Mahmoud IS, Msallam MM, et al. Hotspot mutations of PIK3CA and AKT1 genes are absent in multiple myeloma. Leuk Res. 2010;34:824–826.
  • Ramakrishnan V, Kimlinger T, Haug J, et al. Anti-myeloma activity of Akt inhibition is linked to the activation status of PI3K/Akt and MEK/ERK pathway. Srivastava RK, editor. Plos One. 2012;7:e50005.
  • Spencer A, Sutherland HJ, O’Dwyer ME, et al. Novel AKT inhibitor afuresertib in combination with bortezomib and dexamethasone demonstrates favorable safety profile and significant clinical activity in patients with relapsed/refractory multiple myeloma. Blood. 2013;122:283.
  • Trudel S, Spencer A, Sutherland H, et al. A phase IB study of the akt inhibitor afuresertib in combination. EHA Learning Center. Copenhagen. Trudel S; Jun 10 2016. p.133260.
  • Cuypers HT, Selten G, Quint W, et al. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell. 1984;37:141–150.
  • Lu J, Zavorotinskaya T, Dai Y, et al. Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylation. Blood. 2013;122:1610–1620.
  • Hiasa M, Teramachi J, Oda A, et al. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma. Leukemia. 2015;29:207–217.
  • Paíno T, Garcia-Gomez A, González-Méndez L, et al. The novel pan-PIM kinase inhibitor, PIM447, displays dual antimyeloma and bone-protective effects, and potently synergizes with current standards of care. Clin Cancer Res. 2017;23:225–238.
  • Keane N, Reidy M, Natoni A, et al. Concurrent inhibition of pim and Akt pathways with pim447 and afuresertib activates FOXO3a and depletes c-myc to induce synergistic cell death in multiple myeloma. Blood. 2015;126:3007.
  • Kortuem KM, Zidich K, Schuster SR, et al. Activity of 129 single-agent drugs in 228 phase I and II clinical trials in multiple myeloma. Clin Lymphoma Myeloma Leuk. 2014;14:284–290.e5.
  • 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;120:552–559.
  • Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–631.
  • A study to evaluate the safety, pharmacokinetics, and efficacy of isatuximab in patients with multiple myeloma - full text view - clinicaltrials.gov [Internet]. [ cited 2017 Feb 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT02514668?term=sar650984&rank=5.
  • Mateos M-V, Hernández M-T, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369:438–447.
  • Leung-Hagesteijn C, Erdmann N, Cheung G, et al. Xbp1s-negative tumor B cells and pre-plasmablasts mediate therapeutic proteasome inhibitor resistance in multiple myeloma. Cancer Cell. 2013;24:289–304.
  • Boise LH, Kaufman JL, Bahlis NJ, et al. The Tao of myeloma. Blood. 2014;124:1873–1879.
  • Mina R, D’Agostino M, Cerrato C, et al. Plasma cell leukemia: update on biology and therapy. Leuk Lymphoma. 2017;58(7):1538–1547.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.