Melphalan hydrochloride for the treatment of multiple myeloma

References

• Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008 Mar 15;111(6):2962–2972.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17; 364(11):1046–1060.
   PubMed Web of Science ®Google Scholar
• Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004 Oct 28;351(18):1860–1873.
   PubMed Web of Science ®Google Scholar
• Moreau P, Attal M, Facon T. Frontline therapy of multiple myeloma. Blood. 2015 May 14;125(20):3076–3084.
   PubMed Web of Science ®Google Scholar
• Rajkumar SV, Harousseau JL. Next-generation multiple myeloma treatment: a pharmacoeconomic perspective. Blood. 2016 Dec 15;128(24):2757–2764.
   PubMed Web of Science ®Google Scholar
• Bianchi G, Munshi NC. Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood. 2015 May 14;125(20):3049–3058.
   PubMed Web of Science ®Google Scholar
• Medicines Agency E Guideline on good pharmacovigilance practices (GVP) Module VIII – Post-authorisation safety studies (Rev 2) Date for coming into effect of first version 2 July 2012 Date for coming into effect of Revision 1 Date for coming into effect of Revision 2* [Internet]. 2016. [cited 2017 Apr 21]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129137.pdf
   Google Scholar
• FDA cde. Prescribing information. Alkeran (Melphalan). Internet. [cited 2017 Apr 21]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf
   Google Scholar
• Aljitawi OS, Ganguly S, Abhyankar SH, et al. Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and alkeran in multiple myeloma autologous transplantation. Bone Marrow Transplant. 2014 Aug 9;49(8):1042–1045.
   PubMed Web of Science ®Google Scholar
• Bergel F, Stock J. Cytotoxic alpha amino acids and peptides. Br Emp Cancer Campain. 1953;31:6–7.
   Google Scholar
• Schmidt LH, Fradkin R, Sullivan R, et al. COMPARATIVE PHARMACOLOGY OF ALKYLATING AGENTS. II. THERAPEUTIC ACTIVITIES OF ALKYLATING AGENTS AND REFERENCE COMPOUNDS AGAINST VARIOUS TUMOR SYSTEMS. Cancer Chemother Reports. 1965 Jan;18(SUPPL 2):403.
   Google Scholar
• Polavarapu A, Stillabower JA, Stubblefield SGW, et al. The mechanism of guanine alkylation by nitrogen mustards: a computational study. J Org Chem. 2012 Jul 20;77(14):5914–5921.
   PubMed Web of Science ®Google Scholar
• Vistica DT. Cytotoxicity as an indicator for transport mechanism: evidence that melphalan is transported by two leucine-preferring carrier systems in the L1210 murine leukemia cell. Biochim Biophys Acta. 1979 Jan 19;550(2):309–317.
   PubMed Web of Science ®Google Scholar
• Samuels BL, Bitran JD. High-dose intravenous melphalan: a review. J Clin Oncol. 1995 Jul;13(7):1786–1799.
   PubMed Web of Science ®Google Scholar
• Price CC, Gaucher GM, Koneru P, et al. Relative reactivities for monofunctional nitrogen mustard alkylation of nucleic acid components. Biochim Biophys Acta. 1968 Sep 24;166(2):327–359.
   PubMed Web of Science ®Google Scholar
• Spanswick VJ, Craddock C, Sekhar M, et al. Repair of DNA interstrand crosslinks as a mechanism of clinical resistance to melphalan in multiple myeloma. Blood. 2002 Jul 1;100(1):224–229.
   PubMed Web of Science ®Google Scholar
• Rellick SL, Piktel D, Walton C, et al. Melphalan exposure induces an interleukin-6 deficit in bone marrow stromal cells and osteoblasts. Cytokine. 2012 May;58(2):245–252.
   PubMed Web of Science ®Google Scholar
• Thabard W, Barillé S, Collette M, et al. Myeloma cells release soluble interleukin-6Ralpha in relation to disease progression by two distinct mechanisms: alternative splicing and proteolytic cleavage. Clin Cancer Res. 1999 Oct;5(10):2693–2697.
   PubMed Web of Science ®Google Scholar
• Lu X, Ding Z-C, Cao Y, Liu C, Habtetsion T, Yu M, et al. Alkylating agent melphalan augments the efficacy of adoptive immunotherapy using tumor-specific CD4 + T Cells. J Immunol. 2015 Feb 15;194(4):2011–2021.
   PubMed Web of Science ®Google Scholar
• Alexanian R, Haut A, Khan AU, et al. Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens. Jama. 1969 Jun 2;208(9):1680–1685.
   PubMed Web of Science ®Google Scholar
• San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28;359(9):906–917.
   PubMed Web of Science ®Google Scholar
• Fayers PM, Palumbo A, Hulin C, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011 Aug 4;118(5):1239–1247.
   PubMed Web of Science ®Google Scholar
• Attal M, Harousseau J-L, Stoppa A-M, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996 Jul;335(2):91–97.
   PubMed Web of Science ®Google Scholar
• Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875–1883.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895–905.
   PubMed Web of Science ®Google Scholar
• Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors. Nat Med. 2009 Oct 20;15(10):1170–1178.
   PubMed Web of Science ®Google Scholar
• Sarosy G, Leyland-Jones B, Soochan P, et al. The systemic administration of intravenous melphalan. J Clin Oncol. 1988 Nov;6(11):1768–1782.
   PubMed Web of Science ®Google Scholar
• Choi KE, Ratain MJ, Williams SF, et al. Plasma pharmacokinetics of high-dose oral melphalan in patients treated with trialkylator chemotherapy and autologous bone marrow reinfusion. Cancer Res. 1989 Mar 1;49(5):1318–1321.
   PubMed Web of Science ®Google Scholar
• Loos U, Musch E, Engel M, et al. The pharmacokinetics of melphalan during intermittent therapy of multiple myeloma. Eur J Clin Pharmacol. 1988;35(2):187–193.
   PubMed Web of Science ®Google Scholar
• Reece PA, Kotasek D, Morris RG, et al. The effect of food on oral melphalan absorption. Cancer Chemother Pharmacol. 1986;16(2):194–197.
   PubMed Web of Science ®Google Scholar
• Alberts DS, Chang SY, Chen HS, et al. Kinetics of intravenous melphalan. Clin Pharmacol Ther. 1979 Jul;26(1):73–80.
   PubMed Web of Science ®Google Scholar
• San Miguel JF, Lahuerta JJ, García-Sanz R, et al. Are myeloma patients with renal failure candidates for autologous stem cell transplantation?. Hematol J Off J Eur Haematol Assoc. 2000;1(1):28–36.
   Google Scholar
• Badros A, Barlogie B, Siegel E, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol. 2001 Sep;114(4):822–829.
   PubMed Web of Science ®Google Scholar
• Terpos E, Kleber M, Engelhardt M, et al. European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica. 2015 Oct 1;100(10):1254–1266.
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Terpos E, Chanan-Khan A, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the international myeloma working group. J Clin Oncol. 2010 Nov 20;28(33):4976–4984.
   PubMed Web of Science ®Google Scholar
• Bosanquet AG, Gilby ED. Pharmacokinetics of oral and intravenous melphalan during routine treatment of multiple myeloma. Eur J Cancer Clin Oncol. 1982 Apr;18(4):355–362.
   PubMedGoogle Scholar
• Blokhin N, Larionov L, Perevodchikova N, et al. [Clinical experiences with sarcolysin in neoplastic diseases]. Ann N Y Acad Sci. 1958 Apr 24;68(3):1128–1132.
   PubMed Web of Science ®Google Scholar
• Larocca A, Palumbo A. How I treat fragile myeloma patients. Blood. 2015 Nov 5;126(19):2179–2185.
   PubMed Web of Science ®Google Scholar
• Bayraktar UD, Bashir Q, Qazilbash M, et al. Fifty Years of melphalan use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013 Mar;19(3):344–356.
   PubMed Web of Science ®Google Scholar
• Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of. 6,633 patients from 27 randomized trials. Myeloma Trialists’ Collaborative Group. J Clin Oncol. 1998 Dec;16(12):3832–3842.
   PubMedGoogle Scholar
• Wijermans P, Schaafsma M, Termorshuizen F, et al. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul;28(19):3160–3166.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825–831.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Bringhen S, Liberati AM, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107–3114.
   PubMed Web of Science ®Google Scholar
• Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet (London, England). 2007 Oct 6;370(9594):1209–1218.
   PubMed Web of Science ®Google Scholar
• Hulin C, Facon T, Rodon P, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009 Aug 1;27(22):3664–3670.
   PubMed Web of Science ®Google Scholar
• Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010 Sep 2;116(9):1405–1412.
   PubMed Web of Science ®Google Scholar
• Beksac M, Haznedar R, Firatli-Tuglular T, et al. Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol. 2011 Jan;86(1):16–22.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Hajek R, Delforge M, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759–1769.
   PubMed Web of Science ®Google Scholar
• Zweegman S, Van Der Holt B, Mellqvist U-H, et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 Mar 3;127(9):1109–1116.
   PubMed Web of Science ®Google Scholar
• Davis K, Neese K, Sood A Amgen announces topline results from phase 3 KYPROLIS Carfilzomib CLARION study in newly diagnosed multiple myeloma patients [internet]. 2016. [cited 2017 Apr 21]. Available from: https://www.amgen.com/media/news-releases/2016/09/amgen-announces-topline-results-from-phase-3-kyprolis-carfilzomib-clarion-study-in-newly-diagnosed-multiple-myeloma-patients/
   Google Scholar
• Mateos M-V, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1;28(13):2259–2266.
   PubMed Web of Science ®Google Scholar
• Phase 3 study of carfilzomib, melphalan, prednisone vs bortezomib, melphalan, prednisone in newly diagnosed multiple myeloma (CLARION) (CLARION) [Internet]. [ cited 2017 Apr 27]. Available from: https://clinicaltrials.gov/ct2/show/NCT01818752?term=carfilzomib+melphalan&rank=5 (accessed 1 June, 2017)
   Google Scholar
• McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet (London, England). 1983 Oct 8;2(8354):822–824.
   PubMed Web of Science ®Google Scholar
• Selby PJ, McElwain TJ, Nandi AC, et al. Multiple myeloma treated with high dose intravenous melphalan. Br J Haematol. 1987 May;66(1):55–62.
   PubMed Web of Science ®Google Scholar
• Harousseau JL, Milpied N, Guilhot F, et al. [First-line treatment of severe myelomas of the young subject by high-dose melphalan]. Presse Med. 1983;17(29):1471–1474.
   Google Scholar
• Barlogie B, Alexanian R, Smallwood L, et al. Prognostic factors with high-dose melphalan for refractory multiple myeloma. Blood. 1988 Dec;72(6):2015–2019.
   PubMed Web of Science ®Google Scholar
• Lokhorst HM, Meuwissen OJ, Verdonck LF, et al. High-risk multiple myeloma treated with high-dose melphalan. J Clin Oncol. 1992 Jan;10(1):47–51.
   PubMed Web of Science ®Google Scholar
• Cunningham D, Paz-Ares L, Gore ME, et al. High-dose melphalan for multiple myeloma: long-term follow-up data. J Clin Oncol. 1994 Apr;12(4):764–768.
   PubMed Web of Science ®Google Scholar
• Barlogie B, Jagannath S, Dixon DO, et al. High-dose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma. Blood. 1990 Aug 15;76(4):677–680.
   PubMed Web of Science ®Google Scholar
• Barlogie B, Hall R, Zander A, et al. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298–1301.
   PubMed Web of Science ®Google Scholar
• Barlogie B, Alexanian R, Dicke KA, et al. High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood. 1987 Sep;70(3):869–872.
   PubMed Web of Science ®Google Scholar
• Gay F, Oliva S, Petrucci MT, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617–1629.
   PubMed Web of Science ®Google Scholar
• Cavo M, Palumbo A, Zweegman S, et al. Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): a randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial). J Clin Oncol. 2016;suppl:abstr 8000.
   Google Scholar
• Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017 Apr 6;376(14):1311–1320.
   PubMed Web of Science ®Google Scholar
• Fermand JP, Ravaud P, Chevret S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998 Nov 1;92(9):3131–3136.
   PubMed Web of Science ®Google Scholar
• Bladé J, Rosiñol L, Sureda A, et al. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005 Dec 1;106(12):3755–3759.
   PubMed Web of Science ®Google Scholar
• Fermand J-P, Katsahian S, Divine M, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005 Dec 20;23(36):9227–9233.
   PubMed Web of Science ®Google Scholar
• Barlogie B, Kyle RA, Anderson KC, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup trial S9321. J Clin Oncol. 2006 Feb 20;24(6):929–936.
   PubMed Web of Science ®Google Scholar
• Gay F, Oliva S, Petrucci MT, et al. Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis. Leukemia. 2016 Dec 23.
   Google Scholar
• Moreau P, Milpied N, Mahé B, et al. Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma. Bone Marrow Transplant. 1999 May 25;23(10):1003–1006.
   PubMed Web of Science ®Google Scholar
• Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002 Feb 1;99(3):731–735.
   PubMed Web of Science ®Google Scholar
• Blanes M, Lahuerta JJ, González JD, et al. Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant. 2013 Jan;19(1):69–74.
   PubMed Web of Science ®Google Scholar
• Palumbo A, Bringhen S, Bruno B, et al. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010 Mar 11;115(10):1873–1879.
   PubMed Web of Science ®Google Scholar
• 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 Sep 1;6(9):2409–2417.
   PubMed Web of Science ®Google Scholar
• Chauhan D, Ray A, Viktorsson K, et al. In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells. Clin Cancer Res. 2013 Jun 1;19(11):3019–3031.
   PubMed Web of Science ®Google Scholar
• 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 May 1;79(9):1281–1290.
   PubMed Web of Science ®Google Scholar
• Strese S, Wickström M, Fuchs PF, et al. The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo. Biochem Pharmacol. 2013 Oct;86(7):888–895.
   PubMed Web of Science ®Google Scholar
• 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;126:23.
   Web of Science ®Google Scholar
• 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 (accessed 1 June, 2017)
   Google Scholar
• Hari P, Aljitawi OS, Arce-Lara C, et al. A Phase IIb, multicenter, open-label, safety, and efficacy study?of high-dose, propylene glycol-free melphalan hydrochloride for injection (EVOMELA) for myeloablative conditioning in multiple myeloma patients undergoing autologous transplantation. Biol Blood Marrow Transplant. 2015 Dec;21(12):2100–2105.
   PubMed Web of Science ®Google Scholar
• US Food & Drug Administration. Questions and Answers on FDA’s Adverse Event Reporting System (FAERS) [Internet]. Center for Drug Evaluation and Research; 2009. [cited 2017 Apr 21]. Available from: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm
   Google Scholar
• US Food & Drug Administration. FDA adverse events reporting system (FAERS) - FAERS reporting by healthcare providers and consumers by year [Internet]. Center for Drug Evaluation and Research; 2011. [cited 2017 Apr 21]. Available from: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm070456.htm
   Google Scholar
• Fda, Cder. Guideline for postmarketing reporting of adverse drug experiences [Internet]. [ cited 2017 Apr 21]. p. 301–827. Available from: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm299138.pdf (accessed 1 June, 2017)
   Google Scholar
• CFR - Code of Federal Regulations Title 21 [Internet]. [ cited 2017 Apr 28]. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=201.57 (accessed 1 June, 2017)
   Google Scholar
• Garg V, Raisch DW, McKoy JM, et al. Impact of United States food and drug administration’s boxed warnings on adverse drug reactions reporting rates and risk mitigation for multiple myeloma drugs. Expert Opin Drug Saf. 2013 May 12;12(3):299–307.
   PubMed Web of Science ®Google Scholar
• Fram DM, Almenoff JS, DuMouchel W Empirical Bayesian data mining for discovering patterns in post-marketing drug safety. In: Proceedings of the ninth ACM SIGKDD international conference on Knowledge discovery and data mining - KDD ’03. New York, New York, USA: ACM Press; 2003. p. 359.
   Google Scholar
• Inoba A, Kadoyama K, Minami K, et al. Anti-multiple myeloma drug-associated taste dysfunction: an analysis of the FAERS database. Asian J Pharm Sci. 2016;11(1):140–141.
   Google Scholar
• Facon T, Mary J-Y, Pégourie B, et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292–1298.
   PubMed Web of Science ®Google Scholar
• Hernández JM, García-Sanz R, Golvano E, et al. Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma. Br J Haematol. 2004 Oct;127(2):159–164.
   PubMed Web of Science ®Google Scholar
• McElwain TJPR. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983;2(8354):822–824.
   PubMed Web of Science ®Google Scholar
• H V W, Clarkson JE, Bryan G, et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. In: Worthington HV, editor. Cochrane database of systematic reviews. Chichester, UK: John Wiley & Sons, Ltd; 2011.
   Google Scholar
• Spencer A, Horvath N, Gibson J, et al. Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplant. 2005 May 21;35(10):971–977.
   PubMed Web of Science ®Google Scholar
• Sweiss K, Patel S, Culos K, et al. Melphalan 200 mg/m(2) in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival. Bone Marrow Transplant. 2016 Oct 16;51(10):1337–1341.
   PubMed Web of Science ®Google Scholar
• Drugs@FDA: FDA Approved Drug Products [Internet]. [ cited 2017 Apr 28]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=014691 (accessed 30 May, 2017)
   Google Scholar
• Drugs@FDA: FDA Approved Drug Products [Internet]. [ cited 2017 Apr 28]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020207 (accessed 30 May, 2017)
   Google Scholar
• Drugs@FDA: FDA Approved Drug Products [Internet]. [ cited 2017 Apr 28]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=207809 (accessed 30 May, 2017)
   Google Scholar
• Lindberg J Oncopeptides Receives EMA and FDA Orphan Drug Designation for Melflufen in the Treatment of Multiple Myeloma – Oncopeptides [Internet]. 2015. [cited 2017 Apr 21]. Available from: https://www.oncopeptides.se/en/oncopeptides-receives-ema-and-fda-orphan-drug-designation-for-melflufen-in-the-treatment-of-multiple-myeloma/
   Google Scholar
• Drugs@FDA: FDA Approved Drug Products [Internet]. [ cited 2017 Apr 28]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=207155 (accessed 1 June, 2017)
   Google Scholar
• Fda, Cder. HIGHLIGHTS OF PRESCRIBING INFORMATION.
   Google Scholar
• Moreau P, Rajkumar SV. Multiple myeloma–translation of trial results into reality. Lancet (London, England). 2016 Jul 9;388(10040):111–113.
   PubMed Web of Science ®Google Scholar
• Niphadkar S, Varadarajan I, Pompa T, et al. Autologous stem cell transplant: a cost effective and efficacious treatment for newly diagnosed multiple myeloma. Blood. 2016;128(22):abstract2358.
   Google Scholar
• Lisenko K, Sauer S, Bruckner T, et al. High-dose chemotherapy and autologous stem cell transplantation of patients with multiple myeloma in an outpatient setting. BMC Cancer. 2017 Feb 22;17(1):151.
   PubMed Web of Science ®Google Scholar