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Drug Evaluation

Update on elotuzumab, a novel anti-SLAMF7 monoclonal antibody for the treatment of multiple myeloma

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Pages 1291-1301 | Received 11 Apr 2016, Accepted 04 Aug 2016, Published online: 17 Aug 2016

References

  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Multiple Myeloma. Version 3; 2016 [cited 2016 Feb 2]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. doi:10.3322/caac.21254.
  • Smith BD, Smith GL, Hurria A, et al. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27:2758–2765. doi:10.1200/JCO.2008.20.8983.
  • Moreau P, San Miguel JF, Ludwig H, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:vi133–vi137. doi:10.1093/annonc/mdt297.
  • Palumbo A, Rajkumar SV, San Miguel JF, et al. International Myeloma working group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol. 2014;32:587–600. doi:10.1200/JCO.2013.48.7934.
  • Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–2520. doi:10.1182/blood-2007-10-116129.
  • Kumar L, Verma R, Radhakrishnan VR. Recent advances in the management of multiple myeloma. Natl Med J India. 2010;23:210–218.
  • Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119:4375–4382. doi:10.1182/blood-2011-11-395749.
  • Holstein SA, Richardson PG, Laubach JP, et al. Management of relapsed multiple myeloma after autologous stem cell transplant. Biol Blood Marrow Transplant. 2015;21:793–798. doi:10.1016/j.bbmt.2014.12.026.
  • 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;26:149–157. doi:10.1038/leu.2011.196.
  • Ninlaro (ixazomib) Prescribing Information. Cambridge, MA: Takeda Pharmaceutical Company Limited; 2015 [cited 4 Mar 2016]. Available from: https://www.ninlarohcp.com/prescribing-information.pdf.
  • Farydak (panobinostat) prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corporation; 2016 [cited 4 Mar 2016]. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/farydak.pdf.
  • Finn OJ. Cancer immunology. N Engl J Med. 2008;358:2704–2715. doi:10.1056/NEJMra072739.
  • Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012;23:viii6–viii9. doi:10.1093/annonc/mds256.
  • Luptakova K, Avigan D. Immune therapy in multiple myeloma. Clin Adv Hematol Oncol. 2015;13:767–775.
  • Darzalex (daratumumab) Prescribing information. Horsham (PA): Janssen Biotech, Inc.; 2015 [cited 4 Mar 2016]. Available from: http://www.darzalex.com/shared/product/darzalex/darzalex-prescribing-information.pdf.
  • 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. doi:10.1016/S0140-6736(15)01120-4.
  • Krejcik J, Casneuf T, Nijhof I, et al. Immunomodulatory effects and adaptive response to daratumumab in multiple myeloma. Blood. 2015;126:3037. [abstract]
  • Raab M, Goldschmidt H, Agis H, et al. A phase I/IIa Study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma. J Clin Oncol. 2015;33(suppl):8574. [abstract]
  • Empliciti (elotuzumab) prescribing Information. Princeton (NJ): Bristol-Myers Squibb; 2015 [cited 4 Mar 2016]. Available from: http://packageinserts.bms.com/pi/pi_empliciti.pdf.
  • 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;14:2775–2784. doi:10.1158/1078-0432.CCR-07-4246.
  • Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–631.
  • ClinicalTrials.gov. Phase III Study of lenalidomide and dexamethasone with and without elotuzumab to treat newly diagnosed, previously untreated multiple myeloma. 2015 [cited 2016 Apr 3]. Available from: https://clinicaltrials.gov/ct2/show/NCT01335399?term=01335399&rank=1.
  • Tai YT, Dillon M, Song W, et al. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood. 2008;112:1329–1337. doi:10.1182/blood-2007-08-107292.
  • Glavey S, Reagan M, Manier S, et al. Dissecting the mechanisms of activity of SLAMF7 and the targeting antibody elotuzumab in multiple myeloma. Blood. 2014;124:3431.
  • 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;62:1841–1849. doi:10.1007/s00262-013-1493-8.
  • Guo H, Cruz-Munoz ME, Wu N, et al. Immune cell inhibition by SLAMF7 is mediated by a mechanism requiring Src kinases, CD45, and SHIP-1 that is defective in multiple myeloma cells. Mol Cell Biol. 2015;35:41–51. doi:10.1128/MCB.01107-14.
  • Lonial S, Kaufman JL, Laubach J, et al. Elotuzumab: a novel anti-CS1 monoclonal antibody for the treatment of multiple myeloma. Expert Opin Biol Ther. 2013;13:1731–1740. doi:10.1517/14712598.2013.847919.
  • Bezman N, Kearney A, Praveen P, et al. Differential effects of elotuzumab (anti-SLAMF7) and anti-CD38 monoclonal antibodies in preclinical models. Haematologica. 2016;101:[P646].
  • 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. doi:10.1182/blood-2011-06-360552.
  • Jakubowiak AJ, Benson DM, Bensinger W, et al. Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma. J Clin Oncol. 2012;30:1960–1965. doi:10.1200/JCO.2011.37.7069.
  • Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol. 2012;30:1953–1959. doi:10.1200/JCO.2011.37.2649.
  • Berdeja J, Jagannath S, Zonder J, et al. Pharmacokinetics and safety of elotuzumab in combination with lenalidomide and dexamethasone in patients with multiple myeloma and various levels of renal impairment: results of a phase 1b study. Clin Lymphoma Myeloma Leuk. 2016;16:129–138.
  • Berenson J, Swift R, Hobson S, et al. Elotuzumab administered over approximately 60 minutes in combination with lenalidomide and dexamethasone in patients with multiple myeloma: a phase 2 safety study. J Oncol Pharm Pract. 2016;22:22–3[CT31].
  • Richardson PG, Jagannath S, Moreau P, et al. 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. 2015;2:e516–e527.
  • Jakubowiak A, Offidani M, Pegourie B, et al. A randomized, open-label, Phase 2 study of bortezomib and dexamethasone with and without elotuzumab in patients with relapsed/refractory multiple myeloma. The 20th Congress of the European Hematology Association (EHA); 2015 June 11–14; Vienna, Austria, The European Hematology Association (EHA), S103 [Oral].
  • Palumbo A, Offidani M, Pegourie B, et al. Elotuzumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma: 2-year follow-up. Blood. 2015;126:510. [abstract]
  • Dimopoulos MA, Lonial S, White D, et al. ELOQUENT-2 update: a phase 3, randomized, open-label study of elotuzumab in combination with lenalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma - 3-year safety and efficacy follow-up. Blood. 2015;126:2093. [abstract]
  • Dimopoulos M, Alegre A, Stadtmauer EA, et al. The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function. Cancer. 2010;116:3807–3814. doi:10.1002/cncr.25139.
  • Klein U, Neben K, Hielscher T, et al. Lenalidomide in combination with dexamethasone: effective regimen in patients with relapsed or refractory multiple myeloma complicated by renal impairment. Ann Hematol. 2011;90:429–439. doi:10.1007/s00277-010-1080-4.
  • 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;127:2833–2840. doi:10.1182/blood-2016-01-694604.
  • Poulart V, Jou Y-M, Delmonte T, et al. Fc-gamma receptor polymorphisms and progression-free survival: analysis of three clinical trials of elotuzumab in multiple myeloma. Haematologica. 2016;101:[E1281].
  • Genzen JR, Kawaguchi KR, Furman RR. Detection of a monoclonal antibody therapy (ofatumumab) by serum protein and immunofixation electrophoresis. Br J Haematol. 2011;155:123–125. doi:10.1111/j.1365-2141.2011.08644.x.
  • McCudden CR, Voorhees PM, Hainsworth SA, et al. Interference of monoclonal antibody therapies with serum protein electrophoresis tests. Clin Chem. 2010;56:1897–1899. doi:10.1373/clinchem.2010.152116.
  • van de Donk NW, Otten HG, El HO, et al. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA). Clin Chem Lab Med. 2016;54:1105–1109. doi:10.1515/cclm-2015-0888.
  • Dimopoulos M, Lonial S, Casado LF, et al. Elotuzumab: serum protein electrophoresis and immunofixation interference with clinical assessment of M-protein response in relapsed/refractory multiple myeloma (RRMM). Clin Lymphoma Myeloma Leuk. 2015;15:e267–e268. doi:10.1016/j.clml.2015.07.561.
  • Dimopoulos MA, Lonial S, White D, et al. ELOQUENT-2 update: a phase 3, randomized, open-label study of elotuzumab in combination with lenalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma - 3-year safety and efficacy follow-up. 57th Annual Meeting & Exposition of American Society of Hematology (ASH); 2015 December 5–8; Orlando (FL). [Oral #28]. [cited 2016 Mar 4]. Available from: http://www.myelomabeacon.com/docs/ash2015/28.pdf.
  • ClinicalTrials.gov. S1211, bortezomib, dexamethasone, and lenalidomide with and without elotuzumab in treating patients with newly diagnosed high-risk multiple myeloma. 2015 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT01668719?term=NCT01668719&rank=1.
  • ClinicalTrials.gov. A Phase I open label study of the safety and tolerability of elotuzumab (BMS-901608) administered in combination with either lirilumab (BMS-986015) or urelumab (BMS-663513) in subject with multiple myeloma (Study 028) (NCT02252263). 2015 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02252263?term=02252263&rank=1.
  • ClinicalTrials.gov. Japanese study of (BMS-901608) (elotuzumab) in combination with lenalidomide and low dose dexamethasone. 2015 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT01241292.
  • ClinicalTrials.gov. Elotuzumab in autologous stem cell transplantation (ASCT) and lenalidomide maintenance for multiple myeloma. 2016 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02655458?term=NCT02655458&rank=1.
  • ClinicalTrials.gov. Study of elotuzumab with lenalidomide as maintenance after autologous stem cell transplant (ASCT). 2015 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02420860?term=NCT02420860&rank=1.
  • ClinicalTrials.gov. Study of bortezomib, lenalidomide, dexamethasone & elotuzumab in newly diagnosed MM. 2015 [cited 2016] Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02375555?term=NCT02375555&rank=1
  • ClinicalTrials.gov. Safety study of elotuzumab in combination with thalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. 2015 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT01632150?term=NCT01632150&rank=1.
  • ClinicalTrials.gov. Trial of elotuzumab with or without pomalidomide and low-dose dexamethasone to treat refractory and relapsed and refractory multiple myeloma. 2015 [cited 2016 Feb 2]. Available from: https://clinicaltrials.gov/ct2/show/NCT02654132?term=NCT02654132&rank=1.
  • ClinicalTrials.gov. A study of Elotuzumab in combination with pomalidomide and low dose dexamethasone (EPd) in patients with multiple myeloma relapsed or refractory to prior treatment with lenalidomide (Study 142) (NCT02612779). 2015 [cited 2016 Mar 4]. Available from: https://www.clinicaltrial.gov/ct2/show/NCT02612779?term=02612779&rank=1
  • ClinicalTrials.gov. Biomarker study of elotuzumab in high risk smoldering myeloma. 2015 [cited 2016] Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT01441973?term=NCT01441973&rank=1.
  • ClinicalTrials.gov. Trial of combination of elotuzumab and lenalidomide ± dexamethasone in high-risk smoldering multiple myeloma. 2015 [cited 2016. Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02279394?term=NCT02279394&rank=1.
  • ClinicalTrials.gov. PH III study of lenalidomide and dexamethasone with and without elotuzumab to treat previously untreated multiple myeloma (ELO 1 Substudy). 2015 [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT01891643?term=NCT01891643&rank=1.
  • ClinicalTrials.gov. A Phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (GMMG-HD6). 2015 [cited 2016 Mar 4]. Availablefrom: https://clinicaltrials.gov/ct2/show/NCT02495922?term=NCT02495922&rank=1.
  • ClinicalTrials.gov. Study of Combinations of Nivolumab, Elotuzumab, Pomalidomide and Dexamethasone in Multiple Myeloma (CheckMate 602) (NCT02726581). 2016 [cited 2016 Apr 6]. Available from: https://clinicaltrials.gov/ct2/show/NCT02726581.
  • Usmani SZ, Sexton R, Ailawadhi S, et al. Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211. Blood Cancer J. 2015;5:e334. doi:10.1038/bcj.2015.62.
  • EMA. Elotuzumab: Summary of product characteristics. 2016 [cited 2016 May 26]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003967/WC500206673.pdf.

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