Clinical and Pharmacologic Features of Monoclonal Antibodies and Checkpoint Blockade Therapy in Multiple Myeloma

Author(s): Mattia D’Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 32 , 2019

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Abstract:

Background: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies.

Methods: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy.

Results: Anti-CD38 monoclonal antibodies including daratumumab, isatuximab and MOR202 have shown outstanding results in relapsed and/or refractory multiple myeloma patients. The addition of daratumumab to bortezomib-dexamethasone or lenalidomidedexamethasone substantially improved patients’ outcome in this patient population. The anti- SLAMF7 molecule elotuzumab in combination with lenalidomide-dexamethasone showed to be superior to lenalidomide-dexamethasone alone, without adding meaningful toxicity. Checkpoint blockade therapy in combination with immunomodulatory agents produced objective responses in more than 50% of treated patients. However, this combination was also associated with an increase in toxicity and a thorough safety evaluation is currently ongoing.

Conclusion: Monoclonal antibodies are reshaping the standard of care for multiple myeloma and ongoing trials will help physicians to optimize their use in order to further improve patients’ outcome.

Keywords: Multiple myeloma (MM), monoclonal antibodies (mAbs), checkpoint blockade therapy (CBT), SLAMF7, CD38, PD-1, PD-L1.

[1]
Palumbo, A.; Anderson, K. Multiple myeloma. N. Engl. J. Med., 2011, 364(11), 1046-1060.
[http://dx.doi.org/10.1056/NEJMra1011442] [PMID: 21410373]
[2]
Pozzi, S.; Marcheselli, L.; Bari, A.; Liardo, E.V.; Marcheselli, R.; Luminari, S.; Quaresima, M.; Cirilli, C.; Ferri, P.; Federico, M.; Sacchi, S. Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis. Br. J. Haematol., 2013, 163(1), 40-46.
[http://dx.doi.org/10.1111/bjh.12465] [PMID: 23889344]
[3]
Costa, L.J.; Brill, I.K.; Omel, J.; Godby, K.; Kumar, S.K.; Brown, E.E. Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Adv., 2017, 1(4), 282-287.
[http://dx.doi.org/10.1182/bloodadvances.2016002493] [PMID: 29296944]
[4]
D’Agostino, M.; Boccadoro, M.; Smith, E.L. Novel Immunotherapies for Multiple Myeloma. Curr. Hematol. Malig. Rep., 2017, 12(4), 344-357.
[http://dx.doi.org/10.1007/s11899-017-0397-7] [PMID: 28819882]
[5]
Romano, A.; Conticello, C.; Cavalli, M.; Vetro, C.; La Fauci, A.; Parrinello, N.L.; Di Raimondo, F. Immunological dysregulation in multiple myeloma microenvironment. BioMed Res. Int., 2014, 2014198539
[http://dx.doi.org/10.1155/2014/198539] [PMID: 25013764]
[6]
Gay, F.; D’Agostino, M.; Giaccone, L.; Genuardi, M.; Festuccia, M.; Boccadoro, M.; Bruno, B. Immuno-oncologic approaches: CAR-T cells and checkpoint inhibitors. Clin. Lymphoma Myeloma Leuk., 2017, 17(8), 471-478.
[http://dx.doi.org/10.1016/j.clml.2017.06.014] [PMID: 28689001]
[7]
van de Donk, N.W.C.J.; Moreau, P.; Plesner, T.; Palumbo, A.; Gay, F.; Laubach, J.P.; Malavasi, F.; Avet-Loiseau, H.; Mateos, M.V.; Sonneveld, P.; Lokhorst, H.M.; Richardson, P.G. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma. Blood, 2016, 127(6), 681-695.
[http://dx.doi.org/10.1182/blood-2015-10-646810] [PMID: 26631114]
[8]
Dunkelberger, J.R.; Song, W.C. Complement and its role in innate and adaptive immune responses. Cell Res., 2010, 20(1), 34-50.
[http://dx.doi.org/10.1038/cr.2009.139] [PMID: 20010915]
[9]
Dong, J.Q.; Salinger, D.H.; Endres, C.J.; Gibbs, J.P.; Hsu, C.P.; Stouch, B.J.; Hurh, E.; Gibbs, M.A. Quantitative prediction of human pharmacokinetics for monoclonal antibodies: retrospective analysis of monkey as a single species for first-in-human prediction. Clin. Pharmacokinet., 2011, 50(2), 131-142.
[http://dx.doi.org/10.2165/11537430-000000000-00000] [PMID: 21241072]
[10]
Mould, D.R.; Green, B. Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and lessons for drug development. BioDrugs, 2010, 24(1), 23-39.
[http://dx.doi.org/10.2165/11530560-000000000-00000] [PMID: 20055530]
[11]
Vugmeyster, Y.; Xu, X.; Theil, F.P.; Khawli, L.A.; Leach, M.W. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges. World J. Biol. Chem., 2012, 3(4), 73-92.
[http://dx.doi.org/10.4331/wjbc.v3.i4.73] [PMID: 22558487]
[12]
Deaglio, S.; Mehta, K.; Malavasi, F. Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk. Res., 2001, 25(1), 1-12.
[http://dx.doi.org/10.1016/s0145-2126(00)00093-x] [PMID: 11137554]
[13]
Lin, P.; Owens, R.; Tricot, G.; Wilson, C.S. Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple Myeloma. Am. J. Clin. Pathol., 2004, 121(4), 482-488.
[http://dx.doi.org/ 10.1309/74R4-TB90-BUWH-27JX] [PMID: 15080299]
[14]
Dianzani, U.; Funaro, A.; DiFranco, D.; Garbarino, G.; Bragardo, M.; Redoglia, V.; Buonfiglio, D.; De Monte, L.B.; Pileri, A.; Malavasi, F. Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule. J. Immunol., 1994, 153(3), 952-959.
[PMID: 7913116]
[15]
An, G.; Jiang, H.; Acharya, C. SAR 650984, a Therapeutic Anti-CD38 monoclonal antibody, blocks CD38-CD31 interaction in multiple myeloma. Blood, 2014, 124(21), 4729.
[http://dx.doi.org/ https://doi.org/10.1182/blood.V124.21.4729.4729]
[16]
van de Donk, N.W.C.J.; Janmaat, M.L.; Mutis, T.; Lammerts van Bueren, J.J.; Ahmadi, T.; Sasser, A.K.; Lokhorst, H.M.; Parren, P.W. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol. Rev., 2016, 270(1), 95-112.
[http://dx.doi.org/10.1111/imr.12389] [PMID: 26864107]
[17]
Lammerts van Bueren, J.; Jakobs, D.; Kaldenhoven, N. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 Antibodies MOR03087, SAR650984 and Ab79. Blood, 2014, 124(21), 3474.
[http://dx.doi.org/ 10.1182/blood.V124.21.3474.3474]
[18]
Mattes, M.J.; Michel, R.B.; Goldenberg, D.M.; Sharkey, R.M. Induction of apoptosis by cross-linking antibodies bound to human b-lymphoma cells: expression of annexin v binding sites on the antibody cap. Cancer Biother. Radiopharm., 2009, 24(2), 185-193.
[http://dx.doi.org/10.1089/cbr.2008.0567] [PMID: 19409040]
[19]
Oostendorp, M.; Lammerts van Bueren, J.J.; Doshi, P.; Khan, I.; Ahmadi, T.; Parren, P.W.; van Solinge, W.W.; De Vooght, K.M. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy. Transfusion, 2015, 55(6 Pt 2), 1555-1562.
[http://dx.doi.org/ 10.1111/trf.13150] [PMID: 25988285]
[20]
van de Donk, N.W.C.J.; Richardson, P.G.; Malavasi, F. CD38 antibodies in multiple myeloma: back to the future. Blood, 2018, 131(1), 13-29.
[http://dx.doi.org/ 10.1182/blood-2017-06-740944] [PMID: 29118010]
[21]
Kotlikoff, M.I.; Kannan, M.S.; Solway, J.; Deng, K.Y.; Deshpande, D.A.; Dowell, M.; Feldman, M.; Green, K.S.; Ji, G.; Johnston, R.; Lakser, O.; Lee, J.; Lund, F.E.; Milla, C.; Mitchell, R.W.; Nakai, J.; Rishniw, M.; Walseth, T.F.; White, T.A.; Wilson, J.; Xin, H.B.; Woodruff, P.G. Methodologic advancements in the study of airway smooth muscle. J. Allergy Clin. Immunol., 2004, 114(2 Suppl.), S18-S31.
[http://dx.doi.org/ 10.1016/j.jaci.2004.04.040] [PMID: 15309016]
[22]
Engelhardt, M.; Berger, D.P.; Mertelsmann, R.; Duyster, J., Eds.; The Blue Book Chemotherapy Manual Hematology and Oncology; Springer-Verlag: Berlin, 2016.
[23]
Scheid, C.; Munder, M.; Salwender, H.; Engelhardt, M. [Infusion of daratumumab in combination therapies - practical information for the outpatient area]. Dtsch. Med. Wochenschr., 2018, 143(16), 1201-1206.
[http://dx.doi.org/10.1055/a-0595-5397] [PMID: 29874684]
[24]
Köhler, M.; Greil, C.; Hudecek, M.; Lonial, S.; Raje, N.; Wäsch, R.; Engelhardt, M. Current developments in immunotherapy in the treatment of multiple myeloma. Cancer, 2018, 124(10), 2075-2085.
[http://dx.doi.org/10.1002/cncr.31243] [PMID: 29409124]
[25]
Chari, A.; Mark, T.M.; Krishnan, A. Use of montelukast to reduce infusion reactions in an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma. Blood, 2016, 128(22), 2142.
[http://dx.doi.org/ 10.1182/blood.V128.22.2142.2142]
[26]
de Weers, M.; Tai, Y-T.; van der Veer, M.S.; Bakker, J.M.; Vink, T.; Jacobs, D.C.; Oomen, L.A.; Peipp, M.; Valerius, T.; Slootstra, J.W.; Mutis, T.; Bleeker, W.K.; Anderson, K.C.; Lokhorst, H.M.; van de Winkel, J.G.; Parren, P.W. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J. Immunol., 2011, 186(3), 1840-1848.
[http://dx.doi.org/10.4049/jimmunol.1003032] [PMID: 21187443]
[27]
Clemens, P.L.; Yan, X.; Lokhorst, H.M.; Lonial, S.; Losic, N.; Khan, I.; Jansson, R.; Ahmadi, T.; Lantz, K.; Zhou, H.; Puchalski, T.; Xu, X.S. Pharmacokinetics of Daratumumab following intravenous infusion in relapsed or refractory multiple myeloma after prior proteasome inhibitor and immunomodulatory drug treatment. Clin. Pharmacokinet., 2017, 56(8), 915-924.
[http://dx.doi.org/10.1007/s40262-016-0477-1] [PMID: 27896689]
[28]
Lokhorst, H.M.; Plesner, T.; Laubach, J.P. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N. Engl. J. Med., 2015, 373, 1207-1219.
[http://dx.doi.org/10.1056/NEJMoa1506348]
[29]
Zirkelbach, J.F.; Habtermariam, B.; Ma, L. 761036Orig1s000. Clinical Pharmacology and Biopharmaceutics Review(s). 2017. Accessed on: Dec. 14, 2017). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/761036Orig1s000ClinPharmR.pdf
[30]
Lonial, S.; Weiss, B.M.; Usmani, S.Z.; Singhal, S.; Chari, A.; Belch, N.J.B.; Krishnan, A.Y.; Vescio, R.A.; Mateos, M-V.; Mazumder, A.; Orlowski, R.Z.; Sutherland, H.J.; Blade, J.; Scott, E.C.; Feng, H.; Khan, I.; Uhlar, C.M.; Ahmadi, T.; Voorhees, P.M. Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). J. Clin. Oncol., 2015, 33Abstract LBA8512.
[31]
Xu, X.; Yan, X.; Puchalski, T.; Lonial, S.; Lokhorst, H.M.; Voorhees, P.M.; Plesner, T.; Liu, K.; Khan, I.; Jansson, R.; Ahmadi, T.; Ruixo, J.P.; Zhou, H.; Clemens, P.L. Clinical implications of complex pharmacokinetics for daratumumab dose regimen in patients with relapsed/refractory multiple myeloma. Clin. Pharmacol. Ther., 2017, 101(6), 721-724.
[http://dx.doi.org/10.1002/cpt.577] [PMID: 27859027]
[32]
Palumbo, A.; Chanan-Khan, A.; Weisel, K. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N. Engl. J. Med., 2016, 375, 754-766.
[http://dx.doi.org/10.1056/NEJMoa1606038]
[33]
Dimopoulos, M.A.; Oriol, A.; Nahi, H.; San-Miguel, J.; Bahlis, N.J.; Usmani, S.Z.; Rabin, N.; Orlowski, R.Z.; Komarnicki, M.; Suzuki, K.; Plesner, T.; Yoon, S-S.; Yehuda, D.B.; Richardson, P.G.; Goldschmidt, H.; Reece, D.; Lisby, S.; Khokhar, N.Z.; O’Rourke, L.; Chiu, C.; Qin, X.; Guckert, M.; Ahmadi, T.; Moreau, P. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N. Engl. J. Med., 2016, 375, 1319-1331.
[http://dx.doi.org/10.1056/NEJMoa1607751]
[34]
Plesner, T.; Arkenau, H-T.; Gimsing, P.; Krejcik, J.; Lemech, C.; Minnema, M.C.; Lassen, U.; Laubach, J.P.; Palumbo, A.; Lisby, S.; Basse, L.; Wang, J.; Sasser, A.K.; Guckert, M.E.; de Boer, C.; Khokhar, N.Z.; Yeh, H.; Clemens, P.L.; Ahmadi, T.; Lokhorst, H.M.; Richardson, P.G. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood, 2016, 128(14), 1821-1828.
[http://dx.doi.org/10.1182/blood-2016-07-726729] [PMID: 27531679]
[35]
Weisel, K.C.; San Miguel, J.; Cook, G.; Leiba, M.; Suzuki, K.; Kumar, S.; Cavo, M.; Avet-Loiseau, H.; Quach, H.; Hungria, V.; Lentzsch, S.; Hajek, R.; Sonneveld, P.; Wu, K.; Qin, X.; Chiu, C.; Soong, D.; Qi, M.; Schecter, J.M.; Dimopoulos, M.A. Efficacy of daratumumab in combination with lenalidomide plus dexamethasone (DRd) or bortezomib plus dexamethasone (DVd) in relapsed or refractory multiple myeloma (RRMM) based on cytogenetic risk status. J. Clin. Oncol., 2017, 35(15), 8006.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.8006]
[36]
Chari, A.; Suvannasankha, A.; Fay, J.W.; Arnulf, B.; Kaufman, J.L.; Ifthikharuddin, J.J.; Weiss, B.M.; Krishnan, A.; Lentzsch, S.; Comenzo, R.; Wang, J.; Nottage, K.; Chiu, C.; Khokhar, N.Z.; Ahmadi, T.; Lonial, S. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood, 2017, 130(8), 974-981.
[http://dx.doi.org/10.1182/blood-2017-05-785246] [PMID: 28637662]
[37]
San Miguel, J.; Weisel, K.; Moreau, P.; Lacy, M.; Song, K.; Delforge, M.; Karlin, L.; Goldschmidt, H.; Banos, A.; Oriol, A.; Alegre, A.; Chen, C.; Cavo, M.; Garderet, L.; Ivanova, V.; Martinez-Lopez, J.; Belch, A.; Palumbo, A.; Schey, S.; Sonneveld, P.; Yu, X.; Sternas, L.; Jacques, C.; Zaki, M.; Dimopoulos, M. 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(11), 1055-1066.
[http://dx.doi.org/10.1016/S1470-2045(13)70380-2] [PMID: 24007748]
[38]
DARZALEX®. Daratumumab. Product Information. JANSSEN-CILAG Pty Ltd. Macquarie Park NSW 2113-- Auckland (AU--NZN); 2017. Available at:. http://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/darzalex_pi.pdf [Accessed: 2017 Dec 15]
[39]
Mateos, M-V.; Dimopoulos, M.A.; Cavo, M.; Suzuki, K.; Jakubowiak, A.; Knop, S.; Doyen, C.; Lucio, P.; Nagy, Z.; Kaplan, P.; Pour, L.; Cook, M.; Grosicki, S.; Crepaldi, A.; Liberati, A.M.; Campbell, P.; Shelekhova, T.; Yoon, S-S.; Iosava, G.; Fujisaki, T.; Garg, M.; Chiu, C.; Wang, J.; Carson, R.; Crist, W.; Deraedt, W.; Nguyen, H.; Qi, M.; San-Miguel, J. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N. Engl. J. Med., 2018, 378, 518-528.
[http://dx.doi.org/10.1056/NEJMoa1714678]
[40]
Chari, A.; Nahi, H.; Mateos, M-V. Subcutaneous delivery of daratumumab in patients (pts) with relapsed or refractory multiple myeloma (RRMM): PAVO, an open-label, multicenter, dose escalation phase 1b study. Blood, 2017, 130, 838.
[41]
Usmani, S.Z.; Nahi, H.; Mateos, M-V.; Lokhorst, H.M.; Chari, A.; Kaufman, J.L.; Moreau, P.; Oriol, A.; Plesner, T.; Benboubker, L.; Hellemans, P.; Masterson, T.; Clemens, P.L.; Ahmadi, T.; Liu, K.; San-Miguel, J. 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, 2016, 128(22), 1149.
[http://dx.doi.org/10.1182/blood.V128.22.1149.1149]
[42]
Deckert, J.; Wetzel, M-C.; Bartle, L.M.; Skaletskaya, A.; Goldmacher, V.S.; Vallée, F.; Zhou-Liu, Q.; Ferrari, P.; Pouzieux, S.; Lahoute, C.; Dumontet, C.; Plesa, A.; Chiron, M.; Lejeune, P.; Chittenden, T.; Park, P.U.; Blanc, V. 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(17), 4574-4583.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0695] [PMID: 24987056]
[43]
Martin, T.; Richter, J.; Vij, R.; Cole, C.; Atanackovic, D.; Zonder, J.; Kaufman, J.L.; Bensinger, W.; Dimopoulos, M.A.; Miguel, J.S.; Zimmerman, T.; Lendvai, N.; Hari, P.; Ocio, E.M.; Gasparetto, C.; Kumar, S.; Hsu, K.; Charpentier, E.; Strickland, S.A.; Mikhael, J. A dose finding phase ii trial of isatuximab (SAR650984, Anti-CD38 mAb) as a single agent in relapsed/refractory multiple myeloma. Blood, 2015, 126(23), 509.
[http://dx.doi.org/https://doi.org/10.1182/blood.V126.23.509.509]
[44]
Martin, T.; Strickland, S.; Glenn, M.; Mikhael, J.; Charpentier, E.; Hsu, K. Phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma.Am. Soc. Clin. Oncol; [ASCO] Annu. Meet. Chicago: ASCO. , 2014, p. Poster Abstract 8532.
[45]
D’Agostino, M.; Salvini, M.; Palumbo, A.; Larocca, A.; Gay, F. Novel investigational drugs active as single agents in multiple myeloma. Expert Opin. Investig. Drugs, 2017, 26(6), 699-711.
[http://dx.doi.org/10.1080/13543784.2017.1324571] [PMID: 28448171]
[46]
Martin, T.; Baz, R.; Benson, D.M.; Lendvai, N.; Wolf, J.; Munster, P.; Lesokhin, A.M.; Wack, C.; Charpentier, E.; Campana, F.; Vij, R. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood, 2017, 129(25), 3294-3303.
[http://dx.doi.org/10.1182/blood-2016-09-740787] [PMID: 28483761]
[47]
Mikhael, J.; Richardson, P.G.; Usmani, S.Z.; Raje, N.; Bensinger, W; Kanagavel, D.; Gao, L.; Ziti-ljajic, S.; Anderson, K. A phase Ib study of isatuximab in combination with pomalidomide (Pom) and dexamethasone (Dex) in relapsed/refractory multiple myeloma (RRMM). Am. Soc. Clin. Oncol., 2017.Abstract 144708.
[48]
Tawara, T.; Hasegawa, K.; Sugiura, Y.; Harada, K.; Miura, T.; Hayashi, S.; Tahara, T.; Ishikawa, M.; Yoshida, H.; Kubo, K.; Ishida, I.; Kataoka, S. Complement activation plays a key role in antibody-induced infusion toxicity in monkeys and rats. J. Immunol., 2008, 180(4), 2294-2298.
[http://dx.doi.org/10.4049/jimmunol.180.4.2294] [PMID: 18250438]
[49]
Raab, M.; Chatterjee, M.; Goldschmidt, H.; Agis, H.; Blau, I.W.; Einsele, H.; Engelhardt, M.M.; Ferstl, B.; Gramatzki, M.; Röllig, C.; Weisel, K.C.; Jarutat, T.; Weinelt, D.; Winderlich, M.; Boxhammer, R.; Peschel, C. MOR202 with low-dose dexamethasone (Dex) and in combination with pomalidomide/dex and lenalidomide/dex in relapsed or refractory multiple myeloma (RRMM): interim analysis of a phase I/IIa dose-escalation study. J. Clin. Oncol., 2017, 35(Suppl. 15), 8024.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.8024]
[50]
Raab, M.S.; Goldschmidt, H.; Agis, H.; Agis, H.; Blau, I.; Einsele, H.; Engelhardt, M.M.; Ferstl, B.; Gramatzki, M.; Röllig, C.; Weisel, K. Kloepfer, p.; Weinelt, D.; Härtle, S.; Peschel, C. A phase I/IIa study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma (rrMM). J. Clin. Oncol., 2015.Abstract 8574.
[http://dx.doi.org/www.myelomabeacon.com/docs/asco2015/8574.pdf]
[51]
Veillette, A.; Guo, H. CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma. Crit. Rev. Oncol. Hematol., 2013, 88(1), 168-177.
[http://dx.doi.org/10.1016/j.critrevonc.2013.04.003] [PMID: 23731618]
[52]
Cruz-Munoz, M-E.; Dong, Z.; Shi, X.; Zhang, S.; Veillette, A. Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function. Nat. Immunol., 2009, 10(3), 297-305.
[http://dx.doi.org/10.1038/ni.1693] [PMID: 19151721]
[53]
Tai, Y-T.; Dillon, M.; Song, W.; Leiba, M.; Li, X.F.; Burger, P.; Lee, A.I.; Podar, K.; Hideshima, T.; Rice, A.G.; van Abbema, A.; Jesaitis, L.; Caras, I.; Law, D.; Weller, E.; Xie, W.; Richardson, P.; Munshi, N.C.; Mathiot, C.; Avet-Loiseau, H.; Afar, D.E.; Anderson, K.C. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood, 2008, 112(4), 1329-1337.
[http://dx.doi.org/10.1182/blood-2007-08-107292] [PMID: 17906076]
[54]
Zonder, J.A.; Mohrbacher, A.F.; Singhal, S.; van Rhee, F.; Bensinger, W.I.; Ding, H.; Fry, J.; Afar, D.E.; Singhal, A.K. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood, 2012, 120(3), 552-559.
[http://dx.doi.org/10.1182/blood-2011-06-360552] [PMID: 22184404]
[55]
Lonial, S.; Vij, R.; Harousseau, J-L.; Facon, T.; Moreau, P.; Mazumder, A.; Kaufman, J.L.; Leleu, X.; Tsao, L.C.; Westland, C.; Singhal, A.K.; Jagannath, S. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J. Clin. Oncol., 2012, 30(16), 1953-1959.
[http://dx.doi.org/10.1200/JCO.2011.37.2649] [PMID: 22547589]
[56]
Jakubowiak, A.; Offidani, M.; Pégourie, B.; De La Rubia, J.; Garderet, L.; Laribi, K.; Bosi, A.; Marasca, R.; Laubach, J.; Mohrbacher, A.; Carella, A.M.; Singhal, A.K.; Tsao, L.C.; Lynch, M.; Bleickardt, E.; Jou, Y.M.; Robbins, M.; Palumbo, A. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood, 2016, 127(23), 2833-2840.
[http://dx.doi.org/10.1182/blood-2016-01-694604] [PMID: 27091875]
[57]
Lonial, S.; Dimopoulos, M.; Palumbo, A.; White, D.; Grosicki, S.; Spicka, I.; Walter-Croneck, A.; Moreau, P.; Mateos, M.V.; Magen, H.; Belch, A.; Reece, D.; Beksac, M.; Spencer, A.; Oakervee, H.; Orlowski, R.Z.; Taniwaki, M.; Röllig, C.; Einsele, H.; Wu, K.L.; Singhal, A.; San-Miguel, J.; Matsumoto, M.; Katz, J.; Bleickardt, E.; Poulart, V.; Anderson, K.C.; Richardson, P. Elotuzumab therapy for relapsed or refractory multiple myeloma. N. Engl. J. Med., 2015, 373(7), 621-631.
[http://dx.doi.org/10.1056/NEJMoa1505654] [PMID: 26035255]
[58]
Dimopoulos, M.A.; Lonial, S.; White, D. Phase 3 Eloquent-2 Study: Extended 4-Year Follow-Up of Elotuzumab Plus Lenalidomide/Dexamethasone Vs Lenalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma. Eur. Hematol. Assoc; EHA Learning Center: Madrid, 2017, p. 181754.Available at:. https://learningcenter.ehaweb.org/eha/2017/22nd/18 1743/meletios.a.dimopoulos.phase.3.eloquent-2.study.extended.4-year.follow-up.of.html [Accessed: 2018 Feb 1]
[59]
Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[60]
Riley, J.L. PD-1 signaling in primary T cells. Immunol. Rev., 2009, 229(1), 114-125.
[http://dx.doi.org/10.1111/j.1600-065X.2009.00767.x] [PMID: 19426218]
[61]
Day, C.L.; Kaufmann, D.E.; Kiepiela, P.; Brown, J.A.; Moodley, E.S.; Reddy, S.; Mackey, E.W.; Miller, J.D.; Leslie, A.J.; DePierres, C.; Mncube, Z. Duraiswamy. J.; Zhu, B.; Eichbaum, Q.; Altfeld, M.; Wherry, E.J.; Coovadia, H.M.; Goulder, P.J.; Klenerman, P.; Ahmed, R.; Freeman, G.J.; Walker, B.D. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature, 2006, 443(7019), 350-354.
[http://dx.doi.org/10.1038/nature05115] [PMID: 16921384]
[62]
Nishimura, H.; Nose, M.; Hiai, H.; Minato, N.; Honjo, T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM Motif-carrying immunoreceptor. Immunity, 1999, 11(2), 141-151.
[http://dx.doi.org/10.1016/s1074-7613(00)80089-8] [PMID: 10485649]
[63]
Latchman, Y.; Wood, C.R.; Chernova, T.; Chaudhary, D.; Borde, M.; Chernova, I.; Iwai, Y.; Long, A.J.; Brown, J.A.; Nunes, R.; Greenfield, E.A.; Bourque, K.; Boussiotis, V.A.; Carter, L.L.; Carreno, B.M.; Malenkovich, N.; Nishimura, H.; Okazaki, T.; Honjo, T.; Sharpe, A.H.; Freeman, G.J. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol., 2001, 2(3), 261-268.
[http://dx.doi.org/10.1038/85330] [PMID: 11224527]
[64]
Brahmer, J.R.; Drake, C.G.; Wollner, I.; Powderly, J.D.; Picus, J.; Sharfman, W.H.; Stankevich, E.; Pons, A.; Salay, T.M.; McMiller, T.L.; Gilson, M.M.; Wang, C.; Selby, M.; Taube, J.M.; Anders, R.; Chen, L.; Korman, A.J.; Pardoll, D.M.; Lowy, I.; Topalian, S.L. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol., 2010, 28(19), 3167-3175.
[http://dx.doi.org/10.1200/JCO.2009.26.7609] [PMID: 20516446]
[65]
OPDIVO® (nivolumab) injection, for intravenous use - Full prescribing information. Available at:. https://packageinserts.bms.com/pi/pi_opdivo.pdf [Accessed: 2017 December14]
[66]
Lesokhin, A.M.; Ansell, S.M.; Armand, P.; Scott, E.C.; Halwani, A.; Gutierrez, M.; Millenson, M.M.; Cohen, A.D.; Schuster, S.J.; Lebovic, D.; Dhodapkar, M.; Avigan, D.; Chapuy, B.; Ligon, A.H.; Freeman, G.J.; Rodig, S.J.; Cattry, D.; Zhu, L.; Grosso, J.F.; Bradley Garelik, M.B.; Shipp, M.A.; Borrello, I.; Timmerman, J. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a Phase Ib Study. J. Clin. Oncol., 2016, 34(23), 2698-2704.
[http://dx.doi.org/10.1200/JCO.2015.65.9789] [PMID: 27269947]
[67]
Funt, S.A.; Page, D.B.; Cattry, D.; Lendvai, N.; Hassoun, H.; Landgren, O.; Borrello, I.M.; Lesokhin, A.M. The long PD-1 receptor binding kinetics of Nivolumab may increase efficacy of subsequent therapy in relapsed and refractory multiple myeloma patients. Blood, 2015, 126(23), 3057.
[http://dx.doi.org/10.1182/blood.V126.23.3057.3057]
[68]
Ahamadi, M.; Freshwater, T.; Prohn, M.; Li, C.H.; de Alwis, D.P.; de Greef, R.; Elassaiss-Schaap, J.; Kondic, A.; Stone, J.A. Model-based characterization of the pharmacokinetics of pembrolizumab: A humanized anti-PD-1 monoclonal antibody in advanced solid tumors. CPT Pharmacometrics Syst. Pharmacol., 2017, 6(1), 49-57.
[http://dx.doi.org/10.1002/psp4.12139] [PMID: 27863186]
[69]
Mateos, M-V.; Orlowski, R.Z.; Siegel, D.S.D.; Reece, D.A.; Moreau, P.; Ocio, E.M.; Shah, J.J.; Rodríguez-Otero, P.; Munshi, N.C.; Avigan, D.; Ge, J.Y.; Marinello, P.M.; Miguel, J.S. Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma (RRMM): Final efficacy and safety analysis. J. Clin. Oncol., 2016, 34(Suppl. 15), 8010.
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.8010]
[70]
Badros, A.; Hyjek, E.; Ma, N.; Lesokhin, A.; Dogan, A.; Rapoport, A.P.; Kocoglu, M.; Lederer, E.; Philip, S.; Milliron, T.; Dell, C.; Goloubeva, O.; Singh, Z. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood, 2017, 130(10), 1189-1197.
[http://dx.doi.org/10.1182/blood-2017-03-775122] [PMID: 28461396]
[71]
U.S. Food & Drug Administration [FDA] - Center for Drug Evaluation and Research. FDA Alerts Healthcare Professionals and Oncology Clinical Investigators about Two Clinical Trials on Hold Evaluating KEYTRUDA® (pembrolizumab) in Patients with Multiple Myeloma. Available from:. https://www.fda.gov/Drugs/DrugSafety/ucm574305.htm [Accessed: 2017 Dec 15]
[72]
Baverel, P.; Dubois, V.; Jin, C.; Xuyang, Song.; Jin, X.; Mukhopadhyay, P.; Gupta, A.K.; Dennis, P.A.; Ben, Y.; Roskos, L.; Narwal, R. Population pharmacokinetics of durvalumab and fixed dosing regimens in patients with advanced solid tumors. J. Clin. Oncol., 2017, 35(Suppl. 15), 2566.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.2566]
[73]
Dimopoulos, M.A.; Lonial, S.; White, D.; Moreau, P.; Palumbo, A.; Miguel, J.S.; Shpilberg, O.; Anderson, K.C.; Grosicki, S.; Spicka, I.; Walter-Croneck, A.; Magen-Nativ, H.; Mateos, M-V.; Belch, A.; Reece, D.; Beksac, M.; Bleickhardt, E.; Poulart, V.; Katz, J.; Singhal, A.K.; Richardson, P.G. 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(23), 28.
[http://dx.doi.org/10.1182/blood.V126.23.28.28]
[74]
DARZALEX®(daratumumab) injection, for intravenous use. Full Prescribing Information 2017. Available from:. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761036s005lbl.pdf [Accessed: 2017 Dec 15]
[75]
Gibiansky, L.; Passey, C.; Roy, A.; Bello, A.; Gupta, M. Model-based pharmacokinetic analysis of elotuzumab in patients with relapsed/refractory multiple myeloma. J. Pharmacokinet. Pharmacodyn., 2016, 43(3), 243-257.
[http://dx.doi.org/10.1007/s10928-016-9469-x] [PMID: 26993283]
[76]
Waddell, J.A.; Solimando, D.A. Jr. Alectinib, Ceritinib, Elotuzumab, and Venetoclax. Hosp. Pharm., 2016, 51(7), 524-534.
[http://dx.doi.org/10.1310/hpj5107-524] [PMID: 27559185]
[77]
Elassaiss-Schaap, J.; Rossenu, S.; Lindauer, A.; Kang, S.P.; de Greef, R.; Sachs, J.R.; de Alwis, D.P. Using model-based “learn and confirm” to reveal the pharmacokinetics-pharmacodynamics relationship of pembrolizumab in the KEYNOTE-001 trial. CPT Pharmacometrics Syst. Pharmacol., 2017, 6(1), 21-28.
[http://dx.doi.org/10.1002/psp4.12132] [PMID: 27863143]
[78]
Freshwater, T.; Kondic, A.; Ahamadi, M.; Li, C.H.; de Greef, R.; de Alwis, D.; Stone, J.A. Evaluation of dosing strategy for pembrolizumab for oncology indications. J. Immunother. Cancer, 2017, 5, 43.
[http://dx.doi.org/10.1186/s40425-017-0242-5] [PMID: 28515943]
[79]
Bajaj, G.; Wang, X.; Agrawal, S.; Gupta, M.; Roy, A.; Feng, Y. Model-based population pharmacokinetic analysis of Nivolumab in patients with solid tumors. CPT Pharmacometrics Syst. Pharmacol., 2017, 6(1), 58-66.
[http://dx.doi.org/10.1002/psp4.12143] [PMID: 28019091]
[80]
Yamamoto, N.; Nokihara, H.; Yamada, Y.; Shibata, T.; Tamura, Y.; Seki, Y.; Honda, K.; Tanabe, Y.; Wakui, H.; Tamura, T. Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors. Invest. New Drugs, 2017, 35(2), 207-216.
[http://dx.doi.org/10.1007/s10637-016-0411-2] [PMID: 27928714]
[81]
Jeanson, A.; Barlesi, F. MEDI 4736 (durvalumab) in non-small cell lung cancer. Expert Opin. Biol. Ther., 2017, 17(10), 1317-1323.
[http://dx.doi.org/10.1080/14712598.2017.1351939] [PMID: 28705024]


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