Role of investigational monoclonal antibodies in the treatment of multiple myeloma: A systematic review.

Hamza Hassan Rochester General Hospital, Rochester, NY info_outline Hamza Hassan, Ahmad Iftikhar, Nimra Iftikhar, Adeela Mushtaq, Abdul Rafae, Faryal Razzaq, Jason Neil Valent, Abraham Sebastian Kanate, Rajshekhar Chakraborty, Faiz Anwer

Authors Hamza Hassan Rochester General Hospital, Rochester, NY info_outline Hamza Hassan, Ahmad Iftikhar, Nimra Iftikhar, Adeela Mushtaq, Abdul Rafae, Faryal Razzaq, Jason Neil Valent, Abraham Sebastian Kanate, Rajshekhar Chakraborty, Faiz Anwer Organizations Rochester General Hospital, Rochester, NY, University Of Arizona, Tucson, AZ, Rawalpindi Medical University, Rawalpindi, Pakistan, University of Arizona, Tucson, AZ, Cleveland Clinic, Eastlake, OH, West Virginia University, Morgantown, WV, Cleveland Clinic, Cleveland, OH, Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland, OH Abstract Disclosures Research Funding Other Background: Immunotherapy for multiple myeloma (MM) has been of focus in recent years due to its myeloma-specific immune responses. We reviewed literature on non-FDA approved monoclonal antibodies (MoAbs) to highlight future perspectives. Methods: We searched PubMed, EMBASE, Web of Science, Cochrane and Clinicaltrilas.gov to include phase I/II clinical trials. Results: 40 studies (1917 patients) were included. Isatuximab (anti-CD38) and F50067 (anti-CXCR4) were the only MoAbs which produced encouraging results as monotherapy with ORR of 66.7% and 32% respectively. Isatuximab use in combination with Len-Dex produced CBR of 83%, and in combination with pomalidomide and dexamethasone CBR of 73%. Indatuximab Ravtansine, an antibody-drug conjugate, produced ORR 78% and 79% in combination with Len-Dex and pomalidomide + dexamethasone respectively. Conclusions: CD38 remains an important target for further clinical trials in combination therapy. Trials using indatuximab, pembrolizumab, lorvotuzumab, siltuximab, and dacetuzumab in combination therapy produced better outcomes as compared to monotherapies. Author, Year No of patients/REP Antibody Target Median prior therapies Outcome Agura E, 2009 36/33 Dacetuzumab + Len + Dex CD 40 4 ORR = 39% Husein, 2010 44 Dacetuzumab CD 40 5 SD = 20% Martin, 2014 35 Isatuximab CD 38 6 ORR = 32% Richter, 2016 97 Isatuximab CD 38 5 ORR = 24% Martin, 2014 31 Isatuximab + Len + Dex CD-38 6 ORR = 64.5% Martin 57 Isatuximab + Len + Dex CD 38 5 ORR = 56% Lendvai, 2016 26 Isatuximab + Len + Dex CD 38 4.5 & 6 ORR: 50% & 50% Benson, 2015 15 IPH 2101 + Len KIR 1-2 VGPR 13%, PR 20% Kaufman, 2013 25 Milatuzumab CD74 5 No ORR, SD = 26% Hansson, 2015 35/29 BI-505 ICAM-1 6 SD = 24% (2m), PD = 65% Lacy, 2008 47 Figitumumab +/- Dex IGF-1 4 No ORR 27 Figitumumab + Dex IGF-1 4 PR n = 6 Moreau, 2011 15 AVE1642 IGF-1 4 MR n = 1, SD n = 7, PD n = 4 11 AVE1642 + Bort IGF-1 4 CR n = 1, PR n = 1, SD n = 3 Rasche, 2015 12 PAT-SM6 GRP-78 4 No OR, SD: 33.3% Surface receptor targeting antibodies in relapsed refractory multiple myeloma. REP; Response evaluable patients, Len; Lenalidomide, Dex; Dexamethasone, ORR; Objective response rate, SD;Stable disease, PD; Progressive disease, CR; Complete response, PR; Partial response, VGPR; Very good partial response, MR; Minimal response