Bispecific antibodies in the treatment of multiple myeloma.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
12 Sep 2024
12 Sep 2024
Historique:
received:
24
07
2024
accepted:
02
09
2024
revised:
29
08
2024
medline:
13
9
2024
pubmed:
13
9
2024
entrez:
12
9
2024
Statut:
epublish
Résumé
The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various target antigens like B-cell membrane antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5). These agents have proven to induce deep and durable responses in heavily pre-treated myeloma patients with a predictable safety profile and the ease of off-the-shelf availability. Significant research is ongoing to overcome resistance mechanisms like T cell exhaustion, target antigen mutation or loss and high disease burden. Various trials are also studying these agents as first line options in the newly diagnosed setting. These agents play an important role in the relapsed setting, and efforts are underway to optimize their sequencing in the myeloma treatment algorithm.
Identifiants
pubmed: 39266530
doi: 10.1038/s41408-024-01139-y
pii: 10.1038/s41408-024-01139-y
doi:
Substances chimiques
Antibodies, Bispecific
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
158Informations de copyright
© 2024. The Author(s).
Références
Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136:936–45.
pubmed: 32325490
pmcid: 7441167
doi: 10.1182/blood.2020005288
Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:1582–96.
pubmed: 34655533
doi: 10.1016/S1470-2045(21)00466-6
Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, et al. Phase 3 randomized study of daratumumab (DARA) + bortezomib, lenalidomide, and dexamethasone (VRd) versus Vrd alone in patients (Pts) with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplantation (ASCT): primary results of the perseus trial. Blood. 2023;142:LBA-1-LBA.
doi: 10.1182/blood-2023-191911
Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33:2266–75.
pubmed: 30858549
pmcid: 6820050
doi: 10.1038/s41375-019-0435-7
Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol. 2016;34:539–73.
pubmed: 26927206
doi: 10.1146/annurev-immunol-032414-112049
June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359:1361–5.
pubmed: 29567707
doi: 10.1126/science.aar6711
Goebeler ME, Bargou RC. T cell-engaging therapies - BiTEs and beyond. Nat Rev Clin Oncol. 2020;17:418–34.
pubmed: 32242094
doi: 10.1038/s41571-020-0347-5
Brinkmann U, Kontermann RE. Bispecific antibodies. Science. 2021;372:916–7.
pubmed: 34045345
doi: 10.1126/science.abg1209
Huehls AM, Coupet TA, Sentman CL. Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol. 2015;93:290–6.
pubmed: 25367186
doi: 10.1038/icb.2014.93
Hosny M, Verkleij CPM, van der Schans J, Frerichs KA, Mutis T, Zweegman S, et al. Current state of the art and prospects of T cell-redirecting bispecific antibodies in multiple myeloma. J Clin Med. 2021;10:4593.
pubmed: 34640611
pmcid: 8509238
doi: 10.3390/jcm10194593
Hipp S, Tai YT, Blanset D, Deegen P, Wahl J, Thomas O, et al. A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia. 2017;31:1743–51.
pubmed: 28025583
doi: 10.1038/leu.2016.388
Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA. CD28 costimulation: from mechanism to therapy. Immunity. 2016;44:973–88.
pubmed: 27192564
pmcid: 4932896
doi: 10.1016/j.immuni.2016.04.020
Wu L, Seung E, Xu L, Rao E, Lord DM, Wei RR, et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation. Nat Cancer. 2020;1:86–98.
pubmed: 35121834
doi: 10.1038/s43018-019-0004-z
Gantke T, Weichel M, Herbrecht C, Reusch U, Ellwanger K, Fucek I, et al. Trispecific antibodies for CD16A-directed NK cell engagement and dual-targeting of tumor cells. Protein Eng Des Sel. 2017;30:673–84.
pubmed: 28981915
doi: 10.1093/protein/gzx043
Hoyos V, Borrello I. The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T-cell therapies. Blood. 2016;128:1679–87.
pubmed: 27506540
doi: 10.1182/blood-2016-05-636357
Watkins-Yoon J, Guzman W, Oliphant A, Haserlat S, Leung A, Chottin C, et al. CTX-8573, an innate-cell engager targeting BCMA, is a highly potent multispecific antibody for the treatment of multiple myeloma. Blood. 2019;134:3182.
doi: 10.1182/blood-2019-128749
Frerichs KA, Broekmans MEC, Marin Soto JA, van Kessel B, Heymans MW, Holthof LC, et al. Preclinical activity of JNJ-7957, a novel BCMA×CD3 bispecific antibody for the treatment of multiple myeloma, is potentiated by daratumumab. Clin Cancer Res. 2020;26:2203–15.
pubmed: 31969333
doi: 10.1158/1078-0432.CCR-19-2299
Seckinger A, Delgado JA, Moser S, Moreno L, Neuber B, Grab A, et al. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T Cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017;31:396–410.
pubmed: 28262554
doi: 10.1016/j.ccell.2017.02.002
Gantke T, Reusch U, Kellner C, Ellwanger K, Fucek I, Weichel M, et al. AFM26 is a novel, highly potent BCMA/CD16A-directed bispecific antibody for high affinity NK-cell engagement in multiple myeloma. J Clin Oncol. 2017;35:8045.
doi: 10.1200/JCO.2017.35.15_suppl.8045
Zou J, Chen D, Zong Y, Ye S, Tang J, Meng H, et al. Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma. Cancer Sci. 2015;106:512–21.
pubmed: 25664501
pmcid: 4452151
doi: 10.1111/cas.12631
Chen D, Zou J, Zong Y, Meng H, An G, Yang L. Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization. Immunopharmacol Immunotoxicol. 2016;38:175–83.
pubmed: 26954291
doi: 10.3109/08923973.2016.1153110
He X, Zhang Y, Lai YW, Baguley S, Li Y, Cao X, et al. Preclinical characterization of an ANTI-CD38/CD3 T CELL-redirecting bispecific antibody. Blood. 2019;134:4463.
doi: 10.1182/blood-2019-131540
Kodama T, Kochi Y, Nakai W, Mizuno H, Baba T, Habu K, et al. Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma. Mol Cancer Ther. 2019;18:1555–64.
pubmed: 31270154
doi: 10.1158/1535-7163.MCT-18-1216
Chan WK, Kang S, Youssef Y, Glankler EN, Barrett ER, Carter AM, et al. A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma. Cancer Immunol Res. 2018;6:776–87.
pubmed: 29769244
pmcid: 6030494
doi: 10.1158/2326-6066.CIR-17-0649
Wang Y, Li H, Xu W, Pan M, Qiao C, Cai J, et al. BCMA-targeting bispecific antibody that simultaneously stimulates NKG2D-enhanced efficacy against multiple myeloma. J Immunother. 2020;43:175–88.
pubmed: 32349046
doi: 10.1097/CJI.0000000000000320
Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, et al. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016;174:911–22.
pubmed: 27313079
doi: 10.1111/bjh.14145
Wei J, Han X, Bo J, Han W. Target selection for CAR-T therapy. J Hematol Oncol. 2019;12:62.
pubmed: 31221182
pmcid: 6587237
doi: 10.1186/s13045-019-0758-x
Tai YT, Anderson KC. B cell maturation antigen (BCMA)-based immunotherapy for multiple myeloma. Expert Opin Biol Ther. 2019;19:1143–56.
pubmed: 31277554
pmcid: 6785394
doi: 10.1080/14712598.2019.1641196
Coquery CM, Erickson LD. Regulatory roles of the tumor necrosis factor receptor BCMA. Crit Rev Immunol. 2012;32:287–305.
pubmed: 23237506
pmcid: 3548317
doi: 10.1615/CritRevImmunol.v32.i4.10
Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol. 2007;179:7276–86.
pubmed: 18025170
doi: 10.4049/jimmunol.179.11.7276
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, et al. γ-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015;6:7333.
pubmed: 26065893
doi: 10.1038/ncomms8333
Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, et al. γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134:1585–97.
pubmed: 31558469
pmcid: 6871311
doi: 10.1182/blood.2019000050
Smith EL, Harrington K, Staehr M, Masakayan R, Jones J, Long TJ, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med. 2019;11:eaau7746.
pubmed: 30918115
pmcid: 7508042
doi: 10.1126/scitranslmed.aau7746
Pillarisetti K, Edavettal S, Mendonça M, Li Y, Tornetta M, Babich A, et al. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020;135:1232–43.
pubmed: 32040549
pmcid: 7146017
doi: 10.1182/blood.2019003342
Rodriguez-Otero P, van de Donk N, Pillarisetti K, Cornax I, Vishwamitra D, Gray K, et al. GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review. Blood Cancer J. 2024;14:24.
pubmed: 38307865
pmcid: 10837198
doi: 10.1038/s41408-023-00966-9
Verkleij CPM, Broekmans MEC, van Duin M, Frerichs KA, Kuiper R, de Jonge AV, et al. Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Adv. 2021;5:2196–215.
pubmed: 33890981
pmcid: 8095149
doi: 10.1182/bloodadvances.2020003805
Consortium TU. UniProt: the Universal Protein Knowledgebase in 2023. Nucleic Acids Res. 2022;51:D523–31.
doi: 10.1093/nar/gkac1052
Inoue S, Nambu T, Shimomura T. The RAIG family member, GPRC5D, is associated with hard-keratinized structures. J Invest Dermatol. 2004;122:565–73.
pubmed: 15086536
doi: 10.1046/j.0022-202X.2004.12628.x
Goldsmith R, Cornax I, Ma JY, Yao X, Peng P, Carreira V. P-095: normal human tissue expression of G-protein coupled receptor 5D (GPRC5D), a promising novel target for Multiple Myeloma, is restricted to plasma cells and hard keratinized tissues. Clin Lymphoma Myeloma Leuk. 2021;21:S91.
doi: 10.1016/S2152-2650(21)02229-1
Atamaniuk J, Gleiss A, Porpaczy E, Kainz B, Grunt TW, Raderer M, et al. Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest. 2012;42:953–60.
pubmed: 22591013
doi: 10.1111/j.1365-2362.2012.02679.x
Cohen YC, Morillo D, Gatt ME, Sebag M, Kim K, Min C-K, et al. First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41:8002.
doi: 10.1200/JCO.2023.41.16_suppl.8002
US- and drug administration. FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma. FDA.gov. August 10, 2023. Accessed July 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma .
Elkins K, Zheng B, Go M, Slaga D, Du C, Scales SJ, et al. FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. Mol Cancer Ther. 2012;11:2222–32.
pubmed: 22807577
doi: 10.1158/1535-7163.MCT-12-0087
Davis RS, Ehrhardt GR, Leu CM, Hirano M, Cooper MD. An extended family of Fc receptor relatives. Eur J Immunol. 2005;35:674–80.
pubmed: 15688344
doi: 10.1002/eji.200425886
Dement-Brown J, Newton CS, Ise T, Damdinsuren B, Nagata S, Tolnay M. Fc receptor-like 5 promotes B cell proliferation and drives the development of cells displaying switched isotypes. J Leukoc Biol. 2012;91:59–67.
pubmed: 22028333
doi: 10.1189/jlb.0211096
Polson AG, Zheng B, Elkins K, Chang W, Du C, Dowd P, et al. Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia. Int Immunol. 2006;18:1363–73.
pubmed: 16849395
doi: 10.1093/intimm/dxl069
Li J, Stagg NJ, Johnston J, Harris MJ, Menzies SA, DiCara D, et al. Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing. Cancer Cell. 2017;31:383–95.
pubmed: 28262555
pmcid: 5357723
doi: 10.1016/j.ccell.2017.02.001
Dekhtiarenko I, Lelios I, Jacob W, Schneider M, Weisser M, Carlo-Stella C, et al. Co-expression of GPRC5D, FcRH5 and BCMA suggests that targeting more than one cell surface marker may be a viable strategy in relapsed/refractory multiple myeloma (RRMM): biomarker results from the phase I study of forimtamig, a GPRC5DxCD3 bispecific antibody. Blood. 2023;142:1948.
doi: 10.1182/blood-2023-177669
Stewart AK, Krishnan AY, Singhal S, Boccia RV, Patel MR, Niesvizky R, et al. Phase I study of the anti-FcRH5 antibody-drug conjugate DFRF4539A in relapsed or refractory multiple myeloma. Blood Cancer J. 2019;9:17.
pubmed: 30718503
pmcid: 6362066
doi: 10.1038/s41408-019-0178-8
Kumar S, Bachier CR, Cavo M, Corradini P, Delforge M, Janowski W, et al. CAMMA 2: A phase I/II trial evaluating the efficacy and safety of cevostamab in patients with relapsed/refractory multiple myeloma (RRMM) who have triple-class refractory disease and have received a prior anti-B-cell maturation antigen (BCMA) agent. J Clin Oncol. 2023;41:TPS8064.
doi: 10.1200/JCO.2023.41.16_suppl.TPS8064
Mastelic-Gavillet B, Navarro Rodrigo B, Décombaz L, Wang H, Ercolano G, Ahmed R, et al. Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8(+) T cells. J Immunother Cancer. 2019;7:257.
pubmed: 31601268
pmcid: 6788118
doi: 10.1186/s40425-019-0719-5
Kennedy BE, Sadek M, Elnenaei MO, Reiman A, Gujar SA. Targeting NAD(+) synthesis to potentiate CD38-based immunotherapy of multiple myeloma. Trends Cancer. 2020;6:9–12.
pubmed: 31952784
doi: 10.1016/j.trecan.2019.11.005
Doucey M-A, Pouleau B, Estoppey C, Stutz C, Croset A, Laurendon A, et al. ISB 1342: a first-in-class CD38 T cell engager for the treatment of relapsed refractory multiple myeloma. J Clin Oncol. 2021;39:8044.
doi: 10.1200/JCO.2021.39.15_suppl.8044
Pouleau B, Estoppey C, Suere P, Nallet E, Laurendon A, Monney T, et al. Preclinical characterization of ISB 1342, a CD38 × CD3 T-cell engager for relapsed/refractory multiple myeloma. Blood. 2023;142:260–73.
pubmed: 37192303
pmcid: 10644056
Moreau P, Garfall AL, van de Donk N, Nahi H, San-Miguel JF, Oriol A, et al. Teclistamab in relapsed or refractory multiple myeloma. N. Engl J Med. 2022;387:495–505.
pubmed: 35661166
pmcid: 10587778
doi: 10.1056/NEJMoa2203478
Donk NWCJvd, Moreau P, Garfall AL, Bhutani M, Oriol A. et al. Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41:8011.
doi: 10.1200/JCO.2023.41.16_suppl.8011
Garfall AL, Nooka AK, Donk Nvd, NWCJvd, Moreau P, Bhutani M. et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42:7540.
doi: 10.1200/JCO.2024.42.16_suppl.7540
Cai Z, Xia Z-j, He A-L, Dong Y, Wang Y, Liao A, et al. Results from the China Cohort of the Phase 1/2 MajesTEC-1 study of Teclistamab (TEC) treatment in patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Paper presented at the 29th European Hematology Association conference, Madrid, Spain. May 14, 2024. Accessed on July, 24, 2024. https://library.ehaweb.org/eha/2024/eha2024-congress/421483/zhen.cai.results.from.the.china.cohort.of.the.phase.1.2.majestec-1.study.of.html .
Iida S, Kuroda Y, Matsue K, Komeno T, Ishiguro T, Ito T, et al. Primary results of a phase 1/2 study of Teclistamab, a B cell maturation antigen ((BCMA) X CD3 bispecific antibody, in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Paper presented at the 29th European Hematology Association conference, Madrid Spain, May 14, 2024. Accessed on July 24, 2024. https://library.ehaweb.org/eha/2024/eha2024-congress/421489/shinsuke.iida.primary.results.of.a.phase.1.2.study.of.teclistamab.a.b-cell.html .
Firestone R, Shekarkhand T, Patel D, Tan CRC, Hultcrantz M, Lesokhin AM, et al. Evaluating the efficacy of commercial teclistamab in relapsed refractory multiple myeloma patients with prior exposure to anti-BCMA therapies. J Clin Oncol. 2023;41:8049.
doi: 10.1200/JCO.2023.41.16_suppl.8049
Karwacz K, Hooper AT, Chang C-PB, Krupka H, Chou J, Lam V, et al. Abstract 4557: BCMA-CD3 bispecific antibody PF-06863135: preclinical rationale for therapeutic combinations. Cancer Res. 2020;80:4557.
doi: 10.1158/1538-7445.AM2020-4557
Lesokhin AM, Tomasson MH, Arnulf B, Bahlis NJ, Miles Prince H, Niesvizky R, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29:2259–67.
pubmed: 37582952
pmcid: 10504075
doi: 10.1038/s41591-023-02528-9
Mohty M, Tomasson MH, Arnulf B, Bahlis NJ, Prince HM, Niesvizky R, et al. Elranatamab, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, for patients (pts) with relapsed/refractory multiple myeloma (RRMM): extended follow up and biweekly administration from the MagnetisMM-3 study. J Clin Oncol. 2023;41:8039.
doi: 10.1200/JCO.2023.41.16_suppl.8039
Tomasson M, Iida S, Niesvizky R, Mohty M, Bahlis NJ, Martinez-Lopez J, et al. Long-term efficacy and safety of elranatamab monotherapy in the phase 2 magnetismm-3 trial in relapsed or refractory multiple myeloma (RRMM). Blood. 2023;142:3385.
doi: 10.1182/blood-2023-182130
Lee HC, Bumma N, Richter JR, Dhodapkar MV, Hoffman JE, Suvannasankha A, et al. LINKER-MM1 study: linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41:8006.
doi: 10.1200/JCO.2023.41.16_suppl.8006
Bumma N, Richter J, Jagannath S, Lee HC, Hoffman JE, Suvannasankha A, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol 2024;42:2702–2712.
Regeneron. New York. Linvoseltamab Biologics License Application for treatment of relapsed/refractory multiple myeloma accepted for FDA priority review. investor.regeneron.com. February 21, 2024. Accessed July 14, 2024. https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-bla-treatment-relapsedrefractory-multiple-myeloma .
Voorhees PM, D’Souza A, Weisel K, Hurd DD, Teipel R, Chung A, et al. A phase 1 first-in-human study of Abbv-383, a BCMA × CD3 bispecific T-cell-redirecting antibody, as monotherapy in patients with relapsed/refractory multiple myeloma. Blood. 2022;140:4401–4.
doi: 10.1182/blood-2022-167008
Sharon D, Robinson V, Hecquet C, Calabrese K, Cosgrove C, Mantis C, et al. Bivalent BCMA binding and low affinity CD3 T-cell engagement by abbv-383 drives sustained activation with reduced T-cell exhaustion in preclinical models of multiple myeloma. Blood. 2023;142:4666.
doi: 10.1182/blood-2023-179039
Costa LJ, Wong SW, Bermúdez A, de la Rubia J, Mateos M-V, Ocio EM, et al. First clinical study of the B-cell maturation antigen (BCMA) 2+1 T cell engager (TCE) CC-93269 in patients (Pts) with relapsed/refractory multiple myeloma (RRMM): interim results of a phase 1 multicenter trial. Blood. 2019;134:143.
doi: 10.1182/blood-2019-122895
Sun M, Qiu L, Wei Y, Jin J, Li X, Liu X, et al. Results from a first-in-human phase I study of F182112, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41:8038.
doi: 10.1200/JCO.2023.41.16_suppl.8038
Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, et al. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. J Clin Oncol. 2020;38:775–83.
pubmed: 31895611
doi: 10.1200/JCO.19.02657
Harrison SJ, Minnema MC, Lee HC, Spencer A, Kapoor P, Madduri D, et al. A phase 1 first in human (FIH) study of AMG 701, an anti-B-cell maturation antigen (BCMA) half-life extended (HLE) BiTE® (bispecific T-cell engager) molecule, in relapsed/refractory (RR) multiple myeloma (MM). Blood. 2020;136:28–9.
doi: 10.1182/blood-2020-134063
Schinke, Touzeau CD, Minnema C, Donk MC, NWCJvd, Rodríguez-Otero P, et al. Pivotal phase 2 monumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41:8036.
doi: 10.1200/JCO.2023.41.16_suppl.8036
Rasche L, Schinke C, Trouzeau C, Minnema M, Donk NWCJV, Otero PR, et al. Long- term efficacy and safety results from the phase 1/2 MonumenTAL -1 study of Talquetamab, a GPRC5D×CD3 bispecific antibody in patients with relapsed/ refractory multiple myeloma. EHA Libr. 2024;420979:P915.
Carlo-Stella C, Mazza R, Manier S, Facon T, Yoon S-S, Koh Y, et al. RG6234, a GPRC5DxCD3 T-cell engaging bispecific antibody, is highly active in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated intravenous (IV) and first subcutaneous (SC) results from a phase I dose-escalation study. Blood. 2022;140:397–9.
doi: 10.1182/blood-2022-157988
Trudel S, Cohen AD, Krishnan AY, Fonseca R, Spencer A, Berdeja JG, et al. Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pre-treated relapsed/refractory multiple myeloma (RRMM): updated results from an ongoing phase I study. Blood. 2021;138:157.
doi: 10.1182/blood-2021-147983
Lesokhin AM, Richter J, Trudel S, Cohen AD, Spencer A, Forsberg PA, et al. Enduring responses after 1-year, fixed-duration cevostamab therapy in patients with relapsed/refractory multiple myeloma: early experience from a phase I study. Blood. 2022;140:4415–7.
doi: 10.1182/blood-2022-157547
Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384–94.
pubmed: 27222480
pmcid: 4957162
doi: 10.1182/blood-2015-12-687749
Krämer I, Engelhardt M, Fichtner S, Neuber B, Medenhoff S, Bertsch U, et al. Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro. Oncoimmunology. 2016;5:e1139662.
pubmed: 27467960
pmcid: 4910703
doi: 10.1080/2162402X.2016.1139662
Cho SF, Lin L, Xing L, Li Y, Wen K, Yu T, et al. The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models. Blood Adv. 2020;4:4195–207.
pubmed: 32898244
pmcid: 7479960
doi: 10.1182/bloodadvances.2020002524
Meermeier EW, Welsh SJ, Sharik ME, Du MT, Garbitt VM, Riggs DL, et al. Tumor burden limits bispecific antibody efficacy through T cell exhaustion averted by concurrent cytotoxic therapy. Blood Cancer Discov. 2021;2:354–69.
pubmed: 34258584
pmcid: 8266040
doi: 10.1158/2643-3230.BCD-21-0038
Searle E, Quach H, Wong SW, Costa LJ, Hulin C, Janowski W, et al. Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma: results from one cohort of MajesTEC-2, a Phase1b, multicohort study. Blood. 2022;140:394–6.
doi: 10.1182/blood-2022-159711
Dholaria BR, Weisel K, Mateos M-V, Goldschmidt H, Martin TG, Morillo D, et al. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated TRIMM-2 results. J Clin Oncol. 2023;41:8003.
doi: 10.1200/JCO.2023.41.16_suppl.8003
Matous J, Biran N, Perrot A, Berdeja JG, Dorritie K, Elssen JV, et al. Talquetamab + pomalidomide in patients with relapsed/refractory multiple myeloma: safety and preliminary efficacy results from the phase 1b monumenTAL-2 study. Blood. 2023;142:1014.
doi: 10.1182/blood-2023-187706
Kumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2020;21:1630–42.
pubmed: 33129376
doi: 10.1016/S1470-2045(20)30525-8
Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, et al. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022;9:e98–110.
pubmed: 35032434
doi: 10.1016/S2352-3026(21)00381-1
Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019;6:e459–69.
pubmed: 31327687
doi: 10.1016/S2352-3026(19)30110-3
Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, et al. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019;6:e448–58.
pubmed: 31327689
doi: 10.1016/S2352-3026(19)30109-7
Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, et al. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000;1:252–6.
pubmed: 10973284
doi: 10.1038/79802
Van Oekelen O, Gleason CR, Agte S, Srivastava K, Beach KF, Aleman A, et al. Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma. Cancer Cell. 2021;39:1028–30.
pubmed: 34242572
pmcid: 8238657
doi: 10.1016/j.ccell.2021.06.014
Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, Malandrakis P, et al. Booster BNT162b2 optimizes SARS-CoV-2 humoral response in patients with myeloma: the negative effect of anti-BCMA therapy. Blood. 2022;139:1409–12.
pubmed: 34986251
pmcid: 8736278
doi: 10.1182/blood.2021014989
Ramasamy K, Sadler R, Jeans S, Weeden P, Varghese S, Turner A, et al. Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response. Br J Haematol. 2022;197:293–301.
pubmed: 35064676
pmcid: 9306522
doi: 10.1111/bjh.18066
Abdallah AO, Mahmoudjafari Z, Atieh T, Ahmed N, Cui W, Shune L, et al. Neutralizing antibody responses against SARS-CoV-2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination. Eur J Haematol. 2022;109:458–64.
pubmed: 35810359
doi: 10.1111/ejh.13826
Wu X, Wang L, Shen L, He L, Tang K. Immune response to vaccination against SARS-CoV-2 in hematopoietic stem cell transplantation and CAR T-cell therapy recipients. J Hematol Oncol. 2022;15:81.
pubmed: 35710431
pmcid: 9200932
doi: 10.1186/s13045-022-01300-9
Frerichs KA, Verkleij CPM, Mateos MV, Martin TG, Rodriguez C, Nooka A, et al. Teclistamab impairs humoral immunity in patients with heavily pretreated myeloma: importance of immunoglobulin supplementation. Blood Adv. 2024;8:194–206.
pubmed: 38052042
doi: 10.1182/bloodadvances.2023011658
Raje N, Anderson K, Einsele H, Efebera Y, Gay F, Hammond SP, et al. Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel. Blood Cancer J. 2023;13:116.
pubmed: 37528088
pmcid: 10394080
doi: 10.1038/s41408-023-00879-7
Lancman G, Parsa K, Rodriguez C, Richter J, Cho HJ, Parekh S, et al. Infections and severe hypogammaglobulinemia in multiple myeloma patients treated with anti-BCMA bispecific antibodies. Blood. 2022;140:10073–4.
doi: 10.1182/blood-2022-163733
Lancman G, Parsa K, Kotlarz K, Avery L, Lurie A, Lieberman-Cribbin A, et al. IVIg use associated with ten-fold reduction of serious infections in multiple myeloma patients treated with anti-BCMA bispecific antibodies. Blood Cancer Discov. 2023;4:440–51.
pubmed: 37769148
pmcid: 10618720
doi: 10.1158/2643-3230.BCD-23-0049
Lancman G, Shyu M, Metzger M, Parsa K, Cho HJ, Parekh S, et al. Timing and nature of infections in multiple myeloma patients treated with anti-BCMA CAR-T cells. Blood. 2022;140:7198–9.
doi: 10.1182/blood-2022-163757
Golmohammadi M, Dima D, Albayyadhi M, Moradi A, Raza S, Jaberi-Douraki M. Pooled analysis on bispecific antibody-related toxicities in multiple myeloma. Blood. 2023;142:1953.
doi: 10.1182/blood-2023-191305
van de Donk N, Garfall A, Benboubker L, Uttervall K, Groen K, Rosiñol Dachs L, et al. Evaluation of prophylactic Tocilizumab (Toci) for the reduction of cytokie release syndrome (CRS) to inform the management of patients (pts) treated with Teclistamab in MajesTEC-1. Hemasphere. 2023;7:e43149cb.
Trudel S, Bahlis NJ, Spencer A, Kaedbey R, Rodriguez Otero P, Harrison SJ, et al. Pretreatment with tocilizumab prior to the CD3 bispecific cevostamab in patients with relapsed/refractory multiple myeloma (RRMM) showed a marked reduction in cytokine release syndrome incidence and severity. Blood. 2022;140:1363–5.
doi: 10.1182/blood-2022-159381
Iida S, Ito S, Yokoyama H, Ishida T, Nagai Y, Handa H, et al. Elranatamab in Japanese patients with relapsed/refractory multiple myeloma: results from MagnetisMM-2 and MagnetisMM-3. Jpn J Clin Oncol. 2024;24:hyae068.
Chari A, Oriol A, Krishnan A, Martinez Chamorro MDC, Costa L, Mateos MV, et al. Efficacy and safety of less frequent/lower intensity dosing of talquetamab in patients with relapsed/refractory multiple myeloma: results from the phase 1/2 monumenTAL-1 study. Blood. 2023;142:1010.
doi: 10.1182/blood-2023-181228
Lee H, Neri P, Bahlis NJ. BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: efficacy, safety, and resistance mechanisms. Blood. 2024;143:1211–7.
pubmed: 38194680
doi: 10.1182/blood.2023022499
Bahlis NJ, Costello CL, Raje NS, Levy MY, Dholaria B, Solh M, et al. Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial. Nat Med. 2023;29:2570–6.
pubmed: 37783970
pmcid: 10579053
doi: 10.1038/s41591-023-02589-w
Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk N, Rodríguez-Otero P, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N. Engl J Med. 2022;387:2232–44.
pubmed: 36507686
doi: 10.1056/NEJMoa2204591
Verkleij CPM, Broekmans M, Wong A, Zweegman S, Verona R, Adams H, et al. Mechanisms of resistance and determinants of response of the GPRC5D-targeting T-cell redirecting bispecific antibody JNJ-7564 in multiple myeloma. Blood. 2020;136:8–9.
doi: 10.1182/blood-2020-141187
Friedrich MJ, Neri P, Kehl N, Michel J, Steiger S, Kilian M, et al. The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients. Cancer Cell. 2023;41:711–25.e6.
pubmed: 36898378
doi: 10.1016/j.ccell.2023.02.008
Lee H, Ahn S, Maity R, Leblay N, Ziccheddu B, Truger M, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med. 2023;29:2295–306.
pubmed: 37653344
pmcid: 10504087
doi: 10.1038/s41591-023-02491-5
Dhodapkar MV, Krasovsky J, Osman K, Geller MD. Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy. J Exp Med. 2003;198:1753–7.
pubmed: 14638846
pmcid: 2194131
doi: 10.1084/jem.20031030
Garfall AL, Dancy EK, Cohen AD, Hwang WT, Fraietta JA, Davis MM, et al. T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma. Blood Adv. 2019;3:2812–5.
pubmed: 31575532
pmcid: 6784521
doi: 10.1182/bloodadvances.2019000600
Ghermezi M, Li M, Vardanyan S, Harutyunyan NM, Gottlieb J, Berenson A, et al. Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients. Haematologica. 2017;102:785–95.
pubmed: 28034989
pmcid: 5395119
doi: 10.3324/haematol.2016.150896
Sanchez E, Li M, Kitto A, Li J, Wang CS, Kirk DT, et al. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012;158:727–38.
pubmed: 22804669
doi: 10.1111/j.1365-2141.2012.09241.x
Cortes-Selva D, Casneuf T, Vishwamitra D, Stein S, Perova T, Skerget S, et al. Teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): correlative analyses from MajesTEC-1. Blood. 2022;140:241–3.
doi: 10.1182/blood-2022-162709
Chen H, Yu T, Lin L, Xing L, Cho SF, Wen K, et al. γ-secretase inhibitors augment efficacy of BCMA-targeting bispecific antibodies against multiple myeloma cells without impairing T-cell activation and differentiation. Blood Cancer J. 2022;12:118.
pubmed: 35973981
pmcid: 9381512
doi: 10.1038/s41408-022-00716-3
Offner F, Decaux O, Hulin C, Anguille S, Sophie Michallet A, Costa L, et al. Teclistamab (tec) + Nirogacestat (niro) in relapsed/refractory multiple myeloma (RRMM): The phase 1b MajesTEC-2 study. Hemasphere. 2023;7:e1257964.
America Society of Hematology. MajesTEC-2: future of BCMA-targeted bispecific, gamma secretase inhibitor combo in question. ASH clinical news. July 2023. Accessed July 24, 2024. https://ashpublications.org/ashclinicalnews/news/7213/MajesTEC-2-Future-of-BCMA-targeted-Bispecific .
Samur MK, Fulciniti M, Aktas Samur A, Bazarbachi AH, Tai Y-T, Prabhala R, et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat Commun. 2021;12:868.
pubmed: 33558511
pmcid: 7870932
doi: 10.1038/s41467-021-21177-5
Da Vià MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, et al. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat Med. 2021;27:616–9.
pubmed: 33619368
doi: 10.1038/s41591-021-01245-5
Truger MS, Duell J, Zhou X, Heimeshoff L, Ruckdeschel A, John M, et al. Single- and double-hit events in genes encoding immune targets before and after T cell-engaging antibody therapy in MM. Blood Adv. 2021;5:3794–8.
pubmed: 34471932
pmcid: 8679680
doi: 10.1182/bloodadvances.2021004418
Feyler S, Scott GB, Parrish C, Jarmin S, Evans P, Short M, et al. Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent. PLoS ONE. 2012;7:e35981.
pubmed: 22666318
pmcid: 3362588
doi: 10.1371/journal.pone.0035981
Röllinghoff M, Starzinski-Powitz A, Pfizenmaier K, Wagner H. Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes. J Exp Med. 1977;145:455–9.
pubmed: 299883
pmcid: 2180611
doi: 10.1084/jem.145.2.455
Schiavoni G, Sistigu A, Valentini M, Mattei F, Sestili P, Spadaro F, et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 2011;71:768–78.
pubmed: 21156650
doi: 10.1158/0008-5472.CAN-10-2788
Zhang Z, Liu S, Zhang B, Qiao L, Zhang Y, Zhang Y. T cell dysfunction and exhaustion in cancer. Front Cell Dev Biol. 2020;8:17.
pubmed: 32117960
pmcid: 7027373
doi: 10.3389/fcell.2020.00017
Paiva B, Gaffney B, Burnett K, Castiglioni P, Angelo M, Pierce DW, et al. Synergistic antitumor activity of alnuctamab (ALNUC; BMS-986349; CC-93269), a BCMA 2+1 T cell engager (TCE), and celmod agents in multiple myeloma (MM) preclinical models. Blood. 2022;140:7054–5.
doi: 10.1182/blood-2022-157987
Görgün G, Samur MK, Cowens KB, Paula S, Bianchi G, Anderson JE, et al. Lenalidomide enhances immune checkpoint blockade-induced immune response in multiple myeloma. Clin Cancer Res. 2015;21:4607–18.
pubmed: 25979485
pmcid: 4609232
doi: 10.1158/1078-0432.CCR-15-0200
Köhnke T, Krupka C, Tischer J, Knösel T, Subklewe M. Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab. J Hematol Oncol. 2015;8:111.
pubmed: 26449653
pmcid: 4599591
doi: 10.1186/s13045-015-0213-6
Feucht J, Kayser S, Gorodezki D, Hamieh M, Döring M, Blaeschke F, et al. T-cell responses against CD19+ pediatric acute lymphoblastic leukemia mediated by bispecific T-cell engager (BiTE) are regulated contrarily by PD-L1 and CD80/CD86 on leukemic blasts. Oncotarget. 2016;7:76902–19.
pubmed: 27708227
pmcid: 5363558
doi: 10.18632/oncotarget.12357
Swamydas M, Murphy EV, Ignatz-Hoover JJ, Malek E, Driscoll JJ. Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma. J Hematol Oncol. 2022;15:17.
pubmed: 35172851
pmcid: 8848665
doi: 10.1186/s13045-022-01234-2
Mishra AK, Schmidt TM, Martell EB, Chen AS, Dogru RE, Hematti P, et al. PD1(+)TIGIT(+)2B4(+)KLRG1(+) cells might underlie T cell dysfunction in patients treated with BCMA-directed chimeric antigen receptor T cell therapy. Transpl Cell Ther. 2024;30:191–202.
doi: 10.1016/j.jtct.2023.11.014
Danhof S, Schreder M, Knop S, Rasche L, Strifler S, Löffler C, et al. Expression of programmed death-1 on lymphocytes in myeloma patients is lowered during lenalidomide maintenance. Haematologica. 2018;103:e126–9.
pubmed: 29191843
pmcid: 5830376
doi: 10.3324/haematol.2017.178947
Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N. Engl J Med. 2023;388:1002–14.
pubmed: 36762851
doi: 10.1056/NEJMoa2213614
San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N. Engl J Med. 2023;389:335–47.
pubmed: 37272512
doi: 10.1056/NEJMoa2303379
Chung DJ, Pronschinske KB, Shyer JA, Wu V, Hassoun H, Landau H, et al. Immune reconstitution after autologous stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2014;20:S60–2.
doi: 10.1016/j.bbmt.2013.12.068
Nadeem O, Magidson S, Midha S, O’Donnell EK, Hartley-Brown MA, Sperling AS, et al. Immuno-PRISM: a randomized phase II platform study of bispecific antibodies in high-risk smoldering myeloma. Blood. 2023;142:206.
doi: 10.1182/blood-2023-177954
Yong, Harrison K, Mateos SJ, Moreau M-V, Donk P, NWCJvd, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. J Clin Oncol. 2023;41:LBA106.
doi: 10.1200/JCO.2023.41.17_suppl.LBA106
Subklewe M. BiTEs better than CAR T cells. Blood Adv. 2021;5:607–12.
pubmed: 33496755
pmcid: 7839370
doi: 10.1182/bloodadvances.2020001792
Majzner RG, Mackall CL. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med. 2019;25:1341–55.
pubmed: 31501612
doi: 10.1038/s41591-019-0564-6
Lonial S, Nooka AK, Thulasi P, Badros AZ, Jeng BH, Callander NS, et al. Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM). Blood Cancer J. 2021;11:103.
pubmed: 34039952
pmcid: 8155129
doi: 10.1038/s41408-021-00494-4
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer. 2021;127:4198–212.
pubmed: 34314018
doi: 10.1002/cncr.33809
Hansen DK, Sidana S, Peres LC, Colin Leitzinger C, Shune L, Shrewsbury A, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol. 2023;41:2087–97.
pubmed: 36623248
pmcid: 10082273
doi: 10.1200/JCO.22.01365
Cohen AD, Mateos MV, Cohen YC, Rodriguez-Otero P, Paiva B, van de Donk N, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023;141:219–30.
pubmed: 36095849
doi: 10.1182/blood.2022015526
Van Oekelen O, Nath K, Mouhieddine TH, Farzana T, Aleman A, Melnekoff DT, et al. Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy. Blood. 2023;141:756–65.
pubmed: 36327160
doi: 10.1182/blood.2022017848
Touzeau C, Krishnan AY, Moreau P, Perrot A, Usmani SZ, Manier S, et al. Efficacy and safety of teclistamab (tec), a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM) after exposure to other BCMA-targeted agents. J Clin Oncol. 2022;40:8013.
doi: 10.1200/JCO.2022.40.16_suppl.8013
Jakubowiak AJ, Anguille S, Karlin L, Chari A, Schinke C, Rasche L, et al. Updated results of talquetamab, a GPRC5D × CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma with prior exposure to T-cell redirecting therapies: results of the phase 1/2 MonumenTAL-1 study. Blood. 2023;142:3377.
doi: 10.1182/blood-2023-187242