Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
International Journal of Hematology
Erschienen in: International Journal of Hematology 6/2022

18.05.2022 | Progress in Hematology

Novel immunotherapies in multiple myeloma

verfasst von: Ken Ohmine, Ryosuke Uchibori

Erschienen in: International Journal of Hematology | Ausgabe 6/2022

Einloggen, um Zugang zu erhalten

Abstract

For a substantial period, options for the treatment of multiple myeloma (MM) were limited; however, the advent of novel therapies into clinical practice in the 1990s resulted in dramatic changes in the prognosis of the disease. Subsequently, new proteasome inhibitors and immunomodulators with innovations in efficacy and toxicity were introduced; yet there remains a spectrum of patients with poor outcomes with current treatment strategies. One of the causes of disease progression in MM is the loss of the ability of the dysfunctional immune environment to control virulent cell clones. In recent years, therapies to overcome the immunosuppressive tumor microenvironment and activate the host immune system have shown promise in MM, especially in relapsed and refractory disease. Clinical use of this approach has been approved for several immunotherapies, and a number of studies are currently underway in clinical trials. This review outlines three of the newest and most promising approaches being investigated to enhance the immune system against MM: (1) overcoming immunosuppression with checkpoint inhibitors, (2) boosting immunity against tumors with vaccines, and (3) enhancing immune effectors with adoptive cell therapy. Information on the latest clinical trials in each class will be provided, and further developments will be discussed.
Literatur
1.
2.
Takamatsu H. Clinical value of measurable residual disease testing for multiple myeloma and implementation in Japan. Int J Hematol. 2020;111(4):519–29.PubMedCrossRef
3.
Maclachlan KH, Came N, Diamond B, Roshal M, Ho C, Thoren K, et al. Minimal residual disease in multiple myeloma: defining the role of next generation sequencing and flow cytometry in routine diagnostic use. Pathology. 2021;53(3):385–99.PubMedCrossRef
4.
Landgren O, Kyle RA, Rajkumar SV. From myeloma precursor disease to multiple myeloma: new diagnostic concepts and opportunities for early intervention. Clin Cancer Res Official J Am Assoc Cancer Res. 2011;17(6):1243–52.CrossRef
5.
Mikulasova A, Wardell CP, Murison A, Boyle EM, Jackson GH, Smetana J, et al. The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma. Haematologica. 2017;102(9):1617–25.PubMedPubMedCentralCrossRef
6.
Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378(3):241–9.PubMedPubMedCentralCrossRef
7.
8.
Rawstron AC, Davies FE, Owen RG, English A, Pratt G, Child JA, et al. B-lymphocyte suppression in multiple myeloma is a reversible phenomenon specific to normal B-cell progenitors and plasma cell precursors. Brit J Haematol. 1998;100(1):176–83.CrossRef
9.
Koike M, Sekigawa I, Okada M, Matsumoto M, Iida N, Hashimoto H, et al. Relationship between CD4+/CD8+ T cell ratio and T cell activation in multiple myeloma: reference to IL-16. Leukemia Res. 2002;26(8):705–11.CrossRef
10.
Ogawara H, Handa H, Yamazaki T, Toda T, Yoshida K, Nishimoto N, et al. High Th1/Th2 ratio in patients with multiple myeloma. Leukemia Res. 2005;29(2):135–40.CrossRef
11.
Beyer M, Kochanek M, Giese T, Endl E, Weihrauch MR, Knolle PA, et al. In vivo peripheral expansion of naive CD4+CD25highFoxP3+ regulatory T cells in patients with multiple myeloma. Blood. 2006;107(10):3940–9.PubMedCrossRef
12.
Ratta M, Fagnoni F, Curti A, Vescovini R, Sansoni P, Oliviero B, et al. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood. 2002;100(1):230–7.PubMedCrossRef
13.
Brimnes MK, Svane IM, Johnsen HE. Impaired functionality and phenotypic profile of dendritic cells from patients with multiple myeloma. Clin Exp Immunol. 2006;144(1):76–84.PubMedPubMedCentralCrossRef
14.
Ramachandran IR, Martner A, Pisklakova A, Condamine T, Chase T, Vogl T, et al. Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow. J Immunol. 2013;190(7):3815–23.PubMedCrossRef
15.
Dermani FK, Samadi P, Rahmani G, Kohlan AK, Najafi R. PD-1/PD-L1 immune checkpoint: potential target for cancer therapy. J Cell Physiol. 2018;234(2):1313–25.PubMedCrossRef
16.
Tamura H, Ishibashi M, Sunakawa-Kii M, Inokuchi K. PD-L1–PD-1 pathway in the pathophysiology of multiple myeloma. Cancers. 2020;12(4):924.PubMedCentralCrossRef
17.
Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a Phase Ib Study. J Clin Oncol. 2016;34(23):2698–704.PubMedPubMedCentralCrossRef
18.
Ribrag V, Avigan DE, Green DJ, Wise-Draper T, Posada JG, Vij R, et al. Phase 1b trial of pembrolizumab monotherapy for relapsed/refractory multiple myeloma: KEYNOTE-013. Brit J Haematol. 2019;186(3):e41–4.
19.
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(20):4607–18.PubMedPubMedCentralCrossRef
20.
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(9):e459–69.PubMedCrossRef
21.
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(9):e448–58.PubMedCrossRef
22.
Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375–91.PubMedPubMedCentralCrossRef
23.
Lesokhin AM, Chung DJ, Cho HJ, Shohara L, Schwarzenberger P, Ricciardi T, et al. Phase 1 study to evaluate the safety and efficacy of immunotherapy with tremelimumab and durvalumab in multiple myeloma patients receiving high dose chemotherapy and autologous stem cell transplant (HDT/ASCT) + peripheral blood lymphocyte (PBL) reinfusion. J Clin Oncol. 2017;35(15):TPS8051.CrossRef
24.
Skarbnik AP, Donato ML, Feinman R, Rowley SD, Vesole DH, Goy AH, et al. Safety and efficacy of consolidation therapy with ipilimumab plus nivolumab after autologous stem cell transplantation. Transplant Cell Ther. 2021;27(5):391–403.PubMedCrossRef
25.
Benson DM, Cohen AD, Jagannath S, Munshi NC, Spitzer G, Hofmeister CC, et al. A Phase I trial of the anti-KIR antibody iph2101 and lenalidomide in patients with relapsed/refractory multiple myeloma. Clin Cancer Res. 2015;21(18):4055–61.PubMedPubMedCentralCrossRef
26.
Korde N, Carlsten M, Lee MJ, Minter A, Tan E, Kwok M, et al. A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma. Haematologica. 2014;99(6):e81–3.PubMedPubMedCentralCrossRef
27.
28.
Sun J, Muz B, Alhallak K, Markovic M, Gurley S, Wang Z, et al. Targeting CD47 as a novel immunotherapy for multiple myeloma. Cancers. 2020;12(2):305.PubMedCentralCrossRef
29.
Puro RJ, Bouchlaka MN, Hiebsch RR, Capoccia BJ, Donio MJ, Manning PT, et al. Development of AO-176, a next-generation humanized anti-cd47 antibody with novel anticancer properties and negligible red blood cell binding. Mol Cancer Ther. 2020;19(3):835–46.PubMedCrossRef
30.
Andrejeva G, Capoccia BJ, Hiebsch RR, Donio MJ, Darwech IM, Puro RJ, et al. Novel SIRPα antibodies that induce single-agent phagocytosis of tumor cells while preserving T cells. J Immunol. 2021;206(4):712–21.PubMedPubMedCentralCrossRef
31.
Patnaik A, Spreafico A, Paterson AM, Peluso M, Chung JK, Bowers B, et al. Results of a first-in-human phase I study of SRF231, a fully human, high-affinity anti-CD47 antibody. J Clin Oncol. 2020;38(15_suppl):3064.CrossRef
32.
Hansson L, Abdalla AO, Moshfegh A, Choudhury A, Rabbani H, Nilsson B, et al. Long-term idiotype vaccination combined with interleukin-12 (IL-12), or IL-12 and granulocyte macrophage colony-stimulating factor, in early-stage multiple myeloma patients. Clin Cancer Res. 2007;13(5):1503–10.PubMedCrossRef
33.
Ocadlikova D, Kryukov F, Mollova K, Kovarova L, Buresova I, Matejkova E, et al. Generation of myeloma-specific T cells using dendritic cells loaded with MUC1- and hTERT- drived nonapeptides or myeloma cell apoptotic bodies. Neoplasma. 2010;57(5):455–64.PubMedCrossRef
34.
Li R, Qian J, Zhang W, Fu W, Du J, Jiang H, et al. Human heat shock protein-specific cytotoxic T lymphocytes display potent antitumour immunity in multiple myeloma. Brit J Haematol. 2014;166(5):690–701.CrossRef
35.
Lim SH, Wang Z, Chiriva-Internati M, Xue Y. Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma. Blood. 2001;97(5):1508–10.PubMedCrossRef
36.
Qian J, Xie J, Hong S, Yang J, Zhang L, Han X, et al. Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma. Blood. 2007;110(5):1587–94.PubMedPubMedCentralCrossRef
37.
Anderson LD, Cook DR, Yamamoto TN, Berger C, Maloney DG, Riddell SR. Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma. Cancer Immunol Immunother. 2011;60(7):985–97.PubMedPubMedCentralCrossRef
38.
Batchu RB, Moreno AM, Szmania SM, Bennett G, Spagnoli GC, Ponnazhagan S, et al. Protein transduction of dendritic cells for NY-ESO-1-based immunotherapy of myeloma. Cancer Res. 2005;65(21):10041–9.PubMedCrossRef
39.
Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci. 1993;90(8):3539–43.PubMedPubMedCentralCrossRef
40.
Nemunaitis J. Vaccines in cancer: GVAX®, a GM-CSF gene vaccine. Expert Rev Vaccines. 2005;4(3):259–74.PubMedCrossRef
41.
Biavati L, Huff CA, Ferguson A, Sidorski A, Stevens MA, Rudraraju L, et al. An allogeneic multiple myeloma GM-CSF-secreting vaccine with lenalidomide induces long-term immunity and durable clinical responses in patients in near complete remission. Clin Cancer Res Official J Am Assoc Cancer Res. 2021;27(24):6696–708.CrossRef
42.
Rosenblatt J, Avivi I, Vasir B, Uhl L, Munshi NC, Katz T, et al. Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin Cancer Res. 2013;19(13):3640–8.PubMedPubMedCentralCrossRef
43.
Rosenberg SA. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. New Eng J Med. 1988;319(25):1676–80.PubMedCrossRef
44.
Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. Jnci J Natl Cancer Inst. 1994;86(15):1159–66.PubMedCrossRef
45.
46.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.PubMedPubMedCentralCrossRef
47.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2018;380(1):45–56.PubMedCrossRef
48.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48.PubMedPubMedCentralCrossRef
49.
Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet (London, England). 2015;385(9967):517–28.CrossRef
50.
Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra38.PubMedPubMedCentralCrossRef
51.
Turtle CJ, Hanafi LAA, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Investig. 2016;126(6):2123–38.PubMedPubMedCentralCrossRef
52.
Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. New Engl J Med. 2021.
53.
Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19(8):2048–60.PubMedPubMedCentralCrossRef
54.
Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18(5):263–75.PubMedCrossRef
55.
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. New Eng J Med. 2019;380(18):1726–37.PubMedCrossRef
56.
Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New Engl J Med. 2021;384(8):705–16.PubMedCrossRef
57.
Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y, et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018;11(1):141.PubMedPubMedCentralCrossRef
58.
Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314–24.PubMedCrossRef
59.
Mateos MV, Weisel K, Stefano VD, Goldschmidt H, Delforge M, Mohty M, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia. 2022;1–6.
60.
Mateos MV, Weisel K, Martin T, Berdeja JG, Jakubowiak A, Stewart AK, et al. Ciltacabtagene autoleucel for triple-class exposed multiple myeloma: adjusted comparisons of CARTITUDE-1 patient outcomes versus therapies from real-world clinical practice from the LocoMMotion Prospective Study. Blood. 2021;138(Supplement 1):550–550.CrossRef
61.
Cohen YC, Cohen AD, Delforge M, Hillengass J, Goldschmidt H, Weisel K, et al. Efficacy and safety of ciltacabtagene autoleucel (Cilta-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1–3 prior lines of therapy: updated results from CARTITUDE-2. Blood. 2021;138(Supplement 1):3866–3866.CrossRef
62.
Cordoba S, Onuoha S, Thomas S, Pignataro DS, Hough R, Ghorashian S, et al. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nat Med. 2021;27(10):1797–805.PubMedPubMedCentralCrossRef
63.
Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5(12):1282–95.PubMedPubMedCentralCrossRef
64.
Gardner R, Wu D, Cherian S, Fang M, Hanafi LAA, Finney O, et al. Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood. 2016;127(20):2406–10.PubMedPubMedCentralCrossRef
65.
Ruella M, Xu J, Barrett DM, Fraietta JA, Reich TJ, Ambrose DE, et al. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nat Med. 2018;24(10):1499–503.PubMedPubMedCentralCrossRef
66.
Fischer J, Paret C, Malki K, Alt F, Wingerter A, Neu MA, et al. CD19 isoforms enabling resistance to CART-19 immunotherapy are expressed in B-all patients at initial diagnosis. J Immunother (Hagerstown, Md : 1997). 2017;40(5):187–95.PubMedCentral
67.
Paiva B, Puig N, Cedena M, de Jong B, Ruiz Y, Rapado I, et al. Differentiation stage of myeloma plasma cells: biological and clinical significance. Leukemia. 2017;31(2):382–92.PubMedCrossRef
68.
69.
Jiang H, Dong B, Gao L, Liu L, Ge J, He A, et al. Clinical results of a multicenter study of the first-in-human dual BCMA and CD19 targeted novel platform fast CAR-T cell therapy for patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):25–6.
70.
Lee L, Draper B, Chaplin N, Philip B, Chin M, Galas-Filipowicz D, et al. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. 2018;131(7):746–58.PubMedPubMedCentralCrossRef
71.
Schmidts A, Ormhøj M, Choi BD, Taylor AO, Bouffard AA, Scarfò I, et al. Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma. Blood Adv. 2019;3(21):3248–60.PubMedPubMedCentralCrossRef
72.
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(1):7333.PubMedCrossRef
73.
Cowan AJ, Pont M, Sather BD, Turtle CJ, Till BG, Libby E, et al. Safety and efficacy of fully human BCMA CAR T cells in combination with a gamma secretase inhibitor to increase BCMA surface expression in patients with relapsed or refractory multiple myeloma. Blood. 2021;138(Supplement 1):551–551.CrossRef
74.
Li C, Mei H, Hu Y, Guo T, Liu L, Jiang H, et al. A Bispecific CAR-T cell therapy targeting Bcma and CD38 for relapsed/refractory multiple myeloma: updated results from a phase 1 Dose-Climbing Trial. Blood. 2019;134(Supplement_1):930–930.CrossRef
75.
Zah E, Nam E, Bhuvan V, Tran U, Ji BY, Gosliner SB, et al. Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. Nat Commun. 2020;11(1):2283.PubMedPubMedCentralCrossRef
76.
Sun C. Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma.
77.
Baumeister SH, Murad J, Werner L, Daley H, Trebeden-Negre H, Gicobi JK, et al. Phase 1 trial of autologous CAR T cells targeting NKG2D ligands in patients with AML/MDS and multiple myeloma. Cancer Immunol Res. 2018;7(1):100–12.PubMedPubMedCentralCrossRef
78.
Ramos CA, Savoldo B, Torrano V, Ballard B, Zhang H, Dakhova O, et al. Clinical responses with T lymphocytes targeting malignancy-associated κ light chains. J Clin Investig. 2016;126(7):2588–96.PubMedPubMedCentralCrossRef
79.
Zannetti BA, Faini AC, Massari E, Geuna M, Maffini E, Poletti G, et al. Novel insights in anti-CD38 therapy based on CD38-receptor expression and function: the multiple myeloma model. Cells. 2020;9(12):2666.PubMedCentralCrossRef
80.
Campbell KS, Cohen AD, Pazina T. Mechanisms of NK Cell activation and clinical activity of the therapeutic SLAMF7 antibody, elotuzumab in multiple myeloma. Front Immunol. 2018;9:2551.PubMedPubMedCentralCrossRef
81.
Goldsmith R, Cornax I, Ma JY, Yao X, Peng P, Carreira V. 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 Leukemia. 2021;21:S91.CrossRef
82.
83.
Neri P, Ren L, Azab AK, Brentnall M, Gratton K, Klimowicz AC, et al. Integrin β7-mediated regulation of multiple myeloma cell adhesion, migration, and invasion. Blood. 2011;117(23):6202–13.PubMedPubMedCentralCrossRef
84.
Hosen N, Matsunaga Y, Hasegawa K, Matsuno H, Nakamura Y, Makita M, et al. The activated conformation of integrin β7 is a novel multiple myeloma-specific target for CAR T cell therapy. Nat Med. 2017;23(12):1436–43.PubMedCrossRef
85.
Jain T, Bar M, Kansagra AJ, Chong EA, Hashmi SK, Neelapu SS, et al. Utilization of chimeric antigen receptor (CAR) T cell therapy in clinical practice for relapsed/refractory aggressive B cell non-Hodgkin lymphoma: an expert panel opinion from the American society for transplantation and cellular therapy. Biol Blood Marrow Transplant. 2019;25(12):2305–21.PubMedCrossRef
86.
Yakoub-Agha I, Chabannon C, Bader P, Basak GW, Bonig H, Ciceri F, et al. Management of adults and children undergoing CAR t-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica. 2019;105(2):297–316. https://​doi.​org/​10.​3324/​haematol.​2019.​229781.CrossRef
87.
Gagelmann N, Ayuk F, Atanackovic D, Kröger N. B cell maturation antigen-specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: a meta-analysis. Eur J Haematol. 2020;104(4):318–27.PubMedCrossRef
88.
Kansagra AJ, Frey NV, Bar M, Laetsch TW, Carpenter PA, Savani BN, et al. Clinical utilization of chimeric antigen receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Bone Marrow Transplant. 2019;54(11):1868–80.PubMedPubMedCentralCrossRef
89.
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62.PubMedCrossRef
90.
Oekelen OV, Aleman A, Upadhyaya B, Schnakenberg S, Madduri D, Gavane S, et al. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nat Med. 2021;27(12):2099–103.PubMedCrossRef
91.
Schumacher TN, Scheper W, Kvistborg P. Cancer neoantigens. Annu Rev Immunol. 2018;37(1):1–28.
92.
Coulie PG, den Eynde BJV, van der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer. 2014;14(2):135–46.PubMedCrossRef
93.
van Rhee F, Szmania SM, Zhan F, Gupta SK, Pomtree M, Lin P, et al. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood. 2005;105(10):3939–44.PubMedPubMedCentralCrossRef
94.
95.
Stadtmauer EA, Faitg TH, Lowther DE, Badros AZ, Chagin K, Dengel K, et al. Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma. Blood Adv. 2019;3(13):2022–34.PubMedPubMedCentralCrossRef
96.
Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367(6481):eaba7365.PubMedCrossRef
97.
Jahn L, Hombrink P, Hagedoorn RS, Kester MG, van der Steen DM, Rodriguez T, et al. TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1. Blood. 2017;129(10):1284–95.PubMedCrossRef
98.
Meeuwsen MH, Wouters AK, Jahn L, Hagedoorn RS, Kester MGD, Remst DFG, et al. A broad and systematic approach to identify B cell malignancy-targeting TCRs for multi-antigen-based T cell therapy. Mol Ther. 2022;30(2):564–78.PubMedCrossRef
99.
Görgün G, Calabrese E, Soydan E, Hideshima T, Perrone G, Bandi M, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010;116(17):3227–37.PubMedPubMedCentralCrossRef
100.
Nencioni A, Grünebach F, Patrone F, Ballestrero A, Brossart P. Proteasome inhibitors: antitumor effects and beyond. Leukemia. 2006;21(1):30–6.PubMedCrossRef
101.
van de Donk NWCJ. Immunomodulatory effects of CD38-targeting antibodies. Immunol Lett. 2018;199:16–22.PubMedCrossRef
102.
Jones JR, Weinhold N, Ashby C, Walker BA, Wardell C, Pawlyn C, et al. Clonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients. Haematologica. 2019;104(7):1440–50.PubMedPubMedCentralCrossRef
103.
Corre J, Cleynen A, du Pont SR, Buisson L, Bolli N, Attal M, et al. Multiple myeloma clonal evolution in homogeneously treated patients. Leukemia. 2018;32(12):2636–47.PubMedPubMedCentralCrossRef
104.
Fraietta JA, Lacey SF, Orlando EJ, Pruteanu-Malinici I, Gohil M, Lundh S, et al. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med. 2018;24(5):563–71.PubMedPubMedCentralCrossRef
105.
Deng Q, Han G, Puebla-Osorio N, Ma MCJ, Strati P, Chasen B, et al. Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas. Nat Med. 2020;26(12):1878–87.PubMedPubMedCentralCrossRef
106.
Heipertz EL, Zynda ER, Stav-Noraas TE, Hungler AD, Boucher SE, Kaur N, et al. Current perspectives on “Off-The-Shelf” allogeneic NK and CAR-NK cell therapies. Front Immunol. 2021;12: 732135.PubMedPubMedCentralCrossRef
107.
Kawamoto H, Masuda K, Nagano S. Regeneration of antigen-specific T cells by using induced pluripotent stem cell (iPSC) technology. Int Immunol. 2021;33(12):827–33.PubMedCrossRef
Metadaten
Titel
Novel immunotherapies in multiple myeloma
verfasst von
Ken Ohmine
Ryosuke Uchibori
Publikationsdatum
18.05.2022
Verlag
Springer Nature Singapore
Erschienen in
International Journal of Hematology / Ausgabe 6/2022
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-022-03365-1

Weitere Artikel der Ausgabe 6/2022

International Journal of Hematology 6/2022 Zur Ausgabe

Progress in Hematology

Bringing mass spectrometry into the care of patients with multiple myeloma

Progress in Hematology

Progress of modern imaging modalities in multiple myeloma

Case Report

Hemophilic pseudotumor of the maxillary sinus in an inhibitor-positive patient with hemophilia A receiving emicizumab: a case report

Case Report

Paravertebral extramedullary hematopoiesis in a case of myelodysplastic syndrome with ring sideroblasts and an SF3B1 mutation

Original Article

T cell clonal expansion and STAT3 mutations: a characteristic feature of acquired chronic T cell-mediated pure red cell aplasia

Correction

Correction to: Patients with B-cell lymphoma receiving anti-CD20 monoclonal antibody-containing chemotherapies and seroreactive patterns in response to COVID-19 vaccination

Neu im Fachgebiet Onkologie

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

27.05.2024 Blut im Stuhl Nachrichten

Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.

Mammakarzinom: Brustdichte beeinflusst rezidivfreies Überleben

26.05.2024 Mammakarzinom Nachrichten

Frauen, die zum Zeitpunkt der Brustkrebsdiagnose eine hohe mammografische Brustdichte aufweisen, haben ein erhöhtes Risiko für ein baldiges Rezidiv, legen neue Daten nahe.

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise