Skip to main content
Erschienen in: Current Hematologic Malignancy Reports 1/2019

21.01.2019 | T-Cell and Other Lymphoproliferative Malignancies (J Zain, Section Editor)

Immunotherapeutic Approaches for Multiple Myeloma: Where Are We Now?

verfasst von: Myo Htut

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The treatment landscape for multiple myeloma has evolved rapidly with the availability of multiple new drugs; however, although patient survival has improved, the disease remains incurable. Multiple myeloma is characterized by the unregulated growth of malignant plasma cells accompanied by immune dysfunction as well as disrupted immune surveillance mechanisms. Here, we analyze clinical modalities, with a focus on monoclonal antibodies and adoptive cellular therapy that enhance patients’ immune systems and overcome these defects.

Recent Findings

Early clinical trials with PD-1 inhibitors were promising, but randomized phase III trials with immunomodulatory drugs showed increased toxicities. Monoclonal antibodies targeting surface antigens led to substantial clinical efficiency in relapsed myeloma. Chimeric antigen receptor (CAR) T cell therapy for multiple myeloma represents a significant advance, as exciting and dramatic responses in early clinical trials have been seen.

Summary

Immunotherapeutic approaches are promising and can augment or replace the current standard of care, with the potential to offer extended survival for myeloma patients.
Literatur
1.
Zurück zum Zitat Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Goldin LR, Blimark C, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica. Ferrata Storti Foundation. 2012;97(6):854–8.CrossRef Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Goldin LR, Blimark C, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica. Ferrata Storti Foundation. 2012;97(6):854–8.CrossRef
2.
Zurück zum Zitat 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. Leuk Res. 2002;26(8):705–11.CrossRefPubMed 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. Leuk Res. 2002;26(8):705–11.CrossRefPubMed
3.
Zurück zum Zitat Ogawara H, Handa H, Yamazaki T, Toda T, Yoshida K, Nishimoto N, et al. High Th1/Th2 ratio in patients with multiple myeloma. Leuk Res. 2005;29(2):135–40.CrossRefPubMed Ogawara H, Handa H, Yamazaki T, Toda T, Yoshida K, Nishimoto N, et al. High Th1/Th2 ratio in patients with multiple myeloma. Leuk Res. 2005;29(2):135–40.CrossRefPubMed
4.
Zurück zum Zitat Dosani T, Carlsten M, Maric I, Landgren O. The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies. Blood Cancer J. 2015;5:e306.CrossRefPubMedPubMedCentral Dosani T, Carlsten M, Maric I, Landgren O. The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies. Blood Cancer J. 2015;5:e306.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Brown RD, Pope B, Yuen E, Gibson J, Joshua DE. The expression of T cell related costimulatory molecules in multiple myeloma. Leuk Lymphoma. 1998;31(3–4):379–84.CrossRefPubMed Brown RD, Pope B, Yuen E, Gibson J, Joshua DE. The expression of T cell related costimulatory molecules in multiple myeloma. Leuk Lymphoma. 1998;31(3–4):379–84.CrossRefPubMed
6.
Zurück zum Zitat Romano A, Conticello C, Cavalli M, Vetro C, La Fauci A, Parrinello NL, et al. Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int. 2014;2014:198539.PubMedPubMedCentral Romano A, Conticello C, Cavalli M, Vetro C, La Fauci A, Parrinello NL, et al. Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int. 2014;2014:198539.PubMedPubMedCentral
7.
Zurück zum Zitat Yousef S, Marvin J, Steinbach M, Langemo A, Kovacsovics T, Binder M, et al. Immunomodulatory molecule PD-L1 is expressed on malignant plasma cells and myeloma-propagating pre-plasma cells in the bone marrow of multiple myeloma patients. Blood Cancer J. 2015;5(3):e285.CrossRefPubMedPubMedCentral Yousef S, Marvin J, Steinbach M, Langemo A, Kovacsovics T, Binder M, et al. Immunomodulatory molecule PD-L1 is expressed on malignant plasma cells and myeloma-propagating pre-plasma cells in the bone marrow of multiple myeloma patients. Blood Cancer J. 2015;5(3):e285.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Gahrton G, Iacobelli S, Bjorkstrand B, Hegenbart U, Gruber A, Greinix H, et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: longterm results of the EBMT-NMAM2000 study. Blood. 2013;121(25):5055–63.CrossRefPubMed Gahrton G, Iacobelli S, Bjorkstrand B, Hegenbart U, Gruber A, Greinix H, et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: longterm results of the EBMT-NMAM2000 study. Blood. 2013;121(25):5055–63.CrossRefPubMed
9.
Zurück zum Zitat Sahebi F, Iacobelli S, Biezen AV, et al. Comparison of upfront tandem autologous-allogeneic transplantation versus reduced intensity allogeneic transplantation for multiple myeloma. Bone Marrow Transplant. 2015;50(6):802–7.CrossRefPubMed Sahebi F, Iacobelli S, Biezen AV, et al. Comparison of upfront tandem autologous-allogeneic transplantation versus reduced intensity allogeneic transplantation for multiple myeloma. Bone Marrow Transplant. 2015;50(6):802–7.CrossRefPubMed
10.
Zurück zum Zitat Auner HW, Szydlo R, van Biezen A, et al. Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2013;48(11):1395–400.CrossRefPubMed Auner HW, Szydlo R, van Biezen A, et al. Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2013;48(11):1395–400.CrossRefPubMed
11.
Zurück zum Zitat Zhu YX, Kortuem KM, Stewart AK. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013;54(4):683–7.CrossRefPubMed Zhu YX, Kortuem KM, Stewart AK. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013;54(4):683–7.CrossRefPubMed
13.
Zurück zum Zitat Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric Immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121(4):482–8.CrossRefPubMed Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric Immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121(4):482–8.CrossRefPubMed
14.
Zurück zum Zitat Deaglio S, Vaisitti T, Billington R, Bergui L, Omede' P, Genazzani AA, et al. CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. 2007;109:5390–8.CrossRefPubMed Deaglio S, Vaisitti T, Billington R, Bergui L, Omede' P, Genazzani AA, et al. CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. 2007;109:5390–8.CrossRefPubMed
15.
Zurück zum Zitat •• Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with Daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19 This study was one of the first to study daratumumab as single agent therapy and provided justification for the development of combinatorial therapies containing daratumumab. CrossRefPubMed •• Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with Daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19 This study was one of the first to study daratumumab as single agent therapy and provided justification for the development of combinatorial therapies containing daratumumab. CrossRefPubMed
16.
Zurück zum Zitat Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Phase II study of daratumumab (DARA) monotherapy in patients with >= 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). ASCO Meet Abstr. 2015;33(18_suppl):LBA 8512. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Phase II study of daratumumab (DARA) monotherapy in patients with >= 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). ASCO Meet Abstr. 2015;33(18_suppl):LBA 8512.
17.
Zurück zum Zitat Plesner T, Arkenau H-T, Lokhorst HM, Gimsing P, Krejcik J, Lemech C, et al. Safety and efficacy of Daratumumab with Lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. Blood. 2014;124(21):84. Plesner T, Arkenau H-T, Lokhorst HM, Gimsing P, Krejcik J, Lemech C, et al. Safety and efficacy of Daratumumab with Lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. Blood. 2014;124(21):84.
18.
Zurück zum Zitat •• Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, for the POLLUX Investigators, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375:1319–31. https://doi.org/10.1056/NEJMoa1607751 Potentially practice-changing data in RRMM patients treated with daratumumab/lenalidomide-based backbone treatment. CrossRefPubMed •• Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, for the POLLUX Investigators, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375:1319–31. https://​doi.​org/​10.​1056/​NEJMoa1607751 Potentially practice-changing data in RRMM patients treated with daratumumab/lenalidomide-based backbone treatment. CrossRefPubMed
19.
Zurück zum Zitat •• Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, Bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754–66 Potentially practice-changing data in RRMM patients treated with daratumumab/bortezomib-based backbone treatment. CrossRefPubMed •• Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, Bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754–66 Potentially practice-changing data in RRMM patients treated with daratumumab/bortezomib-based backbone treatment. CrossRefPubMed
21.
Zurück zum Zitat Lonial S, San-Miguel JF, Martínez-Lopez J, Mateos M-V, Blade J, Benboubker L, et al. Daratumumab in combination with carfilzomib and dexamethasone in patients (pts) with relapsed multiple myeloma (MMY1001): an open-label, phase 1b study. Blood. 2017;130:1869.CrossRef Lonial S, San-Miguel JF, Martínez-Lopez J, Mateos M-V, Blade J, Benboubker L, et al. Daratumumab in combination with carfilzomib and dexamethasone in patients (pts) with relapsed multiple myeloma (MMY1001): an open-label, phase 1b study. Blood. 2017;130:1869.CrossRef
23.
Zurück zum Zitat Chari A, Nahi H, Mateos M-V, Lokhorst HM, Kaufman JL, Moreau P, et al. 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.CrossRef Chari A, Nahi H, Mateos M-V, Lokhorst HM, Kaufman JL, Moreau P, et al. 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.CrossRef
24.
25.
Zurück zum Zitat Mikhael J, Richardson PG, Usmani Z, Raje N, Bensinger W, Kanagavel D, et al. A phase Ib study of isatuximab in combination with pomalidomide (Pom) and dexamethasone (Dex) in relapsed/refractory multiple myeloma (RRMM). 2017 ASCO Annual Meeting Abstracts. JCO. 2017;(35 suppl):abstr 8007. Mikhael J, Richardson PG, Usmani Z, Raje N, Bensinger W, Kanagavel D, et al. A phase Ib study of isatuximab in combination with pomalidomide (Pom) and dexamethasone (Dex) in relapsed/refractory multiple myeloma (RRMM). 2017 ASCO Annual Meeting Abstracts. JCO. 2017;(35 suppl):abstr 8007.
27.
Zurück zum Zitat Raab MS, Chatterjee M, Goldschmidt H, Agis H, Blau I, Einsele H, et al. A phase I/IIa study of the CD38 antibody MOR202 alone and in combination with pomalidomide or lenalidomide in patients with relapsed or refractory multiple myeloma. Blood. 2016;128:1152.CrossRef Raab MS, Chatterjee M, Goldschmidt H, Agis H, Blau I, Einsele H, et al. A phase I/IIa study of the CD38 antibody MOR202 alone and in combination with pomalidomide or lenalidomide in patients with relapsed or refractory multiple myeloma. Blood. 2016;128:1152.CrossRef
29.
Zurück zum Zitat 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;88:168–77.CrossRef 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;88:168–77.CrossRef
30.
Zurück zum Zitat Zonder JA, Mohrbacher AF, Singhal S, Van Rhee F, Bensinger WI, Ding H, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood. 2012;120(3):552–9.CrossRefPubMedPubMedCentral Zonder JA, Mohrbacher AF, Singhal S, Van Rhee F, Bensinger WI, Ding H, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood. 2012;120(3):552–9.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Jakubowiak A, Offidani M, Brigitte P, La Rubia JD, Garderet L, Laribi K, et al. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016;127(23):2833–41.CrossRefPubMedPubMedCentral Jakubowiak A, Offidani M, Brigitte P, La Rubia JD, Garderet L, Laribi K, et al. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016;127(23):2833–41.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Richardson PG, Jagannath S, Moreau P, Jakubowiak AJ, Raab MS, Facon T, et al. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. Lancet Haematol. 2015;2(12):e516–27.CrossRefPubMedPubMedCentral Richardson PG, Jagannath S, Moreau P, Jakubowiak AJ, Raab MS, Facon T, et al. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. Lancet Haematol. 2015;2(12):e516–27.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat •• Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373:621–31. https://doi.org/10.1056/NEJMoa1505654 Potentially practice-changing data in RRMM patients treated with elotuzumab-/lenalidomide-based backbone treatment. CrossRefPubMed •• Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373:621–31. https://​doi.​org/​10.​1056/​NEJMoa1505654 Potentially practice-changing data in RRMM patients treated with elotuzumab-/lenalidomide-based backbone treatment. CrossRefPubMed
34.
Zurück zum Zitat •• Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379:1811–22 Potentially practice-changing data in RRMM patients treated with elotuzumab-/pomalidomide-based backbone treatment. CrossRefPubMed •• Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379:1811–22 Potentially practice-changing data in RRMM patients treated with elotuzumab-/pomalidomide-based backbone treatment. CrossRefPubMed
35.
Zurück zum Zitat Heffner LT, Jagannath S, Zimmerman TM, Lee KP, Rosenblatt J, Lonial S, et al. BT062, an antibody-drug conjugate directed against CD138, given weekly for 3 weeks in each 4 week cycle: safety and further evidence of clinical activity. Am Soc Hematol Annu Meet Proc. 2012;120(21):653. Heffner LT, Jagannath S, Zimmerman TM, Lee KP, Rosenblatt J, Lonial S, et al. BT062, an antibody-drug conjugate directed against CD138, given weekly for 3 weeks in each 4 week cycle: safety and further evidence of clinical activity. Am Soc Hematol Annu Meet Proc. 2012;120(21):653.
36.
Zurück zum Zitat Kelly KR, Chanan-Khan A, Heffner LT, Somlo G, Siegel DS, Zimmerman T, et al. Indatuximab Ravtansine (BT062) in combination with Lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma: clinical activity in patients already exposed to Lenalidomide and Bortezomib. Blood. 2014;124(21):4736. Kelly KR, Chanan-Khan A, Heffner LT, Somlo G, Siegel DS, Zimmerman T, et al. Indatuximab Ravtansine (BT062) in combination with Lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma: clinical activity in patients already exposed to Lenalidomide and Bortezomib. Blood. 2014;124(21):4736.
37.
Zurück zum Zitat Kumar SK, Anderson KC. Immune therapies in multiple myeloma. Clin Cancer Res. 2016;22(22):5453–60.CrossRefPubMed Kumar SK, Anderson KC. Immune therapies in multiple myeloma. Clin Cancer Res. 2016;22(22):5453–60.CrossRefPubMed
38.
Zurück zum Zitat Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, et al. Treatment with AMG 420, an anti-B-cell maturation antigen (BCMA) bispecific T-cell engager (BiTEs) antibody construct, induces minimal residual disease (MRD) negative complete responses in relapsed and/or refractory (R/R) multiple myeloma (MM) patients: results of a first-in-human (fih) phase i dose escalation study. ASH Annual meeting. 2018:abstract 1010. Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, et al. Treatment with AMG 420, an anti-B-cell maturation antigen (BCMA) bispecific T-cell engager (BiTEs) antibody construct, induces minimal residual disease (MRD) negative complete responses in relapsed and/or refractory (R/R) multiple myeloma (MM) patients: results of a first-in-human (fih) phase i dose escalation study. ASH Annual meeting. 2018:abstract 1010.
39.
Zurück zum Zitat Tamura H, Ishibashi M, Yamashita T, Tanosaki S, Okuyama N, Kondo A, et al. Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. Leukemia. Nature Publishing Group. 2012;27(2):464–72. Tamura H, Ishibashi M, Yamashita T, Tanosaki S, Okuyama N, Kondo A, et al. Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. Leukemia. Nature Publishing Group. 2012;27(2):464–72.
40.
Zurück zum Zitat Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, et al. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood. 2007;110(1):296–304.CrossRefPubMed Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, et al. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood. 2007;110(1):296–304.CrossRefPubMed
42.
Zurück zum Zitat Hallett WHD, Jing W, Drobyski WR, Johnson BD. Immunosuppressive effects of multiple myeloma are overcome by PD-L1 blockade. Biol Blood Marrow Transplant. 2011;17(8):1133–45.CrossRefPubMed Hallett WHD, Jing W, Drobyski WR, Johnson BD. Immunosuppressive effects of multiple myeloma are overcome by PD-L1 blockade. Biol Blood Marrow Transplant. 2011;17(8):1133–45.CrossRefPubMed
43.
Zurück zum Zitat Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.CrossRefPubMedPubMedCentral Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Görgün G, Samur MK, Cowens KB, et al. Lenalidomide enhances immune checkpoint blockade-induced immune response in multiple myeloma. Clin Cancer Res. 2015;21(20):4607–18.CrossRefPubMedPubMedCentral Görgün G, Samur MK, Cowens KB, et al. Lenalidomide enhances immune checkpoint blockade-induced immune response in multiple myeloma. Clin Cancer Res. 2015;21(20):4607–18.CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Benson DM Jr, Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood. 2010;116:2286–94.CrossRefPubMedPubMedCentral Benson DM Jr, Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood. 2010;116:2286–94.CrossRefPubMedPubMedCentral
50.
Zurück zum Zitat Bae J, Song W, Smith R, Daley J, Tai YT, Anderson KC, et al. A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma. Br J Haematol. 2012;157(6):687–701.CrossRefPubMed Bae J, Song W, Smith R, Daley J, Tai YT, Anderson KC, et al. A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma. Br J Haematol. 2012;157(6):687–701.CrossRefPubMed
51.
Zurück zum Zitat McCann KJ, Godeseth R, Chudley L, et al. Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study. Cancer Immunol Immunother. 2015;64(8):1021–32.CrossRefPubMedPubMedCentral McCann KJ, Godeseth R, Chudley L, et al. Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study. Cancer Immunol Immunother. 2015;64(8):1021–32.CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Xu YY, Kalos M, et al. Combination immunotherapy after ASCT for multiple myeloma using MAGEA3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res. 2014;20(5):1355–65.CrossRefPubMedPubMedCentral Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Xu YY, Kalos M, et al. Combination immunotherapy after ASCT for multiple myeloma using MAGEA3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res. 2014;20(5):1355–65.CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Szmania S, Gnjatic S, Tricot G, Stone K, Zhan F, Moreno A, et al. Immunization with a recombinant MAGEA3 protein after high-dose therapy for myeloma. J Immunother. 2007;30(8):847–54.CrossRefPubMed Szmania S, Gnjatic S, Tricot G, Stone K, Zhan F, Moreno A, et al. Immunization with a recombinant MAGEA3 protein after high-dose therapy for myeloma. J Immunother. 2007;30(8):847–54.CrossRefPubMed
54.
Zurück zum Zitat Tsuboi A, Oka Y, Nakajima H, Fukuda Y, Elisseeva OA, Yoshihara S, et al. Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy- resistant multiple myeloma. Int J Hematol. 2007;86(5):414–7.CrossRefPubMed Tsuboi A, Oka Y, Nakajima H, Fukuda Y, Elisseeva OA, Yoshihara S, et al. Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy- resistant multiple myeloma. Int J Hematol. 2007;86(5):414–7.CrossRefPubMed
55.
Zurück zum Zitat Rosenblatt J, Vasir B, Uhl L, Blotta S, MacNamara C, Somaiya P, et al. Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. Blood. 2011;117(2):393–402.CrossRefPubMedPubMedCentral Rosenblatt J, Vasir B, Uhl L, Blotta S, MacNamara C, Somaiya P, et al. Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. Blood. 2011;117(2):393–402.CrossRefPubMedPubMedCentral
56.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat • Garfall AL, Maus MV, Hwang W-T, Lacey SF, Mahnke YD, Melenhorst JJ, et al. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N Engl J Med. 2015;373(11):1040–7 This study was one of the first to investigate CAR T cells for MM and demonstrated efficacy in a subset of patients despite the lack of CD19 expression in most MM cells. CrossRefPubMedPubMedCentral • Garfall AL, Maus MV, Hwang W-T, Lacey SF, Mahnke YD, Melenhorst JJ, et al. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N Engl J Med. 2015;373(11):1040–7 This study was one of the first to investigate CAR T cells for MM and demonstrated efficacy in a subset of patients despite the lack of CD19 expression in most MM cells. CrossRefPubMedPubMedCentral
58.
Zurück zum Zitat Guo B, Chen M, Han Q, Hui F, Dai H, Zhang W, et al. CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma. J Cell Immunother. 2016;2(1):28–35.CrossRef Guo B, Chen M, Han Q, Hui F, Dai H, Zhang W, et al. CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma. J Cell Immunother. 2016;2(1):28–35.CrossRef
59.
Zurück zum Zitat 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 Invest. 2016;126(7):2588–96.CrossRefPubMedPubMedCentral 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 Invest. 2016;126(7):2588–96.CrossRefPubMedPubMedCentral
60.
Zurück zum Zitat 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(3):396–410.CrossRefPubMed 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(3):396–410.CrossRefPubMed
61.
Zurück zum Zitat • Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, et al. T cells genetically modified to express an anti–B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36(22):2267–80. https://doi.org/10.1200/JCO.2018.77.8084 An early trial of BCMA-directed CAR T cells, demonstrating responses in the majority of patients. CrossRefPubMedPubMedCentral • Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, et al. T cells genetically modified to express an anti–B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36(22):2267–80. https://​doi.​org/​10.​1200/​JCO.​2018.​77.​8084 An early trial of BCMA-directed CAR T cells, demonstrating responses in the majority of patients. CrossRefPubMedPubMedCentral
62.
Zurück zum Zitat Berdeja JG, Lin Y, Raje N, Munshi N, Siegel D, Liedtke M, et al. Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy. Blood. 2017;130:740. Berdeja JG, Lin Y, Raje N, Munshi N, Siegel D, Liedtke M, et al. Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy. Blood. 2017;130:740.
63.
Zurück zum Zitat Zhao W-H, Liu J, Wang B-Y, Chen Y-X, et al. Updated analysis of 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/refractory multiple myeloma. 2018 ASH annual meeting. Abstract – 955. Zhao W-H, Liu J, Wang B-Y, Chen Y-X, et al. Updated analysis of 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/refractory multiple myeloma. 2018 ASH annual meeting. Abstract – 955.
64.
Zurück zum Zitat Cohen AD, Garfall AL, Stadtmauer EA, Lacey SF, Lancaster E, Vogl DT, et al. Safety and efficacy of B-cell maturation antigen (BCMA)-specific chimeric antigen receptor T cells (CART-BCMA) with cyclophosphamide conditioning for refractory multiple myeloma (MM). Blood. 2017;130:505.CrossRef Cohen AD, Garfall AL, Stadtmauer EA, Lacey SF, Lancaster E, Vogl DT, et al. Safety and efficacy of B-cell maturation antigen (BCMA)-specific chimeric antigen receptor T cells (CART-BCMA) with cyclophosphamide conditioning for refractory multiple myeloma (MM). Blood. 2017;130:505.CrossRef
65.
Zurück zum Zitat Mailankody S, Ghosh A, Staehr M, et al. Clinical responses and pharmacokinetics of MCARH171, a human-derived BCMA targeted CAR T cell therapy in relapsed/refractory multiple myeloma: final results of a phase I clinical trial. 2018 ASH Annual meeting. Abstract 959. Mailankody S, Ghosh A, Staehr M, et al. Clinical responses and pharmacokinetics of MCARH171, a human-derived BCMA targeted CAR T cell therapy in relapsed/refractory multiple myeloma: final results of a phase I clinical trial. 2018 ASH Annual meeting. Abstract 959.
66.
Zurück zum Zitat Mailankody S, Htut M, Lee K, Bensinger W, DeVries T, Piasecki J, et al. First-in human multicenter study of JCARH125, anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma. 2018 ASH annual meeting. Abstract: 957. Mailankody S, Htut M, Lee K, Bensinger W, DeVries T, Piasecki J, et al. First-in human multicenter study of JCARH125, anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma. 2018 ASH annual meeting. Abstract: 957.
67.
Zurück zum Zitat Gregory T, Cohen AD, Costello CL, Ali SA, Berdeja JG, Ostertag EM, et al. Efficacy and safety of P-BCMA-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM): ASH; 2018. abstract 1012 Gregory T, Cohen AD, Costello CL, Ali SA, Berdeja JG, Ostertag EM, et al. Efficacy and safety of P-BCMA-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM): ASH; 2018. abstract 1012
68.
Zurück zum Zitat •• Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, et al. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015;7(288):288ra78 The first clinical trial using marrow infiltrating lymphocytes in MM, demonstrating feasibility and efficacy. CrossRefPubMedPubMedCentral •• Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, et al. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015;7(288):288ra78 The first clinical trial using marrow infiltrating lymphocytes in MM, demonstrating feasibility and efficacy. CrossRefPubMedPubMedCentral
69.
Zurück zum Zitat •• Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914–21 Supports that encouraging clinical responses can be associated with T cells engineered to express an affinity-enhanced T cell receptor. CrossRefPubMedPubMedCentral •• Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914–21 Supports that encouraging clinical responses can be associated with T cells engineered to express an affinity-enhanced T cell receptor. CrossRefPubMedPubMedCentral
70.
Zurück zum Zitat Turtle CJ, Hanafi L-A, Berger C, Hudecek M, Pender B, Robinson E, et al. Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified Tcells. Sci Transl Med. 2016;8(355):355ra116.CrossRefPubMedPubMedCentral Turtle CJ, Hanafi L-A, Berger C, Hudecek M, Pender B, Robinson E, et al. Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified Tcells. Sci Transl Med. 2016;8(355):355ra116.CrossRefPubMedPubMedCentral
71.
Zurück zum Zitat • Sommermeyer D, Hudecek M, Kosasih PL, Gogishvili T, Maloney DG, Turtle CJ, et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 2015;30(2):492–500 Suggests that CAR T cells derived from defined subsets may improve activity and provide uniform potency. CrossRefPubMedPubMedCentral • Sommermeyer D, Hudecek M, Kosasih PL, Gogishvili T, Maloney DG, Turtle CJ, et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 2015;30(2):492–500 Suggests that CAR T cells derived from defined subsets may improve activity and provide uniform potency. CrossRefPubMedPubMedCentral
72.
Zurück zum Zitat Wang X, Walter M, Urak R, Weng L, Huynh C, Lim L, et al. Lenalidomide enhances the function of CS1 chimeric antigen receptor-redirected T cells against multiple myeloma. Clin Cancer Res. 2018 Jan 1;24(1):106–19.CrossRefPubMed Wang X, Walter M, Urak R, Weng L, Huynh C, Lim L, et al. Lenalidomide enhances the function of CS1 chimeric antigen receptor-redirected T cells against multiple myeloma. Clin Cancer Res. 2018 Jan 1;24(1):106–19.CrossRefPubMed
Metadaten
Titel
Immunotherapeutic Approaches for Multiple Myeloma: Where Are We Now?
verfasst von
Myo Htut
Publikationsdatum
21.01.2019
Verlag
Springer US
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 1/2019
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-019-0492-z

Weitere Artikel der Ausgabe 1/2019

Current Hematologic Malignancy Reports 1/2019 Zur Ausgabe

Stem Cell Transplantation (R Maziarz, Section Editor)

Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials?

T-Cell and Other Lymphoproliferative Malignancies (J Zain, Section Editor)

The Emerging Role of Liquid Biopsies in Lymphoproliferative Disorders

Chronic Myeloid Leukemias (M Mauro, Section Editor)

Treatment-Free Remission in CML: the US Perspective

Stem Cell Transplantation (R Maziarz, Section Editor)

Determination of Minimal Residual Disease in Multiple Myeloma: Does It Matter?

Update Onkologie

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