Top

Published in:

01-06-2013 | Rapid Communication

Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma

Authors: Takeshi Harada, Shuji Ozaki, Asuka Oda, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Kyoko Takeuchi, Toshio Matsumoto, Masahiro Abe

Published in: International Journal of Hematology | Issue 6/2013

Abstract

Transient inflammatory reactions have been reported in a subpopulation of patients with multiple myeloma (MM) during lenalidomide (Len) plus dexamethasone (DEX) therapy. Here, we examined serum levels of Th1 (IL-2 and IFN-γ) and Th2 cytokines (IL-6 and TNF-α) in nine refractory or relapsed MM patients treated with Len plus low-dose DEX. Six patients showed elevation of C-reactive protein (CRP) after the initiation of therapy. In these patients, IFN-γ and IL-6 were also elevated in two and three patients, respectively. The remaining three patients showed no appreciable changes in CRP or these cytokines. Furthermore, Len enhanced the production of both Th1 and Th2 cytokines in normal peripheral blood mononuclear cells and in patient bone marrow mononuclear cells containing primary myeloma cells and lymphocytes. These results suggest that the modulation of the Th1 and Th2 cytokine production by Len may contribute to transient inflammatory reaction in MM patients.

Available only for authorised users

Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357(21):2133–42.PubMedCrossRef

Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29–37.PubMedCrossRef

Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005;106(13):4050–3.PubMedCrossRef

Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23(11):2147–52.PubMedCrossRef

Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357(21):2123–32.PubMedCrossRef

Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24(1):22–32.PubMedCrossRef

Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009;2(36):36.PubMedCrossRef

Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999;163(1):380–6.PubMed

Ozaki S, Harada T, Fujii S, Nakamura S, Miki H, Nakano A, et al. Transient inflammatory reaction during lenalidomide plus reduced-dose dexamethasone therapy in two patients with relapsed multiple myeloma. Int J Hematol. 2011;93(2):257–9.PubMedCrossRef

10.

Morita Y, Shimada T, Yamaguchi T, Rai S, Hirase C, Emoto M, et al. Cytokine profiles in relapsed multiple myeloma patients undergoing febrile reactions to lenalidomide. Int J Hematol. 2011;94(6):583–4.PubMedCrossRef

11.

Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36(3):842–54.PubMedCrossRef

12.

Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412–20.PubMedCrossRef

13.

Picker LJ, Singh MK, Zdraveski Z, Treer JR, Waldrop SL, Bergstresser PR, et al. Direct demonstration of cytokine synthesis heterogeneity among human memory/effector T cells by flow cytometry. Blood. 1995;86(4):1408–19.PubMed

14.

Openshaw P, Murphy EE, Hosken NA, Maino V, Davis K, Murphy K, et al. Heterogeneity of intracellular cytokine synthesis at the single-cell level in polarized T helper 1 and T helper 2 populations. J Exp Med. 1995;182(5):1357–67.PubMedCrossRef

15.

Pelliniemi TT, Irjala K, Mattila K, Pulkki K, Rajamaki A, Tienhaara A, et al. Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. Blood. 1995;85(3):765–71.PubMed

16.

Gandhi AK, Kang J, Capone L, Parton A, Wu L, Zhang LH, et al. Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets. 2010;10(2):155–67.PubMedCrossRef

17.

Hsu AK, Quach H, Tai T, Prince HM, Harrison SJ, Trapani JA, et al. The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy. Blood. 2011;117(5):1605–13.PubMedCrossRef

18.

Ferrajoli A, Lee BN, Schlette EJ, O’Brien SM, Gao H, Wen S, et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008;111(11):5291–7.PubMedCrossRef

19.

Chanan-Khan AA, Chitta K, Ersing N, Paulus A, Masood A, Sher T, et al. Biological effects and clinical significance of lenalidomide-induced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response. Br J Haematol. 2011;155(4):457–67.PubMedCrossRef

20.

Aue G, Njuguna N, Tian X, Soto S, Hughes T, Vire B, et al. Lenalidomide-induced upregulation of CD80 on tumor cells correlates with T-cell activation, the rapid onset of a cytokine release syndrome and leukemic cell clearance in chronic lymphocytic leukemia. Haematologica. 2009;94(9):1266–73.PubMedCrossRef

Title: Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma
Authors: Takeshi Harada
Shuji Ozaki
Asuka Oda
Shiro Fujii
Shingen Nakamura
Hirokazu Miki
Kumiko Kagawa
Kyoko Takeuchi
Toshio Matsumoto
Masahiro Abe
Publication date: 01-06-2013
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 6/2013
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-013-1321-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2013

Acute myeloid leukemia associated with FGFR1 abnormalities

Guest editorial: efficacy of and resistance to molecularly targeted therapy for myeloid malignancies

Efficacy and resistance of gemtuzumab ozogamicin for acute myeloid leukemia

Spontaneous remission of 2-chlorodeoxyadenosine (2-CdA)-related secondary myelodysplastic syndrome in a patient with refractory Langerhans cell histiocytosis

Successful treatment with bortezomib in type-1 cryoglobulinemic vasculitis patient after rituximab failure: a case report and literature review

Bisphosphonate treatment and renal function in 201 myeloma patients undergoing stem cell transplantation

Keynote webinar | Spotlight on antibody–drug conjugates in cancer