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Dermatology and Therapy
Published in: Dermatology and Therapy 4/2016

Open Access 01-12-2016 | Review

Pruritus Reduction with Systemic Anti-lymphoma Treatments in Patients with Cutaneous T Cell Lymphoma: A Narrative Review

Authors: Halle Field, Ling Gao, Pooja Motwani, Henry K. Wong

Published in: Dermatology and Therapy | Issue 4/2016

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Abstract

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous and relatively rare group of non-Hodgkin lymphomas arising from neoplastic skin-homing memory T cells. There is no known cure for CTCL, and current treatments focus on achieving and maintaining remission, controlling symptoms, limiting toxicities and maintaining or improving quality of life. Patients with CTCL often suffer from pruritus (itching), which can be debilitating and can have a significant impact on physical well-being and quality of life. Although progress has been made towards understanding the mechanisms of pruritus, the pathophysiology of CTCL-related pruritus remains unclear. Currently, there is neither a step-wise treatment algorithm for CTCL nor a standardized approach to treating pruritus in patients with CTCL. Treatments which specifically target pruritus have been reported with varying effectiveness. However, systemic treatments that target CTCL have the potential to alleviate pruritus by treating the underlying disease. Several systemic CTCL treatments have reported anti-pruritic properties, some in both objective responders and nonresponders, but the lack of a standardized method to measure and report pruritus makes it difficult to compare the effectiveness of systemic treatments. In this review, we provide an overview of approved and investigational systemic CTCL treatments that report anti-pruritic properties. For each study, the methods used to measure and report pruritus, as well as the study design are examined so that the clinical benefits of each systemic treatment can be more readily evaluated.
Funding: Financial support for medical editorial assistance and article processing charge were provided by Celgene Corporation.
Literature
1.
Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973–2002. Arch Dermatol. 2007;143:854–9.CrossRefPubMed
2.
Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768–85.CrossRefPubMed
3.
Nagatani T, Matsuzaki T, Iemoto G, et al. Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. Clinical, histopathologic, and immunohistochemical analyses. Cancer. 1990;66:2380–6.CrossRefPubMed
4.
Ferenczi K, Fuhlbrigge RC, Pinkus J, Pinkus GS, Kupper TS. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119:1405–10.CrossRefPubMed
5.
6.
Meyer N, Paul C, Misery L. Pruritus in cutaneous T-cell lymphomas: frequent, often severe and difficult to treat. Acta Derm Venereol. 2010;90:12–7.CrossRefPubMed
7.
Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the international society for cutaneous lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110:1713–22.CrossRefPubMed
8.
Parker SR, Bradley B. Treatment of cutaneous T-cell lymphoma/mycosis fungoides. Dermatol Nurs. 2006;18(6):566–70, 573–5.
9.
Zackheim HS, McCalmont TH. Mycosis fungoides: the great imitator. J Am Acad Dermatol. 2002;47:914–8.CrossRefPubMed
10.
Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: Clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014;70:205.e1–16.CrossRef
11.
Agar NS, Wedgeworth E, Crichton S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol. 2010;28:4730–9.CrossRefPubMed
12.
Demierre MF, Gan S, Jones J, Miller DR. Significant impact of cutaneous T-cell lymphoma on patients’ quality of life: results of a 2005 national cutaneous lymphoma foundation survey. Cancer. 2006;107:2504–11.CrossRefPubMed
13.
Wright A, Wijeratne A, Hung T, et al. Prevalence and severity of pruritus and quality of life in patients with cutaneous T-cell lymphoma. J Pain Symptom Manag. 2013;45:114–9.CrossRef
14.
Vij A, Duvic M. Prevalence and severity of pruritus in cutaneous T cell lymphoma. Int J Dermatol. 2012;51:930–4.CrossRefPubMed
15.
Gerami P, Rosen S, Kuzel T, Boone SL, Guitart J. Folliculotropic mycosis fungoides: an aggressive variant of cutaneous T-cell lymphoma. Arch Dermatol. 2008;144:738–46.PubMed
16.
Demierre M. Mycosis fungoides and Sézary syndrome: the burden of pruritus. Commun Oncol. 2010;7:399–404.CrossRef
17.
Demierre MF, Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2006;55:543–4.CrossRefPubMed
18.
Lehman JS, Cook-Norris RH, Weed BR, et al. Folliculotropic mycosis fungoides: single-center study and systematic review. Arch Dermatol. 2010;146:607–13.PubMed
19.
Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. 2010;162:587–93.CrossRefPubMed
20.
21.
DeLoach LJ, Higgins MS, Caplan AB, Stiff JL. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg. 1998;86:102–6.PubMed
22.
Kim YH, Demierre MF, Kim EJ, et al. Clinically meaningful reduction in pruritus in patients with cutaneous T-cell lymphoma treated with romidepsin. Leuk Lymphoma. 2013;54:284–9.CrossRefPubMed
23.
Kindler CH, Harms C, Amsler F, Ihde-Scholl T, Scheidegger D. The visual analog scale allows effective measurement of preoperative anxiety and detection of patients’ anesthetic concerns. Anesth Analg. 2000;90:706–12.CrossRefPubMed
24.
Marsh-Richard DM, Hatzis ES, Mathias CW, Venditti N, Dougherty DM. Adaptive visual analog scales (AVAS): a modifiable software program for the creation, administration, and scoring of visual analog scales. Behav Res Methods. 2009;41:99–106.CrossRefPubMedPubMedCentral
25.
U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research, U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research, U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006;4:79.CrossRefPubMedCentral
26.
Prince HM, Whittaker S, Hoppe RT. How I treat mycosis fungoides and Sézary syndrome. Blood. 2009;114:4337–53.CrossRefPubMed
27.
Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions. J Am Acad Dermatol. 2014;70:223e.1–.17.CrossRef
28.
Garibyan L, Rheingold CG, Lerner EA. Understanding the pathophysiology of itch. Dermatol Ther. 2013;26:84–91.CrossRefPubMed
29.
Hassan I, Haji ML. Understanding itch: an update on mediators and mechanisms of pruritus. Indian J Dermatol Venereol Leprol. 2014;80:106–14.CrossRefPubMed
30.
Malek M, Gleń J, Rębała K, et al. Il-31 does not correlate to pruritus related to early stage cutaneous T-cell lymphomas but is involved in pathogenesis of the disease. Acta Derm Venereol. 2015;95:283–8.CrossRefPubMed
31.
32.
Saed G, Fivenson DP, Naidu Y, Nickoloff BJ. Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sézary syndrome expresses a Th2-type profile. J Invest Dermatol. 1994;103:29–33.CrossRefPubMed
33.
Vowels BR, Lessin SR, Cassin M, et al. Th2 cytokine mRNA expression in skin in cutaneous T-cell lymphoma. J Invest Dermatol. 1994;103:669–73.CrossRefPubMed
34.
Asadullah K, Docke WD, Haeussler A, Sterry W, Volk HD. Progression of mycosis fungoides is associated with increasing cutaneous expression of interleukin-10 mRNA. J Invest Dermatol. 1996;107:833–7.CrossRefPubMed
35.
Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117:411–7.CrossRefPubMed
36.
Singer EM, Shin DB, Nattkemper LA, et al. IL-31 is produced by the malignant T-cell population in cutaneous T-cell lymphoma and correlates with CTCL pruritus. J Invest Dermatol. 2013;133:2783–5.CrossRefPubMed
37.
Cedeno-Laurent F, Singer EM, Wysocka M, et al. Improved pruritus correlates with lower levels of IL-31 in CTCL patients under different therapeutic modalities. Clin Immunol. 2015;158:1–7.CrossRefPubMedPubMedCentral
38.
Andoh T, Nagasawa T, Satoh M, Kuraishi Y. Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther. 1998;286:1140–5.PubMed
39.
Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011;164:665–7.PubMed
40.
41.
Kumagai H, Ebata T, Takamori K, et al. Efficacy and safety of a novel k-agonist for managing intractable pruritus in dialysis patients. Am J Nephrol. 2012;36:175–83.CrossRefPubMed
42.
Sullivan JR, Watson A. Naltrexone: a case report of pruritus from an antipruritic. Australas J Dermatol. 1997;38:196–8.CrossRefPubMed
43.
Steinhoff M, Neisius U, Ikoma A, et al. Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci. 2003;23:6176–80.PubMed
44.
Nomura I, Goleva E, Howell MD, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003;171:3262–9.CrossRefPubMed
45.
Zelenetz AD, Abramson JS, Advani RH, et al. NCCN clinical practice guidelines in oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010;8(3):288–334.PubMed
46.
Querfeld C, Rosen ST, Kuzel TM, et al. Long-term follow-up of patients with early-stage cutaneous T-cell lymphoma who achieved complete remission with psoralen plus UV-A monotherapy. Arch Dermatol. 2005;141:305–11.CrossRefPubMed
47.
Lowe NJ, Cripps DJ, Dufton PA, Vickers CF. Photochemotherapy for mycosis fungoides: a clinical and histological study. Arch Dermatol. 1979;115:50–3.CrossRefPubMed
48.
Kovary PM, Frosch P, Macher E. Photochemotherapy of Sézary syndrome. Dermatologica. 1981;162:112–7.CrossRefPubMed
49.
50.
Samson Yashar S, Gielczyk R, Scherschun L, Lim HW. Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses. Photodermatol Photoimmunol Photomed. 2003;19:164–8.CrossRefPubMed
51.
Lessin SR, Duvic M, Guitart J, et al. Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013;149:25–32.CrossRefPubMedPubMedCentral
52.
Heald P, Mehlmauer M, Martin AG, et al. Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol. 2003;49:801–15.CrossRefPubMed
53.
Arundell FD, Chan WH. Mycosis fungoides. Topical use of nitrogen mustard in recurrent cases. Calif Med. 1968;109:458–61.PubMedPubMedCentral
54.
55.
ISTODAX (romidepsin) [package insert] 2014.
56.
Whittaker SJ, Demierre M, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28:4485–91.CrossRefPubMed
57.
Piekarz RL, Frye R, Turner M, et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009;27:5410–7.CrossRefPubMedPubMedCentral
58.
Kim EJ, Kim YH, Rook AH, et al. Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma. Leuk Lymphoma. 2015;56:2847–54.CrossRefPubMedPubMedCentral
59.
Foss FM, Duvic M, Lerner A, et al. Responses to romidepsin in patients with cutaneous T-cell lymphoma (CTCL) with tumors and/or folliculotropic involvement. J Clin Oncol 2014;32:Abstract 8575.
60.
Duvic M, Kim YH, Rook AH, et al. Responses to romidepsin in patients with cutaneous T-cell lymphoma (CTCL) and prior treatment with systemic chemotherapy: Subanalysis from the pivotal phase II study. T-Cell Lymphoma Forum 2014:Abstract TS15_3.
61.
TARGRETIN (bexarotene [package insert]. Laval, Canada: Valeant Pharmaceuticals; 2013.
62.
Duvic M, Hymes K, Heald P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II–III trial results. J Clin Oncol. 2001;19:2456–71.PubMed
63.
Duvic M, Martin AG, Kim Y, et al. Phase 2 and 3 clinical trial of oral bexarotene (targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001;137:581–93.PubMed
64.
Straus DJ, Duvic M, Horwitz SM, et al. Final results of phase II trial of doxorubicin HCl liposome injection followed by bexarotene in advanced cutaneous T-cell lymphoma. Ann Oncol. 2014;25:206–10.CrossRefPubMed
65.
Sepmeyer JA, Greer JP, Koyama T, Zic JA. Open-label pilot study of combination therapy with rosiglitazone and bexarotene in the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol. 2007;56:584–7.CrossRefPubMed
66.
ONTAK (denileukin diftiox) [package insert]. Tokyo, Japan: Esai CO LTD; 2008.
67.
Prince HM, Duvic M, Martin A, et al. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2010;28:1870–7.CrossRefPubMed
68.
Olsen E, Duvic M, Frankel A, et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol. 2001;19:376–88.PubMed
69.
Duvic M, Kuzel TM, Olsen EA, et al. Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with denileukin diftitox (ONTAK). Clin Lymphoma. 2002;2:222–8.CrossRefPubMed
70.
ZOLINZA (vorinostat) [package insert]. Kenilworth, NJ: Merck Pharmaceuticals; 2015.
71.
Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007;109:31–9.CrossRefPubMedPubMedCentral
72.
Olsen EA, Kim YH, Kuzel TM, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25:3109–15.CrossRefPubMed
73.
Dummer R, Beyer M, Hymes K, et al. Vorinostat combined with bexarotene for treatment of cutaneous T-cell lymphoma: in vitro and phase I clinical evidence supporting augmentation of retinoic acid receptor/retinoid X receptor activation by histone deacetylase inhibition. Leuk Lymphoma. 2012;53:1501–8.CrossRefPubMed
74.
Lundin J, Hagberg H, Repp R, et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sézary syndrome. Blood. 2003;101:4267–72.CrossRefPubMed
75.
Kennedy GA, Seymour JF, Wolf M, et al. Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab. Eur J Haematol. 2003;71:250–6.CrossRefPubMed
76.
Bouwhuis SA, el-Azhary RA, Gibson LE, McEvoy MT, Pittelkow MR. Effect of insulin-dependent diabetes mellitus on response to extracorporeal photopheresis in patients with Sézary syndrome. J Am Acad Dermatol. 2002;47:63–7.CrossRefPubMed
77.
Zackheim HS, Kashani-Sabet M, Hwang ST. Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol. 1996;34:626–31.CrossRefPubMed
78.
Nicolas JF, Balblanc JC, Frappaz A, Chouvet B, Delcombel M, Thivolet J. Treatment of cutaneous T cell lymphoma with intermediate doses of interferon alpha 2a. Dermatologica. 1989;179:34–7.CrossRefPubMed
79.
Kim YH, Duvic M, Obitz E, et al. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma. Blood. 2007;109:4655–62.CrossRefPubMed
80.
Foss F, Advani R, Duvic M, et al. A phase II trial of belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015;168:811–9.CrossRefPubMed
81.
Duvic M, Dummer R, Becker JC, et al. Panobinostat activity in both bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer. 2013;49:386–94.CrossRefPubMed
82.
Bates SE, Eisch R, Ling A, et al. Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data. Br J Haematol. 2015;170:96–109.CrossRefPubMedPubMedCentral
83.
Pohlman B, Advani R, Duvic M, et al. Final results of a phase II trial of belinostat (PXD101) in patients with recurrent or refractory peripheral or cutaneous T-cell lymphoma. Blood 2009;114:Abstract 920.
84.
Olsen EA, Whittaker S, Kim YH, et al. Clinical end points and response criteria in mycosis fungoides and Sezary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the cutaneous lymphoma task force of the European Organisation for Research and Treatment of Cancer. J Clin Oncol. 2011;29:2598–607.CrossRefPubMedPubMedCentral
Metadata
Title
Pruritus Reduction with Systemic Anti-lymphoma Treatments in Patients with Cutaneous T Cell Lymphoma: A Narrative Review
Authors
Halle Field
Ling Gao
Pooja Motwani
Henry K. Wong
Publication date
01-12-2016
Publisher
Springer Healthcare
Published in
Dermatology and Therapy / Issue 4/2016
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI
https://doi.org/10.1007/s13555-016-0143-4

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