Publications by authors named "Madeleine Duvic"

372 Publications

Primary Cutaneous Lymphoma: Recommendations for Clinical Trial Design and Staging Update from the ISCL, USCLC, and EORTC.

Blood 2021 Nov 10. Epub 2021 Nov 10.

Leiden University Medical Center, Leiden, Netherlands.

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome (MF/SS), the most common type of PCL, none exist for the other PCLs. In addition, staging in the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous Lymphoma Consortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
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http://dx.doi.org/10.1182/blood.2021012057DOI Listing
November 2021

Monitoring malignant T-cell clones by direct TCR expression assay in patients with leukemic cutaneous T-cell lymphoma during extracorporeal photopheresis.

Photodermatol Photoimmunol Photomed 2021 Sep 20. Epub 2021 Sep 20.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background/purpose: Accurate assessment of malignant T-cell clones in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) is crucial for diagnosis, treatment, and monitoring disease. Although multiple approaches to quantitate malignant T-cell clones have been reported, a cost-effective assay with broad coverage is not available. We report a NanoString-nCounter-Technology-based direct TCR expression assay (DTEA) that was previously developed to quantify both TCR-Vα and TCR-Vβ usages after adoptive immunotherapy. This study was performed to test the effectiveness of DTEA in assessing malignant T-cell clones in L-CTCL patients.

Methods: Total RNAs extracted from peripheral blood mononuclear cells of patients before starting extracorporeal photopheresis (ECP) (n = 15) and during therapy at 3 months and 6 months (n = 12) were used for DTEA, with customized probes for 45 TCR-Vα and 46 TCR-Vβ family members.

Results: At baseline, DTEA detected TCR-Vβ clones in all 15 patients (100%) compared to flow cytometry that detected TCR-Vβ clones in 9 of 13 patients (69.2%). In addition to predominant TCR-Vβ clones, DTEA also detected additional TCR-Vβ clones in 8 of 15 patients (53.3%). Furthermore, DTEA simultaneously identified clonal TCR-Vα usages, which allowed us to pair TCR-Vα and TCRVβ usages by malignant T-cells and identify diversified clonotypes. Changes in the relative frequencies of clonal TCR-Vβ and TCRVα usages over therapy were consistent with patients' clinical responses.

Conclusions: Our results indicate that DTEA can effectively assess malignant T-cell clones by detecting clonal TCR-Vα and TCR-Vβ usages. By providing a global view of TCR repertoires, DTEA may also help us understand the origin(s) of malignant T-cells and pathogenesis of CTCL.
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http://dx.doi.org/10.1111/phpp.12732DOI Listing
September 2021

Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data.

Blood Adv 2021 Dec;5(23):5098-5106

Division of Cancer Medicine, Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Oncology and Epworth Healthcare, The University of Melbourne, Melbourne, VIC, Australia.

The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499.
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http://dx.doi.org/10.1182/bloodadvances.2021004710DOI Listing
December 2021

Granuloma Annulare: An Updated Review of Epidemiology, Pathogenesis, and Treatment Options.

Am J Clin Dermatol 2021 Sep 8. Epub 2021 Sep 8.

Department of Dermatology, MD Anderson Cancer Center, Houston, TX, USA.

Granuloma annulare (GA) is an inflammatory granulomatous skin disease that can be localized (localized GA) or disseminated (generalized GA), with patch, perforating, and subcutaneous subtypes being less common variants of this benign condition. Recently, new research has emerged that further elucidates GA epidemiology and etiopathogenesis; importantly, new therapeutic options for GA have also been described, although there remains a paucity of randomized controlled studies. In this review, we summarize recent updates on GA epidemiology and etiopathogenesis and offer an updated review of the therapeutic options for GA currently reported in the literature. We hope that the current review galvanizes randomized controlled studies that will in turn help lead to the recommendation of evidence-based treatments for GA.
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http://dx.doi.org/10.1007/s40257-021-00636-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423598PMC
September 2021

Post-transplantation donor-derived Sezary syndrome in a patient with A91V PRF1 variant hemophagocytic lymphohistiocytosis.

Am J Hematol 2021 09 28;96(9):E350-E353. Epub 2021 Jun 28.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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http://dx.doi.org/10.1002/ajh.26266DOI Listing
September 2021

Teledermatology During COVID-19: An Updated Review.

Am J Clin Dermatol 2021 Jul 9;22(4):467-475. Epub 2021 Apr 9.

School of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.

The coronavirus disease 2019 (COVID-19) pandemic has fundamentally transformed the landscape of providing dermatologic care. In an age of lockdowns and social distancing, teledermatology (TD) has emerged as a powerful tool to deliver remote care. Here, we review literature on TD use during the pandemic to evaluate the positives and negatives of TD implementation. We especially consider the reception of TD in underserved communities and the developing world as well as the ethico-legal challenges wrought by the burgeoning utilization of this new paradigm of care. The potential of TD to occupy a more prominent role in dermatologic care in a post-COVID-19 world is also discussed.
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http://dx.doi.org/10.1007/s40257-021-00601-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032846PMC
July 2021

Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: An ALCANZA sub-analysis.

Eur J Cancer 2021 05 29;148:411-421. Epub 2021 Mar 29.

Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, 40 Landsdowne Street, 02139, Cambridge, MA, USA. Electronic address:

Introduction: Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, can lead to disfiguring lesions, debilitating pruritus and frequent skin infections. This study assessed response to brentuximab vedotin in patients with MF in the phase III ALCANZA study.

Methods: Baseline CD30 levels and large-cell transformation (LCT) status were centrally reviewed in patients with previously-treated CD30-positive MF using ≥2 skin biopsies obtained at screening; eligible patients required ≥1 biopsy with ≥10% CD30 expression. Patients were categorised as CD30 < 10% (≥1 biopsy with <10% CD30 expression), or CD30 ≥ 10% (all biopsies with ≥10% CD30 expression) and baseline LCT present or absent. Efficacy analyses were the proportion of patients with objective response lasting ≥4 months (ORR4) and progression-free survival (PFS).

Results: Clinical activity with brentuximab vedotin was observed across all CD30 expression levels in patients with ≥1 biopsy showing ≥10% CD30 expression. Superior ORR4 was observed with brentuximab vedotin versus physician's choice in patients: with CD30 < 10% (40.9% versus 9.5%), with CD30 ≥ 10% (57.1% versus 10.3%), with LCT (64.7% versus 17.6%) and without LCT (38.7% versus 6.5%). Brentuximab vedotin improved median PFS versus physician's choice in patients: with CD30 < 10% (16.7 versus 2.3 months), with CD30 ≥ 10% (15.5 versus 3.9 months), with LCT (15.5 versus 2.8 months) and without LCT (16.1 versus 3.5 months). Safety profiles were generally comparable across subgroups.

Conclusion: These exploratory analyses demonstrated that brentuximab vedotin improved rates of ORR4 and PFS versus physician's choice in patients with CD30-positive MF and ≥1 biopsy showing ≥10% CD30 expression, regardless of LCT status.

Clinical Trial Registration: Clinicaltrials.gov, NCT01578499.
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http://dx.doi.org/10.1016/j.ejca.2021.01.054DOI Listing
May 2021

Vulvar Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma.

Int J Gynecol Pathol 2021 May;40(3):229-233

Cutaneous T-cell lymphomas may present with a clinical course that is incongruent with the associated histologic findings. Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma classically presents as an abrupt eruption of disseminated ulcerated annular plaques with aggressive behavior and a poor prognosis. Herein we describe a vulvar primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma with a locally aggressive clinical course that was strikingly responsive to radiation therapy. As aggressive therapy involving systemic chemotherapy is indicated for primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, appropriate clinico-pathologic correlation is crucial for preventing potentially excessive or insufficient therapeutic intervention. Our case also highlights the pivotal role of both radiation therapy and infection control in the management of aggressive cutaneous vulvar lymphomas.
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http://dx.doi.org/10.1097/PGP.0000000000000648DOI Listing
May 2021

Is immunohistochemical expression of GATA3 helpful in the differential diagnosis of transformed mycosis fungoides and primary cutaneous CD30-positive T cell lymphoproliferative disorders?

Virchows Arch 2021 Aug 18;479(2):377-383. Epub 2021 Feb 18.

Department of Pathology, Dermatopathology Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.
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http://dx.doi.org/10.1007/s00428-021-03056-yDOI Listing
August 2021

Renal Cell Carcinoma Associated with Mycosis Fungoides: A Paraneoplastic Syndrome.

Case Rep Nephrol 2020 29;2020:8897183. Epub 2020 Oct 29.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Patients with mycosis fungoides have an increased risk for additional malignancies, particularly hematologic malignancies. Of the malignancies that have been associated with mycosis fungoides, renal cell carcinoma and other solid tumor malignancies have not been studied extensively. In this case series, we describe three mycosis fungoides patients who were diagnosed with clear cell renal cell carcinoma and discuss the potential pathophysiology underlying this association.
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http://dx.doi.org/10.1155/2020/8897183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647747PMC
October 2020

Quality of Life Effect of the Anti-CCR4 Monoclonal Antibody Mogamulizumab Versus Vorinostat in Patients With Cutaneous T-cell Lymphoma.

Clin Lymphoma Myeloma Leuk 2021 02 18;21(2):97-105. Epub 2020 Sep 18.

Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX.

Background: Sézary syndrome (SS) and mycosis fungoides (MF), 2 types of cutaneous T-cell lymphoma, cause significant morbidity and adversely affect patients' quality of life (QoL). The present study assessed the QoL measurement changes in patients receiving mogamulizumab versus vorinostat.

Patients And Methods: A multicenter phase III trial was conducted of patients with stage IB-IV MF/SS with ≥ 1 failed systemic therapy. The QoL measures included Skindex-29 and the Functional Assessment of Cancer Therapy-General. The symptoms, function, and QoL subdomains were longitudinally modeled using mixed models with prespecified covariates. Meaningful change thresholds (MCTs) were defined using distribution-based methods. The categorical changes by group over time and the time to clinically meaningful worsening were analyzed.

Results: Of the 372 randomized patients, mogamulizumab demonstrated improvement in Skindex-29 symptoms (cycles 3, 5, and 7; P < .05) and functional (cycles 3 and 5; P < .05) scales. A significantly greater proportion of mogamulizumab-treated patients improved by MCTs or more from baseline in the Skindex-29 symptoms domain (cycles 3, 5, 7, and 11) and functioning domain (cycle 5). Significant differences in the Functional Assessment of Cancer Therapy-General physical well-being (cycles 1, 3, and 5; P < .05) were observed in favor of mogamulizumab and a greater proportion of patients had declined by MCTs or more at cycles 1, 3, 5, and 7 with vorinostat treatment. The median time to symptom worsening using Skindex-29 was 27.4 months for mogamulizumab versus 6.6 months for vorinostat. In the patients with SS, the time to worsening favored mogamulizumab (P < .005) for all Skindex-29 domains. The time to worsening was similar for the 2 MF treatment arms.

Conclusion: The symptoms, function, and overall QoL of patients with MF/SS favored mogamulizumab over vorinostat across all time points. Patients with the greatest symptom burden and functional impairment derived the most QoL benefit from mogamulizumab.
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http://dx.doi.org/10.1016/j.clml.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878351PMC
February 2021

Anaphylaxis following administration of extracorporeal photopheresis for cutaneous T cell lymphoma.

Dermatol Online J 2020 Sep 15;26(9). Epub 2020 Sep 15.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Extracorporeal photopheresis is a non-invasive therapy used for the treatment of a range of T cell disorders, including cutaneous T cell lymphoma. During extracorporeal photopheresis, peripheral blood is removed from the patient and the white blood cells are separated from whole blood via centrifugation. The white blood cells are exposed to psoralen (a photosensitizing agent) and ultraviolet A radiation, causing cell apoptosis. The apoptotic leukocytes are subsequently re-infused into the patient, resulting in the production of tumor suppressor cells and clinical improvement. Extracorporeal photopheresis is generally regarded as safe with few side effects. We report a dermatology patient who developed anaphylaxis after receiving extracorporeal photopheresis for the treatment of leukemic mycosis fungoides. We suspect that our patient's anaphylaxis resulted from exposure to an agent used in extracorporeal photopheresis.
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September 2020

Unmasking a T cell lymphoma: Folliculotropic mycosis fungoides with a gamma-delta phenotype.

JAAD Case Rep 2020 Dec 23;6(12):1316-1319. Epub 2020 Sep 23.

Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1016/j.jdcr.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510555PMC
December 2020

Determination of immunophenotypic aberrancies provides better assessment of peripheral blood involvement by mycosis fungoides/Sézary syndrome than quantification of CD26- or CD7- CD4+ T-cells.

Cytometry B Clin Cytom 2021 03 15;100(2):183-191. Epub 2020 Jul 15.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: Blood involvement by mycosis fungoides (MF)/Sézary syndrome (SS) influences prognosis and therapeutic decisions. MF/SS blood stage is currently determined by absolute CD4 + CD26- or CD4 + CD7-cell counts, which quantification method may overestimate MF/SS by including CD26- or CD7- normal CD4+ T-cells, or underestimate disease burden when MF/SS cells show incomplete loss of CD26 and/or CD7. Recently, through the standardization effort led by the International Clinical Cytometry Society (ICCS), recommendation was made to quantify MF/SS by enumerating immunophenotypically aberrant CD4+ T-cells, rather than CD26- or CD7- in isolation.

Methods: We compared these two quantitation methods in 309 MF/SS patients who had blood samples analyzed by flow cytometry immunophenotyping (FCI) over a 1-year period.

Results: Using the European Organization of Research and Treatment of Cancer (EORTC)/International Society for Cutaneous Lymphomas (ISCL) criteria, 221 (71.5%) patients had a blood stage corresponding to B0, 57 (18.4%) to B1, and 31 (10%) to B2. By FCI analysis, a total of 62 patients (20.0%) were found positive for MF/SS. Among EORTC B0 patients, 11/221 (5%) were positive by FCI (false negatives), and among EORTC Stage B1 patients, 35/57 (61%) were negative by FCI (false positives). Regarding patients positive for MF/SS cells by FCI, there was an overall excellent correlation (r = .999, p < .001) between the EORTC/ISCL method and FCI method; however, four (6.5%) patients would have an altered B stage between B0 and B1.

Conclusion: The MF/SS cell quantification method using immunophenotypic aberrancies, as recommended by the ICCS, allows to distinguish MF/SS cells from background benign T-cells and enables for more accurate staging, especially among patients currently being considered to have B0 and B1 stage diseases.
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http://dx.doi.org/10.1002/cyto.b.21933DOI Listing
March 2021

Development of Sézary syndrome following the administration of dupilumab.

Dermatol Online J 2020 Apr 15;26(4). Epub 2020 Apr 15.

The University of Texas MD Anderson Cancer Center, Houston, TX.

Dupilumab is a monoclonal antibody that inhibits interleukin-4 and interleukin-13 signaling. It is the first biologic agent to demonstrate efficacy in treating moderate-to-severe refractory atopic dermatitis [1, 2]. Although dupilumab provides promise for the treatment of atopic and allergic conditions, clinicians should take into account its novelty and the potential for unexpected adverse events. We present a patient who developed Sézary syndrome following the initiation of dupilumab.
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April 2020

Lymphomatoid Papulosis With a Unique T Follicular Helper-Like Phenotype.

Am J Dermatopathol 2020 Oct;42(10):776-779

Department of Pathology, Dermatopathology Section, The University of Texas MD Anderson Cancer Center, Houston, TX.

Lymphomatoid papulosis (LyP) is a benign skin condition that typically presents with grouped or scattered lesions on the body that self-resolve within weeks or months of onset. LyP belongs to the group of CD30-positive lymphoproliferative disorders. Several histological variants of LyP exist, and the histological features of LyP can overlap with other lymphoproliferative disorders; therefore, both histological and clinical correlations are needed for a proper diagnosis of LyP. We report an unusual case of LyP displaying a T follicular helper cell-like phenotype and histopathologically resembling the primary cutaneous CD4-positive small-sized to medium-sized T-cell lymphoproliferative disorder.
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http://dx.doi.org/10.1097/DAD.0000000000001693DOI Listing
October 2020

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study.

Eur J Cancer 2020 07 2;133:120-130. Epub 2020 Jun 2.

University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1452, Houston, TX, USA. Electronic address:

Background: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined.

Methods: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires.

Results: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores.

Conclusions: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients.

Clinical Trial Registration: NCT01578499.
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http://dx.doi.org/10.1016/j.ejca.2020.04.010DOI Listing
July 2020

Second primary malignancies in blastic plasmacytoid dendritic cell neoplasm: A national database study.

J Am Acad Dermatol 2020 Dec 9;83(6):1786-1789. Epub 2020 Apr 9.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1016/j.jaad.2020.03.101DOI Listing
December 2020

CD209 monocyte-derived myeloid dendritic cells were increased in patients with leukemic cutaneous T-cell lymphoma undergoing extracorporeal photopheresis via the CELLEX system.

Photodermatol Photoimmunol Photomed 2020 Jul 16;36(4):290-298. Epub 2020 Apr 16.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background/purpose: We previously reported that myeloid dendritic cells (mDC) were increased in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) following extracorporeal photopheresis (ECP) using the Therakos UVAR XTS system. We now assessed monocyte-derived mDCs (Mo-DCs) in L-CTCL patients treated with the CELLEX photopheresis system. CD209, a transmembrane receptor, was used to define Mo-DCs.

Methods: Peripheral blood samples from baseline pre-ECP and at Day 2, 1 month, 3 months, and 6 months post-ECP were analyzed by flow cytometry for Lin HLA-DR CD123 plasmacytoid dendritic cells (pDCs), Lin HLA-DR CD11c mDCs, and CD209 mDCs. The expression of CD209 mRNA was assessed by real-time PCR.

Results: At baseline, 7 of 19 patients had lower than normal mDCs, and all patients had lower than normal CD209 mDCs in peripheral blood mononuclear cells (0.005% in patients, n = 19, vs 0.50% in healthy donors, n = 7, P < .0001). The CD209 mDC numbers only accounted for 3.28% out of total mDCs in patients compared with 66.51% in healthy donors. After treatment, the CD209 mDC numbers showed increasing trends in patients. The average absolute numbers of CD209 mDCs went up by 4.8-fold at 3 months (n = 10, P = .103) and by 6.4-fold at 6 months (n = 9, P = .100). CD209 mRNA expression went up in two patients responsive to therapy, parallel to CD209 mDC numbers. L-CTCL patients achieved 70% overall clinical response rate (7/10) following ECP therapy with the CELLEX system.

Conclusions: Our results suggest that the CELLEX photopheresis system is effective for treating L-CTCL patients like the UVAR XTS system, and in vivo-generated Mo-DCs increase following ECP.
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http://dx.doi.org/10.1111/phpp.12552DOI Listing
July 2020

T-cell lymphoma secondary to checkpoint inhibitor therapy.

J Immunother Cancer 2020 02;8(1)

University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Murine model suggests programmed cell death-1 (PD-1), an immune checkpoint not only plays role in tumor escape but is also a tumor suppressor for T-cells. But until, no reports of secondary T-cell lymphoma postuse of immune checkpoint inhibitors (ICIs) has been reported. Herein, we present a hitherto unreported phenomenon of secondary T-cell lymphoma when PD-1 inhibitor was used in a patient diagnosed with a tumor of epithelial origin.

Case Report: A man in mid-70s presented with biopsy-proven metastatic tumor of epithelial origin. Patient received carboplatin in combination with paclitaxel for four cycles leading to partial remission. The patient was subsequently switched to pembrolizumab due to persistent disease in the mediastinum. After four cycles of PD-1 inhibitor, patient presented with progression of disease and was diagnosed with biopsy-proven peripheral T-cell lymphoma-not otherwise specified. Based on the reported tumor suppressor function of PD-1 in murine models, we hypothesized that the use of PD-1 inhibitor caused clonal proliferation of abnormal T-cell clone leading to T-cell lymphoma. T-cell receptor (TCR) sequencing was performed by TCRβ sequencing and T-cell clones from pre-ICI treatment specimen were compared with post-ICI treatment specimens. We show that one of the T-cell clones present in pre-ICI treatment specimen at a low frequency of had massive expansion to become most dominant clone in post-ICI treatment specimens leading to lymphoma. Moreover, targeted exome sequencing revealed a new TET2 mutation in the clone representing the lymphoma.Next, we retrospectively reviewed the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), the pharmacovigilance database from 2012 to 2018 to find the reported incidence of this phenomenon and calculated the reporting OR (ROR) for disproportionality analysis for risk of T-cell lymphoma due to checkpoint inhibitors compared with other drugs. In FAERS, the incidence of T-cell lymphoma post-ICIs (pembrolizumab, nivolumab and ipilimumab) was found to be 0.02% with 17% mortality. The ROR probability of risk of T-cell lymphoma compared with other drugs in pharmacovigilance database was increased at 1.91.

Conclusions: T-cell lymphoma is a rare sequela of ICIs with high mortality. Larger studies with long-term follow-up of patients receiving ICIs is needed.
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http://dx.doi.org/10.1136/jitc-2019-000104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057430PMC
February 2020

Diagnosis of cutaneous T-cell lymphoma by insurance type before and after the Affordable Care Act: a national database study.

Dermatol Online J 2019 Nov 15;25(11). Epub 2019 Nov 15.

Baylor College of Medicine, Houston, Texas, USA The University of Texas MD Anderson Cancer Center, Houston, TX.

The Affordable Care Act (ACT) was implemented to increase health care access and reduce the uninsured in the age group between pediatric and Medicare populations (18-64). The association of the ACA with insurance type upon diagnosis (uninsured, Medicaid, non-Medicaid) has been investigated for otolaryngologic, gynecologic, and the top five non-skin malignancies. Such studies for cutaneous malignancies are lacking. We conducted a retrospective analysis of the prospective National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer database to assess the impact of the ACA on new diagnoses of cutaneous T-cell lymphoma (CTCL) by insurance type. Unlike prior studies of other malignancies, we did not observe significant differences between rate of diagnosis of CTCL by insurance type before and after full implementation of the ACA in all states, expansion states, and non-expansion states. Skin cancers do not have screening guidelines and CTCL is an uncommon malignancy, both of which may contribute to these findings. However, Medicaid-expansion states were much closer to reducing the percentage of newly diagnosed uninsured patients with CTCL than non-expansion states. As such, it may be prudent to investigate intrinsic socioeconomic barriers to care in Medicaid patients to improve their access to care to decrease the uninsured population and improve outcomes.
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November 2019

Non-Classic Signs of Sézary Syndrome: A Review.

Am J Clin Dermatol 2020 Jun;21(3):383-391

Department of Dermatology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 1452, Houston, TX, 77030, USA.

The majority of patients with Sézary syndrome (SS) present with classic symptoms of erythroderma, lymphadenopathy, and pruritus. However, there have been numerous reports of patients with SS who have non-classic signs. In this review, we report the less common clinical presentations of SS and discuss their relevant treatments. Our search included all literature on SS since 2008, the year the World Health Organization (WHO) incorporated the diagnostic criteria for SS into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. We reviewed 896 articles and identified 505 patients with non-classic presentations of SS. Of these 505 patients, the most common non-classic signs of SS were keratoderma, onychodystrophy, alopecia, leonine facies, and ectropion. Given the aggressive and highly symptomatic nature of SS, it is imperative that clinicians recognize the less common signs of the disease to prevent delays in diagnosis and treatment. To our knowledge, this is the first review of the clinical variations of SS with a focus on non-classic signs and symptoms.
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http://dx.doi.org/10.1007/s40257-020-00501-7DOI Listing
June 2020

Necrotizing Granulomatous Dermatitis and Panniculitis Masquerading as T Cell Lymphoma.

Skinmed 2019 1;17(6):406-408. Epub 2019 Nov 1.

Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX.

A 51-year-old white woman with a past medical history significant for steroid-dependent ulcerative colitis, rheumatoid arthritis, and diabetes mellitus presented to the hospital with fever and painful, erythematous subcutaneous nodules on the medical aspects of both thighs. Histopathologic examination showed features suggestive of an abscess, but her condition failed to improve with intravenous broad-spectrum antibiotics. Molecular studies detected T cell receptor-β gene rearrangements. The lesions later exhibited signs of necrosis, requiring multiple debridements as well as therapy with hyperbaric oxygen. She was later referred to the MD Anderson Cancer Center for evaluation for possible subcutaneous panniculitis-like T cell lymphoma.
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August 2020

Waistband Mycosis Fungoides: A New Clinical Variant of Early-Stage Disease.

Skinmed 2019 1;17(5):329-332. Epub 2019 Sep 1.

Department of Dermatology, the University of Texas MD Anderson Cancer Center, Houston, TX.

Case 1: A 17-year-old white man was referred for evaluation of biopsy-proven patch-stage mycosis fungoides (MF) that had first appeared 5 years previously. Asymptomatic "bruises" had appeared under his football padding in a waistband distribution, and these lesions improved during each offseason but never fully resolved. His exposure history was only positive for swimming pool water and his athletic pads. On physical examination, large, irregular, geometric tan-colored patches were present along his waistband area, in areas of contact with his football padding, with an involved body surface area (BSA) of 23.7% (Figure 1A). Examination of scale for fungal hyphae under potassium hydroxide was negative. No lymphadenopathy was present.
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May 2020

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in erythrodermic cutaneous T-cell lymphoma (CTCL) patients.

Arch Dermatol Res 2020 May 27;312(4):283-288. Epub 2019 Nov 27.

Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Erythroderma can occur in cutaneous T-cell lymphoma (CTCL). Staphylococcus aureus (S. aureus) prevalence is increased in CTCL patients and contributes to CTCL disease flares. Our primary aim was to describe S. aureus infections, including resistance patterns and the antibiotic treatment regimens used, in erythrodermic CTCL patients. This was a retrospective chart review of erythrodermic CTCL patients who had S. aureus infection or colonization and were treated at the UT MD Anderson Cancer Center's Melanoma Skin Center between 2012 and 2016. Twenty-six erythrodermic CTCL patients had 50 documented S. aureus colonization or infection events. Patients had an improvement in body surface area (BSA) or modified Severity Weighted Assessment Tool (mSWAT) in 53% events treated for S. aureus. Seventeen of the 50 (34%) events were due to methicillin-resistant S. aureus (MRSA). One-third (33%) of MRSA events were initially treated with dicloxacillin. The MRSA isolates were sensitive to trimethoprim-sulfamethoxazole (92%) and doxycycline (88%). Patients treated in the outpatient setting (OR 0.073; 95% CI 0.008-0.627; p = 0.017) and patients with a previous history of topical anti-S. aureus decolonization treatments before S. aureus event as stand-alone (OR 0.125; 95% CI 0.018-0.887; p = 0.038) or in combination treatment with systemic antibiotics (OR 0.094; 95% CI 0.009-0.944; p = 0.045) were less likely to see improvement in BSA or mSWAT from S. aureus treatment. Treatment of S. aureus improved CTCL skin score in a high number of erythrodermic patients. The MRSA prevalence was high in erythrodermic CTCL patients. Clinicians should consider using empiric MRSA antibiotic coverage for these patients.
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http://dx.doi.org/10.1007/s00403-019-02015-7DOI Listing
May 2020

Correction: Blood transcriptional profiling reveals IL-1 and integrin signaling pathways associated with clinical response to extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma.

Oncotarget 2019 Sep 10;10(52):5492. Epub 2019 Sep 10.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

[This corrects the article DOI: 10.18632/oncotarget.26900.].
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http://dx.doi.org/10.18632/oncotarget.27197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739216PMC
September 2019

Cutaneous manifestations of genodermatoses and primary immunodeficiency.

Dermatol Online J 2019 Jun 15;25(6). Epub 2019 Jun 15.

Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC Departments of Pathology and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC.

Immunodeficiency is most commonly related to inherited syndromes, infections, chemotherapy, or aging. As the population of individuals with immunodeficiency continues to grow, physicians are confronted with the task of diagnosing dermatologic disease in this population. Cutaneous involvement in immunodeficiency disorders serves as a useful tool that aids diagnosis and provides prognostic value. Given that cutaneous manifestations often herald an underlying immunodeficiency disorder, understanding the complexities of these diseases is important for appropriate clinical management. Although certain diseases may present with stereotypical cutaneous lesions, others may involve more variable lesions that require specialized consultation for diagnosis and treatment recommendations. In this review, we discuss a number of cutaneous findings associated with primary immunodeficiencies. Awareness of these cutaneous associations may aid in the early detection and prompt treatment of these potentially serious immunologic disorders.
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June 2019
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