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ImportanceGiven that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).ObjectivesTo determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.Design, Settings, and ParticipantsThis was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.InterventionsIn cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.Main Outcomes and MeasuresThe primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.ResultsThe study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P P Conclusion and RelevanceThe findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.Trial RegistrationClinicalTrials.gov Identifier: NCT02448381

Keywords: CTCL classifications; CTCL, cutaneous T-cell lymphoma; LDH, lactate dehydrogenase; MF, mycosis fungoides; SS, Sezary syndrome; Sezary syndrome; T cell; WBC, white blood cell; clinical cases; leukemic progression; lymphoma; medical dermatology; mycosis fungoides. Conflict of interest statement Dr Dummer reports intermittent, project-focused consulting and/or advisory relationships with Novartis, Merck Sharp and Dhome, Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, and Alligator outside the submitted work. Dr Ramelyte reports intermittent, project-focused consulting and/or advisory relationships with Amgen, Novartis, Sanofi, Pierre Fabre, and Sun Pharma outside the submitted work. Dr Kim reports grants and personal fees from Actelion and 10.13039/501100009754Galderma; personal fees from Helsinn and Almirall; and grants from 10.13039/501100004628MedImmune, Kyowa Kirin, and Soligenix outside the submitted work. Drs Maredia, Cozzio, and Rozati have no conflicts of interest to declare.

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, the most common type of PCL, none exist for the other PCLs. In addition, staging of 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 LymphomaConsortium (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.

Mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma, is a disease typically with an indolent course that is initially characterized by localized patches and plaques. In the early stages of the disease, treatment involves skin-directed therapies (SDTs) such as topical corticosteroids and retinoids. Chlormethine gel (also known as mechlorethamine) was the first SDT purposely developed to treat MF and is currently endorsed by international guidelines for the treatment of adult patients with MF as a first-line therapy. While chlormethine is an efficacious therapy, its usage may be complicated by the development of cutaneous reactions at the sites of application. Herein, we discuss the supportive guidelines for MF and the suitability of chlormethine as a therapeutic option in patients with MF. In addition, we present real-world experience on the use of chlormethine gel from clinics in the USA, Israel, and France with the aim of demonstrating the efficacy of chlormethine gel in routine clinical practice and outlining strategies that are being used to manage emergent cutaneous reactions.

Background Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking. Objective Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. Methods This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA–IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. Results In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. Conclusions This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with refractory cutaneous T-cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft-versus-lymphoma effect. However, allo-HSCT is not always curative; relapse of CTCL occurs in about half of patients post-transplant. Treatment of relapsed CTCL after allo-HSCT is challenging because post-transplant patients are at high risk of graft-versus-host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies. The benefit of each potential therapy must therefore be weighed against its risk of graft versus host disease (GVHD). In this article, we review the management of relapsed CTCL after allo-HSCT. We begin with an exemplative patient whose relapsed Sezary syndrome was successfully treated without development of GVHD. We also report high-throughput T-cell receptor sequencing data obtained during the patient's disease relapse and remission. We then review general guidelines for management of relapsed CTCL and summarize all reported cases and outcomes of relapsed CTCL after transplant. We conclude by reviewing the current CTCL therapies and their risk of GVHD.

Parapsoriasis is an uncommon inflammatory skin disease characterized by chronic patches that may be resistant to therapy. It was primarily introduced and classified 120 years ago, and the original classification incorporated parapsoriasis and pityriasis lichenoides under the umbrella term parapsoriasis. After a major change in classification, parapsoriasis now exclusively refers to small plaque parapsoriasis (SPP) and large plaque parapsoriasis (LPP). However, debates still frequently occur regarding various nomenclatures and classifications used by different authors. Moreover, parapsoriasis may progress to overt cutaneous lymphoma, most commonly mycosis fungoides (MF), and it is very difficult to distinguish these two conditions despite modern histologic and molecular testing techniques.As parapsoriasis is a rare disease, there is a lack of studies and clinical guidelines to assist physicians in clinical practice. In our comprehensive review, we review several aspects of parapsoriasis, from the history of nomenclature and classification, clinical characteristics, immunohistopathology, and advanced molecular techniques for the diagnosis of this condition, to the most current treatments. We also propose a scheme for distinguishing parapsoriasis from early-stage MF in this review.

Background: The existing body of literature suggests that modifiable lifestyle behaviors such as alcohol consumption and dietary behaviors were linked to viral hepatitis B/C and liver cancer. So far, most of the liver cancer awareness campaigns and behavioral interventions have focused on preventive behaviors such as screening, vaccination, and early diagnosis. Not enough efforts have been made to raise awareness of behavioral mechanism of liver cancer prevention, especially in the medically underserved populations. Methods: We used the community-based participatory research (CBPR) approach to implement an education initiative regarding the promotion of liver cancer among the African, Asian, and Hispanic populations within the Philadelphia metropolitan area and New York City. In this study, we used data from the pre-education surveys and follow-up assessments at 6 months post-education to assess the changes in dietary behaviors and alcohol consumption among participants. Results: The study sample includes 344 participants recruited through community-based organizations. The sample consists of 31 African Americans, 174 Asian Americans, and 139 Hispanic Americans. Among the African Americans participants, the consumption of scores such as fruits (2.710 to 3.581) and poultry (2.613 to 3.677) increased significantly, while vegetables and red meats decreased. In Asian Americans, the consumption of non-refined cereals (3.362 to 4.282), red meats (2.655 to 3.195), and dairy (2.851 to 3.701) products decreased. Lastly, among the Hispanic American participants poultry (2.173 to 3.554), dairy products (2.101 to 3.863), and olive oil (3.022 to 3.849) increased, as well as the consumption of alcohol. Conclusion: This community-based educational imitative generated different impacts in the three populations, further highlighting the needs for more targeted, culturally tailored efforts in health promotion among these underprivileged communities. Citation Format: Tamar Tertulien, Ellen J. Kim, Wenyue Lu, Steven Zhu, Nathaly Rubio-Torio, Evelyn González, Marilyn A. Fraser, Ming-Chin Yeh, Lin Zhu, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Reducing liver cancer risk through dietary change: Positive results from a community-based educational initiative in three racial/ethnic groups [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C069.

Background: Colorectal cancer (CRC) screening such as colonoscopy and stool test has been shown to be effective in reducing CRC burden, especially in the underprivileged communities. However, CRC awareness and screening uptake remained suboptimal, especially in racial/ethnic minority populations and non-Hispanic whites. Both CRC incidence and mortality rates are highest in non-Hispanic blacks (approximately 20% and 40%, respectively), and CRC screening uptake rates are lower in racial/ethnic minorities relative to non-Hispanic whites (NHWs). The cause for the disparities in incidence and mortality is multifactorial. One important aspect is the suboptimal knowledge and awareness of risk factors. Methods: To increase awareness of CRC prevention and screening, we collaborated with community-based organizations (CBOs) to develop culturally tailored educational materials targeting African/Black Americans (BAs), Asian Americans (AAs), and Hispanic Americans (HAs). The topics included essential CRC and screening knowledge, a healthy diet (Mediterranean diet), and at-home workout routines. Eligible participants from the Greater Philadelphia area and New York City participated in one-time education. Pre- and post-intervention surveys were designed based on the Colorectal Cancer Quiz provided by the Centers for Disease Control and Prevention (CDC) and were administered to assess the immediate impact of the educational sessions. Results: The analysis sample included 413 participants, among which 388 completed the post-survey. One in ten (10.3%) reported a family history of CRC, and a half (50.6%) had never had a colonoscopy. The baseline CRC knowledge score was 9.5 out of 16, indicating a moderately low level of knowledge. Participants scored particularly low on the age of CRC screening initiation, needs for screening even without symptoms, and the impact of physical activity on CRC risk. The knowledge score significantly increased to 10.9 (p < .001) at post-survey, indicating a significant impact of the educational workshops. Conclusion: The findings of our project confirm that the CRC screening rates are low in racial/ethnic minorities compared to the U.S. national rate of 71.6%. Meanwhile, it also confirmed that culturally tailored, community-based educational initiatives can effectively raise knowledge of CRC in medically underserved populations. Citation Format: Ellen J. Kim, LIn Zhu, Wenyue Lu, Safa Ibrahim, Steven Zhu, Nathaly Rubio-Torio, Evelyn González, Marilyn A. Fraser, Ming-Chin Yeh, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Increasing knowledge of colorectal cancer (CRC) risk factors and screening through a community-based education initiative [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B056.

Background: The Temple University Fox Chase Cancer Center and Hunter College Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership) is a comprehensive collaborative cancer health research infrastructure in Pennsylvania, New Jersey, and New York City (PNN) Region. Its goals are to enhance equity in cancer health through rigorous and sustainable cancer research, train the next generation of researchers, and establish community outreach programs. Establishing and strengthening a bidirectional academic-community partnership is a key component of this partnership. While such collaborative relationships have been strongly endorsed by the National Institutes of Health (NIH), little has been documented demonstrating how such partnership can be created and maintained. Objectives: Building on previous established collaborative relationships with the community-based organizations (CBOs), we created and expanded a bidirectional, academic–community partnership in African American, Asian American, and Latinx communities in the PNN region to (1) assess the level of awareness of cancer prevention knowledge; (2) identify community needs and barriers to cancer prevention healthcare services; (3) jointly develop and implement community-based educational initiatives to promote cancer prevention in medically underserved communities. Methods: In this presentation, we established a comprehensive evaluation metric to assess the bidirectional partnership. The metric, its outputs, and outcomes were adapted from the Evaluation Metrics Manual published by the National Institute of Environmental Health Services of NIH. We also formed a Community Advisory Board (CAB) to guide our bidirectional communication and jointly develop a community-driven cancer education agenda. Results: The CAB played a critical role in the development of the bidirectional partnership. They provided key inputs in identifying the goals and benchmarks of the educational initiative, and in facilitating the recruitment and implementation of the initiative. Our evaluation indicated that a bidirectional partnership is an interactive and non-linear process that requires constant feedback and communication. We identified several successes and challenges during our co-learning and co-implementing process. We also identified areas for improvement, specifically, establishing a more efficient channel for information and resource sharing, and greater efforts on dissemination of scientific findings to the community. Conclusions: Actively engaging CAB and CBOs in the cancer prevention educational initiatives from the onset enhanced the efficacy of the initiatives and strengthened the research training capacity of the academic institutions. We will share best practices in our bidirectional, academic–community partnership building and discuss next steps in adaptation and further development of the partnership. Citation Format: Lin Zhu, Ellen J. Kim, Steven Zhu, Nathaly Rubio-Torio, Evelyn González, Marilyn A. Fraser, Ming-chin Yeh, Marsha Zibalese-Crawford, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Evaluating a bidirectional academic–community partnership with multiple racial/ethnic communities for cancer prevention initiatives and cancer health disparities research [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR010.

Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immune receptor repertoires and the landscape of potential antigens. To address this, we present RAPTR (Receptor-Antigen Pairing by Targeted Retroviruses). RAPTR combines viral pseudotyping and molecular engineering approaches to enable one-pot library on library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cells allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable, and compatible with any cell type, making it easily implemented. These techniques provide a suite of new tools for targeted viral entry, molecular engineering, and interaction screens with broad potential applications.

Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immunoreceptor repertoires and the landscape of potential antigens. To address this, we present receptor-antigen pairing by targeted retroviruses, which combines viral pseudotyping and molecular engineering approaches to enable one-pot library-on-library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cell lines expressing human T or B cell receptors allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable and compatible with any cell type. These techniques provide a suite of tools for targeted viral entry, molecular engineering and interaction screens with broad potential applications.

Summary Background Patients with cutaneous T‐cell lymphoma (CTCL) often have indolent but symptomatic disease. Objective Assessment of the health‐related quality of life (HRQoL) of patients with CTCL. Methods Cross‐sectional survey study. HRQoL was measured by Skindex‐16 and FACT‐G. Results A total of 372 responses were received; 80 incomplete/ineligible responses were excluded. A majority of respondents identified as white (87%; 250/288) and female (67%; 193/286) with a mean age of 57 ± 14 years. Most patients had early‐stage (IA–IIA) (74%; 162/203) mycosis fungoides (87%; 241/279). There were 33 (12%; 33/279) patients with Sézary syndrome. Mean itch score (visual analogue scale; VAS) was 3.2 ± 2.8, overall; 2.7 ± 2.6 for early, and 4.2 ± 2.9 for advanced disease (p = 0.008). Thirty‐eight percent (108/284) and 24% (69/284) reported head/neck and groin/genital involvement, respectively. Overall HRQoL was 46 ± 27 (Skindex‐16) and 71 ± 19 (FACT‐G), with worse HRQoL for patients with advanced versus early disease (Skindex‐16: 67 vs. 40; p=15 min daily treating CTCL. Limitations Include anonymous survey methodology, underrepresentation of certain CTCL subtypes and non‐white respondents. Conclusions Patients with CTCL, particularly those with advanced disease or involvement of the head/neck, acral or groin/genital sites, experience significant impact on HRQoL.

Background: Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for the treatment of early-stage mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). In previously published data, topical steroids and phototherapy were found to be commonly used by patients treated with chlormethine gel. Post-hoc analyses on the PROVe study were carried out to describe the specific treatment sequence and timing of these concomitant therapies and chlormethine gel in a real-world setting among MF-CTCL patients. Methods: Data analyzed derives from the observational PROVe study using US-based registry of MF-CTCL patients treated with chlormethine gel and enrolled across 46 centers between March 2015 and October 2018. Patients were followed for up to 2 years after chlormethine gel initiation. Due to the observational nature of the study, patients had visits at irregular intervals. Information on patient demographics, medical history, clinical characteristics, ongoing treatments for MF-CTCL and response were collected. Concomitant use of chlormethine gel with topical steroids or phototherapy were assessed using treatment start and stop dates recorded in the registry, and descriptive statistics were calculated. Results: A total of 298 eligible patients were analyzed with a mean ± standard deviation (SD) age of 61±13 years. Approximately 60% were males, 69% had Stage IA/IB and their duration of MF-CTCL was 4.8±6.5 years at chlormethine gel initiation. A total of 186 (85%) reported concomitant use of topical steroids with chlormethine gel during the study period. Of these 186 patients, 138 (74%) patients were already using steroids prior to chlormethine gel initiation, 14 (8%) started chlormethine gel and steroids on same day and the remaining 34 (18%) added steroids later. A total of 81 (27%) reported concomitant use of phototherapy with chlormethine gel during the study period. Of these 81 patients, 67 (83%) patients were already on phototherapy prior to chlormethine gel initiation and the remaining 14 (17%) initiated phototherapy later. Conclusions: Among the patients with concomitant therapies, the majority had started steroids or phototherapy and then added chlormethine gel. These observations suggest that in real life settings, combination treatments are standard practice as physicians expect improved outcomes with an acceptable tolerability profile.

Importance Treatment options for Sezary syndrome (SS) are limited and associated with low response rates. Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for refractory CD30-positive cutaneous T-cell lymphoma. However, limited data exist on its efficacy in SS, including in the pivotal phase 3 ALCANZA (A Phase 3 Trial of Brentuximab Vedotin (SGN-35) Versus Physician’s Choice [Methotrexate or Bexarotene] in Participants With CD30-Positive Cutaneous T-Cell Lymphoma) trial. Objective To assess the preliminary efficacy and tolerability of brentuximab vedotin for SS. Design, Setting, and Participants From January 1, 2017, to July 31, 2020, a total of 13 patients with SS received brentuximab vedotin and were analyzed as part of a retrospective case series. Median follow-up was 10.4 months (range, 1.4-34.6 months). All patients were 18 years or older with a diagnosis of SS and with B2 blood involvement at the time brentuximab vedotin therapy was initiated. This single-center study was conducted at a major academic referral center. Interventions Intravenous brentuximab vedotin administration approximately every 3 weeks. Main Outcomes and Measures The primary end point was the global response rate. Outcomes were assessed in the skin and lymph nodes per the 2011 European Organization for Research and Treatment of Cancer–International Society of Cutaneous Lymphoma response criteria and in the blood per the 2018 Prospective Cutaneous Lymphoma International Prognostic Index revised blood response criteria. Results The study included 13 patients (8 [62%] male; mean [SD] age, 68.2 [8.6] years). Of these 13 patients, 5 (38%) achieved a global response after a median of 6 cycles, including 1 complete response. Response rates by disease compartment were 38% in the skin, 63% in the blood, and 50% in the lymph nodes. Three of 11 patients (27%) with pruritus reported improvement. Skin CD30 positivity (>10%) was detected in 9 patients but was not associated with responses. Among responders, the median time to response was 6 weeks (range, 6-9 weeks), and the median duration of response was 5.5 months (range, 2.5-28.9 months). The median time to next treatment was 3.2 months (range, 1.5-36.7 months). Peripheral neuropathy occurred in 4 patients but resolved in 2 patients. Grade 2 adverse events were neuropathy (n = 2), constipation (n = 1), and hand-foot syndrome (n = 1). Conclusions and Relevance In this case series, brentuximab vedotin use was associated with some efficacy in SS across multiple disease compartments and in the setting of refractory disease or low CD30 skin expression. Brentuximab vedotin may offer a manageable treatment schedule and low incidence of significant toxic effects.

Background The pivotal 201 Study investigated chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time. Methods This post hoc analysis re-evaluated chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response. Results By-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that ∼ 33% of patients could expect to have very good to complete response within 1 year. Conclusion By-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.

Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking.Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting.This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA-IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire.In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores.This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.

Cutaneous T-cell lymphoma (CTCL) represents a diagnostic challenge because of its large symptomatic overlap with other common skin conditions such as atopic dermatitis (AD) and psoriasis. Dupilumab has offered promising results in AD treatment; however, concerns exist that its use may exacerbate undiagnosed CTCL. We present a patient with CTCL and concomitant AD who experienced improvement in both CTCL blood involvement and AD following the addition of dupilumab therapy.

Background: Chlormethine gel is a skin-directed therapy approved in US for daily treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). Based on a previous study it has been observed that the alternative treatment schedules and the schedule changes may benefit patients by improving tolerability and response to treatment [ 1 ]. This study was carried out to better understand schedule changes before and after achieving partial response (PR) and effect of maintenance therapy i.e., continuing treatment with chlormethine gel after achieving PR, in a real-world setting among MF-CTCL patients. Methods: Data is derived from the observational PROVe study using US-based registry of MF-CTCL patients treated with chlormethine gel in combination with other treatments between March 2015 and October 2018. Patients were enrolled across 46 centers and were followed for up to 2 years. Information on patient demographics, clinical characteristics, treatments received for MF-CTCL (including chlormethine gel, topical steroids, phototherapy, radiation therapy, chemotherapy, retinoids and other topical). Responses were collected at enrollment and ongoing visits with no specific visit schedules or clinical assessments due to expected variability in practice patterns. Episodes of treatments with chlormethine gel with start date, stop date and schedule changes were recorded and analyzed. Partial response (PR) was defined as either ≥50% improvement in body surface area (BSA) at least once from gel initiation to the end of study participation or based on the clinical assessment of the physician. For those who achieved PR and following the date of PR, deepening response was defined as achieving either ≥10% additional improvement in BSA (i.e., 60% or more improvement in BSA after achieving 50% improvement at the time of PR) or achieving complete response based on the clinical assessment by physician. Descriptive statistics were reported for schedule changes and maintenance therapy with chlormethine gel. Results: Of 298 eligible patients with mean age 61±13 years, 60% were males, and 69% had clinical stage IA/IB. A total of 222 (75%) patients achieved PR following chlormethine gel initiation and during study period. Of these 222, 81% patients did not change their schedule prior to achieving PR and 61% were on a daily schedule immediately prior to PR. Of 203 patients receiving maintenance chlormethine gel post PR, 153 (75%) maintained, 29 (14%) reduced and 24 (12%) increased their dosing schedule in the post-PR period as compared to their schedule prior to PR. Of these 203, 53 (26%) later achieved deepening response. Conclusions: 75% of the patients received maintenance therapy with chlormethine gel in combination with other therapies and continued with the same schedule after PR. The study results suggest that continuing maintenance therapy and adjusting chlormethine gel dosing schedule may contribute to deepen treatment responses.

Objectives To characterize patterns of integrative medicine (IM) use and health-related quality of life (HRQoL) in patients with cutaneous T-cell lymphoma (CTCL). Design Cross-sectional, online survey, created in conjunction with the Cutaneous Lymphoma Foundation (CLF). Setting A link to the online survey was posted on the CLF Facebook page and emailed to the CLF listserv; 372 survey responses were received. Main outcome measures The study outcomes were IM use, cancer symptoms, and HRQoL measured via the Skindex-16 and Functional Assessment of Cancer Therapy-General (FACT-G). Results A total of 292 patient responses (66 % female, median age 59y) were included in analysis. 87 % had mycosis fungoides and 12 % had Sezary syndrome. A majority (59 %) of patients reported using IM for their CTCL, with 48 % using IM to treat their disease and 47 % using IM to manage their symptoms. The most commonly used IM were vitamins/minerals (32 %), prayer/meditation (26 %), diet (24 %), and exercise/yoga (22 %). Higher itch scores were reported by patients using IM compared to non-users (31 (IQR 10–62) and 18 (IQR 3–46) respectively; p = 0.002). HRQoL was worse among patients who reported IM use; median Skindex-16 scores were 54 (IQR 28–72) among IM users compared to 33 (IQR 19–57) for non-IM users (p Conclusions IM use is common among patients with CTCL, particularly those with worse itching and worse HRQoL. IM interventions require further study given use by CTCL patients to treat disease and ameliorate symptoms.

Diagnosis and management of mycosis fungoides and Sézary syndrome (MF/SS) require accurate clinicopathological correlation and a multidisciplinary approach. We reviewed major advances in the field regarding diagnostic and prognostic tools as well as skin-directed therapies (SDTs) and systemic agents for MF/SS published in the past 2 years.Improved technology (T-cell receptor high-throughput sequencing) and increased multicenter collaboration (Cutaneous Lymphoma International Consortium) have led to diagnostic/prognostic advances. Concurrently, numerous genomic studies have enhanced understanding of disease pathogenesis. Advances in SDTs include topical resiquimod, a novel potent Toll-like receptor (TLR) agonist; consensus CTCL phototherapy guidelines; and use of low-dose radiation therapy. Novel systemic therapies for advanced disease of note include targeted antibody drug conjugates (brentuximab vedotin), immune checkpoint inhibitors, and allogeneic hematopoietic stem cell transplantation (HSCT). Our "toolbox" to diagnose and treat the spectrum of MF/SS continues to expand. Further characterization of genomic data going forward will enable a rational approach to selecting and combining therapies to improve patient care.

Loss of CD26 surface expression on the circulating malignant T-cell is the most widely accepted diagnostic marker in patients with leukemic cutaneous T-cell lymphoma (CTCL). CTCL cases with reemergence of CD7 and/or CD26 surface expression are unusual and of uncertain prognosis. We report the case of an erythrodermic leukemic mycosis fungoides patient who had achieved temporary remission after several months on multimodality immunotherapy and extracorporeal photopheresis, but who relapsed with aggressive disease phenotypically characterized by CD4+ T-cells with high CD26 expression. Polymerase chain reaction studies and high-throughput sequencing analyses from peripheral blood mononuclear cells at presentation and relapse consistently showed an identical clonal T-cell receptor suggesting evolution of her original malignant clone which lacked CD26 expression. Interestingly, quantitative expression of the sialomucin, CD164, mirrored her clinical picture, thus favoring its reliability as a novel biomarker in CTCL.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) has been associated with considerable physical, psychological, and financial burden in recent literature. Despite these findings, its impact on health-related quality of life (QoL) and economic cost have not been well-studied. OBJECTIVES: To measure the overall QoL impact and financial burden of CTCL. METHODS: A cross-sectional survey of 67 adult CTCL patients was conducted at an academic medical center. Normative population data (N=3310) was obtained from the 2002–2003 Joint Canada/United States Survey of Health (JCUSH). QoL was measured using the Ontario Health Utilities Index Mark III (HUI3) questionnaire. Economic cost was estimated using quality-adjusted life year (QALY) loss derived from HUI3 scores. RESULTS: Compared to the U.S. general population, CTCL patients had significantly lower unadjusted aggregate HUI3 scores (0.68 vs 0.87, p

Most physicians have multiple mentors and technology has facilitated long distance mentoring which can provide a different perspective from workplace mentoring. This article discusses the value and inherent challenges in a long distance mentoring relationship and tips for success.

Importance Sezary syndrome (SS) is an advanced form of cutaneous T-cell lymphoma with few long-term remissions observed. Objective To profile 3 patients with SS who have experienced long-term remission following the addition of low-dose total skin electron beam therapy (TSEBT) to systemic regimens of extracorporeal photopheresis, bexarotene, and interferon-γ. Design, setting, and participants This is a retrospective case series with additional investigations of patient-donated samples to assess therapeutic response. The study was conducted at the University of Pennsylvania Cutaneous Lymphoma Clinic and follows 3 patients with stage IVA1 CD4+ SS who presented to the clinic between November 1, 2009, and November 1, 2017, and who had a history of SS that was refractory to multimodality systemic therapy prior to receiving low-dose TSEBT. Interventions Patients were treated in a multimodality fashion with combined extracorporeal photopheresis, bexarotene, interferon-γ, and low-dose TSEBT. Main outcomes and measures To characterize treatment responses in these patients, the extent of skin disease was measured with the modified severity weighted assessment tool. Blood disease was measured with flow cytometric assessments of Sezary cell count, CD4:CD8 ratio, and high throughput sequencing of the T-cell receptors. To assess for restoration of immune function, we measured markers of immune exhaustion, including PD-1 (programmed cell death 1), TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domains), CTLA4 (cytotoxic T-lymphocyte-associated protein 4), TOX (thymocyte selection-associated high mobility group box protein), and Foxp3 (forkhead box P3) on circulating CD4 and CD8 T cells, along with production capacity of interferon-γ by lymphocytes following activation stimuli. Results Following administration of low-dose TSEBT and maintenance of the other therapies, remissions ranged from 24 to 30 months, with complete responses in 2 patients ongoing. Markers of immune exhaustion including PD-1, TIGIT, CTLA4, TOX, and Foxp3 were significantly reduced from baseline following TSEBT, along with enhanced production capacity of interferon-γ by lymphocytes following activation stimuli. High throughput sequencing demonstrated near-complete eradication of the circulating clone among 2 of 3 patients with stable levels in 1. Conclusions and relevance We describe 3 patients who achieved long-term clinical and molecular remissions following low-dose TSEBT as part of a multimodality regimen for treatment of SS. As long-term remissions in SS are uncommon, this approach demonstrates promise, and clinical trials should be considered.

Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma.In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805.Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related.Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma.Kyowa Kirin.

Graft versus host disease (GVHD) is a common, morbid, and potentially fatal complication of allogeneic hematopoietic stem cell transplantation (aHSCT).1-3 The exact timing of the arrival of donor-derived immune cells and their profile in the skin have not been well described in humans.4-6 Fluorescent in situ hybridization (FISH) is a technique that has been used to distinguish host versus donor-derived immune cells in patients who have undergone sex-mismatched aHSCT.7 This article is protected by copyright. All rights reserved.

Retinoids are natural and synthetic vitamin A analogs with effects on cell proliferation, differentiation, and apoptosis. They have significant activity in hematologic malignancies and have been studied extensively in cutaneous T-cell lymphoma. Retinoids bind to nuclear receptors and exert their effects through moderation of gene expression. Retinoic acid receptor and retinoic X receptor exert regulatory activity in vivo, binding to distinct ligands. Studies investigating systemic retinoids as monotherapy and in combination with other agents active against cutaneous lymphoma are reviewed. Side effects associated with retinoids include teratogenicity, dyslipidemias, and hypothyroidism, which should be carefully monitored in patients receiving treatment.

Early-stage cutaneous T-cell lymphoma (CTCL) is a skin-limited lymphoma with no cure aside from stem cell transplantation. Twelve patients with stage IA-IIA CTCL were treated in a phase 1 trial of 0.03% and 0.06% topical resiquimod gel, a Toll-like receptor 7/8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. Ninety-two percent of patients had more than a 50% improvement in body surface area involvement by the modified Severity-Weighted Assessment Tool analysis and 2 patients experienced complete clearing of disease. Four of 5 patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. T-cell receptor sequencing and flow cytometry studies of T cells from treated lesions demonstrated decreased clonal malignant T cells in 90% of patients and complete eradication of malignant T cells in 30%. High responses were associated with recruitment and expansion of benign T-cell clones in treated skin, increased skin T-cell effector functions, and a trend toward increased natural killer cell functions. In patients with complete or near eradication of malignant T cells, residual clinical inflammation was associated with cytokine production by benign T cells. Fifty percent of patients had increased activation of circulating dendritic cells, consistent with a systemic response to therapy. In summary, topical resiquimod is safe and effective in early-stage CTCL and the first topical therapy to our knowledge that can induce clearance of untreated lesions and complete remissions in some patients. This trial was registered at www.clinicaltrials.gov as #NCT813320.

Background Cutaneous graft-versus-host disease (GVHD) is classically described as morbilliform when acute and lichen planus–like or sclerotic when chronic. In addition to these well-known clinical forms, there are many other presentations of GVHD that are important to recognize. As the number of patients undergoing stem cell transplantation increases and the survival after transplantation improves, the prevalence of GVHD is expected to rise, and its various presentations will be increasingly encountered in clinical practice. Objective We sought to report unusual manifestations of skin GVHD and provide a summary of typical and atypical presentations of GVHD reported in the literature. Methods Patients with stem cell transplantation who developed unusual eruptions after transplantation had biopsy specimens taken to evaluate for histopathologic evidence of GVHD. Results Six patients presented with unusual cases of biopsy-proven GVHD, including follicular hyperkeratosis, thick-appearing white tongue, inverse pityriasis rosea–like, and eczema craquele–like GVHD. Limitations This study is limited by case number. Conclusions Because of the high rate of cutaneous involvement with GVHD, the accessibility of the skin for diagnosis, and the morbidity associated with severe or long-standing skin involvement, it is important for dermatologists to recognize and accurately diagnose cutaneous GVHD in all its protean manifestations.

Purpose Brentuxiumab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate approved in 2011 for treating anaplastic large cell and Hodgkin lymphomas. The product label indicates that three BV-treated patients developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC-virus induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. We report 5 patients who developed BV-associated PML, including two immunocompetent patients.

Primary cutaneous anaplastic large-cell lymphoma (pcALCL) is part of a spectrum of CD30+ primary cutaneous lymphoproliferative disorders (pcLPDs) that also includes lymphomatoid papulosis (LyP). Localized radiotherapy at doses of 34 to 44 Gy is first-line treatment of pcALCL, but the use of low-dose radiotherapy for pcALCL has not been reported. We present the case of a patient with a history of pcALCL/LyP who was treated with low-dose radiotherapy while on oral low-dose methotrexate (MTX) once weekly. This report suggests that low-dose radiotherapy can be an effective palliative treatment of pcALCL. Low-dose radiotherapy may offer certain advantages over traditional radiotherapy, such as a more economical and efficient treatment for patients, potentially fewer short-term and long-term side effects, and the potential for concomitant use with low-dose MTX.

Cell surface major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity to microbes and tumors by presenting intracellular peptides for recognition by CD8+ T cells. Since the repertoire of bound peptides is crucial to MHC-I stability as well as to T cell and NK cell recognition, the molecular mechanism by which peptides are selectively loaded onto MHC-I molecules is of considerable interest. A key role is played by the well-characterized chaperone tapasin as indicated by reduced cell surface MHC-I levels and altered peptide repertoires in tapasin deficient cell lines and mice. Despite extensive studies of the functional role of tapasin in shaping peptide repertoires, direct structural information on its interaction with MHC-I is lacking. Following the recent biochemical and crystallographic studies of the interaction of the tapasin homolog, TAPBPR, with MHC-I, we have engineered soluble versions of tapasin for comparison with TAPBPR. Using surface plasmon resonance assays of purified, untethered proteins, we observe that tapasin binds directly to an MHC-I molecule loaded with truncated peptides but with lower apparent affinity than TAPBPR. Similarly, using fluorescence polarization, we find that tapasin facilitates peptide exchange onto MHC-I with a lower efficiency than TAPBPR. These experiments permit direct comparisons of tapasin/MHC-I and TAPBPR/MHC-I interactions and help elucidate the functional relationship of these two distinct chaperones in shaping the MHC-I peptide repertoire.