CD30-positive lymphoproliferative disorders-An Australian Clinical Practice Statement from the Peter MacCallum Cancer Centre.

The CD30-postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.

Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: A case series of 13 patients.

We present a case series of 13 patients, the first Australian single-centre study of bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICI): cytotoxic T-lymphocyte antigen (CTLA4) and programmed cell death receptor (PD1) inhibitors. All our patients achieved adequate control of BP with a combination of treatments including oral prednisolone, intravenous immunoglobulin, rituximab and omalizumab. The majority of patients ceased or interrupted immunotherapy treatment upon diagnosis of BP and greater tumour progression was seen in the cohort who ceased immunotherapy.

Development of melanoma clinical quality indicators for the Australian melanoma clinical outcomes registry (MelCOR): A modified Delphi study.

BACKGROUND: Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty-six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry. METHODS: Potential clinical quality indicators were identified by examining the literature, including Australian and international melanoma guidelines, and by consulting with key melanoma and registry opinion leaders. A modified two-round Delphi survey method was used, with participants invited from relevant health professions routinely managing melanoma as well as relevant consumer organisations. RESULTS: Nineteen participants completed at least one round of the Delphi process. 12 of 13 proposed clinical quality indictors met the validity criteria. The clinical quality indicators included acceptable biopsy method, appropriate excision margins, standardised pathology reporting, indications for sentinel lymph node biopsy, and involvement of multidisciplinary care and referrals. CONCLUSION: This study provides a multi-stakeholder consensus for important clinical quality indicators that define optimal practice that will now be used in the Australian Melanoma Clinical Outcomes Registry (MelCOR).

Impact of chronic lymphocytic leukaemia on melanoma outcomes: A retrospective case-control study.

With new, effective treatments for chronic lymphocytic leukaemia (CLL) the impact of second malignancies is increasingly important. We performed a retrospective case-controlled study examining the effect of CLL and its treatment on melanoma-specific survival and recurrence. A total of 56 patients with melanoma with CLL were matched 1:1 to patients without CLL for age, date of diagnosis, gender and melanoma tumour, node, metastasis (TNM) stage. Multivariate analysis found CLL was associated with significantly worse melanoma-specific mortality (hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.27-4.74, p = 0.007) and recurrence (HR 3.44, 95% CI 1.79-6.63, p < 0.001). Patients with CLL had poor immunotherapy tolerance and prior CLL treatment was not associated with melanoma outcomes.

Successful secukinumab treatment of active bullous pemphigoid and chronic severe psoriasis: a case report.

Since the concurrence of bullous pemphigoid (BP) and psoriasis was first reported in 1929, an increasing number of studies has been published to analyse their relationship in recent years. However, the pathogenesis of the concurrence is not yet well understood, and the coexistence of the two conditions imposes a difficult therapeutic challenge. This case report demonstrates the first case of secukinumab achieving a dramatic clinical improvement of both chronic psoriasis and active BP.

Mycosis fungoides and Sézary syndrome: Australian clinical practice statement.

Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).

Patients' Experiences of Using Skin Self-monitoring Apps With People at Higher Risk of Melanoma: Qualitative Study.

BACKGROUND: Melanoma is the fourth most commonly diagnosed cancer in Australia. Up to 75% of melanomas are first detected by patients or their family or friends. Many mobile apps for melanoma exist, including apps to encourage skin self-monitoring to improve the likelihood of early detection. Previous research in this area has focused on their development, diagnostic accuracy, or validation. Little is known about patients' views and experiences of using these apps. OBJECTIVE: This study aims to understand patients' views and experiences of using commercially available melanoma skin self-monitoring mobile apps for a period of 3 months. METHODS: This qualitative study was conducted in two populations: primary care (where the MelatoolsQ tool was used to identify patients who were at increased risk of melanoma) and secondary care (where patients had a previous diagnosis of melanoma, stages T0-T3a). Participants downloaded 2 of the 4 mobile apps for skin self-monitoring (SkinVision, UMSkinCheck, Mole Monitor, or MySkinPal) and were encouraged to use them for 3 months. After 3 months, a semistructured interview was conducted with participants to discuss their experiences of using the skin self-monitoring mobile apps. RESULTS: A total of 54 participants were recruited in the study, with 37% (20) of participants from primary care and 62% (34) from secondary care. Interviews were conducted with 34 participants when data saturation was reached. Most participants did not use the apps at all (n=12) or tried them once but did not continue (n=14). Only 8 participants used the apps to assist with skin self-monitoring for the entire duration of the study. Patients discussed the apps in the context of the importance of early detection and their current skin self-monitoring behaviors. A range of features of perceived quality of each app affected engagement to support skin self-monitoring. Participants described their skin self-monitoring routines and potential mismatches with the app reminders. They also described the technical and practical difficulties experienced when using the apps for skin self-monitoring. The app's positioning within existing relationships with health care providers was crucial to understand the use of the apps. CONCLUSIONS: This study of patients at increased risk of melanoma highlights several barriers to engagement with apps to support skin self-monitoring. The results highlight the wide-ranging and dynamic influences on engagement with mobile apps, which extend beyond app design and relate to broader contextual factors about skin self-monitoring routines and relationships with health care providers.

Time to Next Treatment as a Meaningful Endpoint for Trials of Primary Cutaneous Lymphoma.

Time to next treatment (TTNT) is an emerging endpoint in clinical studies of primary cutaneous T-cell lymphomas (CTCL), with utility as a surrogate marker for the "duration of clinical benefit". TTNT provides a highly clinically meaningful endpoint that uniquely reflects not only the duration of treatment efficacy on disease and symptom control, but also incorporates the patient experience by accounting for patient compliance and tolerance to the studied therapy(s). Given the distinct challenges of pin-pointing the exact date of progression in patients with multi-compartmental CTCL, TTNT overcomes many of the shortcomings of conventional, disease-focused, clinical endpoints in primary CTCL research. Although widely accepted in clinical research for numerous other incurable malignancies, TTNT currently lacks a standardised definition. In this paper, we describe the value of TTNT as a clinical endpoint, review the applications of TTNT in primary CTCL research, and propose a standardised definition of TTNT to be applied in future clinical research of primary CTCL therapies.

Trends in the incidence of Merkel cell carcinoma in Victoria, Australia, between 1986 and 2016.

BACKGROUND/OBJECTIVES: Merkel cell carcinoma (MCC) is a highly invasive cutaneous malignancy. The objective of this study was to investigate the incidence and trends of MCC in Victoria, Australia, between 1986 and 2016. METHODS: Population-based, descriptive analysis of Victorian Cancer Registry (VCR) data. The de-identified records of patients with MCC were obtained from Victoria residents diagnosed between 1986 and 2016. Trends in age-standardised incidences were examined using joinpoint analysis. RESULTS: A total of 1095 cases were found. Incidence of MCC was 3.9 per 100 000 for men and 1.5 per 100 000 for women. The incidence of MCC in men 66-85 is increasing at an annual rate of 4.2% (2.8-5.8%, 95% CI). However, since 2002 the incidence in women in the same age group has been decreasing. Whilst there is an overall stabilisation in the incidence of MCC, incidence of MCC for males is increasing. For MCC in males 85 years old and over, the incidence of MCC was 26.8 per 100 000 between 2012 and 2016. Relative 5-year survival for patients diagnosed between 2008 and 2012 is 50%. CONCLUSION: Merkel cell carcinoma remains an aggressive cancer, especially among older men. Differences in trends seen in local data can help target preventative and early intervention management strategies in specific groups.

Lack of Durable Remission with Conventional-Dose Total Skin Electron Therapy for the Management of Sezary Syndrome and Multiply Relapsed Mycosis Fungoides.

Mycosis fungoides (MF) and Sezary syndrome (SS) are multi-relapsing, morbid, cutaneous T-cell lymphomas. Optimal treatment sequencing remains undefined. Total skin electron therapy (TSE) is a highly technical, skin-directed treatment, uniquely producing symptom-free and treatment-free intervals. Recent publications favour low-dose TSE for reduced toxicity, but early data support conventional-dose TSE (cdTSE) for longer disease control. Patient selection requires weighing-up tolerability against response durability. We investigated duration of benefit from cdTSE in patients with poorer prognosis diseases: SS and heavily pre-treated MF. Endpoints were overall survival, and "time to next treatment" (TTNT) as surrogate for clinical benefit duration. Seventy patients (53 MF, 17 SS) were eligible: median prior treatments, 4; median cdTSE dose, 30 Gy; median follow-up, 5.8 years. SS patients had worse prognosis (HR = 5.0, p < 0.001) and shorter TTNT (HR = 4.5, p < 0.001) than MF patients; median TTNT was only 3.7 months. Heavily pre-treated MF patients had inferior prognosis (HR = 1.19 per additional line, p = 0.005), and shorter TTNT (HR = 1.13 per additional line, p = 0.031). Median TTNT for MF patients with ≥3 prior treatments was 7.1 months, versus 23.2 months for 0-2 prior treatments. In conclusion, cdTSE has a limited role in SS. TTNT is reduced in heavily pre-treated MF patients, suggesting greater benefit when utilized earlier in treatment sequencing.

Prolonged survival with the early use of a novel extracorporeal photopheresis regimen in patients with Sézary syndrome.

Extracorporeal photopheresis (ECP) has demonstrated therapeutic benefit in patients with Sézary syndrome (SS) and erythrodermic mycosis fungoides (e-MF). To examine the efficacy of ECP in the modern era of novel therapies, we conducted a retrospective analysis of 65 patients with a diagnosis of SS or e-MF with blood involvement who were treated with ECP at our institute. Overall survival (OS), time to next treatment (TTNT), and skin response rate (RR) were used as the study end points to determine patient outcome. The median follow-up from diagnosis was 48 months (range 1-225 months), with a median predicted OS of 120 months. The majority (88%) of patients commenced ECP at treatment lines 1 to 3, either as a monotherapy or in conjunction with other systemic agents. The use of ECP monotherapy resulted in a significantly longer median TTNT when compared with interferon-α (P = .0067), histone deacetylase inhibitors (P = .0003), novel immunotherapy agents (P = .028), low-dose methotrexate (P < .0001), and chemotherapy (P < .0001). In particular, early commencement of ECP at treatment lines 1 to 3 yielded a TTNT of 47 months. The results of our study support the utilization of ECP for SS/e-MF, and we recommend that ECP should be considered as early as possible in the treatment paradigm for these patients.

Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient.

Pembrolizumab is an immune checkpoint inhibitor with antitumor activity in other organ malignancies. We present this case -demonstrating multiple inflammatory adverse events associated with Pembrolizumab (in a single patient), in order to increase awareness and facilitate earlier identification of the wide-ranging cutaneous side effects associated with immunotherapy.

Systemic Treatment Options for Advanced-Stage Mycosis Fungoides and Sézary Syndrome.

PURPOSE OF REVIEW: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. Globally, the most common subtypes of CTCL are mycosis fungoides and Sézary syndrome. CTCL can confer significant morbidity and even mortality in advanced disease. Here we review the current and potential future treatments for advanced-stage CTCL. RECENT FINDINGS: Heterogeneity of treatment choice has been demonstrated both in US and non-US centers. Systemic treatment choice is currently guided by prognostic features, incorporating stage, immunophenotypic and molecular findings, and patient-specific factors such as age and comorbidities. Randomized controlled studies are uncommon, and the literature is composed predominantly of retrospective, cohort, and early-phase studies. International consensus guidelines are available; however, the lack of comparative trials means that there is no clear algorithmic approach to treatment. This review article reports on the systemic treatment options in current use for advanced CTCL, and on the possible future therapies, acknowledging that an algorithmic approach is not yet forthcoming to guide treatment prioritization.