Daniel J. Lewis

Brentuximab Vedotin for Patients With Refractory Lymphomatoid Papulosis: An Analysis of Phase 2 Results

Importance Brentuximab vedotin is a monomethyl auristatin E–conjugated monoclonal antibody directed against CD30. It represents a potential treatment for the CD30+ lymphoproliferative disorder lymphomatoid papulosis (LyP), which currently has no approved treatment. Objective To assess the efficacy and safety of brentuximab vedotin for the treatment of LyP. Design, Setting, and Participants In this study conducted at The University of Texas MD Anderson Cancer Center from May 10, 2011, to March 31, 2017, a total of 12 patients with LyP received brentuximab vedotin. All patients were 18 years or older with a diagnosis of LyP and were also required to have scarring, more than 10 lesions, or active lesions on the face, hands, or feet. Nine patients were enrolled in a physician-initiated, open-label, single-center, phase 2 clinical trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and LyP from 2011 to 2013. Three patients were later treated outside of the trial from 2013 to 2017. Five patients continued to be followed up as of March 2017. Interventions Intravenous brentuximab vedotin 1.8 mg/kg infused over 30 minutes every 21 days. Main Outcomes and Measures The primary end point was the overall response rate. Complete response was defined as zero lesions, and partial response was defined as a 50% or greater reduction in lesion count from baseline. A relapse was defined as loss of partial response. Results All 12 patients (8 men and 4 women; median age, 46 years) responded to brentuximab vedotin, and 7 exhibited a complete response. Time to response was 3 weeks in all patients. The median duration of response was 20 weeks (range, 6-103 weeks). For 5 patients who relapsed, the median time to relapse was 12 weeks (range, 6-41 weeks). One patient who relapsed was retreated and has remained in partial response for more than 23 months. Grade 1 to 2 neuropathy occurred in 10 patients but resolved in 5. Adverse events of grade 3 or higher were neutropenia (n = 2) and dizziness/vertigo (n = 1). Three patients withdrew owing to adverse events. Conclusions and Relevance Brentuximab vedotin is effective in treating LyP (overall response rate, 100%; complete response rate, 58%), but its use should be reserved for patients with truly severe and refractory LyP. More work is needed to optimize its dosing to minimize adverse events, such as peripheral neuropathy. Trial Registration clinicaltrials.gov Identifier: NCT01352520

Forodesine in the treatment of cutaneous T-cell lymphoma

ABSTRACT Introduction: Cutaneous T-cell lymphoma (CTCL) is characterized by the accumulation of neoplastic CD4+ T lymphocytes in the skin. Given the lack of curative treatments for CTCL, there is a significant need for new, superior therapies. Forodesine is a transition-state analogue that inhibits purine nucleoside phosphorylase. Because it selectively targets T lymphocytes, it represents a drug of interest for the treatment of CTCL. Areas covered: Phase I/II dose-ranging studies of intravenous (IV) and oral forodesine demonstrated its activity, safety, and tolerability for refractory CTCL. Response rates were 31% and 27%, respectively. No dose-limiting toxicities were observed. These studies were followed by a phase II trial of oral forodesine 200 mg daily. This oral formulation showed only partial activity, with a response rate of 11%, likely attributable to underdosing. Common adverse events in these trials included infection, fatigue, peripheral edema, nausea, pruritus, headache, and insomnia. Expert opinion: IV and oral formulations of forodesine have demonstrated partial activity and an acceptable safety profile in patients with refractory CTCL. A higher oral dose, or sequential therapy consisting of IV forodesine followed by maintenance oral forodesine, may be more effective. With proper dosing, forodesine may emerge as a safe and effective treatment for refractory CTCL.

A Rare Case of Mycosis Fungoides in the Oral Cavity and Small Intestine Complicated by Perforation

Extracutaneous involvement in mycosis fungoides (MF) carries a poor prognosis. Oral and gastrointestinal (GI) tract lesions are both rare locations of disease. We describe the clinical findings of one case with oral and GI MF complicated by perforation after systemic antineoplastic treatment, and review the relevant literature. The patient had a 1-year history of MF before development of tongue and palate tumors. He was treated with local electron beam radiation, but re-presented to the hospital after what was found to be small intestine perforation following systemic antineoplastic therapy. The case reveals key insights into the progression and complications of lymphomas with GI tract involvement.

Juvenile mycosis fungoides with large-cell transformation: Successful treatment with psoralen with ultraviolet A light, interferon-alfa, and localized radiation

Mycosis fungoides with large‐cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large‐cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large‐cell transformation shortly after administration of psoralen plus ultraviolet A, interferon‐alfa, and localized radiation.

How to Discern Folliculotropic Mycosis Fungoides From Follicular Mucinosis Using a Pediatric Case

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) with folliculotropic, atypical lymphocytes that may or may not have mucin deposition surrounding the hair follicle. Follicular mucinosis (FM) is a primary or secondary finding in FMF, lupus, or collagen vascular diseases that is only a histological process of mucin deposition surrounding the hair follicles. We present a case of a 6-year-old boy who had features of both FMF and primary follicular mucinosis (PFM). The case reveals key insights on FMF with concurrent FM in pediatric patients and how to differentiate between FMF and PFM.

The "Duvic regimen" for erythrodermic flares secondary to Staphylococcus aureus in mycosis fungoides and Sézary syndrome

can be displaced into the injection fluid and injected inadvertently, potentially causing tissue reactions such as sclerosing lipogranuloma (Fig. 1). Skin adverse reactions might be underdiagnosed by unawareness of the presence of silicone oil inside empty syringes and by the assumption that these reactions occur from the injectable drug itself, such as reported granulomatous reactions after injections of botulinum toxin type A. Dislocation of silicone droplets into the injectable fluid could be precipitated by tapping to remove bubbles and the presence of chemicals that could act as emulsifiers promoting interactions between hydrophilic (OH group of emulsifier/water molecules) and hydrophobic phase (nonpolar chain of emulsifier/methyl groups of polydimethylsiloxane). Awareness of the presence of silicone oil as a syringe lubricant is crucial for the formulation of proper clinical and histopathological diagnosis when facing skin adverse reactions triggered by injections. Further studies are needed to determine ways to further increase the safety of everyday office injections.

Pruritic arthropod bite-like papules in T-cell large granular lymphocytic leukaemia and chronic myelomonocytic leukaemia

T‐cell large granular lymphocytic leukaemia (T‐LGLL) is a clinically indolent mature T‐cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features. Because of the rarity of T‐LGLL, its cutaneous manifestations are poorly documented, but include vasculitis, vasculopathy, persistent ulcerations, generalized pruritus and disseminated granuloma annulare. Various types of skin lesions have been observed in patients with CMML and reportedly occur in approximately 10% of cases. We report the extraordinary case of a patient with MDS who developed T‐LGLL, and subsequently the MDS progressed to CMML. The patient then developed diffuse arthropod bite‐like papules and intractable pruritus.

Nonepidemic Kaposi sarcoma: A recently proposed category

No abstract available Keywords: HHV-8, human herpesvirus-8; KS, Kaposi sarcoma; Kaposi sarcoma; MSM, men who have sex with men; epidemiology; human herpes virus-8; immunocompetent; nonepidemic.

Primary cutaneous anaplastic large-cell lymphoma: Complete remission for 13 years after denileukin diftitox

CLS: capillary leak syndrome CR: complete remission CTCL: cutaneous T-cell lymphoma DD: denileukin diftitox pcALCL: primary cutaneous anaplastic large-cell lymphoma Treg: T-regulatory cell INTRODUCTION Denileukin diftitox (DD) is a recombinant fusion protein that consists of the interleukin-2 molecule conjugated to the catalytic domain of diphtheria toxin. It targets cells expressing the high-affinity interleukin-2 receptor, such as activated T lymphocytes in cutaneous T-cell lymphoma (CTCL). After binding to the interleukin-2 receptor, DD undergoes endocytosis followed by release of diphtheria toxin, which inhibits protein synthesis and induces subsequent cell apoptosis. DD was approved by the US Food and Drug Administration in 1999 for the treatment of persistent or recurrent CTCL. However, the pivotal trial leading to the drug’s approval only included patients with mycosis fungoides or S ezary syndrome. Although its clinical activity in other forms of CTCL remains unclear, DD may be useful for primary cutaneous anaplastic large-cell lymphoma (pcALCL). We report the case of a patient with recurrent pcALCL who has maintained complete remission (CR) for 13 years after treatment with DD.

Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia-lymphoma

ABSTRACT Introduction: Adult T-cell leukemia-lymphoma (ATL) is an aggressive variant of peripheral T-cell lymphoma of CD4+ T-malignant cells caused by human T-lymphotropic virus type-1. Despite aggressive treatment with multidrug combination chemotherapies, ATL confers a poor prognosis and commonly develops resistance to conventional treatments. Areas covered: Mogamulizumab is a humanized, defucosylated monoclonal antibody that acts by targeting the CC chemokine receptor 4 (CCR4) on malignant cells of ATL. In phase I and II clinical trials, it has achieved overall response rates of 31–50% in CCR4+ malignancies. The most commonly observed hematologic and non-hematologic adverse events included lymphocytopenia, neutropenia, leukocytopenia, infusion reaction, rash, and pyrexia. Expert commentary: Mogamulizumab has shown significant efficacy in treating ATL with moderately high response rates and has been approved in Japan for use in ATL. It may serve as a bridge therapy to achieve disease control prior to allogeneic hematopoietic stem cell transplantation. It also offers potential for use in combination with conventional chemotherapy. Determining the optimal combination of mogamulizumab with conventional and novel therapies remains an important strategy to improve the prognosis of patients with ATL.