Rakhshandra Talpur

Long-term Outcomes of 1,263 Patients with Mycosis Fungoides and Sézary Syndrome from 1982 to 2009

Purpose: The purpose of this prospectively collected single center study cohort of 1,263 patients with mycosis fungoides (MF)/Sézary syndrome (SS) is to evaluate the significance of stage and risk of disease progression from initial presentation and to examine other prognostic factors. Patients and Methods: The prognostic variables effecting overall survival (OS) were examined in a unique prospective cohort of 1,263 patients with MF and SS seen by one investigator at MD Anderson Cancer Center (Houston, TX) from 1982 to 2009. Kaplan–Meier estimates were used to determine median OS, progression-free survival (PFS), and disease-specific survival (DSS). Cox proportional hazards regression model assessed prognostic factors. Results: Mean age at diagnosis was 55.33 years. Early mycosis fungoides (stage IA–IIA) represented 71.5% (903 of 1,263) and advanced (stage IIB–IVB) 28.5% (360 of 1,263) patients. Progression to a higher stage occurred in 147 patients (11.6%) of whom 112 (12%) were early and 35 (9.7%) advanced. Death from disease occurred in 102 of 1,263 (8.1%) patients. Median OS was 24.44 years, PFS was 16 years, and median DSS was not reached. OS and PFS were significantly better for early-stage patients with patches (T1a/T2a) than with patches/plaques (T1b/T2b). The PFS analyzed in 1,241 patients found that only 337 (27.2%) had disease progression or had died from disease. Risk factors associated with progression or deaths were advanced age, plaque stage, lactate dehydrogenase (LDH) level, and tumor area. Conclusions: Improved outcome of MF/SS, reflected by OS and PFS for all stages, may result from earlier diagnosis, new therapies, and aggressive treatment of infections. Clin Cancer Res; 18(18); 5051–60. ©2012 AACR.

Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis

PURPOSE Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30(+) receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30(+) cutaneous T-cell lymphomas. PATIENTS AND METHODS Forty-eight patients with CD30(+) lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. RESULTS Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1), and arthralgias and fatigue (n = 2). CONCLUSION Brentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and complete response rate of 35%.

Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome

Background  Mycosis fungoides (MF) and Sézary syndrome (SS), variants of cutaneous T‐cell lymphoma, may arise from antigen‐driven clonal expansion and accumulation of helper‐memory T cells. Superantigens from Staphylococcus aureus can stimulate T cells.

Overall survival in erythrodermic cutaneous T‐cell lymphoma: an analysis of prognostic factors in a cohort of patients with erythrodermic cutaneous T‐cell lymphoma

Background  The most common cutaneous T‐cell lymphomas (CTCLs) are mycosis fungoides and Sézary syndrome.

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PURPOSE Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). RESULTS Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). CONCLUSION To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.

Treatment of refractory peripheral T-cell lymphoma with denileukin diftitox (ONTAK).

Peripheral T-cell lymphomas (PTCLs) are an uncommon and heterogeneous group of well-differentiated, post-thymic T-cell malignancies that can present in the skin as cutaneous T-cell lymphomas. In general, their prognosis is poor, and specific therapy is not well defined. We report the successful treatment of a patient with relapsed, refractory PTCL who after failing 13 standard single and multiple chemotherapy regimens and experimental agents had a dramatic prolonged response to diftitoxin denileukin (ONTAK ® ). This fusion protein, composed of diphtheria toxin coupled to interleukin-2, is approved for cutaneous T-cell lymphomas, including mycosis fungoides, and should be considered for treatment of the rare subset of peripheral T-cell lymphomas.

Optimizing denileukin diftitox (Ontak®) therapy

Denileukin diftitox (Ontak) is a novel recombinant fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domain of diphtheria toxin linked to human IL-2. Denileukin diftitox specifically binds to IL-2 receptors on the cell membrane, is internalized via receptor-mediated endocytosis and inhibits protein synthesis by ADP ribosylation of elongation factor 2, resulting in cell death. This article focuses on the clinical trial that led to the US FDA approval of the drug for cutaneous T-cell lymphoma in 1999, and other investigational studies for hematologic malignancies, recurrent and refractory chronic lymphocytic leukemia, non-Hodgkin B-cell lymphoma, graft-versus-host disease and autoimmune disease, demonstrating the activity and adverse effects of the drug.

Phase I/II randomized bilateral half-head comparison of topical bexarotene 1% gel for alopecia areata

BACKGROUND Alopecia areata, hair loss caused by perifollicular T-cell infiltrates, is refractory to therapy. Bexarotene, a retinoid X receptor is a selective retinoid, induces T-cell apoptosis. OBJECTIVE We sought to determine the safety, including the dose-limiting toxicities with adverse events, and efficacy, ie, response rate, of bexarotene in alopecia areata. METHODS We conducted a phase I/II randomized, half-head trial of 1% bexarotene gel applied twice daily for 6 months. RESULTS In all, 42 patients (11 male and 31 female) with alopecia totalis (n = 3), alopecia universalis (n = 5), or alopecia areata (n = 34) applied 1% bexarotene gel for 24 weeks. Five of 42 (12%) had 50% or more partial hair regrowth on the treated side, and 6 of 42 (14%) on both sides including 3 complete responders. In all, 31 patients had mild irritation; 4 had grade-3 irritation. LIMITATIONS This design cannot differentiate between drug-induced and spontaneous regrowth. CONCLUSION Topical bexarotene 1% application is well tolerated and possibly effective. A randomized placebo-controlled trial should be conducted.

Lymphomatoid papulosis: Treatment response and associated lymphomas in a study of 180 patients

BACKGROUND Lymphomatoid papulosis (LyP) is a CD30(+) lymphoproliferative disorder, with a self-regressing clinical course and malignant histopathology. OBJECTIVE The aim of this study was to evaluate characteristics, risk factors, associated malignancies, long-term outcome, and treatment of LyP in a large cohort representing the experience of the MD Anderson Cancer Center. METHODS Patient charts and clinical and histopathologic data of 180 patients with LyP were retrospectively assessed. RESULTS A total of 56.7% of patients was men. Histologic subtype A was found in 47.2%, type B in 17.2%, type C in 22.8%, type D in 7.8%, type E in 0.6%, and mixed subtype in 4.4% of the patients. One hundred fourteen lymphomas were observed in 93 patients, with mycosis fungoides (61.4%) and anaplastic large cell lymphoma (26.3%) being the most common forms. Risk factors for development of lymphoma included sex and histologic subtype. Number of lesions and symptom severity were not associated with lymphoma development. Patients with type D were less likely to have lymphomas. Treatment provided symptomatic relief but did not prevent progression to lymphoma. LIMITATIONS The limitation of this study is the retrospective study design. CONCLUSION Patients with LyP are at increased risk of associated lymphomas. Thorough patient counseling is needed and long follow-up periods are required to detect and treat secondary lymphomas.

Multicenter Photopheresis Intervention Trial in Early-Stage Mycosis Fungoides

PURPOSE To demonstrate the efficacy of the UVAR XTS Photopheresis System and evaluate health-related quality of life in patients with early-stage mycosis fungoides (MF). PATIENTS AND METHODS Extracorporeal photopheresis was administered 2 days every 4 weeks for 6 months. Patients with partial responses by skin weighted assessment continued for 6 months; nonresponders added oral bexarotene and/or interferon α. Health-related quality of life was assessed at baseline and every 3 months with 3 validated tools. RESULTS Nineteen patients with early-stage MF (7 men, 12 women; 16 white, 3 African Americans) with median age of 63.5 years (range, 46-85 years) participated. Their stages were IA (n = 3), IB (n = 14), and IIA (n = 2). The overall response rate for extracorporeal photopheresis (ECP) alone, was 42% (8/19; including 7 partial response, 1 complete response), with a median of 12 ECP sessions (range, 3-32) given over a median of 12 months (3-32 months) and with an overall duration of response of 6.5 months (range, 1-48 months). Seven patients with stable disease at 3 months received additional bexarotene (3/5; 1 complete response) or bexarotene plus interferon α (1/2), and 4 (57%) of 7 responded. Treatment-related adverse effects were limited to those expected with interferon (fatigue, nausea, vomiting, and diarrhea), or with hypertriglyceridemia and bexarotene. Trends in health-related quality of life indicated an improvement in emotional scores over time. CONCLUSIONS ECP is effective for patients with early-stage MF alone or in combination with biologic response modifiers with low toxicity and improved quality of life.