243 Pooled analyses of two phase II trials of Brentuximab vedotin in patients with Mycosis Fungoides (MF) and Sézary Syndrome (SS)

Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.

Download Full-text

Faculty Opinions recommendation of Pembrolizumab in relapsed and refractory mycosis fungoides and sézary syndrome: A multicenter phase II study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736628042.793573979 ◽

2020 ◽

Author(s):

Robert Knobler

Keyword(s):

Mycosis Fungoides ◽

Phase Ii ◽

Phase Ii Study ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Multicenter Phase

Download Full-text

Multicenter Phase II Trial of Temozolomide in Mycosis Fungoides/Sézary Syndrome: Correlation with O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Proteins

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-11-0556 ◽

2011 ◽

Vol 17 (17) ◽

pp. 5748-5754 ◽

Cited By ~ 22

Author(s):

Christiane Querfeld ◽

Steven T. Rosen ◽

Joan Guitart ◽

Alfred Rademaker ◽

David S. Pezen ◽

...

Keyword(s):

Mismatch Repair ◽

Mycosis Fungoides ◽

Phase Ii ◽

Dna Methyltransferase ◽

Phase Ii Trial ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Methylguanine Dna Methyltransferase ◽

Multicenter Phase ◽

Mismatch Repair Proteins

Download Full-text

Treatment of mycosis fungoides/Sezary syndrome with brentuximab vedotin on the compassionate use program and CDF: outcomes and toxicities

European Journal of Cancer ◽

10.1016/s0959-8049(19)30589-1 ◽

2019 ◽

Vol 119 ◽

pp. S29 ◽

Cited By ~ 1

Author(s):

S. Enefer ◽

V. Grandi ◽

I. De Francesco ◽

S. Morris

Keyword(s):

Mycosis Fungoides ◽

Brentuximab Vedotin ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Compassionate Use

Download Full-text

Mycosis fungoides and the Sézary syndrome: a review of pathogenesis, diagnosis, and therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.7.1298 ◽

1991 ◽

Vol 9 (7) ◽

pp. 1298-1313 ◽

Cited By ~ 95

Author(s):

T M Kuzel ◽

H H Roenigk ◽

S T Rosen

Keyword(s):

Mycosis Fungoides ◽

Treatment Options ◽

Interleukin 2 ◽

Cell Phenotype ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Phase Ii Trials ◽

Biologic Response ◽

Potential Benefits ◽

Hodgkin's Lymphomas

Mycosis fungoides (MF) and the Sézary syndrome (SS) are non-Hodgkin's lymphomas with a T-cell phenotype, which have cutaneous involvement as their predominant feature. These disorders are becoming more common, and the patients are frequently being referred to medical oncologists for assistance in management. The development of advanced laboratory techniques, such as molecular genetics and cell-surface phenotyping, has greatly enhanced our understanding of their pathogenesis and may lead to identification of responsible etiologic factors. A myriad of treatment options have been investigated including topical approaches, systemic chemotherapy, and external radiation. Currently, extensive trials are underway examining the potential benefits of agents such as the interferons, interleukin-2, monoclonal antibodies, the retinoids, 2-chlorodeoxyadenosine, and other novel biologic response modifiers or chemotherapeutics. Although all these therapies have benefit in phase II trials, few randomized comparative trials have been performed to identify optimal therapies. Performance of such trials should now become a priority.

Download Full-text

Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.10.2051 ◽

1994 ◽

Vol 12 (10) ◽

pp. 2051-2059 ◽

Cited By ~ 69

Author(s):

F M Foss ◽

D C Ihde ◽

I R Linnoila ◽

A B Fischmann ◽

G P Schechter ◽

...

Keyword(s):

Mycosis Fungoides ◽

Phase Ii ◽

Low Dose ◽

Pneumocystis Carinii ◽

Interferon Alfa ◽

Survival Duration ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Visceral Involvement ◽

Grade 3

PURPOSE This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. RESULTS Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis. CONCLUSION The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.

Download Full-text