Phase II results suggest that brentuximab vedotin (Adcetris) has encouraging activity in CD30-positive cutaneous T-cell lymphomas and lymphoproliferative disorders, including mycosis fungoides, the most common type of cutaneous T-cell lymphoma. High levels of responses were achieved in a 48-patient trial reported at the 55th American Society of Hematology (ASH) Annual Meeting in New Orleans.

“[Brentuximab vedotin], a conjugated antibody targeting the CD30 receptor, as expected, had a very rapid and 100% response rate for the CD30-positive cutaneous lymphoproliferative disorders. In addition, it produced an unexpectedly high response rate in patients with mycosis fungodies, irrespective of degree of CD30 expression and including [mycosis fungoides] with large cell transformation or folliculotropic morphology,” said lead author Madeleine Duvic, MD, Professor of Medicine and Dermatology and Deputy Chair of the Dermatology Department at The University of Texas MD Anderson Cancer Center, Houston.

Study Background

CD30-positive cutaneous T-cell lymphomas/lymphoproliferative disorders include primary cutaneous anaplastic T-cell lymphomas, secondary cutaneous anaplastic T-cell lymphomas, lymphomatoid papulosis, and  transformed CD30-positive mycosis fungoides. Brentuximab vedotin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma, and is investigational in cutaneous T-cell lymphoma.

The single-center, open-label study enrolled 48 patients diagnosed with established CD30-positive cutaneous T-cell lymphoma within the past 3 years. Of these, 28 patients had mycosis fungoides, 9 had lymphomatoid papulosis, 2 had anaplastic T-cell lymphoma, 7 had lymphomatoid papulosis/mycosis fungoides, and 2 had anaplastic T-cell lymphoma/ lymphomatoid papulosis. The study included 22 women and 26 men with a median age of 59.5 years (range, 31–86).

Brentuximab vedotin was infused over 30 minutes every 21 days for eight cycles; patients who achieved partial remission could get up to 16 doses. Treatment was continued for two doses past complete remission.

Responses were defined for each lesion type as follows: lymphomatoid papulosis, 50% decrease in active lesion count; anaplastic T-cell lymphoma, tumor measurements of index lesions; mycosis fungoides, 50% reduction in modified skin weighted assessment tool (mSWAT). Quality of life was evaluated on a visual analog scale with a patient global assessment.

Key Data

In 48 evaluable patients, the overall response rate was 73%. Breaking response rates down by tumor type, overall response rate was 54% for mycosis fungoides (13 partial remissions, 2 complete remissions), the most common type of cutaneous T-cell lymphoma; for all other tumor types, overall response rate was 100%. Looking at mycosis fungoides patients, best skin response to treatment on mSWAT increased over time. Response was not correlated with level of CD30 expression at baseline in mycosis fungoides.

Median time to response for all patients was 12 weeks. Median duration of response for mycosis fungoides patients was 39 weeks.

Six patients experienced grade 3 or higher adverse events, including neutropenia, nausea, unstable angina, infection, fatigue, deep-vein thrombosis, pulmonary embolism, liver function test abnormalities, dehydration, and arthralgia (some patients experienced multiple events). Six patients withdrew from the study, two due to death.

Peripheral neuropathy was the most common adverse event of concern, occurring in 31 (65%) of 48 patients at least once. Median duration of peripheral neuropathy was 60 weeks. Dose reductions resolved peripheral neuropathy in 14 (45%) of the 31 patients; peripheral neuropathy was unresolved in 17 (55%) of 31 patients at the time of the ASH meeting. Fatigue was reported in 41%, and drug rash in 27%.

The phase III ALCANZA trial is comparing brentuximab vedotin vs investigator’s choice of methotrexate or bexarotene (Targretin) in approximately 124 patients with relapsed CD30-positive cutaneous T-cell lymphoma. Results may determine whether FDA approval will be granted for the disease. ■

Disclosure: Dr. Duvic has received research funding from Seattle Genetics and Millennium.

Reference

1. Duvic M, Tetzlaff M, Clos AL, et al: Phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and lymphoproliferative disorders. 2013 ASH Annual Meeting. Abstract 367. Presented December 9, 2013.