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Brentuximab Vedotin Highly Effective in CD30-Positive Cutaneous T-Cell Lymphoma

According to results of the international, open-label, randomized, phase III ALCANZA trial in 131 adult patients (intent-to-treat [ITT] population = 128) with relapsed CD30-positive cutaneous T-cell lymphoma (CTCL), significantly more patients responded to treatment with brentuximab vedotin than standard of care. Patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large cell lymphoma who had been previously treated received either brentuximab vedotin (1.8 mg/kg every 3 weeks for up to 16 three-week cycles) or physician’s choice of methotrexate (5 mg to 50 mg once weekly) or bexarotene (300 mg/m2 daily) for up to 48 weeks. The primary endpoint was the proportion of patients in the intent-to-treat population who achieved an objective global response at least 4 months in duration (ORR4).

At a median follow-up of 22.9 months, treatment with brentuximab vedotin resulted in ORR4 in 56.3% of patients, compared to 12.5% of patients receiving physician’s choice (P<.0001). Improvement in ORR4 was seen regardless of CTCL subtype and across all patient subgroups, including the entire range of CD30 expression levels. A greater proportion of patients receiving brentuximab vedotin achieved an objective response (ORR: 67% vs 20%; P<.0001) and complete response (CR: 16% vs 2%; P = .0046). Brentuximab vedotin was associated with a 13.2-month improvement in progression-free survival (PFS) over physician’s choice (16.7 months vs 3.5 months; HR 0.27, P<.0001).

There were similar rates of grade 3/4 adverse events (AEs) between the two groups (41% vs 47%). The most common treatment-related AE associated with brentuximab vedotin was peripheral neuropathy, a known complication of this agent, which occurred at much higher rates than in the physician’s choice group (67% vs 6%). There was one treatment-related death in the brentuximab vedotin group and none in the physician’s choice group.

The study investigators concluded that brentuximab vedotin was associated with substantial improvements in ORR4 and CR over standard of care, with few additional toxicities, supporting the use of this therapy over methotrexate or bexorotene for the treatment of relapsed/refractory CD30-positive CTCL.

In an accompanying commentary, the authors noted the large size of this trial, as well as the innovative use of ORR4 as a primary endpoint, calling this study “a major milestone in the development of effective systemic therapies” for CTCL. The authors highlighted that future directions should include testing brentuximab vedotin in earlier lines of therapy and investigating rational combinations with brentuximab vedotin, including checkpoint inhibitors, histone deacetylase inhibitors, lenalidomide, and total skin electron beam radiation.

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