Efficacy of brentuximab vedotin in patients with CD30-positive lymphoproliferative skin diseases: results of the first prospective study in the Russian Federation

Abstract

Background. Primary cutaneous lymphomas are the second most common group of extranodal lymphomas. Unlike nodal lymphomas, which are characterized by predominant B-cell proliferation, primary cutaneous T-cell lymphomas account for 6575% of all cutaneous lymphomas. About 50% of all cutaneous T-cell lymphomas are mycosis fungoides (MF). CD30-positive lymphoproliferative disorders (CD30+ LPD) occupy the second place in the incidence of cutaneous T-cell lymphomas, while 10% are rare disease forms such as primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTLNOS), Szary syndrome (SS), etc.
 Treatment of MF/SS patients in the Russian Federation shows that about 30% of individuals are resistant to various therapeutic effects, especially in the later stages. The problem of CD30+ LPD treatment is extracutaneous dissemination in the case of primary cutaneous anaplastic large cell lymphoma (pcALCL) and steadily relapsing lymphomatoid papulosis (LyP) without symptom-free intervals. These aspects of the therapy of cutaneous lymphomas highlight the need to search for new treatment options.
 According to the results of the international randomized ALCANZA trial, brentuximab vedotin (BV) has shown high efficiency in the treatment of cutaneous T-cell lymphoproliferative disorders.
 Study objective. The study aim is to evaluate BV efficacy in the group of poor prognosis patients with cutaneous T-cell lymphomas who has received at least one line of systemic therapy.
 Materials and methods. The study included 21 patients: 16 men and 5 women. There were 8 patients with MF, 5 patients with SS; 6 individuals had cutaneous CD30+ LPD (including 5 patients with pcALCL and 1 individual with LyP) and 2 patients were diagnosed with PTLNOS. Cutaneous T-cell lymphoma was confirmed based on the medical history, nature of cutaneous lesions, as well as histological, immunohistochemical, and, in some cases, molecular genetic testing of the skin biopsy sample (analysis of T-cell receptor gene rearrangement).
 Results. Late stages of the disease were diagnosed in 12 out of 13 patients with MF/SS. Extracutaneous lesions were diagnosed in 57% of cases. The median of prior lines of therapy was 3 (18 variants of treatment). The overall response to the treatment was achieved in 91% of cases (19 out of 21 patients): complete remission was observed in 53% of patients, very good partial remission was achieved in 31% of individuals, and partial remission was noted in 16% of cases. Disease progression was found in 2 patients (after cycles 1 and 4). Some patients with partial remission after BV therapy underwent additional therapy (radiation therapy, interferon therapy, and cycles of systemic therapy), which made it possible to achieve a more pronounced antitumor response. Early relapse was diagnosed in 2 out of 19 patients who had responded to the treatment. The treatment tolerability was acceptable, and the toxicity did not exceed that described in the previous studies. Thus, the overall stable antitumor response persisted in 89% of patients (the median follow-up was 10 months).
 Conclusion. The use of targeted therapy with BV made it possible to achieve high treatment results in patients with advanced stages of the disease and the absence of response to several lines of therapy.