Mast cells isolated from patients with systemic mastocytosis (SM) often express the Ki-1 antigen CD30 on their surface, and the antibody-conjugate brentuximab-vedotin inhibited growth and promoted apoptosis in neoplastic mast cells expressing CD30.
CD30 cell surface levels roughly correlated with the type of systemic mastocytosis: CD30 was observed in 3 of 25 patients (12%) with indolent SM, 4 of 7 (57%) with aggressive SM, and 4 of 7 (57%) with mast cell leukemia. However, not all patients with aggressive disease exhibited mast cell-surface CD30, and some patients with indolent SM expressed substantial amounts of CD30.
“Our data are in favor of testing for CD30 surface expression on neoplastic [mast cells] by flow cytometry before treatment with brentuximab-vedotin is considered,” wrote Dr. Katharina Blatt of the Medical University of Vienna, and her colleagues (Blood. 2015 Dec 24. doi:10.1182/blood-2015-03-637728).
The antibody-drug conjugate brentuximab-vedotin targets CD30+ cells in patients with Hodgkin lymphoma and anaplastic large-cell lymphoma. This study demonstrated that brentuximab-vedotin inhibited growth of CD30+ mast cells, as well as proliferation of CD30+ mast cell lines, at concentrations within therapeutic range. Analysis was done on bone marrow samples from 45 patients with systemic mastocytosis, as well as human mast cell lines (HMC-1.1, HMC-1.2, MCPV-1.1, and MCPV-1.4) and canine mastocytoma cell line C2.
Increased numbers and activation of mast cells in patients with SM cause mediator-related symptoms, and these may be reduced in the presence of brentuximab-vedotin, which was shown to counteract IgE-dependent secretion of histamine from basophils and mast cells, according to investigators.
Most patients with aggressive SM or mast cell leukemia show clinically meaningful or complete responses to midostaurin (PKC412), but responses are usually short lived. Brentuximab-vedotin acts synergistically with PKC412 to inhibit growth of CD30+ cells.
“Based on these data it seems tempting to propose a clinical trial exploring antineoplastic effects of the drug combination PKC412 and brentuximab-vedotin in advanced SM,” they wrote. A clinical trial of brentuximab-vedotin in advanced SM was initiated late last year.
Dr. Blatt reported having no disclosures. Several of her coauthors reported ties to industry.