Brentuximab Vedotin “Unexpectedly” Ineffective in Patients With Primary Mediastinal B-Cell Lymphoma

Author’s Perspective
Lead author Pier Luigi Zinzani, MD: “This low response rate of brentuximab vedotin (BV) in primary mediastinal B-cell lymphoma was an  unexpected finding because this histologic subtype is typically characterized by high CD30 expression. The potential for BV activity to be independent of the level of CD30 expression is worth additional investigation in order to elucidate its mechanism and identify eligible patients for BV therapy.”

Patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBCL) often have poor outcomes, with approximately 15 to 20 percent of patients relapsing within the first 18 months of treatment.

Though the anti-CD30 antibody brentuximab vedotin (BV) appeared to be a promising treatment option for this patient population, as CD30 expression is present in nearly 80 percent of PMBCL cases, a report published in Blood found “unexpectedly” low overall response rates (ORR) in patients with relapsed/refractory CD30-positive PMBCL.

Pier Luigi Zinzani, MD, from the University of Bologna in Italy, and co-authors conducted a single-arm, open-label, multicenter, phase II study to assess BV monotherapy in 15 patients (median age = 29.3 years; range = 19.5-73.4 years) enrolled between October 2013 and October 2015 from five Italian centers.

Most patients (n=10; 67%) were female, and 34 percent (n=5) presented B symptoms. The median number of prior treatments was three (range = 1-4), with 12 patients who were refractory to their last therapy. Patients had previously received rituximab (n=15; 100%), hematopoietic cell transplantation (n=8; 53.3%), and radiation (n=9; 60%).

Patients received BV 1.8 mg/kg intravenously on day one of each 21-day cycle for up to 16 cycles. According to the report by Dr. Zinzani and colleagues, the ORR (primary endpoint) was just 13.3 percent (n=2). Both of these were partial responses (with no evidence of complete response), though responses lasted less than three to four months. The remaining patients demonstrated disease progression between cycles two and seven.

Six patients (40%) experienced adverse events associated with BV treatment, including peripheral neuropathy (n=1), atrial fibrillation (n=1), increase in alanine transaminase (n=2), increase in gamma-glutamyltransferase (n=2), and anemia (n=2).

Researchers originally planned to include 20 patients, but the study was stopped early because of the drug’s inefficacy. Dr. Zinzani and co-authors are now conducting a retrospective post-hoc analysis at the University of Bologna on CD30 expression in the study participants to compare their CD30 expression pattern with matched Hodgkin lymphoma patients who achieved a response after BV treatment.

The study is limited by its small patient population.

Source: Zinzani PL, Pellegrini C, Chiappella A, et al. Brentuximab vedotin in relapsed primary mediastinal large B-cell lymphoma: results from a phase 2 clinical trial. Blood. 2017 March 6. [Epub ahead of print]