Allogeneic Transplant Following Brentuximab Vedotin Treatment in Patients with Relapsed or Refractory CD30+ Lymphomas

Allogeneic stem cell transplant (allo-SCT) for relapsed or refractory lymphoma is often limited by the amount of residual tumor burden following cytoreductive therapy. Brentuximab vedotin (SGN-35) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). In recent phase 2 trials, brentuximab vedotin induced objective responses in 75% of patients with Hodgkin lymphoma (HL) (Chen 2011) and 86% of patients with systemic ALCL (sALCL) (Pro 2011). Fifteen of 160 patients (9%) who participated in these two phase 2 studies received an allo-SCT as their first subsequent antitumor therapy after treatment with brentuximab vedotin. This case series describes the initial experience of these patients.

Patients received 1.8 mg/kg brentuximab vedotin administered every 3 weeks as a 30-minute outpatient IV infusion for up to 16 cycles of treatment. Antitumor activity was based on objective response assessments according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). After discontinuing brentuximab vedotin, patients were followed for survival/disease status and information regarding subsequent therapy, including allo-SCT, was collected.

Fifteen patients (7 with HL and 8 with sALCL) received an allo-SCT as their first subsequent antitumor therapy following brentuximab vedotin treatment. The median age was 28.0 years (range 17–61 years) and the majority (67%) were female. The median time since initial HL/sALCL diagnosis was 27.3 months (range 6.2–108 months). The median number of therapies patients had received prior to brentuximab vedotin was 3.0 (range 2–5) and 12 patients had previously received an autologous SCT.

Patients received a median of 9.0 cycles (range 4–16) of brentuximab vedotin and all 15 patients achieved an objective response per independent radiological review; best response was CR for 12 patients (5 with HL and 7 with sALCL) and PR for 3 patients (2 with HL and 1 with sALCL). The median time to objective response was 1.4 months (range 1.2–2.6 months) and all 15 patients maintained an objective response at the time of the last assessment prior to allo-SCT. The median time between the last dose of brentuximab vedotin and the start of the SCT conditioning regimen was 1.4 months (range 0.6–3.3 months). Thirteen of the 15 patients (87%) are alive and remain in follow-up post allo-SCT. The median duration of follow-up from first dose of brentuximab vedotin is 16.9 months (range 8.2–21.1 months). Five patients (1 with HL and 4 with sALCL) have either progressed or died post-transplant. Four of these 5 patients had achieved a CR with brentuximab vedotin treatment. Of the 2 patients who died (both patients with sALCL who had achieved a CR with brentuximab vedotin treatment), one death was disease-related (not formally restaged) and the other was due to transplant-related complications. The median PFS at the time of this analysis is 21.1 months (range 8.2–21.1 months).

Treatment-emergent adverse events that occurred prior to allo-SCT in >20% of patients were peripheral sensory neuropathy and pyrexia (53%; n=8), diarrhea and neutropenia (47%; n=7), nausea (33%; n=5), and chills and dyspnea (27%; n=4). Thirteen of 15 patients (87%) experienced AEs of ≥ Grade 3 prior to allo-SCT; the most common (reported in >10% of patients) were neutropenia (47%; n=7), anemia and thrombocytopenia (27%; n=4), and abdominal pain, pain, and peripheral sensory neuropathy (13%; n=2). Two patients discontinued brentuximab vedotin treatment due to an AE (peripheral sensory neuropathy) before subsequently receiving allo-SCT.

Treatment with brentuximab vedotin provided cytoreduction in patients with relapsed or refractory HL and sALCL, many of whom had failed a prior autologous SCT. Thirteen of the 15 patients (87%) achieved an objective response with brentuximab vedotin treatment prior to allo-SCT and remain in follow-up at the time of this analysis. Ten of the 15 patients (67%) remain in remission. Our results suggest that brentuximab vedotin may be an option for reducing tumor burden to facilitate a consolidative allo-SCT and warrants further study.

Illidge:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Honoraria. Off Label Use: Brentuximab vedotin (SGN-35) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). It is an investigational agent that is being studied in CD30+ malignancies. Bouabdallah:Seattle Genetics, Inc.: Research Funding. Chen:Seattle Genetics, Inc.: Consultancy, Research Funding, Travel Expenses. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding; Millennium: Honoraria, Speakers Bureau; Cephalon: Research Funding; Spectrum: Research Funding; Piramal: Research Funding; Merck: Research Funding; Calistoga: Research Funding; Abbott: Research Funding; Pfizer: Research Funding; SBIO: Research Funding; Gilead: Research Funding; Genzyme: Speakers Bureau; Amgen: Speakers Bureau; Cellular Therapeutics Inc.: Speakers Bureau. Moskowitz:Seattle Genetics, Inc.: Consultancy, Research Funding; Cephalon: Research Funding; Genentech: Research Funding; Plexxicon: Research Funding. Ramchandren:Seattle Genetics, Inc.: Research Funding. Rosenblatt:Seattle Genetics, Inc.: Research Funding. Shustov:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium: Honoraria. Tilly:Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau. Trippett:Seattle Genetics, Inc.: Research Funding; OSI Pharmaceuticals: DSMB Chair. Grove:Seattle Genetics, Inc.: Employment; Seattle Genetics, Inc.: Equity Ownership. Advani:Seattle Genetics, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.