Brentuximab Vedotin As First Line Salvage Therapy in Relapsed/Refractory HL

A defining feature of HL is CD30 expression by Reed-Sternberg cells. Brentuximab vedotin, an antibody drug conjugate (ADC), selectively induces apoptotic death of CD30+ cells by binding, internalizing, and releasing monomethyl auristatin E, a microtubule agent. A pivotal phase II trial of brentuximab vedotin in heavily pretreated patients with HL demonstrated an overall objective response rate of 75% (CR, PR) and CR of 34% with manageable toxicities. This novel ADC compares favorably with historical first-line salvage regimens such as ICE and DHAP (CR 17–21%) To examine the outcomes (e.g., toxicity, response) of brentuximab vedotin when given as first-line salvage therapy for HL, we retrospectively analyzed data from a consecutive case-series of patients who received brentuximab vedotin as first -line salvage therapy at COH.

Three patients received brentuximab vedotin as salvage therapy on IRB 10089 (expanded access protocol) and 8 patients received brentuximab vedotin as salvage therapy on IRB 11051 (prospective phase II trial). All patients had relapsed/refractory HL post induction therapy with ABVD, BEACOPP or a combination +/− consolidative XRT. Patients were treated with 1.8 mg/kg of brentuximab vedotin intravenously every 3 weeks as outpatients for a maximum of 4 cycles. Descriptive statistics were generated for response, toxicity, stem cell mobilization/collection and engraftment (for those patients who went on to autologous HCT). Response rate post brentuximab vedotin treatment was determined with either CT or PET at cycle 2 and CT/PET at cycle 4 as per Cheson 2007 criteria.

A total of 11 patients were treated at COH from 8/2011 to 7/2012 (Table 1). The median age was 34 years (22, 64); 7/11 were female. All patients received ABVD or ABVD/BEACOPP combination induction therapy. Three patients had also received consolidative radiation therapy. Six were considered primary refractory and 5 had relapsed HL. Thus far, 8 were evaluable for response and 10 were evaluable for toxicity. The overall response rate was 87.5% (7/8); CR was 50% (4/8) and PR was 37.5% (3/8); one patient achieved SD after 4 cycles. Three out of 4 patients who achieved CR did so after 2 cycles. No one developed progressive disease while on treatment. Overall the regimen is considered well tolerated. No grade 2 neuropathy was reported. The incidence of grade 1 neuropathy was 20% (2/10). There were no grade 3 or 4 adverse events or hospitalizations during brentuximab vedotin treatment. Additionally, the use of growth factors or red blood cell or platelet transfusions was not required.

A total of 6/11 patients have undergone stem cell mobilization with cyclophosphamide/G-CSF priming after the 4th dose of brentuximab vedotin. The median cells dose collected was 5.87 × 10^⋀6 CD34+ cells (2.78–11.13, minimum acceptable is 2 × 10^⋀6 CD 34+ cells). The median time to reach the minimum collection was 1.5 days (1–5). All six patients have undergone ASCT using either BEAM or CBV for conditioning. The median time for neutrophil engraftment (ANC>500) was 10 days (10–11) and platelet engraftment (>20K) was 11 days (10–13). All 6/6 patients achieved CR after stem cell transplantation. The other five patients are undergoing stem cell mobilization or are have not completed brentuximab vedotin treatment.

These data show brentuximab vedotin as first-line salvage therapy can produce an adequate ORR of 87.5% and CR of 50%. Brentuximab vedotin also has acceptable toxicity and does not adversely impact stem cell collection or post autologous HCT engraftment.

Chen:Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Travel Expenses Other. Off Label Use: This clinical trial involves the use of brentuximab vedotin as first line salvage therapy in Hodgkin lymphoma, which is an off-label use. Siddiqi:Seattle Genetics, Inc.: Consultancy, Research Funding.