A Phase 1/2 Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma in the First Salvage Setting: Interim Results

Background

The standard of care for patients (pts) with Hodgkin lymphoma (HL) who are relapsed/refractory (R/R) to frontline therapy is salvage chemotherapy followed by autologous stem cell transplant (auto-SCT), with improved outcomes reported for pts who achieve complete remission (CR) prior to auto-SCT.  Because standard therapies in the first relapse setting produce variable responses (19–60% CR rates) and are associated with significant toxicities, new treatments are needed.  Two highly active therapies in the second salvage setting are the antibody-drug conjugate, brentuximab vedotin (ADCETRIS^®) (34% CR; Younes, 2012), and the bifunctional alkylating agent, bendamustine (33% CR; Moskowitz, 2013).  A phase 1/2, single-arm, 2-stage, open-label study was designed to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for treatment of HL in first relapse.  Interim results from the phase 1 (safety) cohort are presented.

Methods

Pts receive brentuximab vedotin (1.8 mg/kg, up to 16 cycles), in combination with bendamustine (90 mg/m², up to the first 6 cycles).  After Cycle 2, hematopoietic stem cells are mobilized and collected for patients eligible for auto-SCT.  Response is assessed by the investigator per Cheson 2007.

Results

Six HL pts (5 females, 1 male) with a median age of 45 yrs (range, 20 to 61 yrs) have received at least 1 cycle of brentuximab vedotin in combination with bendamustine.  Five pts are relapsed and 1 pt is primary refractory to front-line chemotherapy.  A median of approximately 16 mos (range, 8 to 40 mos) have elapsed since the pts’ initial diagnosis.  To date, a maximum of 4 cycles of the combination regimen have been received and all patients remain on treatment.  Adverse events (AEs) reported for >1 pt are nausea (4 pts); chills, flushing, lymphopenia, and pyrexia (3 pts each); and constipation, dyspnea and throat tightness (2 pts each).  Three pts have had serious AEs:  Gr 1 chills and pyrexia in 1 pt, infusion-related reactions in 1 pt (Gr 1/2 throat tightness, urticaria, pyrexia, papular rash), and Gr 3 diarrhea (unrelated per the investigator) in 1 pt.  Additional Grade ≥3 AEs are lymphopenia (3 pts) and generalized rash and dyspnea (1 pt each).   No dose-limiting toxicities have yet been reported.  CR has been achieved in all 5 patients who have been assessed for response (4 at Cycle 2 and 1 at Cycle 4).

Conclusions

To date, brentuximab vedotin 1.8 mg/kg administered with bendamustine 90 mg/m² has not exceeded the maximum tolerated dose and enrollment to this cohort is ongoing.  CR has been achieved in all patients who have been assessed for response.  Updated safety and response data, as well as feasibility of stem cell mobilization and collection, will be presented at the meeting.