High Response Rates and Safe Toxic Profile of Brentuximab Vedotin/bendamustine Combination in Heavily Pretreated Patients with Relapsed/refractory Hodgkin Lymphoma (HL)

Introduction: HL complete remission rate after first line treatment reaches to 80% to 90%. However, about 10% of these patients (pts) are refractory and 10% to 30% relapse after achieving a complete remission (CR). High dose chemotherapy followed by autologous stem cell transplant (ASCT) has been standard of care for suitable pts with relapsed/refractory (R/R) HL. Patients who relapse after ASCT have a dismal prognosis. Recently, new treatment options have emerged, such as the antiCD30 antibody-drug conjugate brentuximab vedotin (Bv) that is associated with an overall response rate (ORR) of 75% and CR rate of 34%. In the present study, we evaluated toxicity, efficacy, and duration of response (DOR) of Bv and bendamustine (BvB) combination. Methods: We retrospectively analyzed 27 histologically confirmed R/R classical HL pts from 3 cancer centers treated between 2007 and 2016 with at least 3 cycles of BvB. At the time of this analysis, 24 pts were evaluable. The median age was 24 (15-75). Median number of prior treatment lines was 3 (2-5), including ASCT (13 pts, 54%) and allogeneic transplantation (alloSCT, 4 pts, 16.6%). The scheme was administered by i.v. infusion of 1.8 mg/kg brentuximab on day 1 and 90 mg/m2 bendamustine on days 1 and 2 every 3 weeks as an outpatient regimen. Pts received a median of 6 (3-16) cycles. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Response was assessed by PET-CT in 18 pts (75%) and CT-scan in 6 pts (25%). Results: The ORR was 87%; 54% (13/24) achieved CR, and 33%(8/24) partial remission. Toxicity was observed in 10/24 (41%) pts; grade 2 infusion-related reactions in 3/24 (13%) pts, grade 3 hematologic toxicity in 3/24 (13%) pts, neurologic toxicity grade 3 in 3/24 (13%) pts, and grade 4 in 1/24 (4%) pts with no drug discontinuation. One patient (pt) died due to encephalopathy of unknown origin. The median follow-up was 12 (3-29) months since the beginning of BvB. The median OS was not reach. Median DOR in the CR group was 14 months. A PFS of 80% was observed at 12 months. One pt died due to disease progression. Six patients received consolidation treatment, including 4 ASCT with successful stem cell collection (SCC) and 2 alloSCT. Five pts showed disease progression, all of whom received nivolumab as salvage regimen. Conclusions: Our data showed a high response rate (87% ORR and 54% CR) with the BvB combination with a PFS of 80% at 12 months. The median DOR of the CR remission group was 14 months, highlighting durable responses. BvB has shown an acceptable toxic profile with only 1 grade 4 adverse event and was able to be delivered as an outpatient regimen. The combination allowed a successful SCC. BvB is a promising salvage treatment for heavily pretreated R/R HL pts. Large investigational trials are necessary to warrant these results. Keywords: bendamustine; brentuximab vedotin; Hodgkin lymphoma (HL)