preheader BJH 1

header website

Retrospective observational trial evaluating the efficacy and safety of high-dose bendamustine plus brentuximab vedotin in patients with refractory / relapsed Hodgkin lymphoma

The objective of this retrospective observational trial presented by Cerchione et al. during EHA 2017 was to evaluate the efficacy and safety of salvage cytotoxic regimens in patients with refractory/relapsed Hodgkin lymphoma (HL). The management of patients with refractory/relapsed HL, especially after autologous stem cell transplantation (ASCT), remains controversial. Bendamustine has demonstrated efficacy in several lymphoproliferative disorders but limited data are available regarding the schedule in patients with HL, in particular its dosage and the possible combinations for a synergistic effect. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, is currently approved for the treatment of relapsed or refractory HL.

Three different regimens were evaluated in this retrospective observational trial: (Arm A) standard dose bendamustine (90 mg/sqm) days 1 and 2 plus standard DHAP schedule (every 4 weeks) x 3 cycles (n=10), (Arm B) brentuximab vedotin single agent 1.8 mg/kg (every 3 weeks) x 4-8 cycles (n=11), and (Arm C) high dose bendamustine (120 mg/sqm) days 1 and 2 plus brentuximab vedotin 1.8 mg/kg (day 3) x 4-6 cycles (n=11). Each cycle in arm C was repeated every 28 days and growth factor support was systematically administered, in association with antimicrobial prophylaxis.

The median age of the patients was 31.7 years (range 16-73). In arm A, the overall response rate (ORR) was 40% (4/10 patients); these 4 patients had a complete remission (CR). In arm B, the ORR was 63.6% (7/11 patients) of which 5 patients (45%) had a CR and 2 patients (18%) had a partial response (PR). Lastly, in arm C, the ORR was 100% (11/11 patients). All these 11 patients had a CR; 6 patients underwent a second autologous transplant and 5 patients an allo-SCT with persistence of complete remission in all patients at a median follow-up of 33.4 months (range 12-60).

The hematological adverse events were grade 3 thrombocytopenia in 4 patients (40%) in arm A and 4 patients (n=36.3%) in arm C, grade 2 neutropenia in 2 patients (36%) in arm B and aplasia in 1 patient (10%) in arm A. The most common extra-hematological toxicity was gastrointestinal toxicity of grade 2 in 6 patients (60%) and grade 1 in 3 patients (30%) in arm A. In arm B the non-hematological toxicity was grade 3 neuropathy in 2 patients (18%), and grade 2 transaminase flare in 3 patients (27%). In arm C the non-hematological adverse events were increase of transaminase (grade 2) in 3 patients (27%) and cytomegalovirus (CMV) reactivation in 2 patients (18%), treated successfully with valganciclovir. Three patients had fever during infusion at first cycle, together with a skin rash, managed with corticosteroid injections, and a successful antihistamine plus corticosteroid prophylaxis in the next cycles of treatment.

In conclusion, these data demonstrate that high-dose bendamustine plus brentuximab vedotin has relevant efficacy and a relatively good safety profile in a setting of heavily pretreated patients with HL. Adequate monitoring of CMV reactivation is recommended. Furthermore, this combination could be considered as a bridge to second autologous or allogenic SCT. However, these results should be validated by controlled and prospective studies involving larger number of patients.


Cerchione C, Di Perna M, Della Pepa R, et al. High-dose bendamustine plus brentuximab combination is effective and has a favourable toxicity profile in the treatment of refractory and relapsed Hodgkin lymphoma. EHA 2017, poster presentation, abstract E1122


Speaker Claudio Cerchione


Claudio Cerchione, MD, University of Naples Federico II, Napoli, Italy


See: Keyslides


Back to Top