Brentuximab Vedotin Plus Bendamustine Is an Effective Salvage Regimen for Pediatric Patients with Relapsed Hodgkin Lymphoma

Background :

Pediatric patients with relapsed/refractory Hodgkin Lymphoma have superior outcomes when achieving a complete remission prior to autologous stem cell transplant (ASCT). Optimal salvage regimens need to be identified as current approaches result in complete responses (CR) in approximately 25-35% of patients. The combination of brentuximab vedotin and bendamustine is highly active in adult patients with relapsed/refractory Hodgkin Lymphoma, but has not been evaluated in the pediatric population. We report our preliminary experience regarding the safety and efficacy of brentuximab vedotin and bendamustine prior to stem cell transplant (SCT) in pediatric patients treated for relapsed Hodgkin lymphoma at a single center.

Methods:

We performed a retrospective review of pediatric patients with relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine between April 2016 to July 2017. Patients received an infusion of 1.8mg/kg of brentuximab vedotin on Day 1 with bendamustine 90mg/m2 on Days 1 and 2 of 3-week cycles. Response assessment was performed and repeated following 2-3 cycles of therapy. Patients went on to SCT after achieving a CR or best response at the discretion of the treating physicians. Patients resumed post-transplant treatment with brentuximab vedotin as monotherapy for up to 16 doses.

Results:

Five patients (1 female, 4 males) with a median age of 16.5 years at the time of relapse (range, 12.2 -17.9 years) were treated with the combination of brentuximab/bendamustine. Four patients were in first relapse and 1 was treated in second relapse nine months following a prior ASCT. Patients received a median of 5 cycles of therapy (range 2-5 cycles), with 2 patients receiving an additional cycle of brentuximab monotherapy prior to proceeding to SCT. The main toxicity observed was infusion-related reactions, with 2 patients experiencing anaphylaxis. These individuals were able to continue planned therapy following desensitization against brentuximab. All patients were in complete remission by PET prior to SCT. Four patients underwent successful stem cell mobilization and collection. The individual treated following second relapse received an allogeneic transplant from a matched unrelated donor. All patients are alive with no evidence of disease a median of 11.3 months since beginning salvage therapy (range 1.2-15 months). Four patients are a median of 6.5 months (range 4-11 months) post-SCT and continue on brentuximab monotherapy, with 1 individual currently awaiting ASCT.

Conclusions :

Combination therapy with brentuximab vedotin and bendamustine was highly active in pediatric patients with relapsed Hodgkin lymphoma and would compare favorably with currently accepted salvage regimens. Incidence of infusion-related reactions can be minimized through the use of adequate premedication. These results support further evaluation of this regimen in the context of a multicenter prospective clinical trial.