Brentuximab Vedotin in Combination with Bendamustine in Relapsed or Refractory Hodgkin Lymphoma: A Retrospective Analysis on 23 Paediatric Patients or Young Adults

INTRODUCTION:

Hodgkin's lymphoma (HL) is a lymphoproliferative disorder associated with a high cure rate, obtained through the combined use of multiagent conventional chemotherapy and radiotherapy. However, patients with primary resistant disease and some subsets of relapsed patients still have a dismal outcome, thus requiring new and more effective therapeutic options.

Brentuximab vedotin (BV) is an antibody-drug conjugate (ADC) comprising a CD30-directed antibody linked to the cytotoxic payload monomethyl auristatin E (MMAE), that induce apoptosis in CD30-positive cells. Bendamustine has also been shown to be a safe and effective therapy for HL patients experiencing relapse after autologous hematopoietic stem cell transplantation (HSCT) and an interesting cytoreductive agent before allogeneic transplantation. In view of the above reported considerations, we hypothesized that BV in combination with bendamustine could be a suitable salvage therapy for pediatric/young adult patients with relapsed/refractory HL.

PATIENTS AND METHODS:

Data on 23 patients with pathologically confirmed CD30-positive relapsed or refractory HL, treated with BV and bendamustine in 3 Italian sites, were collected in this retrospective analysis. Patients received up to 6 cycles of treatment, each of them including 1.8 mg/kg BV on day 1 and 120 mg/m² Bendamustine on days 2 and 3; cycles were administered every 3-4 weeks. We assessed the objective response rate through high-resolution computed tomography (CT) and FDG-PET scans after the first 2 cycles and at the end of treatment. The toxicity of this combination regimen was evaluated, as well. The median age at the treatment was 16 years (range, 8-25); 9 patients were females (40 %) and 14 males (60 %). Nine patients (40%) had primary refractory disease, while the remaining 14 patients (60%) had experienced relapse. The median number of prior chemotherapy regimens, including also allogenic or autologous HSCT, was 2 (range, 1-6). Twelve patients (52 %) had received prior radiation therapy, and 4 patients (17 %) had been treated with either allogenic or autologous HSCT. Notably, 3 patients (13%) had been given BV as single agent. All patients were evaluated for treatment response, according to Cheson's Criteria.

RESULTS:

The median number of cycles administered was 4 (range, 2-6). After the first 2 cycles, a complete response (CR) was recorded in 10 out of 23 patients (43%). At the end of treatment, 12 of 23 patients (52%) obtained CR, while 3 (13%) obtained a partial response (PR). Seven patients (30%) presented progressive disease (PD) and one child is still on treatment and, thus, not evaluable. Among patients in whom an objective response was observed, 12 and 3 patients were subsequently consolidated with either an autologous or an allogeneic HSCT. The 2-year overall survival is 77%, while the 2-year progression-free survival is 33.3%. The most common treatment-related adverse event was grade 3-4 hematological toxicity, which, however, did not cause treatment discontinuation in any patient. Peripheral neuropathy was observed in 3 patients (13%) and was always reversible.

CONCLUSION:

Despitethe limit of an observational retrospective study, our data confirm in pediatric patients and young adults results previously reported in adults, namely that the combination of BV and bendamustine is tolerable and associated with good response. Our data on the efficacy of this regimen have a particular value because obtained in heavily pretreated patients. Ten of 23 patients are currently alive and disease free. Moreover, in view of the high percentage of patients subsequently consolidated with either autologous or allogeneic transplantation, our results suggest that this treatment can be a suitable option as bridge to HSCT.