BeGEV Regimen Effective Induction Therapy for Hodgkin Lymphoma

Journal of Clinical Oncology.

In the study, 59 patients with relapsed or refractory Hodgkin lymphoma were enrolled before receiving ASCT. After four cycles of induction therapy with BeGEV, 73% of patients achieved CR. Additionally, 10% of patients had a partial response to therapy, for an overall response rate of 83%. Findings from the study provide a strong rationale for further development of the BeGEV regimen, according to the investigators.

"This is the first phase II trial to our knowledge reporting efficacy and toxicity data of a novel bendamustine-containing regimen, namely the BeGEV regimen, administered in an outpatient setting to ASCT-eligible patients with Hodgkin lymphoma who were refractory to or experienced relapse after first-line chemotherapy," the authors noted. "Notably, the BeGEV regimen induced a 73% CR proportion, which was far higher than the threshold applied to define clinical interest (65%)."

The study enrolled 59 patients at a median age of 33 years. Prior to the study, 95% of patients had received frontline ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), and the remaining 5% had received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone). Forty-six percent of patients were refractory to frontline therapy, and 54% had relapsed. CR to frontline therapy lasted less than 1 year for 37% of patients and 41% had extranodal disease.

The primary endpoint was CR rate after four cycles of BeGEV. Secondary endpoints were overall response rate, stem cell mobilization activity, and toxicity. Other analyses looked at progression-free survival (PFS) and overall survival (OS).

Of the 59 enrolled, 1 patient was not evaluable for efficacy. Of the responding patients (n = 49), 88% proceeded to ASCT. The remaining six patients did not receive an ASCT due to mobilization failure (n = 2), physician decision (n = 2), early relapse (n = 1), and patient refusal (n = 1). CD34+ cells were successfully harvested in a majority of patients (96%).

"Notwithstanding the poor prognostic features of study patients…the analysis of clinical response clearly shows the remarkable efficacy of this bendamustine-containing regimen as well as its favorable toxicity profile," the authors noted.

After a median follow-up of 29 months, the 2-year PFS rate was 62.2% with the BeGEV regimen. At this analysis, the 2-year OS rate was 77.6%. In patients who went on to receive ASCT, the 2-year PFS rate was 80.8% and the 2-year OS rate was 89.3%.

"Despite the sample size of our study, which did not allow performance of a multivariable analysis, it seems that completion of the salvage program overcame the negative prognostic impact of disease status before BeGEV, as shown by lack of significant differences in terms of 2-year PFS and OS in patients with relapsed or refractory disease," the authors wrote. "However, future studies with larger series will be required to address this issue definitively."

The most common grade 3/4 nonhematologic adverse events (AEs) included febrile neutropenia (n = 7) and infection (n = 4). The most common grade 3/4 hematologic AEs were thrombocytopenia (n = 8) and neutropenia (n = 8).

"BeGEV showed a favorable toxicity profile, characterized by limited occurrence of grade 3 to 4 nonhematologic and hematologic toxicities, similar to that observed with the IGEV regimen, without hemorrhagic cystitis," the authors said.

Further studies are needed to confirm the benefits associated with BeGEV, as reported in this phase II study. The researchers suggested that direct comparisons between the BeGEV regimen and other induction therapies might be warranted, in order to uncover the best option.

Reference:

Santoro A, Mazza R, Pulsoni A, et al. Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. J Clin Oncol. 2016;34(27:)3293-3299