Promising phase II results of a novel bendamustine-containing regimen (BeGEV) as induction therapy before ASCT

Previous studies have shown an increase of Complete Response (CR) rate upon using bendamustine in combination regimens as second-line salvage chemotherapy in Relapsed/Refractory Hodgkin Lymphoma (R/R HL) patients. In this setting, achievement of a CR after induction chemotherapy before Autologous Stem-Cell Transplantation (ASCT) is the strongest prognostic factor. In this study, Professor Armando Santoro from Humanitas Cancer Center in Italy, and other Italian centers, replaced ifosfamide in the IGEV regimen by bendamustine (BeGEV) as induction chemotherapy before ASCT. The endpoints were CR after 4 cycles (primary) and Overall Response Rate (ORR), stem-cell mobilization activity and toxicity (secondary). This article was published in the Journal of Clinical Oncology in September 2016.

Here are the key findings of the study:

• In an Intention to Treat (ITT) analysis, the responses were:
  • CR = 73%
  • ORR = 83% (73% of which proceeded to ASCT)
• Out of 59 patients, 57 were evaluable for CD34+ cell mobilization
  • Mean peak value of CD34+ cells, after BeGEV, was 89/µL (1–763 cells/µL) on day 12
  • In 2 patient, mobilization failed
  • CD34+ cells successfully harvested in 55 patients
• Toxicity analysis:
  • Non-hematologic: nausea (grade 1–2: 17%, grade 3–4: 7%), fatigue (grade 1–2: 8%), skin rash (grade 1–2: 10%), AST/ALT increase (grade 1–2: 12%, grade 3–4: 3%), infection (grade 1–2: 15%, grade 3–4: 7%)
  • Hematologic (grade 3–4): anemia (3%), neutropenia (14%), febrile neutropenia (12%), thrombocytopenia (14%)
• Survival analysis:
  • 2-year PFS: 62.2%
  • 2-year OS: 77.6%
  • 2-year PFS and OS for patients who received an ASCT: 80.8% and 89.3%, respectively.

Conclusions

BeGV as induction regimen before ASCT in R/R HL patients is effective in terms of achievement of CR and stem-cell mobilization, with a favorable toxicity profile. This regimen was administered in an outpatient setting.

 Abstract

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

Purpose

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL).

Patients and Methods

Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated.

Results

In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively.

Conclusion

This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen.