Bendamustine, Gemcitabine and Dexamethasone Chemotherapy Is Effective Salvage and Stem-Cell Mobilization Regimen in Patients with Relapsed or Refractory Hodgkin Lymphoma — Early Results of the Polish Lymphoma Research Group Study

Introduction

Bendamustine (B) and Gemcitabine (G) are active agents in relapsed or refractory Hodgkin Lymphoma (rHL) with complete response (CR) rates of around 70%. Potential benefit to combination of B, G and dexamethasone (BGD) as a second-line chemotherapy is unexplored. We report on early results of a run-in phase of a prospective, multicenter study by the Polish Lymphoma Research Group (PLRG) here focused on safety and stem-cell collection efficacy.

Methods

Patients with HL were eligible if they had a progressive disease (PD) during initial ABVD treatment or relapsed/progressed after completion of the first-line therapy including irradiation. BGD regimen included bendamustine 90 mg/m² iv, day 1 and 2, gemcytabine 800 mg/m² iv, day 1, 4, dexamethasone 20 to 40 mg po daily dose, day 1-4, in 3 week intervals for 4 cycles. Stem-cell collection was performed mostly after 2^nd BGD cycle. Treatment was discontinued in case of PD, serious adverse events or patient decision. Response to therapy was evaluated according to RECIL criteria (Younes A et al. Ann Oncol 2017). Patients in CR proceeded to ASCT. Patients with partial response (PR) or disease stabilization (SD) could be referred for ASCT off-study at physician's discretion.

Results

19 pts were enrolled, 10 male, median age (range) 27 (22-55). 14 pts (73%) were primary refractory, 4 relapsed more than 1 year after the first-line treatment. Eligible patients received 2 (n=8), 3 (n=4), or 4 (n=6) cycles of BGD. 1 patient discontinued BGD after 2^nd cycle due to skin reaction and received 1 cycle of ICE before ASCT. PET-CT was performed after 2 (n=16), 3 (n=2), or 4 (n=1) BGD cycles. Response rates were: CR 73% (14/19), PR 11 % (2/19), PD 11% (2/18). PR converted to CR after additional 2 BGD cycles. One additional patient had PD after 3^rd BGD . 9 patients received additional BGD cycles awaiting ASCT. At the time of ASCT all 16 patients were in remission with CR rate of 84% by PET-CT. 19 patients were mobilized for stem-cell collection without plerixafor after the second (n=17) or third (n=1) BGD cycle, and 1 patient was mobilized with low-dose cytarabine after the 2^nd BGD. A median (range) CD34 cell harvest was 5.2x10⁶/kg (2.0-42.75x10⁶). 11 patients completed and recovered from ASCT. BGD toxicity included pneumonia Grade 3 in 2 patients, mild cutaneous reaction in 2 patients, and 1 case of Grade 4 skin toxicity resulting in change of therapy to ICE after 2 cycles of BGD, nausea grade 3 and fever in patients each were reported. GCSF prophylaxis was administered by local practice.

Conclusions

Early results of BGD regimen as a second-line treatment in patients with mostly primary refractory HL are encouraging with acceptable toxicity, stem-cell collection efficacy, and complete response rate of 84%. A prospective, multicenter study is ongoing.