Bendamustine in the Treatment of Relapsed/Refractory Hodgkin’s Lymphoma: Literature Review and Clinical Experience

Abstract

Aim. To assess the efficacy of bendamustine combined with dexamethasone in the treatment of relapsed/refractory Hodgkin’s lymphoma (HL). Materials & Methods. The article provides an updated review of literature as well as the data of prospective observational clinical trial in 47 HL patients (17 men and 30 women aged 20-65 years, median age 36 years) with relapses after standard and high-dose chemotherapy with autologous hematopoietic stem cell transplantation. The therapy regimen included 120 mg/m² of bendamustine IV on Days 1 and 2 and 20 mg of dexamethasone IV from Day 1 to Day 4. Retreatment was administered 21 days after the start of the previous one. Radiotherapy was applied only to the regions of massive relapsed lesions and bone destructions with pain syndrome. Results. From April 2011 to September 2017 all 47 patients received 149 bendamustine + dexamethasone therapy regimens with the overall response of 57 % (complete response 27 %, partial response 30 %). Disease progression on therapy was reported in 20 (43 %) patients, its incidence was the highest after the first (n = 8) or the second cycle (n = 4). In the group of 27 patients with overall response 19 (70 %) patients showed new relapses. In these cases the treatment-free period was from 8 to 31 months (median 11 months). The repeated administration of 57 bendamustine + dexamethasone therapy regimens in 12 out of 47 patients achieved clinical effect for 4-36 months (median 6 months). After the first failure of bendamustine-based therapy 13 patients were treated with brentuximab vedotin and nivolumab, the new salvage therapy drugs. With median follow-up of 22 months (range 1-69 months) median overall survival (OS) and time to the next progression were 35 and 10 months, respectively, in all patients. Multivariate analysis showed that OS was unfavorably affected only by B-symptoms on bendamustine + dexamethasone administration (p = 0.046), and the time to the next progression was shorter in the presence of B-symptoms (p = 0.017) and in histological variant “nodular sclerosis type II” (p = 0.006). Conclusion. Bendamustine + dexamethasone therapy is a relatively low-toxic and effective method of life prolongation in HL patients with chemotherapy-refractory tumors and recurrent relapses, provided no B-symptoms occur by the start of antitumor therapy.