Relapsed Refractory Hodgkin Lymphoma and Brentuximab Vedotin-Bendamustine Combination Therapy as a Bridge to Transplantation: Real-World Evidence From a Middle-Income Setting and Literature Review

Abstract

IntroductionDespite high cure rates with standard treatment, 30% patients with Hodgkin lymphoma develop relapsed or refractory (R/R) disease. Salvage therapy followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care. Brentuximab Vedotin (Bv) in combination with Bendamustine (B) has been tested in the salvage setting with promising results.Materials and MethodologyWe conducted a single centre retrospective chart review of patients who received BBv salvage therapy to determine its activity and safety in patients with R/R classical Hodgkin lymphoma (HL). Between May 2011- December 2019, 179 patients were diagnosed with R/R HL.ResultsThirty patients received BBv [median age: 30 (15-59) years, females (n=15)]. Primary refractory disease in 19 patients (63%), and 26 patients (87%) had advanced stage at treatment. Most patients received BBv after 2 prior lines of therapy [n=16 (53%)]. The median number of cycles of BBv were 3 (1-6). The number of BBv cycles delivered as outpatient was 63%. The most common Grade III/IV hematological adverse event was neutropenia [n=21, (70%)], while grade III/IV non-hematological toxicities included infections in 4 (13%), neuropathy in 4(13%), skin rash in 2 (7%), GI toxicities in 3 (10%) and liver dysfunction in 2 (7%) patients. The ORR and CR rates were 79% and 62%, respectively. Seventeen patients (57%) underwent an autologous HCT and 8 (26%) underwent an Allogeneic HCT (all haploidentical). The median follow up time from BBv administration was 12 months. Six patients died: 2 = disease progression, and 4 = non-relapse causes (Infection and sepsis = 2, GVHD=2). In addition to this, one patient progressed soon after HCT and another patient relapsed 22 months post HCT. Three year Overall survival (OS) and Event free survival (EFS) probability post-BBv treatment was 75% and 58%, respectively. OS and EFS analysis based on response (viz., CMR) to BBv demonstrated that patients in CMR had better survival probability [93% (p=0.0022) 3yr-OS and 72% (p=0.038) 3yr-EFS probability].ConclusionsBBv is an active and well-tolerated salvage treatment for patients with R/R HL, even in refractory and advanced settings. In middle-income settings, cost constraints and access determine patient uptake of this regimen.

Current perspectives on the management of refractory or relapsed classic hodgkin lymphoma in brazil: Balancing efficacy, safety, and tolerability

“…In an observational study from the Mayo Clinic involving 207 patients with refractory or relapsed disease eligible to ASCT and treated with a variety of salvage regimens, those treated with BV plus bendamustine had significantly higher overall and CR rates as first salvage therapy, and a larger number of patients were bridged to transplantation after BV plus bendamustine than after ifosfamide, carboplatin and etoposide, leading the authors to conclude that the former combination may be preferable to the latter [ 70 ]. Finally, in third or subsequent lines, the combination of BV and bendamustine led to a response rate of 79% (CR in 62%) among 30 patients treated in the real-life setting [ 71 ].…”

Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review

“…BVB therapy has been widely researched in developed countries and has displayed impressive outcomes as a second-line treatment, with a CR of over 70% (30). In comparison, the CR of BVB combined therapy in a middle-income setting in India was lower at 62% (31). BVB is also highly active in patients with prior BV exposure since the PFS duration was similar to that of patients that had not received BV before (32).…”