Brentuximab vedotin followed by bendamustine supercharge for refractory or relapsed Hodgkin lymphoma

Abstract

We evaluated the impact on progression-free survival (PFS) of achieving a deep metabolic response at 2-deoxy-2[¹⁸F] fluoro-d-glucose positron emission tomography (FDG-PET) in patients with refractory or relapsed (R/R) classic Hodgkin lymphoma (cHL) following a new salvage regimen named Bv+Bs (brentuximab vedotin + bendamustine supercharge), from 2013 to 2017. In this real-life study, 20 consecutive patients (aged <60 years) with R/R cHL after failure of ≥1 salvage treatments received Bv+Bs regimen consisting of 3-days outpatient IV infusions of 1.8 mg/kg of Bv on day 1 of each 3-week cycle combined in sequence to bendamustine on days 2 and 3 of the treatment cycle at a fixed dose of 120 mg/m² per day, for a total of 4 courses. A robust primary prophylaxis approach, including premedication, antimicrobials, stimulating factors, and cytomegalovirus monitoring, was systematically performed. The 20 patients (all evaluable) underwent 4 courses of Bv+Bs with a median dose intensity of 100% for both Bv and Bs. Ten patients (50%) experienced grade ≥3 treatment-related adverse events, without requiring hospitalization. At post-Bv+Bs reevaluation, 80% of patients had deep metabolic responses with Deauville 5-point scale scores ≤2. Thereafter, 14 patients (70%) received autologous hematopoietic stem cell transplantation (HSCT; peripheral blood stem cells previously harvested in 12 cases), and 4 patients (10%) received allogeneic HSCT. At a median follow-up of 27 months from Bv+Bs regimen initiation, the 2-year PFS of the entire population was 93.7% (95% confidence interval, 62.7% to 99.6%). Our data suggest that Bv+Bs regimen-driven strategy may be a promising salvage option to improve long-term control of high-risk Hodgkin lymphoma.

Graphical abstract

Figure 1.

Bv+Bs regimen schedule. Bv, at 1.8 mg/kg IV on day 1 of the 3-week cycle; Bs, at 120 mg/m² IV on days 2 and 3 of the 3-week cycle; P, peg-filgrastim 6 mg subcutaneous on day 6 of the 3-week cycle; FDG-PET, at baseline and 5 weeks after salvage treatment completion; C, serum CMV-DNA monitoring on day 1 of the 3-week cycle. Moreover, as support prophylactic treatment: methylprednisolone at 200 mg IV on days 1 to 3 of the 3-week cycle, diphenhydramine at 50 mg IV on days 1 to 3 of the 3-week cycle, febuxostat at 80 mg orally on days 1 to 5 of the 3-week cycle (plus hyperhydration); trimethropin-sulfamethoxazole at 960 (160 + 800) mg orally every 12 hours 2 times a week and acyclovir at 800 mg orally daily from the start of Bv+Bs regimen until 1 month after the last cycle. Clinical visits were performed on days 1 to 3 of the 3-week cycle. Routine laboratory tests were performed every 2 weeks.

Figure 2.

Bridge to transplant following Bv+Bs regimen. Autologous hematopoietic stem cell transplantation (ASCT; n = 14) was performed with PBSC previously harvested in 12 cases, or with post-Bv+Bs PBSC successfully collected (by G-CSF and cyclophosphamide) in 2 cases. Allogeneic hematopoietic stem cell transplantation (Allo-SCT; n = 4): haploidentical in 3 cases, and sibling in 1 case. Two patients received 2 additional courses of Bv+Bs (for a total of 6).

Figure 3.

PFS. Kaplan-Meier curve of 2-year PFS of 20 patients with R/R cHL who received the Bv+Bs regimen (see “Patients and methods”). Table shows number of events and number at risk during follow-up.

Figure 4.

Swimmers plot. Duration of patients’ response following Bv and Bs salvage treatment. Horizontal arrows denote ongoing response. Arrowheads (▾) denote radiation therapy. Circles (●) denote autologous HSCT. Rhombuses (♦) denote allogeneic HSCT. Squares (▪) denote 2 additional Bv+Bs courses. PR, partial remission; REF, refractory; REL, relapse.