Introduction The majority of children and young people with classical Hodgkin lymphoma (cHL) are cured with first line treatment, with treatment failure rates of 10 to 20% (early to advanced stage disease). [1] Cure may be achieved in the relapsed/refractory (R/R) setting but the optimal salvage treatment has not been defined. Conventional salvage chemotherapy yields complete response (CR) rates ranging from 20-60% [2]. Brentuximab vedotin (Bv) is a novel agent increasingly used in R/R cHL, with CR rates of 33% when used as monotherapy in the phase I/II paediatric trial [3]. A number of studies have reported that the combination of Bv plus bendamustine (Bv+B) achieves superior outcomes to either agent alone [2, 4]. Achievement of complete metabolic remission (CMR) prior to autologous stem cell tranplantation (ASCT) is highly predictive of long term progression free survival in R/R cHL [5].
Methods We present a series of nineteen consecutive patients treated with Bv+B as second line or later relapse therapy with R/R HL at our institution. Patients (age range 9-27 years) were treated from May 2015 to June 2019. Fifteen patients (79%) had primary refractory disease. Median number of prior treatment lines was 2, including ASCT in 4 patients. Patients received bendamustine (90mg/m2) on days 1 and 2, and Bv (1.8mg/kg) on day 2 of a 21 day cycle, with responses assessed after 2 cycles.
Results Of nineteen patients, fourteen (74%) achieved a CMR, 1 achieved a partial response and 1 achieved stable disease. 3 patients (16%) did not complete 2 cycles of treatment due to grade 2 to 4 infusion related reactions (IRR) and so were not efficacy evaluable. CMR amongst the sixteen efficacy-evaluable patients was 88%. All 16 evaluable patients received consolidation therapy, 9 with ASCT and with allogeneic transplant in the remainder.
Due to frequency of IRRs, our treatment protocol was amended to include IV steroids as pre-medication prior to each cycle. Aside from IRRs, 4 of 19 patients (21%) had grade 3 or 4 adverse events comprising cytopenias or GI upset.
Conclusion This series indicates that Bv+B is a safe and highly active salvage regimen for children and young people, achieving a CMR in 74% of patients (88% in efficacy-evaluable patients). The CMR rate in this retrospective series is superior to reported outcomes of either drug as single agent. This combination can facilitate a bridge to HDCT/ASCT in a state of CMR in the majority of cases.
