Brentuximab vedotin plus bendamustine in relapsed and refractory classical Hodgkin lymphoma in children, adolescents and young adults: a single centre experience

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.

Conflict of Interest:

None to declare.

• References

• 1 Daw S, Wynn R. , & Wallace H. . Management of relapsed and refractory Hodgkin lymphoma in children and adolescents. British Journal of Haematology 2011; 152: 249-60 .
• 2 LaCasce A, Bociek G, Sawas A, Caimi P.F, Agura E, Matous J, Ansell S, Crosswell H, Islas-Ohlmayer M, Behler C, Cheung E, Forero-Torres A, Vose J, O’Connor O.A, Josephson N. Advani R. Brentuximab vedotin plus bendamustine: a highly active salvage treatment regimen for patients with relapsed or refractory hodgkin lymphoma. Blood 2015; 126: 3982.
• 3 Locatelli F, Mauz-Koerholz C, Neville K, Llort A, Beishuizen A, Daw S, Pillon M, Aladjidi N, Klingebiel T, Landman-Parker J, Medina-Sanson A, August K, Sachs J, Hoffman K, Kinley J, Song S, Song G, Zhang S, Suri A. , Gore L. . Brentuximab vedotin for paediatric relapsed or refractory Hodgkin’s lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. The Lancet 2018; 5: e450-461 .
• 4 O’Conner O, Lue J, Sawas A, Amengual J, Deng C, Kalac M, Falchi L, Marchi E, Turenne I, Lichtenstein R, Rojas C, Francescone M, Schwartz L, Cheng B, Savage K, Villa D, Crump M, Prica A, Kukreti V, Cremers S, Connors J. , Kuruvilla J. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin’s lymphoma: an international, multicentre, single-arm, phase 1-2 trial. The Lancet Oncology 2018; 19: 257-266 .
• 5 Moskowitz CH, Matasar MJ, Zelenetz AD, Nimer SD, Gerecitano J, Hamlin P, Horwitz S, Moskowitz AJ, Noy A, Palomba L, Perales MA, Portlock C, Staus D, Maraqulia JC, Schoder H. , Yahalom J. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood 2012; 119: 1665-70 .