Discussion
The standard of care, both in adults and paediatric patients, for risk R/R cHL is the HDCT/ASCT1. Achieving cMR before the HDCT/ASCT has been demonstrated as the most impactful factor affecting DFS and OS5,6,7,8,9. For this reason, identifying the best rescue therapy represents the most important challenge. There is no “gold standard” chemotherapy regimen because no randomized trials have been done on children or adolescent; the overall response rates (ORR) of salvage regimens vary between 70% and 90%1,10.
The DHAP regimen has been extensively studied as rescue therapy in high-risk Hodgkin and non-Hodgkin lymphomas with optimal relationship between efficacy and toxicity, in particular ORR of 88% (21% CR, 67% PR) in R/R cHL has been reported11,12,13. Novel agents like BV have gained an increasing role in R/R cHL. The use of BV as single agent for the salvage therapy is reported in adults with ORR of 75%, CR 34%, with manageable toxicity14. Better results have been achieved combining classical chemotherapy regimens and BV1. Despite the widespread use of BV in adults and the large number of prospective and retrospective studies, there are few data on efficacy and safety in paediatrics. The initial experience of BV in pediatric patients with R/R cHL showed 47% ORR15. A retrospective multicentric italian real-life study on 66 young patients demonstrated the efficacy of BV single agent or combined with chemotherapy in R/R cHL with manageable toxicity16. Recently the combination regimen of BV-bendamustine in pediatric patients reported ORR of 81%17. In adults the phase II HOVON/LLPC Transplant BRaVE study investigated the combination BV plus DHAP achieving cMR in 42/52 (81%) evaluable patients and pMR in 5 (10%), with ORR of 90%. After a median follow-up of 27 months, the 2-year PFS by intention-to-treat was 73.5%, and the 2-year OS was 94.9%3. This combination has not been investigated in the pediatric setting, so far. In our experience the BV-DHAP regimen resulted highly effective. The patients we reported on were both characterized by rapid progression and high burden of disease leading to a stage IVB bulky disease in about a two-month lapse. Considering the high-risk disease, our previous experience with DHAP and the encouraging data of BV-DHAP in adults we decided to adopt this regimen. We gained disease control and cMR before the HDCT/ASCT. Furthermore, monitoring haematological toxicity, liver and renal function, ototoxicity and neurotoxicity we found a lower rate of AEs than reported in adults. Both patients did not experience any important AE, exception for a grade II/III neutropenia, and a mild hepatotoxicity. None of these events was likely to cause treatment discontinuation. We then decided to start maintenance with BV following the results of the AETHERA trial18. This choice was also possible because of the low degree of toxicity shown during the previous cycles.
In conclusion, in our experience in two adolescent patients with R/R cHL, the BV-DHAP regimen resulted highly effective to obtain mCR prior to HDC/ASCT in very high risk and aggressive disease. Patients should be closely monitored for toxicity, especially hematological toxicity. Our experience provides initial practical and real-world evidence in favour of the use of BV-DHAP as first-line salvage therapy for high-risk relapsed/refractory HL. This regimen expands the currently existing therapeutic choices making BV-DHAP a suitable salvage therapy.