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.