Dose intensive brentuximab vedotin for platinum resistant recurrent Hodgkin lymphoma is a feasible treatment option - a single center experience
Since 2013, mainly before the introduction of PD-1 inhibitors, we treated Hodgkin lymphoma (HL) patients failing to respond with a complete metabolic remission (CR) after first salvage treatment with a dose intense regimen of 1.2 mg/kg brentuximab vedotin (BV) given days 1, 8, 15 in a 28-day cycle. Patients achieving CR after one cycle received another cycle and proceeded to high dose chemotherapy (HDCT) with autologous stem cell transplant. Patients not reaching metabolic CR received other treatments.
Ten patients were treated with dose intense BV, five patients with primary refractory disesease/early relapse and five patients with later relapses. First salvage regimens were IME x 2 (1 patient), DHAP 2-4 cycles (5 patients), IME x 2 + 2-4 cycles DHAP (2 patients) and ICE x 2-4 (2 patients).
Of the five patients with refractory disease/early relapse, four patients had satisfactory responses and proceeded to HDCT. One patient progressed and received radiotherapy instead.
Four patients of five with later recurrent disease had satisfactory responses and proceeded to HDCT. For one patient with insufficient response, bendamustine was added to BV 1.8 mg/kg and given in further three cycles before HDCT. One patient with PET-positive disease after ICE x 2 and possibly concurrent tuberculosis was for this reason treated with a PD1-inhibitor for 9 months, progressed, received dose intense BV with good effect and proceeded to HDCT.
In total 8/10 (80 %) responded satisfactorily to dose intense BV.
The patient who was not treated with HDCT later succumbed to the disease, and two patients with late relapses have had new relapses. The rest of the patients are free of recurrence. Consolidative treatment after HDCT was given with radiotherapy in two cases and maintenance BV in another two cases. Median follow up is 67 months after ASCT.
Side effects have been mild, mostly grade 1 neuropathy. For one patient with grade 1-2 neuropathies already on primary treatment with ABVD, dose reduction was made to 90 % in the second cycle of induction BV and to 66% for the six cycles of maintenance BV given. For another patient maintenance BV was stopped after 4 cycles due to grade 2 neuropathy.
According to our experience dose intense BV is an effective and feasible treatment option for HL patients with platinum resistant recurrent disease.
We suggest that this way of using BV should be studied in the context of insufficient response to PD-1 inhibitors pre-HDCT.