Brentuximab Vedotin plus ESHAP (BRESHAP) versus ESHAP in Patients with Relapsed or Refractory Classical Hodgkin’s Lymphoma. Interim Results of the BRESELIBET Prospective Clinical Trial.
Best salvage treatment for relapsed/refractory Hodgkin’s lymphoma (RRHL) is still unknown; the superiority of brentuximab vedotin (BV) + chemotherapy (CT) vs CT alone has never been tested in randomized clinical trials. Consolidation with autologous transplant (auto-HCT) is the standard of care for patient (pts) with RRHL but it is unknown if consolidation with BV could spare it in a good risk group. We have conducted a phase IIb prospective clinical trial (BRESELIBET, ClinicalTrials.gov ID: NCT04378647) that evaluates the efficacy of BRESHAP vs ESHAP in RRHL, followed by BV consolidation in those who attained a mCR. 150 adult pts with RRHL were to be included and randomized 1:1 to receive either BRESHAP (x3) or ESHAP (x3). Primary efficacy endpoint was mCR [Deauville Score (DS) of 1-2, DS of 1-3 after the recent amendment of the trial]. Those pts in mCR went on to receive up to 16 doses of BV (1.8 mg/kg iv every 3 weeks). Herein we are reporting preliminary results of the first 92 pts (6 of them, screening failure). Amongst the remaining 86 pts [52 males, median age of 39 (18-64) yrs], 29 were primary refractory, 24 had had an early relapse and 33 a late relapse. 42 pts were randomized into BRESHAP and 44 into ESHAP. 58 pts completed salvage therapy and had their disease status evaluated, 3 pts were discontinued because of an adverse event (AE), 1 pt withdraw consent, 5 pts progressed under therapy and 19 pts are still under treatment. 15 out of 30 (50%) achieved a mCR in the BRESHAP group vs 15 out of 33 (45.5%) in the ESHAP group (NS) (mCR rates were 70% vs 60.6% respectively, when considering DS 1-3). Nine severe AEs were reported in 7 pts [fever (n=3), sepsis (n=2), pneumonia (n=1), pericardial effusion (n=1), diarrhea (n=1), vomiting (n=1)]. 32 pts (15 BRESHAP vs 17 ESHAP) started consolidation with BV; median number of cycles of 9 (1-16). Six pts have finished consolidation with a median follow up after treatment of 3.3 (0.1 – 8) months. Four pts have relapsed after 3, 3, 5 and 9 cycles of BV and two pts stopped BV after 4 and 9 cycles due to grade 2 neurological toxicity. The results of this interim analysis indicate that the mCR rate of BRESHAP is in line to what our GELTAMO group has published before (García-Sanz R, Ann Oncol 2019) and that consolidation strategies with non-HCT approaches appear to be feasible in patients achieving stringent CR assessed by PET-CT. The trial will continue until the recruitment is completed.