Achieving a PET-negative CR with salvage chemotherapy prior to ASCT in r/r HL is a strong predictor for longterm progression-free survival (PFS). This phase 1 dose-escalation study explored the toxicity and feasibility of adding Brentuximab Vedotin (BV) to DHAP and established the recommended Dose Level (DL) for a phase 2 study. Final objective: to increase the metabolic CR rate after BV-DHAP and to make more patients eligible for auto-SCT with curative intent. BV was given at the standard dose of 1.8 mg/kg and combined with 3 courses of DHAP q 3 weeks at 3 DL in 3 patients per DL (3+3 design), i.e. dexamethasone 40 mg iv d1-4, Cisplatin (CP) and Cytarabine at 75% = DL1; CP75% and Cytarabine 100%=DL2 and CP 100 mg/m² iv d1 and Cytarabine 2x2g/m² iv d2 (full dose DHAP)= DL3 (6 patients). Out of 12 patients (8 F, median age 30.5 yr) 2 were primary refractory and 10 were in 1st relapse. 1st line induction: ABVD (n=9) or BEACOPPesc (n=3). Median time between response to 1st line treatment and the first course of BV-DHAP: 9.2 mo (range:2-134.5). Neutropenia grade 4 more than 10 days (causing 1 week delay of BV-DHAP): 2 out of 3 patients at DL1. Neulasta became mandatory after course 1 and 3, reducing the duration of neutropenia. Stem cells were harvested after the 2nd course (median yield:5.3x10E6 CD34+/kg;range:3.0-25.9). Seven AE’s gr3-4 were observed: neutropenia gr4 (n=2), neutropenia gr3 and trombopenia gr4 (n=1), thromboembolism gr3 (n=1), elevated transaminases gr3 (n=1) and hypokalemia gr4 (n=1). SAE’s occurred in 4 patients, all at DL3: CVC-related infection gr3, zoster infection gr3, fever gr3 (n=1), elevated transaminases gr3 (n=1), reduced kidney function gr3, pneumonitis gr3 (n=1), hypokalemia gr4, fever gr3, acute liver failure gr4 lasting longer than 14 days (likely related to antibiotics), atrial fibrillation gr3 (unlikely related;n=1).These last two SAE’s were classified as DLT’s. Sensory PNP gr1-2 was seen in 4 patients which fully resolved in 2. 11/12 patients reached a PET- complete metabolic remission after 3x BV-DHAP. In one PET+ PR a biopsy did not show HL. Thus, 12/12 achieved a CR. With a median FU of 15.4 mo (range:8.4-22.7) all patients are alive and in CR. In conclusion, BV-DHAP given at full doses is feasible with acceptable toxicity with G-CSF support and this dose will be used in the phase 2 part of the study. The CR rate, although assessed in only 12 patients, is 100%. This study is supported by Takeda,USA.
This abstract has been presented as Abstract Talk in “Relapsed HL”
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