The COBRA trial (EORTC-1537) is a fully enrolled, single-arm multicenter phase II study investigating the value of very early FDG-PET-response adapted Brentuximab Vedotin (BV)-based therapy for advanced stage classical Hodgkin Lymphoma (cHL). All patients received one cycle of BV, Doxorubicin, Vinblastine, and Dacarbazine (BV-AVD) followed by an early interim 18F-FDG-PET scan (iPET). Patients with a negative iPET by central assessment continued with five additional BV-AVD cycles, while iPET+ patients escalated to six cycles of BV, Etoposide, Cyclophosphamide, Doxorubicin, Dacarbazine, and Dexamethasone (BV-ECADD). The main objective of this trial is to assess whether treatment adaptation based on iPET results in improved efficacy while minimizing treatment toxicity.
We here report baseline characteristics and iPET results after one cycle of BV-AVD. Deauville scores 4 or 5 were considered positive. In addition, we used ELISA to measure serum thymus and activation regulated chemokine (TARC) levels, which have been reported to reflect cHL disease activity and correspond with treatment response. TARC levels were measured both at baseline (bTARC) and after one cycle of BV-AVD (iTARC). A serum TARC level >1000 pg/ml was considered positive for detecting active disease (PMID 22058214).
A total of 150 patients were included in the trial. Median age at inclusion was 32 years and 46% were females. Patients presented with stage IIB (15%), III (25%) or IV (60%) disease. Bulky disease was present in 56%. bTARC levels are currently available for 96 patients and were positive in 88 (92%), with a median level of 51831 pg/ml (range: 62 - 2033694). There were significant differences in bTARC levels across stages (p_value=0.044, F test), with bTARC levels lower for stage IIIA, as compared to IIB, IIIB or IV, but not with regards to bulky disease, age or gender. After one cycle of BV-AVD, iPET was positive in 40% of the patients. Within the group of patients with available iTARC and positive bTARC (n=84), iPET was positive in 33 cases (39%) and iTARC was positive in 12 cases (14%). Eight out of these 12 iTARC positive cases were also iPET positive.
In conclusion, the majority of advanced stage Hodgkin patients showed a treatment response already after 1 cycle of BV-AVD, as measured by FDG-PET and serum TARC. FDG-PET quantification and tissue analysis for TARC expression are ongoing. These are preliminary data; definitive results will be presented at the symposium.
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