On May 1, 2026 EORTC reported that the choice of treatment for patients with newly diagnosed, advanced classic Hodgkin lymphoma (cHL) is often based on local availability, preference and practice, rather than on the individual’s patient’s characteristics and risk profile. However, results from EORTC-1537-LYMG COBRA study published 01 May 2026 in The Lancet Haematology* show that a very early PET scan—performed after just one cycle of chemotherapy—can help personalise therapy. This approach enables more intensive treatment to be reserved for those who truly need it, sparing others from unnecessary side effects.
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Led by EORTC Lymphoma group, the COBRA study enrolled 150 patients aged 18–60 with newly diagnosed cHL across 16 centres in seven countries. The trial completed recruitment just short of the planned two-year timeframe, highlighting its operational success. All patients received an initial cycle with a chemotherapy regimen known as A-AVD, which combines the targeted agent brentuximab vedotin (BV) with standard cytostatic drugs. Following this, each patient underwent a centrally reviewed 18FDG-PET scan to assess early treatment response.
Patients whose scans were negative—indicating a good early response—continued with five additional cycles of A-AVD. Those with positive scans were switched to a more intensive regimen, BrECADD, for six cycles. The PET scans were centrally reviewed in real time by a panel of expert nuclear medicine physicians, ensuring consistent interpretation and guiding treatment for nearly all patients. This centralised approach enabled rapid decision-making and high protocol adherence.
The primary endpoint was modified progression-free survival rate at two years (2y mPFS), where relapse, progression, death or start of new treatment for cHL when not in complete remission at the end of protocol treatment were considered failures. After a median follow-up of 30.1 months, the 2y mPFS rate was 90% overall. Those who remained on A-AVD had a 2y mPFS rate of 88%, while those who switched to BrECADD achieved a 2y mPFS rate of 91%. Overall survival was 100%. The main side effects were neutropenia (a low white blood cell count), anaemia, and neurological symptoms in the hands and feet (peripheral sensory neuropathy). Serious adverse events occurred in 30% of patients, and no deaths were reported.
In addition to its clinical findings, the COBRA trial incorporated a robust translational research component. Serum samples were collected at multiple timepoints to measure levels of serum TARC (thymus and activation-regulated chemokine), a biomarker associated with treatment response. The study successfully demonstrated that early changes in TARC levels could further refine prognosis, particularly among patients with positive PET scans. This dual-modality approach—combining imaging and biomarker data—represents a significant step forward in personalised cancer care.
Furthermore, the trial implemented central expert review of radiotherapy (RT) plans for the small subset of patients (6%) who required RT. This quality assurance process led to treatment plan modifications in one-third of these cases, ensuring optimal and standardised care across participating centres.
"By assessing response after just one treatment cycle, we can identify which patients truly need treatment intensification and spare others unnecessary toxicity. This marks an important step towards more personalised therapy for advanced Hodgkin lymphoma." said Prof Martin Hutchings, principal investigator of the COBRA study, and past chair of EORTC Lymphoma group." Scanning patients after a single treatment cycle can accurately identify which patients need more intensive treatment, and is an important step along the road to personalised treatment for advanced cHL patients who are treated with BV-based chemotherapy. Our findings underline the importance of adopting PET-adapted strategies to minimise unnecessary toxicities as and when new treatments become available."
(Press release, EORTC, MAY 1, 2026, View Source [SID1234665007])