Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma
- Study type
- Clinical trial
- Study name
- ECHELON-1
- Phase
- Phase 3
- Design
- Randomised (1:1), open-label, international trial; overall survival report with a median follow-up of about 6 years
- Sample size
- 1334 patients (664 A+AVD, 670 ABVD)
- Source
- N Engl J Med · 2022
- Trial registration
- NCT01712490
In plain words
Hodgkin lymphoma has a high chance of cure even at advanced stages. This study showed that replacing the drug bleomycin (which can damage the lungs) with the targeted drug brentuximab vedotin not only reduced relapses but also helped people live longer after 6 years. On the other hand, numbness and tingling in the hands and feet are more likely, and in most people this gets better over time.
Key results
Treatment arms and regimens
Up to six 28-day cycles, IV on days 1 and 15 of each cycle: brentuximab vedotin 1.2 mg per kg (maximum 120 mg; 30-minute infusion), doxorubicin 25 mg/m², vinblastine 6 mg/m² and dacarbazine 375 mg/m². After 75% of patients had been enrolled, primary G-CSF prophylaxis from the start of treatment was recommended for all patients in this group.
Up to six 28-day cycles, on days 1 and 15: doxorubicin 25 mg/m², bleomycin 10 units/m², vinblastine 6 mg/m² and dacarbazine 375 mg/m².
Source of the regimen details: ClinicalTrials.gov NCT01712490; dose cap and G-CSF recommendation from the FDA label for ADCETRIS
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Adults with previously untreated stage 3 or 4 classic Hodgkin lymphoma.
Endpoints
Primary endpoint (previously reported): modified progression-free survival.
Key secondary endpoint: overall survival in the intention-to-treat population; safety.
Safety and side effects
Because of increased febrile neutropenia with A+AVD, primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) was recommended. Peripheral neuropathy was more frequent with A+AVD, but in most patients in both groups it had resolved or improved by the last follow-up. Omitting bleomycin reduces the risk of pulmonary toxicity.
Clinical significance and place in guidelines
A+AVD was approved by the FDA in 2018 for previously untreated stage 3 or 4 classic Hodgkin lymphoma, and this report showed the first overall survival benefit in advanced Hodgkin lymphoma in several decades. Since then, nivolumab + AVD (S1826 study) and BrECADD (HD21 study) have also been added to the first-line options.
Limitations
The study was open-label, and radiotherapy or treatment change based on interim PET was not allowed in ECHELON-1. Febrile neutropenia and peripheral neuropathy were more frequent with A+AVD, and G-CSF prophylaxis is needed. No direct comparison with newer regimens (nivolumab-AVD or BrECADD) was made in this study.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.