Nivolumab regimen ‘a huge advance’ in treatment of classical Hodgkin lymphoma
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Key takeaways:
- Researchers reported 1-year PFS rates of 94% with nivolumab and AVD chemotherapy vs. 86% with brentuximab vedotin AVD chemotherapy.
- The nivolumab regimen appeared well-tolerated.
CHICAGO — The addition of nivolumab vs. brentuximab vedotin to AVD chemotherapy significantly reduced the risk for disease progression and disease-related death among adults with previously untreated advanced classic Hodgkin lymphoma.
Results of the randomized phase 3 SWOG S1826 trial, presented at ASCO Annual Meeting, showed a 52% improvement in PFS with the nivolumab (Opdivo, Bristol Myers Squibb) regimen, researchers wrote.
“This is a huge advance in treatment for patients with Hodgkin lymphoma for a number of reasons,” Alex Herrera, MD, chief of the division of lymphoma at City of Hope, told Healio. “This is a disease where patients are treated with different regimens across the world, both as pediatrics and as adults. So, not only with this study are we able to cure more patients, but also it really harmonizes the treatments of Hodgkin lymphoma across the age spectrum. So, if you are 12 or 80 years old, you can get the same therapy with this treatment now, which is an entirely different world than we’ve been in for the past several decades.”
Background and methodology
The trial evaluated the efficacy of the PD-1 inhibitor nivolumab compared with brentuximab vedotin (Adcetris, Seagen) — an antibody-drug conjugate directed against tumor necrosis factor receptor CD30 — in combination with AVD chemotherapy, which consists of doxorubicin, vinblastine and dacarbazine.
The study population included 976 patients with stage III or stage IV Hodgkin lymphoma aged older than 12 years who had not received previous treatment for their disease.
PFS served as the primary endpoint. Secondary endpoints included EFS, OS, complete response and patient-reported outcomes.
Median follow-up was 12.1 months.
Results
The nivolumab regimen reduced the risk for disease progression or death by 52% compared with the brentuximab vedotin regimen (HR = 0.48; 99% CI, 0.27-0.87), with benefit observed across subgroups based on age and risk.
Researchers reported 1-year PFS rates of 94% with nivolumab and 86% with brentuximab vedotin.
Safety analyses showed a higher rate of neutropenia in the nivolumab group (55% vs. 32%). However, a higher percentage of patients assigned brentuximab vedotin developed sensory neuropathy (55% vs. 29%), reported bone pain (20% vs. 8%) and required granulocyte colony-stimulating factor (95% vs. 54%).
Researchers reported a higher number of deaths (11 vs. 4) and a higher number of deaths due to adverse events (7 vs. 3) in the brentuximab vedotin group.
Next steps
Researchers will continue to follow OS as the data mature, Herrera said.
“Patient-reported outcomes were collected throughout the study and we’ll be reporting those to show how patients felt about receiving these different therapies,” he told Healio. “I think it’s important to remember that brentuximab vedotin is a very effective drug for this disease, and by no means do I think this study means we’re done with brentuximab vedotin. The next question is, what is the best way to incorporate it into the therapy of Hodgkin lymphoma?”
Perspective
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Stephen M. Ansell, MD, PhD
For context, it is important to note this is a hugely successful area of oncology. Patients in general are expected to do well on treatment, and recent outcomes have been really good.
The historical debate had focused on using highly aggressive therapy with very good results but considerable toxicity, or using slightly less aggressive therapy that caused less toxicity but perhaps yielded slightly less favorable results. The sense with the latter option was that you could still salvage patients with subsequent aggressive therapy, such as a stem cell transplant.
However, novel therapies like brentuximab vedotin and PD-1 blockade have proven to be extremely effective, and they have moved into the frontline setting.
About 5 years ago, we learned the combination of brentuximab vedotin plus the less-intensive AVD chemotherapy extended PFS compared with ABVD chemotherapy, which had been a standard at the time. Updated data released last year showed an OS advantage with brentuximab vedotin and AVD. This pushed back on the idea of salvaging patients later and suggested the decisions we make in the frontline setting can lead to better outcomes.
At ASCO, we saw results of the head-to-head comparison of brentuximab vedotin plus AVD vs. nivolumab plus AVD in the front-line setting. The PFS improvement with nivolumab-AVD pushes the envelope even further in terms of even better outcomes.
Hodgkin lymphoma is highly curable and — compared with what we see in many other malignancies — the OS and PFS curves already were phenomenal. However — particularly for younger patients, many of whom are looking for a ‘one-and-done’ approach — the impact of this continued incremental improvement can last the rest of their lives.
OS data from this trial have not matured, and that is one of the consequences of having highly effective therapies. In the earlier study of brentuximab vedotin plus AVD, the OS benefit emerged after about 6 years. If we exercise a little patience with this trial, hopefully we’ll see the same.
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Herrera AF, et al. Abstract LBA4. Presented at: ASCO Annual Meeting 2023; June 2-6, 2023: Chicago.
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