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22-10-2024 | Hodgkin Lymphoma | Editor's Choice | News

Nivolumab outplays brentuximab vedotin in advanced Hodgkin’s lymphoma

Author: Dr. Shreeya Nanda

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medwireNews: Adding nivolumab rather than brentuximab vedotin to the standard chemotherapy backbone for advanced-stage classic Hodgkin’s lymphoma significantly improves progression-free survival (PFS), show phase 3 data.

The S1826 trial, which enrolled adolescents and adults, also showed that nivolumab given alongside doxorubicin, vinblastine, and dacarbazine (N+AVD) had “a better side-effect profile” than brentuximab vedotin with the same chemotherapy regimen (BV+AVD), say the researchers. They highlight that “fewer patients stopped treatment early, fewer deaths occurred during treatment, and the incidence of immune-related toxic effects was low.”

The team writes: “On the basis of the clinically meaningful improvement in progression-free survival and excellent side-effect profile of N+AVD, the opportunity to avoid potentially toxic consolidative radiation therapy, and the decreased drug-acquisition and supportive-care costs, N+AVD should be a strong candidate for primary treatment in adolescent and adult patients with stage III or IV Hodgkin’s lymphoma.”

In the study, 970 patients aged 12 years or older were randomly assigned to receive nivolumab, given at a dose of 240 mg in adults (≥18 years) and 3.0 mg/kg in younger patients, or brentuximab vedotin 1.2 mg/kg alongside AVD on days 1 and 15 of each 28-day cycle for six cycles. The study protocol allowed the use of localized radiation therapy in participants with residual positivity on positron-emission tomography after treatment, and this was needed by just three patients in the N+AVD group and four in the BV+AVD group.

Jonathan Friedberg (University of Rochester Wilmot Cancer Institute, New York, USA) and collaborators report that the prespecified second interim analysis was conducted at a median follow-up of 12.1 months, and at this point, “the threshold for efficacy was crossed,” showing a significant PFS benefit of nivolumab over brentuximab vedotin.

Specifically, the hazard ratio (HR) for disease progression or death was a significant 0.48 in favor of nivolumab. The PFS rate at 1 year was 94% in the N+AVD group and 86% in the BV+AVD group.

The PFS advantage offered by nivolumab was maintained when the analysis was repeated with longer follow-up. At a median of 2.1 years, the HR for progression or death was a significant 0.45 for the nivolumab versus brentuximab vedotin arm, and the 2-year PFS rates were 92% and 83%, respectively.

The corresponding 2-year overall survival rates were 99% and 98%, and although the HR for death of 0.39 favored nivolumab, the between-group difference was not statistically significant in this analysis.

As reported in The New England Journal of Medicine, adverse events of grade 3 or more were less common in the N+AVD versus BV+AVD arm, except for neutropenia, which occurred in a respective 48% and 26% of patients.

The researchers attribute this difference to the mandated use of granulocyte colony-stimulating factor (G-CSF) in the BV+AVD group, and note that “[f]ebrile neutropenia, sepsis, and infections did not occur more frequently with N+AVD than with BV+AVD, and the reduced use of G-CSF led to less bone pain in the N+AVD group.”

Turning to immune-related side effects, they add that “[o]ccurrences of pneumonitis, gastritis, rash, and colitis were similar in the two groups,” but hypothyroidism and hyperthyroidism were more common with nivolumab (7 and 3%, respectively) than with brentuximab vedotin (<1 and 0%).

Friedberg et al conclude: “In the context of a disease in which a high proportion of patients are cured with standard therapy and the bar to change practice is set high, the improvement in efficacy [with nivolumab] and in the risk of adverse events was clinically meaningful.”

The authors of a related editorial agree, saying that “[i]n addition to superior treatment outcomes, several other features strongly favor nivolumab over brentuximab vedotin, including a lower frequency of toxic effects (particularly neurologic toxic effects), bone pain, and abdominal symptoms.”

Moreover, “[a]n enormously beneficial outcome of the trial is the preservation of high rates of complete remission with very little use of radiation therapy,” continue James Armitage (University of Nebraska School of Medicine, Omaha, USA) and Dan Longo (Brigham and Women's Hospital, Boston, Massachusetts, USA).

In conclusion, they say that “[a]t this point, the durability of the remissions is uncertain, although no data suggest that the remissions are likely to be less durable than those seen with chemotherapy alone.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2024; 391: 1379–1389
N Engl J Med 2024; 391: 1452–1454

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