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Compared with brentuximab vedotin and chemotherapy, nivolumab and chemotherapy had longer progression-free survival and a better safety profile.
The combination of nivolumab (Opdivo; Bristol Myers Squibb) and doxorubicin, vinblastine, and dacarbazine (AVD), a chemotherapy regimen, demonstrated longer progression-free survival (PFS) and a more positive safety profile compared with brentuximab vedotin (Adcetris; Seattle Genetics) in patients with stage III or IV advanced-stage classic Hodgkin lymphoma, according to results from a recently conducted trial (NCT03907488).1,2
Finding the most effective immunotherapy for patients with Hodgkin's lymphoma is critical. | Image Credit: © Emile | stock.adobe.com
These positive results build on the lengthy resume of nivolumab, an immune checkpoint inhibitor, which has shown potential in treating multiple other oncologic indications such as non–small cell lung cancer. Brentuximab vedotin in combination with AVD has also improved outcomes in patients with Hodgkin lymphoma but carries with it increased toxic effects while many patients deal with relapse, leading to the conduction of this trial.3
Primarily, the investigators analyzed PFS, with key secondary end points including the incidence of adverse events (AEs), overall survival (OS), and event-free survival (EFS). In total, 970 of the original 994 patients (97.6%) were included in the intention-to-treat cohort, with 483 patients receiving brentuximab vedotin and AVD (BV+AVD) and 487 patients receiving nivolumab and AVD (N+AVD).1
According to the study authors, the efficacy threshold in the interim analysis was successfully crossed, as N+AVD significantly improved PFS compared with BV+AVD (HR: 0.48; 99% CI, 0.27-0.87; P = .001). Disease progression or death at median follow-up of 12.1 months occurred in 30 patients in the N+AVD group and 58 groups in the BV+AVD group. For patients receiving N+AVD, 1-year PFS was 94% (95% CI, 91-96%) compared with 86% (95% CI, 82-90%) for patients receiving BV+AVD.1
Notably, there was a short follow-up time for the primary analysis, which prompted the investigators to repeat the analysis after an additional year of follow-up to assess PFS durability. At the 2.1-year follow-up point, 2-year PFS was 92% (95% CI, 89-94%) following N+AVD and 83% (95% CI, 39-86%) following BV+AVD.1
OS and EFS data were similarly positive. In the N+AVD group, 2-year OS and EFS was 99% and 90%, respectively, while in the BV-AVD group, OS and EFS was 98% and 81%, respectively. In an important development, nearly all AEs that occurred—apart from neutropenia and arthralgia—were more frequent with BV+AVD. Overall, the primary and secondary end points were successfully reached, showing significant improvements in response with N+AVD compared with BV+AVD.1
Trial Name: Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma
ClinicalTrials.gov ID: NCT03907488
Sponsor: National Cancer Institute (NCI)
Estimated Completion Date: April 1, 2025
Patients that received N+AVD had fewer deaths occur during treatment, a lower incidence of immune-related toxic effects, and fewer patients stopping treatment early, making up the superior safety profile it exhibited compared with BV+AVD. There were also a small number of patients that received end-of-treatment radiotherapy, which was a dramatic shift compared with the use of contemporary agents and suggests that radiotherapy has limited help to patients after treatment with N+AVD.1
Of note, BV+AVD was associated with a particularly “unacceptable” safety profile in older patients, with one-third of them discontinuing treatment early, in addition to high mortality rates. Based on these findings, the investigators recommended that the use of BV+AVD probably be avoided in older patients.1
“On the basis of the clinically meaningful improvement in progression-free survival and excellent side-effect profile of N+AVD, N+AVD should be a strong candidate for primary treatment in adolescent and adult patients with stage III or IV Hodgkin’s lymphoma,” the study authors concluded.1
