Nivolumab with AVD Provides PFS Benefit Compared to Brentuximab Vedotin Plus AVD in Advanced Hodgkin Lymphoma

By | June 4, 2023

Treatment with nivolumab (Opdivo) combined with doxorubicin, vinblastine, and dacarbazine (AVD) resulted in prolonged progression-free survival (PFS) compared with brentuximab vedotin (Adcetris) plus AVD in patients with advanced-stage classic Hodgkin lymphoma (cHL ), according to the results of the Phase 3SWOG S1826 study (NCT03907488) presented at the 2023 ASCO Annual Meeting.

At a median follow-up of 12.1 months, results showed that patients who received nivolumab plus AVD (n = 489) experienced an estimated 1-year PFS rate of 94% (95% CI, 91% -96%) versus 86% (95% CI, 82%-90%) among patients treated with brentuximab vedotin plus AVD (n = 487; HR, 0.48; 99% CI, 0.27-0, 87; 1-tailed log-rank P = .0005). Importantly, nivolumab plus AVD improved PFS compared with brentuximab vedotin plus AVD across subgroups.

At the second planned interim analysis, the primary endpoint of PFS crossed the protocol-specified statistical boundary, signifying that the study had met its primary endpoint, Alex F. Herrera, MD, associate professor in the Department’s Division of Lymphoma of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte, Calif., he said. Nivolumab/AVD reduced the risk of disease progression or death [approximately] half.

To be eligible for the study, patients had to be at least 12 years of age, have a Zubrod performance status of 2 or lower, and have a left ventricular ejection fraction of at least 50%. Patients with interstitial lung disease or pneumonitis, active autoimmune disease, or grade 2 or higher peripheral neuropathy were excluded. HIV-positive patients were eligible if their disease was controlled.

SWOG S1826 was an open label study that enrolled patients with newly diagnosed stage III or IV cHL. Patients were randomly assigned 1:1 to receive nivolumab at 240 mg on days 1 and 15 or brentuximab vedotin at 1.2 mg/kg on days 1 and 15. Both arms also received AVD on days 1 and 15. and treatment lasted 6 cycles in each arm. Use of granulocyte colony-stimulating factor (G-CSF) was optional in the nivolumab arm and required in the brentuximab vedotin arm.

Patients were stratified by age (12-17 vs 18-60 vs >60), international prognostic score (IPS; 0-3 vs 4-7), and whether end-of-treatment radiotherapy was planned (yes vs no). The primary end point was PFS. Secondary endpoints included event-free survival (EFS), overall survival (OS), complete response rate, and patient-reported outcomes.

Baseline patient characteristics were well balanced between the 2 arms; the median age was 27 years (range, 12-83) and 26 years (range, 12-81) in the nivolumab and brentuximab vedotin arms, respectively. The majority of patients in both arms were White (77% vs 75%), had stage IV disease (62% vs 65%), and had an International Prognostic Score (IPS) of 0 to 3 (68% vs 68%). Furthermore, the majority of patients in both arms were men (55% vs 56%) and had B symptoms (58% vs 56%).

SWOG S1826 was a representative study, Herrera said. A quarter of the patients were under 18 years old [years, and] 10% of patients were over 60 years old [years]. A quarter of the patients were Hispanic or black. We had a pretty good representation of high-risk clinical subgroups, more than in [other] modern evidence. This was a real-world process. That’s the strength of cooperative groups, you can enroll patients from all over the country into the community.

Additional results revealed that the estimated 1-year EFS rates were 91% (95% CI, 80%-88%) vs 84% ​​(95% CI, 80%-88%) in the nivolumab and brentuximab arms, respectively vedotin (HR, 0.56; 95% CI, 0.33-0.95; log-rank one-tailed P = .0019). The 1-year OS rates were 99% (95% CI, 98%-100%) vs 98% (95% CI, 96%-99%), respectively.

Subgroup efficacy data showed that the PFS benefit with nivolumab plus AVD versus brentuximab vedotin plus AVD was consistent across subgroups, including age, IPS, and disease stage. The benefit was most pronounced among patients older than 60 years (HR, 0.27; 95% CI, 0.10-0.76; P = .013), those with an IPS of 4 to 7 (HR, 0.40; 95% CI, 0.19 to 0.84; P = .015) and those with stage IV disease (HR, 0.44; 95% CI, 0.26-0.75; P = .003).

Study safety results revealed that the most common all-grade adverse effects (AEs) in the nivolumab arm (n = 483) included neutropenia (55%), increased alanine transaminase (32%), and sensory neuropathy (29%). ). These adverse events occurred at any grade with rates of 32%, 41%, and 55%, respectively, in the brentuximab vedotin arm (n = 473).

In the nivolumab arm, grade 3 or higher adverse events included neutropenia (47%), anemia (6%), and thrombocytopenia (2%). These adverse events occurred with grade 3 or greater severity in the brentuximab vedotin arm at rates of 25%, 9%, and 3%, respectively.

Infectious toxicity, peripheral neuropathy, and immune-related toxicities were all adverse events of particular interest. Febrile neutropenia (5%), sepsis (2%), and infections/infestations (5%) were sparingly present in the nivolumab arm. These toxicities occurred at rates of 7%, 3%, and 8%, respectively, in the brentuximab vedotin arm.

Peripheral sensory neuropathy (29%) and peripheral motor neuropathy (4%) of any grade were reported in the nivolumab arm; the incidence of these Grade 3 or higher events was 1% and 0%, respectively. In the brentuximab vedotin arm, the rates of any grade peripheral sensory neuropathy and peripheral motor neuropathy were 55% and 7%, respectively, and the rates of grade 3 or higher for these adverse events were 8% and 1%, respectively .

G-CSF was received by 54% and 95% of patients in the nivolumab and brentuximab vedotin arms, respectively. Radiotherapy was administered to 0.4% and 0.8% of patients, respectively.

There was definitely more bone pain in the brentuximab vedotin arm, [which was] Associated with [G-CSF] use, Herrera said. More importantly, however, there was no increase in infectious toxicity, although there was more neutropenia in the nivolumab/AVD arm.

Eleven percent of patients discontinued nivolumab compared with 22% who discontinued brentuximab vedotin. Reasons for discontinuation included adverse events (8% vs 12%), progression/relapse (0% vs 1.4%), and on-treatment death (0.4% vs 1.6%). Twenty-two and 30 patients, respectively, were still on treatment at the time of the analysis.

SWOG S1826 was a critical step toward harmonizing pediatric and adult Hodgkin’s lymphoma therapy, Herrera said. Based on these data, nivolumab ABD is poised to become a new standard of care for advanced-stage Hodgkin lymphoma.


Herrera AF, LeBlanc ML, Castellino SM, et al. SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced-stage classical Hodgkin lymphoma (HL) (AS). J Clin Oncol. 2023;41(suppl 17):LBA4. doi:10.1200/JCO.2023.41.16_suppl.LBA4

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