Brentuximab Vedotin Combo Exhibits Efficacy in Early-Stage Hodgkin Lymphoma

The addition of brentuximab vedotin (Adcetris) to nivolumab (Opdivo) with doxorubicin and dacarbazine conferred efficacy benefits among patients with non-bulky, early-stage, classical Hodgkin lymphoma, according to findings from the phase 2 SGN35-027 trial (NCT03646123) published in Blood.

Among 154 patients treated with the brentuximab vedotin-based regimen, the objective response rate (ORR) at the end of treatment (EOT) was 96% (95% CI, 91.7%-98.6%), with a complete response (CR) rate of 92% (95% CI, 86.0%-95.4%). Furthermore, the CR rates among patients with unfavorable risk per German Hodgkin Study Group (GHSG) risk criteria was 91% (95% CI, 83.1%-95.7%) vs 95% (95% CI, 85.1%-98.9%) in those with favorable risk. Moreover, the estimated 2-year duration of response (DOR) was 96%, with the proportion of patients with a CR at 2 years being 96% (95% CI, 90.9%-98.4%).

The estimated 2-year progression-free survival (PFS) rate was 97% (95% CI, 92.0%-98.8%) in this patient group after a median follow-up of 27.9 months (95% CI, 27.2-28.6). Additionally, no disease progression-related events were observed among patients with a favorable disease prognosis. The 2-year PFS among those with unfavorable disease at diagnosis was 95%.

Furthermore, 1 overall survival (OS) event was reported after a median follow-up of 30.9 months for OS. The event occurred 215 days following the start of treatment in an elderly female patient with stage II unfavorable disease who died of a second primary malignancy.

“[T]hese results from part C of the SGN35-027 study show that [brentuximab vedotin] and nivolumab without bleomycin and vinblastine (AN+AD) in non-bulky early-stage disease demonstrates excellent efficacy and safety outcomes and facilitates the omission of consolidative [isolated-site radiation therapy (ISRT)],” lead author Jeremy Abramson, MD, MMSC, director of the Jon and Jo Ann Hagler Center for Lymphoma at Massachusetts General Hospital and professor of Medicine at Harvard Medical School, wrote in the publication with study coinvestigators. “The CR rate was 92% and the 24-month PFS rate was 97%, and PFS rates were independent of interim PET or baseline risk status. Furthermore, no febrile neutropenia occurred, and peripheral sensory neuropathy was low grade given vinblastine omission.”

Patients who were 12 years and older in the US and 18 years and older abroad with histologically confirmed Ann Arbor stage I or II classical Hodgkin lymphoma not previously treated were enrolled on the phase 2 trial. All patients received the antibody drug conjugate (ADC)-based regimen, with treatment consisting of brentuximab vedotin at 1.2 mg/kg, capped at a maximum body weight of 100 kg, 240 mg of nivolumab, 25 mg/m² of doxorubicin, and 375 mg/m² of dacarbazine. All agents were given intravenously on days 1 and 15 of each 28-day cycle.

The median age among those treated on the trial was 31 years (range, 18-77), with 84% of patients being younger than 60 years. A total of 55% of patients were female, 81% were non-Hispanic, 84% were White, and 81% had an ECOG performance status of 0. Most patients had stage II non-bulky disease (89%), no presence of extranodal involvement (86%), no B symptoms at initial diagnosis (76%), and unfavorable disease per GHSG risk criteria (63%).

The primary end point of the trial was the CR rate at EOT. Secondary end points included safety, ORR, DOR, duration of CR, event-free survival, PFS, and OS.

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 99% of patients, with 44% of patients experiencing grade 3 or higher events. Moreover, any-grade or grade 3 or higher treatment-related AEs (TRAEs) occurred in 97% and 34% of patients, respectively. Serious TEAEs and TRAEs were reported in 19% and 12% of patients.

The most common any-grade TRAEs included nausea (65%), peripheral neuropathy (47%), fatigue (44%), constipation (29%), and alopecia (22%). The most common grade 3 or higher TRAEs included neutropenia (9%), alanine aminotransferase increases (6%), and aspartate aminotransferase increases (5%). No febrile neutropenia was reported, and any-grade treatment-emergent immune-mediated AEs with potential immunologic cause occurred in 22% of patients.

TEAEs leading to study discontinuation occurred in 10% of patients, including 3% and 1% due to alanine aminotransferase increases and pneumonitis, respectively. TEAEs leading to the discontinuation of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine occurred in 3%, 8%, 1%, and 1% of patients, respectively.

“Future trials evaluating the [doxorubicin and dacarbazine] regimen in early stage [classical Hodgkin lymphoma] can be considered. Both the high excellent CR rate and durable PFS highlight the ability of this [doxorubicin and dacarbazine] regimen to decrease toxicity related to traditional chemotherapy drugs given by eliminating bleomycin and vinblastine,” the study authors concluded.

Reference

Abramson J, Straus D, Bartlett N, et al. Brentuximab vedotin and nivolumab in combination with chemotherapy for nonbulky, early-stage classical Hodgkin lymphoma. Blood. December 29, 2025. doi:10.1182/blood.2025030190