Updated Analysis of Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine for Nonbulky, Early-Stage Classical Hodgkin Lymphoma
Authors: Abramson Jeremy S. , Straus David J. , Bartlett Nancy L. , Burke John M. , Lynch Ryan C. , Domingo Domenech Eva , Hess Brian , Schuster Steven , Linhares Yuliya , Ramchandren Rod , Gandhi Mitul , Shah Harsh R. , Jurczak Wojciech , Re Alessandro , Hahn Uwe , Prince H. Miles , Guo Wenchuan , Davis Griffith , Ho Linda , Yasenchak Christopher , Lee Hun Ju 
Published: December 2024

Introduction
Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved for patients with advanced classical Hodgkin lymphoma (cHL). A study in nonbulky early-stage cHL showed preserved efficacy with improved safety when omitting vinblastine in the BV+AD regimen (Blood Adv. 2023;7[7]:1130-1136). Initial results from the phase 2 SGN35-027 part C study, with a median follow-up of 16.5 months, showed promising efficacy and an acceptable safety profile for BV and nivolumab in combination with chemotherapy (AN+AD) in patients with nonbulky, early-stage cHL. Here, we present updated results from this study after longer follow-up.
Methods
SGN35-027 (NCT03646123) part C enrolled patients with Ann Arbor stage I or II cHL without bulky disease, defined as those with a single node or nodal mass with a &lt;10-cm diameter on computed tomography. Patients received 4 cycles of AN+AD (BV 1.2 mg/kg [A] capped at 100 kg, nivolumab 240 mg [N], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D]) intravenously on days 1 and 15 of each 28-day cycle. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was not required. The primary endpoint is complete response (CR) rate at end of treatment (EOT) by investigator assessment per Lugano 2014 classification with incorporation of LYRIC. Secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), duration of CR (DOCR), and safety analysis. Additional analyses included efficacy assessments for early favorable and early unfavorable subgroups, as defined per German Hodgkin Study Group criteria.
Results
At the data cutoff of May 30, 2024, 154 patients received ≥1 dose of AN+AD (male, 45%; female, 55%; White, 84%; early favorable, 36%; early unfavorable, 64%; median age, 31 years [range, 18-77 years]). The median duration of follow-up was 30.7 months (range, 24-45 months). The ORR at EOT was 96% (95% CI, 92%-99%), and the CR rate was 92% (95% CI, 86%-95%). In the early favorable (n=55) and early unfavorable (n=98) subgroups, CR rates were 95% (95% CI, 85%-99%) and 91% (95% CI, 83%-96%), respectively. Of patients who achieved a CR, the DOCR rate at 36 months was 95% (95% CI, 89%-98%). At a median PFS follow-up of 26.3 months, 6 patients (4%) had progressive disease, all of whom had early unfavorable disease at diagnosis. No progressive disease events were reported in early favorable patients. The 36-month PFS rate was 95% (95% CI, 88%-98%). The planned treatment course of 4 cycles was completed by 98% of patients. Six patients (4%) received subsequent treatment; of them, 2 received consolidative radiotherapy. Overall, 44% of patients received G-CSF at investigator discretion, mostly for primary prophylaxis.
Any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 99% and 44% of patients, respectively; no events of febrile neutropenia were reported. Grade ≥3 treatment-related TEAEs occurred in 34% of patients, most commonly neutropenia (9%), alanine aminotransferase (ALT) increase (7%), aspartate aminotransferase increase (5%), lipase increase (3%), and peripheral sensory neuropathy (3%). Any-grade treatment-emergent immune-mediated adverse events (IMAEs) with a potential immunologic cause occurred in 22% of patients, most commonly hypothyroidism (6%), hyperthyroidism (5%), maculopapular rash (4%), ALT increase (3%), and pneumonitis (2%). Grade ≥3 treatment-emergent IMAEs occurred in 8% of patients, most commonly ALT increase (3%) and maculopapular rash (1%). Serious TEAEs occurred in 19% of patients. Treatment-related serious TEAEs occurred in 12% of patients, with the most common being pyrexia (3%). There was 1 disease-related death reported after the safety reporting period.
Conclusions
This updated analysis from the SGN35-027 part C study demonstrated continued efficacy of this novel regimen, sparing bleomycin, vinblastine, and radiation, in early-stage cHL, with a CR rate of 92% and 36-month PFS rate of 95%. The safety profile remains favorable and consistent with that in the prior analysis. Long-term results from this study support the use of BV and nivolumab in combination with limited chemotherapy in patients with nonbulky, early-stage cHL.