TOPLINE:

Brentuximab vedotin and nivolumab combined with doxorubicin and dacarbazine (AN+AD) was associated with a high complete response rate and encouraging short-term progression‑free survival (PFS) in patients with nonbulky early-stage classical Hodgkin lymphoma (cHL), according to a recent phase 2 study. Any‑grade treatment‑emergent adverse events occurred in almost all patients, and peripheral sensory neuropathy was common, but most cases were low-grade and resolved or improved, and no cases of febrile neutropenia were reported. 

METHODOLOGY:

• Early-stage cHL is highly curable, but combined chemotherapy (commonly doxorubicin, bleomycin, vinblastine, and dacarbazine) and radiation therapy can cause significant short‑ and long‑term toxicities. Prior studies suggest that combining brentuximab vedotin with chemotherapy or PD‑1 inhibitors can improve treatment efficacy in these patients, but data on the combination of AN+AD are more limited.
• To assess the safety and efficacy of AN+AD, researchers conducted a phase 2 study involving 154 patients (median age, 31 years) with histologically confirmed treatment-naive Ann Arbor stage I or II cHL without bulky mediastinal disease (< 10 cm in diameter on CT).
• Patients received one or more doses of AN+AD, consisting of 1.2 mg/kg brentuximab vedotin, 240 mg nivolumab, 25 mg/m² doxorubicin, and 375 mg/m² dacarbazine, administered separately intravenously on days 1 and 15 of each 28-day cycle for four cycles.
• The primary endpoint was the complete response rate at the end of treatment; secondary endpoints included the objective response rate, duration of response, duration of complete response, and PFS.
• Overall, 89% of patients had stage II disease, 11% had extranodal disease, and 23% had B symptoms at diagnosis; 63% had unfavorable disease, and 36% had favorable disease at diagnosis per German Hodgkin Study Group risk criteria. The median follow-up duration for PFS was 27.9 months.

TAKEAWAY:

• At the end of treatment, the complete response rate was 92%, the objective response rate was 96%, and 96% of patients maintained a complete response at 2 years. The complete response rate was slightly higher in the favorable vs unfavorable subgroup (95% vs 91%).
• The estimated 2-year rate of PFS was 97%, with no events of progressive disease reported among patients with favorable disease at diagnosis. The estimated 2‑year rate of PFS was 98% for patients with end-of-treatment Deauville scores of 1-2 and 97% for those with a score of 3, reflecting robust short‑term disease control across these PET response groups.
• Any‑grade treatment‑emergent adverse events occurred in 99% of patients, and grade 3 or higher events occurred in 44%. Any‑grade peripheral sensory neuropathy occurred in 47% of patients (grade ≥ 3 events occurred in 3%), but most events were low grade, with 47% resolving and 5% improving. No febrile neutropenia was reported.
• Any-grade treatment-emergent immune-mediated adverse events occurred in 22% of patients, and those of grade 3 or higher occurred in 8%. The most common any-grade events were hypothyroidism (6%), hyperthyroidism (5%), and maculopapular rash (4%); these events led to nivolumab discontinuation in 3% of patients. One disease-related death was reported after the safety period.

IN PRACTICE:

The findings of the study show that AN+AD has “excellent efficacy and safety outcomes” and “facilitates the omission of consolidative [involved-site radiation therapy],” the authors wrote, noting that findings suggest that the regimen can “decrease toxicity” in nonbulky early‑stage cHL.

SOURCE:

The study, led by Jeremy S. Abramson, Massachusetts General Hospital, Boston, was published online in Blood.

LIMITATIONS:

One limitation of the study was that the doses of steroids were not recorded. Interim PET may not have been a reliable biomarker in the setting of nivolumab-containing chemotherapy. The study’s findings may have limited generalizability as it focused on patients with nonbulky early-stage cHL, and the short follow-up duration may have been insufficient to assess long-term outcomes and late toxicities. 

DISCLOSURES:

This study was sponsored by Seagen (acquired by Pfizer in December 2023), Takeda Development Center Americas, and Bristol Myers Squibb. Abramson disclosed receiving research funding from Merck, Cellectis, Bristol Myers Squibb, Mustang Bio, and Seagen and consulting fees from Bristol Myers Squibb, AbbVie, Interius BioTherapeutics, Incyte, Genmab, Genentech/Roche, AstraZeneca, BeiGene, Caribou Biosciences, Century Therapeutics, Epizyme, and Foresight Diagnostics. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.