Four cycles of brentuximab vedotin (BV) plus doxorubicin, vinblastine, and dacarbazine (AVD) is “highly active” in patients with newly diagnosed, early-stage, unfavorable-risk Hodgkin lymphoma, including bulky disease, researchers reported in the Journal of Clinical Oncology.
In fact, the efficacy of induction with BV plus AVD “supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients,” the researchers wrote.
The group conducted a multicenter pilot study (ClinicalTrials.gov Identifier: NCT01868451) of patients with untreated, stage I/II, biopsy-proven, CD30-positive classical Hodgkin lymphoma.
All patients received 4 cycles of BV plus AVD, but they were divided into 4 cohorts to assess consolidation approaches.
If patients had a PET-negative response after 4 cycles or a negative biopsy, they received 30 Gy involved-site radiation therapy in cohort 1, 20 Gy involved-site radiation therapy in cohort 2, 30 Gy consolidation-volume radiation therapy in cohort 3, and no radiation in cohort 4.
For cohorts 3 and 4, patients were required to have bulky disease according to Memorial Sloan Kettering (MSK) criteria (>7 cm in maximal transverse or coronal diameter on CT).
The primary endpoints were safety in cohort 1 and complete response rate by PET in cohorts 2 to 4.
A total of 117 patients were enrolled from June 3, 2013, to June 14, 2019. There were 30 patients in cohort 1 and 29 patients each in cohorts 2 to 4.
The patients’ median age was 32 years (range, 18-59 years), and 50% were men. Nearly all patients (98%) had stage II disease, 86% had MSK-defined disease bulk, 27% had traditionally defined bulk (>10 cm in transverse dimension), and 23% had advanced-stage disease according to German Hodgkin Study Group criteria.
The overall rates of PET negativity (5-point scale score 1-3) were 87% at PET-2, 88% at PET-4, and 85% at the end of treatment.
The complete response rate at the end of treatment was 93% in cohort 1, 100% in cohort 2, 93% in cohort 3, and 97% in cohort 4. The primary efficacy endpoints were met for cohorts 2 to 4.
At a median follow-up of 3.8 years, the overall 2-year progression-free survival (PFS) rate was 94%, and the 2-year overall survival rate was 99.1%.
The 2-year PFS was 93.1% in cohort 1, 96.6% in cohort 2, 89.7% in cohort 3, and 96.6% in cohort 4. The 4-year PFS was 93.1% in cohorts 1 and 2. Four-year PFS rates weren’t provided for cohorts 3 and 4.
During treatment, 41 serious adverse events that required hospitalization occurred in 24 patients. The most common of these events were fever and neutropenia, abdominal pain, and infection.
The researchers acknowledged that this study was limited by the small number of patients in each cohort, the nonrandomized design, and the fact that the study was not designed to definitively compare the 4 treatment arms.
Still, the researchers concluded that BV plus AVD demonstrated “excellent efficacy across all 4 cohorts.”
Disclosures: This research was supported by Seattle Genetics and the Lymphoma Research Foundation. Some of the study authors declared affiliations with biotechnology and pharmaceutical companies. Please see the original reference for a full list of disclosures.
Kumar A, Casulo C, Advani RH, et al. Brentuximab vedotin combined with chemotherapy in patients with newly diagnosed early-stage, unfavorable-risk Hodgkin lymphoma. J Clin Oncol. Published online April 28, 2021. doi: 10.1200/JCO.21.00108.