In a pilot study reported in the Journal of Clinical Oncology, Kumar et al found that the combination of brentuximab vedotin with AVD (doxorubicin, vinblastine, and dacarbazine) was highly active in patients with newly diagnosed, early-stage, unfavorable-risk Hodgkin lymphoma and may permit the reduction or avoidance of consolidative radiotherapy in this setting.
Study Details
In the U.S. multicenter study, 117 patients enrolled between June 2013 and June 2019 received brentuximab vedotin at 1.2 mg/kg plus AVD with doxorubicin at 25 mg/m2, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m2 on days 1 and 15 of 28-day cycles for four cycles. All patients received growth factor support. Patients with negative positron-emission tomography scans after four cycles (PET-4 scans) received one of four sequential consolidation approaches with de-escalating radiation dose and field:
- 30-Gy involved-site radiotherapy (ISRT) in cohort 1 (n = 30)
- 20-Gy ISRT in cohort 2 (n = 29)
- 30-Gy consolidation-volume radiotherapy (CVRT) in cohort 3 (n = 29)
- No radiotherapy in cohort 4 (n = 29).
Disease bulk on Memorial Sloan Kettering criteria was not required for cohorts 1 (bulky disease in 77%) and 2 (bulky disease in 69%) but was required for cohorts 3 and 4 (total of 87% with bulky disease in total population).
Key Findings
PET-4 negative rates were 93% in the 30-Gy ISRT cohort, 93% in the 20-Gy ISRT cohort, 83% in the CVRT cohort, and 83% in the no-radiotherapy cohort. Complete response rates at end of treatment were 93% in the 30-Gy ISRT cohort, 100% in the 20-Gy ISRT cohort, 93% in the CVRT cohort, and 97% in the no-radiotherapy cohort.
Brentuximab vedotin + AVD for four cycles is a highly active and well-tolerated treatment program for early-stage unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of brentuximab vedotin + AVD supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients.— Kumar et al
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At a median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for the four cohorts, respectively), 2-year progression-free and overall survival rates were 94% and 99% among all patients. Progression-free survival at 2 years was 93% in the 30-Gy ISRT cohort, 97% in the 20-Gy ISRT cohort, 90% in the CVRT cohort, and 97% in the no-radiotherapy cohort.
Toxicity associated with brentuximab vedotin plus AVD included any-grade neutropenia in 44% of patients and febrile neutropenia in 8%. Peripheral sensory neuropathy of any grade occurred in 54%, but was low-grade in 95% of cases, resolved in 76%, or was reduced to grade 1 in 24% at last follow-up. A total of 41 serious adverse events requiring hospitalization occurred in 24 patients, with the most common being fever and neutropenia, abdominal pain, and infection. No clinically significant treatment-associated pulmonary toxicity was reported.
The investigators concluded, “Brentuximab vedotin + AVD for four cycles is a highly active and well-tolerated treatment program for early-stage unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of brentuximab vedotin + AVD supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients.”
Anita Kumar, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Lymphoma Research Foundation and Seattle Genetics. For full disclosures of the study authors, visit ascopubs.org.
