Brentuximab Vedotin Effective in Older Hodgkin Lymphoma Patients

The antibody-drug conjugate brentuximab vedotin is effective as a frontline monotherapy for patients over age 60 with Hodgkin lymphoma who are unfit for chemotherapy, according to a phase II trial published in Blood.

In the small trial (N = 27), the objective response rate with brentuximab vedotin among Hodgkin lymphoma patients who were either ineligible for standard chemotherapy or declined to receive treatment was 92%, with 19 patients (73%) achieving complete remission and 5 patients (19%) achieving partial remission. All patients had stable disease or better and decreased tumor volume following treatment. The median patient age was 78 (range, 64–92).

The median duration of response for the 26 patients who could be evaluated for efficacy was 9.1 months (range, 2.8–20.9-plus months). The median progression-free survival was 10.5 months (range, 2.6–22.3-plus months). The median overall survival has not yet been reached.

“In this population of older patients with Hodgkin lymphoma who were unfit for standard chemotherapy, we observed that brentuximab vedotin as a single agent produced a very high rate of response, including a very high rate of complete remission,” said study author Andres Forero-Torres, MD, of the University of Alabama at Birmingham, in a statement. “While we observed promising responses, the next step is to evaluate this drug in combination with additional chemotherapy or immunotherapies that might allow us to prolong the response without relapse.”

Brentuximab vedotin combines an anti-CD30 antibody linked to a microtubule-disrupting cytotoxic agent, monomethyl auristatin E. According to preclinical studies, after binding to the cell, the antibody-drug conjugate is internalized, releasing the toxin and causing cell cycle arrest and apoptosis.

For patients diagnosed with Hodgkin lymphoma, the standard treatment uses cytotoxic agents, yet the presence of comorbidities such as cardiac issues in those older than 60 can preclude the use of these intensive regimens as they typically include an anthracycline. The rate of remission is lower for these older patients compared to their younger counterparts that are able to tolerate standard chemotherapy regimens.

Patient comorbidities on trial included mild or moderate renal impairment, chronic renal disease, hypertension, diabetes, stroke, and peripheral vascular disorder.

The drug was administered at 1.8 mg/kg intravenously every 3 weeks for up to 16 total doses. Patients who continued to benefit could opt to stay on treatment. Patients received a median of 8 cycles-four patients completed 16 cycles and one patient completed 23 cycles. 

Common adverse events of grade 2 or less were consistent with prior studies of brentuximab vedotin and included peripheral sensory neuropathy in 78% of patients, fatigue in 44%, and nausea in 44%. Grade 3 peripheral neuropathy occurred in 30% of patients and was more common among patients with diabetes or hypothyroidism. Grade 3 rash also occurred in 7% of patients.