Brentuximab vedotin induces durable responses among older patients with Hodgkin’s lymphoma
Brentuximab vedotin monotherapy appears safe and effective as first-line treatment for older patients with Hodgkin’s lymphoma who are unable to tolerate traditional combination chemotherapy, according to phase 2 study results published in Blood.
Older patients with Hodgkin’s lymphoma tend to experience poor outcomes with conventional chemotherapy regimens, according to study background. They carry a significant risk for treatment-related toxicity, and comorbidities can limit treatment options.
Thus, Andres Forero-Torres, MD, professor in the division of hematology and oncology at University of Alabama at Birmingham, and colleagues conducted an open-label, phase 2 study to evaluate the safety and efficacy of the CD-30–directed antibody-drug conjugate brentuximab vedotin (Adcetris, Seattle Genetics) as a first-line therapy in patients aged 60 years or older.
The analysis included 27 patients (median age, 78 years; range, 64-92) who had been deemed ineligible for conventional combined chemotherapy or had refused standard treatments based on risk information. Sixty-three percent of study participants had stage III or stage IV disease.
The researchers assigned patients 1.8-mg/kg doses of IV brentuximab vedotin every 3 weeks for up to 16 doses. Patients with clinical benefit could continue to receive the agent beyond 16 doses until disease progression, unacceptable toxicity or study closure.
Objective response rate served as the primary endpoint. Secondary endpoints included complete remission, disease control rate, duration of response and PFS.
The final analysis included data from 26 patients. The ORR in this cohort was 92%. Nineteen patients (73%) achieved complete remission and five patients (19%) achieved a partial remission; the other two patients achieved stable disease.
At time of analysis, the median duration of response was 9.1 months (95% CI, 2.8-20.9+) and median PFS was 10.5 months (95% CI, 2.6-22.3+). Median OS had not been reached.
The researchers observed that adverse events were generally consistent with the known safety profile of brentuximab vedotin. However, they observed a high rate of peripheral neuropathy (30%), particularly among patients with a known history of diabetes and/or hypothyroidism (46% vs. 14% for patients without risk factors).
These risk factors did not appear associated with delayed time to resolution/improvement of peripheral neuropathy.
The researchers acknowledged study limitations, including the nonrandomized design and the relatively small study population.
“In this population of older patients with Hodgkin's 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,” Forero-Torres said in a press release. “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.” – by Cameron Kelsall
Disclosure: Seattle Genetics provided funding for this study. Forero-Torres reports institutional research funding from Seattle Genetics. Other researchers report research funding and travel expenses from and speakers bureau and employment roles with Seattle Genetics.