Sequencing Brentuximab Vedotin Improves Outcomes in Hodgkin Lymphoma

Sequential therapy with brentuximab vedotin before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) was well-tolerated and associated with optimal outcomes in patients aged 60 years or older with newly diagnosed Hodgkin lymphoma, according to the results of a recent study (J Clin Oncol. 2018 Sep 4. Epub ahead of print).

Adding Brentuximab Vedotin to Standard Therapy

Andrew M. Evens, DO, MSc, FACP, Associate Director for Clinical Services, Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues conducted a multi-center, phase 2 clinical trial with the goal of improving curability among older patients with newly diagnosed Hodgkin lymphoma.

“Historically, survival rates for older patients with Hodgkin lymphoma, typically defined as 60 years and older, have been shown to be disproportionately and markedly inferior compared with younger patients. Compounding this has been the underrepresentation of older Hodgkin lymphoma patients in clinical trials over the past several decades,” Dr Evens said in a press release (September 2018).

The study involved administering brentuximab vedotin sequentially before and after standard AVD therapy in treatment-naïve patients with Hodgkin lymphoma aged 60 years or older (N = 48). After 2 lead-in doses of brentuximab vedotin (1.8 mg/kg once every 3 weeks), patients received 6 cycles of AVD chemotherapy followed by 4 consolidative doses of brentuximab vedotin in patients responding to therapy.

The median patient age was 69 years (range, 60-88 years), 63% were men, 81% had stage III to stage IV disease, and 12% had a loss of instrumental activities of daily living at diagnosis. In addition, participants had a median Eastern Cooperative Oncology Group performance status 1, an International Prognostic Score 3 to 7, and a median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7.

High Rates of Response and Complete Remission

A total of 37 (77%) patients completed 6 cycles of AVD, and 35 (73%) patients received at least 1 brentuximab vedotin consolidation. Following the initial dose of brentuximab vedotin, overall response rates were seen in 18 (82%) of 22 and 8 (36%) of 22, respectively, and the complete remission rates were 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients.

A total of 20 patients had grade 3 to 4 adverse events. The most common adverse events seen in the study population were neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%). Approximately 30% of participants had grade 2 peripheral neuropathy, which was reversible in the majority of patients. 

Dr Evens and colleagues also noted that, by intent-to-treat, the 2-year event-free, progression-free, and overall survival rates were 80%, 84%, and 93%, respectively. Patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of 10 or higher had lower 2-year progression-free survival rates than those with a score of <10 (45% vs 100%, respectively; P <.001); rates of baseline loss versus no loss of instrumental activities of daily living were 25% and 94%, respectively, for these patients (P <.001).

“Altogether, sequential Bv[brentuximab vedotin]-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival,” Dr Evens and colleagues concluded.—Janelle Bradley