Adcetris, Chemotherapy Regimen Benefits Older Patients With Hodgkin Lymphoma

Treating older patients who have Hodgkin lymphoma with Adcetris (brentuximab vedotin) before and after chemotherapy showed improved remission and survival rates, according to phase 2 study findings.

Researchers from multiple cancer centers across the country examined the use of Adcetris — an antibody-drug conjugate binds to CD30, a protein found on some lymphoma cells, to work to kill cancer cells – to improve the curability of newly diagnosed older patients.

Older patients, those 60 years or older, with Hodgkin lymphoma typically have worse survival rates because of comorbidities, poorer performance status and disease and biological differences, according to researchers.

“The patient population of older patients with Hodgkin lymphoma has not just historically, but up until this manuscript, have been associated with very modest outcomes,” said Andrew M. Evens, D.O., M.Sc., FACP, associate director for Clinical Services and director of the Lymphoma Program at Rutgers Cancer Institute in New Brunswick, New Jersey.

“When we hear the cancer Hodgkin lymphoma we usually think you see it in younger people, which you do in their 20s and 30s, and you think of a cure rate that’s 90 percent,” he added. “But the data over the last 40 to 50 years for patients over age 60 has been about 40 to 50 percentage points worse. We know that age is usually an adverse factor in most cancers, but it’s not usually that adverse.”

Researchers enrolled 48 patients — median age was 69 years — from August 2012 to August 2016 who had never been treated for classical Hodgkin lymphoma. Participants were eligible if they had stage 2 or greater disease. Nodular sclerosis Hodgkin lymphoma was the most common subtype among patients (46 percent). Nine patients had a prior malignancy; five of whom had localized or resected cutaneous non-melanoma skin cancer and one each of previously treated early-stage breast, colorectal, kidney and thyroid cancer. In addition, patients were physically fit and capable of self-care, according to Evens.

Patients were given Adcetris before and after standard chemotherapy treatment that included Adriamycin (doxorubicin), Velban (vinblastine) and dacarbazine. Therapy on the protocol was divided into three phases: the first lead-in phase was Adcetris given as a single agent for two doses, the second phase was standard chemotherapy for six cycles and the third phase was Adcetris consolidation given once every three weeks for four cycles.

By the third phase, 28 patients received the protocol regimen, of which 40 patients experienced a response (95 percent), including 39 in complete remission (93 percent). In addition, 84 percent of patients lived without disease worsening at the two-year mark.

“What we showed was not only high complete remission rates but essentially almost every patient stayed in remission. In other words, is likely cured,” said Evens. “This study using the sequential novel targeted agent Brentuximab vedotin followed by chemotherapy was associated with excellent remission rates and excellent survival rates that are among the best published to date.”

Grade 3 or 4 side effects were seen in 42 percent of patients. Side effects experienced by more than one patient included neutropenia (low level of neutrophils), lymphopenia (low level of lymphocytes), leucopenia (shortage of normal white blood cells), pneumonia and diarrhea. Three people died: one from pancreatitis and two from progressive disease.

“It has really been for decades an unmet need,” said Evens. “And what this study showed was the outcomes appear to be markedly improved at least compared with historical control.”

Evens hopes to push research forward by designing a specific study that will be able to identify novel treatments for older patients who are physically compromised. He also would like to see if these remission and survival rates can be maintained if fit patients are treated with less therapy, especially less chemotherapy.