Patients with early stage, unfavorable risk classical Hodgkin’s lymphoma who are treated with Adcetris (brentuximab vedotin) and chemotherapy, followed by radiation therapy, are more likely to achieve complete responses than those given the current standard of care (chemotherapy and radiation), the results of a pilot study suggest.
The study,“Brentuximab Vedotin And AVD Followed By Involved-Site Radiotherapy In Early Stage, Unfavorable Risk Hodgkin Lymphoma,” was developed by Anita Kumar, MD, with the Memorial Sloan Kettering Cancer Center and colleagues, and published in Blood.
Adcetris (produced by Seattle Genetics), a monoclonal antibody that targets CD30-positive cells, seems to be effective in the treatment of Hodgkin lymphoma but little information exists as to the safety and efficacy of combining this drug with other disease treatments. The research team decided to conduct a multicenter study (NCT01868451) to evaluate the use of Adcetris in combination with chemotherapy and radiation therapy. (The trial, taking place in New York, New Jersey and California, is now recruiting more patients; trial enrollment and other information is available by clicking on its clinical trials.gov site or on its identification number, given above.)
The team enrolled 30 newly diagnosed patients with unfavorable risk and Stage 2 disease, ages 18 to 69, but one left due to early toxicity. Of the 29 remaining, all were treated with four cycles of Adcetris and chemotherapy containing Adriamycin (doxorubicin), Velban (vinblastine) and DTIC (dacarbazine). Involved-site radiation therapy (radiation aimed at the affected area) was also given to 25 of the 29 patients, in addition to the four treatment cycles. No clinically significant non-infectious pneumonitis was observed.
After the second cycle of Adcetris and chemotherapy, 90 percent of the patients (26 people) had a negative positron emission tomography (PET) scan, and after the fourth cycle this was observed in 93 percent (27) of patients. Two showed resistance to Adcetris and chemotherapy treatment, and continued to be treated off study. But it is noteworthy that all 25 patients who received the complete treatment — four Adcetris and chemotherapy cycles plus radiation therapy — achieved a complete response, with no cases of disease relapse in the median follow-up of 18.8 months.
“Excluding the [two treatment-resistant] patients, all patients are disease-free, suggesting this is a highly active treatment program even in patients with substantial disease bulk [when tumors can be felt or seen in the scans],” the authors wrote.
Despite the positive results, four patients experienced adverse side effects, including febrile neutropenia (fever associated with a reduction the neutrophils, a type of blood cell), peripheral neuropathy (damage in the nerve cells), and hypertension.
Researchers note that one of the limitations of their study is the reduced number of patients. They have now expanded this study and are adding an additional group of 29 patients to their initial cohort.
In the future, the researchers plan to address whether radiation therapy can be eliminated or reduced in lymphoma patients treated with combinations of Adcetris and chemotherapy.
Adcetris is approved by the U.S. Food and Drug Administration to treat certain Hodgkin’s lymphoma patients and those with a rare lymphoma known as systemic anaplastic large cell lymphoma (ALCL).