Adding Adcetris® (brentuximab vedotin) to the chemotherapy regimen ABVD produces a high complete response rate with a moderate increase in toxicity in patients with advanced Hodgkin’s lymphoma, according to the results of a study presented at the 19th International Symposium on Hodgkin Lymphoma held in Cologne, Germany in 2014.
Hodgkin’s lymphoma is a cancer of the lymph system. First-line treatment of Hodgkin’s lymphoma typically involves chemotherapy, often with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). One problem with this regimen is the toxicity associated wit bleomycin. In fact, older patients may develop bleomycin-related lung toxicity—and some die from this. Researchers are finding that the best way to modify ABVD is to add or substitute a novel agent—such as Adcetris.
Adcetris is a targeted agent that targets a protein known as CD30, which is present on Hodgkin lymphoma cells as well as cells from other cancers. Once Adcetris enters CD30-positive cells, it releases the potent chemotherapy drug monomethyl auristatin E. Adcetris has shown significant clinical activity and a manageable safety profile in patients with relapsed or refractory Hodgkin’s lymphoma.
Researchers conducted a phase I study that evaluated Adcetris as an addition to ABVD or as a substitute for bleomycin (AVD plus Adcetris). The substitution came as a result of observing that Adcetris appeared to create more bleomycin toxicity—so in the second half of the study, the researchers eliminated the bleomycin.
The results of the study indicated that 21 of 22 (95%) of patients who received ABVD plus Adcetris achieved a complete response and the same was true for 24 of 25 (96%) of those who received AVD plus Adcetris. Only one patient had disease progression and this patient was receiving AVD plus Adcetris. One patient. One patient in the ABVD plus Adcetris group developed grade 5 pulmonary toxicity during treatment and was not evaluable.
As a result of the high response rate, researchers have initiated a large, international randomized trial known as ECHELON-1. The study will include more than 1,000 treatment-naive patients with stage IIA bulky or stage IIB–IV disease. Patients will be randomly assigned to two cycles of ABVD or AVD plus Adcetris.
Ansell SM, Conors JM, Park SI, et al. Front-line therapy with brentuximab vedotin combined with ABVD or AVD in patients with newly diagnosed advanced stage Hodgkin lymphoma. 9th International Symposium on Hodgkin Lymphoma. Abstract P005. Presented October 15, 2013.