The U.S. Food and Drug Administration approved the combination of Seattle Genetics’ Adcetris (brentuximab vedotin) with chemotherapy for the treatment of adults with previously untreated stage 3 or 4 classical Hodgkin’s lymphoma (cHL), which is the most common type of Hodgkin’s.
The approval comes in the wake of positive results of the Phase 3 ECHELON-1 clinical trial (NCT01712490), which compared the combination of Adcetris plus chemotherapy – Adriamycin (doxorubicin), vinblastine, and dacarbazine (AVD) – to the standard Hodgkin’s lymphoma regimen of AVD plus bleomycin (ABVD). The study included a total of 1,334 stage 3 or 4 cHL patients.
Results showed that after a median follow-up of 24.6 months, 82.1% of patients taking Adcetris plus AVD were alive, progression-free, and had not required subsequent therapies. This corresponds to a 23% decrease in the risk of progression, death, or need for additional anti-cancer therapy in patients with incomplete response after frontline treatment.
An interim overall survival analysis showed a trend in favor of the Adcetris arm, but the results have not yet reached a significant difference.
Patients receiving the Adcetris combination also exhibited less lung toxicity and reported no new adverse events. Scientists attribute this improvement to the removal of bleomycin from the chemotherapy regimen.
However, patients taking Adcetris experienced more cases of febrile neutropenia (low levels of neutrophils) and infections compared to the standard chemotherapy group. Some of these complications can be treated with additional therapies, researchers noted.
“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective to no avail,” Joseph M. Connors, MD, the study’s first author, said in a press release.
“The ECHELON-1 study results demonstrated superior efficacy of the Adcetris plus chemotherapy regimen when compared to the standard of care while removing bleomycin, an agent that can cause unpredictable and sometimes fatal lung toxicity, completely from the regimen. This represents a meaningful advance for this often younger patient population,” added Connors, clinical director of the Center for Lymphoid Cancer at BC Cancer in Vancouver, Canada.
The study, “Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma,” was published in the New England Journal of Medicine. Results were also recently presented at the 59th American Society of Hematology (ASH) Annual Meeting.
“Currently, up to 30 percent of newly diagnosed advanced-stage classical Hodgkin lymphoma patients will experience disease progression after treatment with the current standard of care, representing a significant need for improved treatment options for these often younger patients,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
“With today’s FDA approval, the physician and patient community have a new treatment option for previously untreated Stage III or IV Hodgkin’s lymphoma patients,” Siegall added.
Results from ECHELON-1 also led the FDA to convert the accelerated approval to regular approval of Adcetris for the treatment of adults with systemic anaplastic large-cell lymphoma (sALCL) — a type of non-Hodgkin’s lymphoma — after patients’ insufficient response to at least one chemotherapy regimen.
Adcetris had already been FDA-approved for four lymphoma indications, including cHL at high risk of relapse or progression as post-autologous stem cell transplant consolidation, and sALCL. It is also approved in Canada for various lymphomas, and received conditional approvals in the E.U. for certain Hodgkin’s lymphomas and sALCL.
In October 2017, the FDA granted breakthrough therapy designation to Adcetris plus chemotherapy for the frontline treatment of patients with previously untreated advanced cHL. The agency had also granted priority review for Seattle Genetics’ supplemental Biologics License Application regarding this combo treatment, which is intended to shorten a medication’s review time.
Adcetris is an antibody-drug conjugate that specifically targets CD30. This protein is expressed by Reed-Sternberg cells, which characterizes classical Hodgkin’s lymphoma. Adcetris contains a molecule called monomethyl auristatin E, which leads to cell death upon specific release in cancer cells.
Seattle Genetics is developing Adcetris in partnership with Takeda.