Robert W. Chen, MD
Brentuximab vedotin (Adcetris) showed a 5-year overall survival (OS) rate of 41% for patients with relapsed or refractory classical Hodgkin lymphoma, suggesting a cure for some patients, according to long-term results from a phase II study published in the journal Blood
Thirty-eight percent of patients who achieved a complete response (CR) when treated with brentuximab vedotin remained in remission for more than 5 years. Of all patients enrolled on the study, 9% have remained in long-term remission without a consolidative allogeneic transplant, the authors noted. The findings suggest that brentuximab vedotin, which is jointly developed by Seattle Genetics and Takeda, could lead to a cure in select patients with classical Hodgkin lymphoma.
“For a patient population that typically only sees an overall survival of 1 to 2 years after relapse from autologous stem cell transplantation, the fact that we can report such durable results after 5 is incredible,” said lead author Robert Chen, MD, of City of Hope Cancer Research Center, in a statement.
In the open-label study, 102 patients were intravenously treated with brentuximab vedotin at 1.8 mg/kg every 3 weeks for up to 16 cycles. Patients had CD30-positive relapsed/refractory and had failed on hematopoietic autologous stem cell transplantation (ASCT). Prior to enrollment, patients had failed to achieve remission on a median of 3.5 treatments, including stem cell transplant. Patients were monitored from their initial response until disease progression or death.
The 5-year progression-free survival (PFS) rate was 22%. The median OS and PFS rates were 40.5 months (95% CI, 28.7-61.9) and 9.3 months (95% CI, 7.1-12.2), respectively. Patients who achieved a CR (n = 34) had estimated OS and PFS rates of 64% (95% CI, .48-.80) and 52% (95% CI, .34-.69), respectively.
A total of 13 patients remained in follow-up and were reported to still be in remission at the end of the study. Of these patients, 4 underwent consolidative hematopoietic allogeneic stem cell transplant. Nine patients remained in a sustained CR without any additional treatment.
“The positive final results from this trial of Adcetris demonstrated that of the patients who had a complete response, 38% achieved long-term disease control for the duration of the study,” said Dirk Huebner, MD, executive medical director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “In addition, the median overall survival of 40.5 months and progression-free survival of 9.3 months observed across the trial further establish the role of Adcetris in improving outcomes for patients with relapsed Hodgkin lymphoma.”
Fifty-six patients experienced treatment-emergent peripheral neuropathy, which resolved or improved for 88% of patients. Aside from this toxicity, the most common adverse events were fatigue, nausea, neutropenia, and diarrhea.
The monoclonal portion of brentuximab vedotin targets CD30, a protein that is found on the surface of select Hodgkin lymphoma cells. Once attached to CD30 a chemotherapy component is then release into the cancer cell. This is the first study to demonstrate encouraging long-term follow-up in this heavily pretreated population, the authors noted.
“Today’s final publication of the Adcetris monotherapy pivotal study in Hodgkin lymphoma patients represents a significant milestone for the trial that supported approval in more than 60 countries globally and established current use as standard-of-care in the relapsed setting,” said Jonathan Drachman, MD, chief medical officer and executive vice president, Research and Development at Seattle Genetics.
The FDA initially approved brentuximab vedotin in August 2011 for the treatment of patients with Hodgkin lymphoma after failure of ASCT or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not ASCT candidates. In August 2015, this approval was expanded to include use as a consolidation therapy following ASCT in patients with CD30-positive Hodgkin lymphoma at risk of relapse or progression.
The consolidation approval was based on the phase III AETHERA trial, in which brentuximab vedotin reduced the risk of disease progression by 43% versus placebo. The median PFS with brentuximab vedotin was 42.9 months versus 24.1 months with placebo (HR, 0.57; 95% CI, 0.40-0.81; P
In early July, European Commission (EC) also approved brentuximab vedotin for use as a consolidation therapy. In addition to the expanded indication, the EC also extended the existing conditional marketing approvals for brentuximab vedotin in Europe. This decision follows a recent positive opinion issued by the EMA’s Committee for Medicinal Products for Human Use, which means that the therapy is now approved for these indications in the European Union, Norway, Liechtenstein, and Iceland.
Brentuximab vedotin is currently being studied in a number of clinical trials, including as a treatment prior to ASCT in patients with Hodgkin lymphoma, patients with CD30-positive lymphomas, and in patients with relapsed or treatment-resistant non-Hodgkin lymphoma.
Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma [published online July 18, 2016]. Blood. doi:10.1182/blood-2016-02-699850.