Brentuximab Vedotin Delivers Unprecedented Posttransplant PFS Benefit in Relapsed Hodgkin Lymphoma

Craig H. Moskowitz, MD

Following treatment with high-dose chemotherapy and stem cell transplant, patients with relapsed and difficult- to-treat Hodgkin lymphoma who received brentuximab vedotin had an unprecedented 50% higher likelihood of continuing to experience progression- free survival (PFS) at 2 years. This is particularly meaningful because most patients in this population who haven’t experienced relapse 2 years after transplant are cured.

The study’s lead author, Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center, reported those results from the phase III, placebo controlled AETHERA trial at the 2014 American Society of Hematology (ASH) Meeting (Abstract 673).While roughly half of patients with this condition are cured through the administration of high-dose chemotherapy and stem cell transplant, maintenance strategies to prolong good health afterward are needed because many others relapse, Moskowitz said.

Brentuximab vedotin is an antibody that targets the CD30 protein on Hodgkin lymphoma cells. The drug has demonstrated an objective response rate of 75% in Hodgkin lymphoma that has relapsed or become refractory after autologous stem cell transplant; the AETHERA trial was initiated to evaluate whether early treatment with brentuximab vedotin after transplant could prevent progression in patients with Hodgkin lymphoma, the authors wrote in the abstract presented at ASH.

“This is the first study in lymphoma to demonstrate that the addition of a maintenance drug after transplant can markedly improve patient outcomes,” Moskowitz said. “Given these extremely positive results, we predict that brentuximab vedotin will soon become the standard of care for Hodgkin lymphoma patients who undergo an autologous stem cell transplant.”

The randomized, multicenter study compared brentuximab vedotin with placebo in 327 patients who had been treated with a minimum of two prior systemic therapies and faced a risk of posttransplant disease progression. All had either achieved remission or had stable, nonprogressing disease at the time of stem cell transplant. Thirty to 45 days after transplant, patients were randomized to receive best supportive care plus either 1.8 mg/kg of brentuximab vedotin or placebo every 3 weeks for up to 16 cycles (approximately 1 year). Patients on the placebo arm who experienced disease progression were allowed to leave the trial and receive brentuximab vedotin as part of a different study.

After a median follow up of 2 years, 65% of patients receiving the drug were still experiencing PFS compared with 45% of patients receiving placebo. In an analysis of blinded, pooled efficacy data, an independent review board found that 63% of patients with Hodgkin lymphoma and risk factors for relapse or progression had continued PFS at 2 years when taking brentuximab vedotin, compared with 51% for those on placebo, meaning that, for the overall study population, the 2-year PFS rate was 54%.

Overall survival, at a rate of 88% at 2 years, was the same in both arms, although that number was confounded by the fact that 85% of patients left the placebo arm to receive brentuximab vedotin, and some patients, upon disease progression, underwent second transplants and were salvaged, Moskowitz said.

The median number of treatment cycles was 15, or about 11 months, and 159 patients received 16 cycles. Reasons patients discontinued treatment included disease progression (n = 93), adverse event (n = 61), patient decision (n = 15), and investigator decision (n = 1).

The most common side effects associated with brentuximab vedotin were peripheral sensory neuropathy, upper respiratory tract infection, neutropenia, fatigue, cough, and pyrexia. These were mostly manageable through dose reductions or delays. There were 50 deaths over the 2-year study period, eight occurring prior to disease progression; two deaths occurred within 40 days of dosing with brentuximab vedotin, the authors reported.

Nurse Perspective

Phyllis McKiernan, MSN, APN, OCN

Blood and Marrow Transplant Programs

John Theurer Cancer Center

Hackensack, NJ

For patients with relapsed Hodgkin lymphoma (HL), the standard treatment is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant, with approximately 50% of patients cured using this approach. Patients with chemosensitive disease have improved posttransplant outcomes over patients who do not respond to salvage therapy (ISRN Oncol. 2014. doi:10.1155/2014/605691). Other high-risk factors include positron emission tomography (PET) positivity postsalvage and extranodal disease.

There are salvage therapies for relapsed HL after autologous transplant, including the use of targeted therapy such as brentuximab vedotin. With a demonstrated response rate of 75%, the drug shows significant activity in relapsed HL posttransplantation. Strategies to prevent relapse after autologous transplant include the use of maintenance therapy. Therefore, the question was raised if posttransplant brentuximab vedotin could improve outcomes by preventing relapse in high risk HL patients.

The results of the study showed the addition of brentuximab vedotin did improve progression-free survival (PFS) after transplant for HL, supporting the role of maintenance therapy. This approach is being explored in other hematologic malignancies posttransplant, including non-Hodgkin lymphoma, leukemia, and multiple myeloma. While improved survival is the ultimate goal, maintenance therapy has other implications for patients, including prolonged treatments and potential side effects. This could have a financial impact for patients unable to return to work during maintenance.

The side effects of brentuximab vedotin, while manageable with dose reductions and treatment delays, can lead to serious complications such as infection, dermatologic reactions, and severe peripheral neuropathy. Vigilant clinical monitoring, side effect management, and assisting patients with establishing a routine that fits their lifestyle may improve adherence and increase the likelihood of therapy completion.

The shift toward maintenance therapy after transplant is likely to continue as positive studies emerge, and nurses will play a pivotal role in navigating patients through the process.