Patients with classical Hodgkin’s lymphoma who are at high risk of progressing after a stem cell transplant may benefit significantly from Adcetris (brentuximab vedotin) consolidation treatment in the long-term, researchers found.
At five years, patients’ risk of disease progression or death had been halved compared to a placebo, and the need for additional therapies was reduced by 34%.
These findings were presented at the 11th International Symposium on Hodgkin Lymphoma, Oct. 27-29, in Cologne, Germany. The oral presentation, “Five-Year Progression-Free Survival Outcomes from a Pivotal Phase 3 Study of Consolidative Brentuximab Vedotin after Autologous Stem-Cell Transplantation (ASCT) in Patients with Hodgkin Lymphoma at Risk of Relapse or Progression (AETHERA),” was delivered by Craig Moskowitz, MD, physician in chief, Sylvester Comprehensive Cancer Center, University of Miami (Florida).
The standard of care for Hodgkin’s lymphoma patients who failed their primary treatment is autologous stem cell transplant, a procedure in which patients’ stem cells are re-injected after high dose chemotherapy. The procedure cures roughly 50% of patients, but some who have unfavorable risk factors often progress after the transplant.
To determine if Adcetris could delay disease progression in these patients, researchers at Seattle Genetics designed the AETHERA Phase 3 trial (NCT01100502), which was conducted at 87 sites across North America and Europe.
In the trial, patients received up to 16 cycles of Adcetris, or a placebo, given into the blood every three weeks. Treatment started 30 to 45 days after the transplant.
Results published in The Lancet showed that Adcetris significantly extended the time patients lived without disease-worsening from 24.1 months to 42.9 months, representing a 43% reduction in the risk of disease progression or death at two years.
The findings led to Adcetris approval in the U.S. and Europe as a consolidation treatment for adults with CD30-positive Hodgkin’s lymphoma at risk of relapse or progression after an autologous stem cell transplant.
Now, researchers have reported the five-year follow-up data of AETHERA, showing that Adcetris has a sustained benefit in the long-term. At five years, only 41% of patients in the Adcetris group had died or seen their disease progress, compared to 59% in the placebo group. At this point, the risk of disease progression or death was reduced by 48%.
Researchers then examined the effects of Adcetris in two groups of patients, those with at least two factors that increased their risk of progression, and those with three or more of these risk factors. Among these patients, Adcetris reduced the risk of disease progression by 58% and 61%, respectively.
The need for additional therapies also was reduced with Adcetris. At five years, only 32% of Adcetris-treated patients had received two or more subsequent therapies or had died. For those on placebo, the number was 54%.
Also, while most patients on placebo received a subsequent Adcetris treatment after relapse, the need for an additional stem cell transplant was reduced among those receiving Adcetris in AETHERA — 17% vs. 31%.
During the trial, 112 patients (67%) experienced peripheral neuropathy, a feeling of numbness or weakness in the hands or feet caused by damage to the peripheral nerves. After five years, 90% of these patients had an improvement of their symptoms, including 73% with a complete resolution.
“After more than a decade of dedicated clinical research with Adcetris, we have made significant progress in improving the treatment outcomes for patients with Hodgkin lymphoma,” Nancy Whiting, PharmD, said in a press release. Whiting is senior vice president, Clinical Development and Global Medical Affairs, at Seattle Genetics. “We are pleased to share these results from our broad Adcetris clinical development program with the Hodgkin lymphoma community,” she said.
“Consolidation with BV [Adcetris] in patients with [classical Hodgkin’s lymphoma] at high risk of relapse/ progression after auto-HSCT [autologous stem cell transplant] confers a sustained [progression-free survival benefit and is safe and well tolerated,” researchers concluded.
“These data demonstrate a reduction in the need for subsequent therapy in patients who received BV as consolidation after first auto-HSCT, even when most patients in the placebo arm received subsequent BV at relapse,” they added.