CancerConnect News– The use of post stem cell transplant (SCT) maintenance therapy with Adcetris®(brentuximab vedotin) significantly improved progression-free survival in Hodgkin’s Lymphoma (HL) according to the results of a clinical trail presented at the 56th American Hematological Society Annual Meeting and Exposition, December 6–9, 2014, in San Francisco, California.
Hodgkin’s lymphoma is a cancer of the lymph system. It is diagnosed by the presence of a cell that is characteristic of the disease, the Reed-Sternberg cell. Hodgkin’s lymphoma typically begins in the lymph nodes in one region of the body and then spreads throughout the lymph system. It may spread outside the lymph system to other organs, such as the lungs, liver, bone, and bone marrow. Although the majority of patients with HL are cured with chemotherapy some will experience a recurrence. Individuals with recurrent HL can still be cured approximately half of the time with SCT.
High-dose chemotherapy and bone marrow or blood SCT remains the best treatment available for individuals with recurrent HL. The SCT process was developed more than 36 years ago and was considered such a major development of biomedical science that the individuals responsible were awarded the Nobel Prize for Medicine in 1990. Continued refinement has made SCT safer and more widely available.
The basic strategy uses higher doses of chemotherapy and radiation therapy, which kill more cancer cells than lower doses. Unfortunately, the higher doses of therapy used to destroy cancer cells also damage normal cells. The body’s normal cells that are most sensitive to destruction by high-dose therapy are the blood-producing stem cells in the bone marrow. To “rescue” the bone marrow and hasten blood cell production and immune system recovery, high-dose therapy is followed by an infusion of stem cells. Although SCT cures half of patients with recurrent HL, there has been no further improvement in these outcomes further in the past 20 years.
Adcetris® is a targeted therapy directed at a protein known as CD30, which is present on HL cells as well as cells from other cancers. Once Adcetris® enters CD30-positive cells, it releases the potent chemotherapy drug monomethyl auristatin E.
Doctors performing SCT have long theorized that administration of targeted therapy following SCT that could be directed at eradicating any minimal residual lymphoma cells might improve on cure rates achieved with high dose therapy.
The AETHERA trial was designed to evaluate whether Adcetris® could improve the outcome of HL patients undergoing SCT. In this trial 329 patients who had either achieved remission or had stable disease at time of transplant were treated with either Adcetris® or placebo for up to 1 year.
Post SCT Adcetris® delayed the time to cancer progression; at 2 years 63% of HL patients who were treated with the drug survived without lymphoma progression compared to only 51% of patients who received placebo. The average time to cancer progression was 43 months for Adcetris® treated patients compared to 24 months for those on placebo resulting in a 43% reduction in risk of disease progression.
Overall survival was similar in both groups at 2 years based on interim analysis, and this was most likely because patients treated with placebo were allowed to cross over and receive Adcetris® when their HL progressed. The study authors believe that Adcetris® will become the standard of care for HL patients who undergo an autologous stem-cell transplant.
Reference: Moskowitz C, Nadamanee A, Masszi T, et al. The Aethera Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma. Presented at the 56th Annual Meeting of the American Society of Hematology, December 6-9, 2014. Abstract 673.