The ongoing open-label phase 2 study presented at the American Society of Hematology (ASH) meeting was designed to test the activity of brentuximab vedotin (Adcetris) in relapsed or refractory non-Hodgkin lymphoma (NHL) including B-cell cancers such as diffuse large B cell lymphoma (DLBCL).
The antibody-toxin compound has been approved for treatment of relapsed or refractory Hodgkin lymphoma and anaplastic T cell lymphoma, and its success prompted the trial in NHL, said Eric Jacobsen, MD, of Dana-Farber, senior author of the study. First author is Nancy Bartlett, MD, of Washington University School of Medicine.
To date, the trial has enrolled 62 patients with B-cell lymphomas, including 44 diagnosed with DLBCL. Most the patients were no longer responding to previous therapy, and 23 percent had never responded to any treatment.
Forty percent of the 43 evaluable DLBCL patients had an objective response to the drug with a median duration of 36 weeks, including some of more than eight months. Seven had complete remissions and 10 had partial remissions. In the other B-cell lymphoma patients, 22 had an objective response.
"In this interim analysis of 62 patients with highly refractory B-cell lymphomas, compelling antitumor activity has been observed with brentuximab vedotin," the authors wrote.
"It was more active than many expected," noted Jacobsen. "In my opinion, these results are encouraging enough to take the drug forward in diffuse large B cell lymphoma."
Brentuximab is a monoclonal antibody that binds to CD30, a molecule found on cells in Hodgkin lymphoma and anaplastic T cell lymphoma. The frequency of CD30 expression varies in other subtypes of lymphoma but is estimated to be present in one-quarter to one-third of B cell NHL cells. In the compound brentuximab vedotin, the targeted antibody is linked to a potent toxin that interferes with cell division and blocks cell growth. Like a chemical Trojan horse, the antibody-toxin compound is swallowed by cancer cells that carry the CD30 molecule on their surface. Once inside the cell, the poisonous cargo separates from the antibody and disables the cell.
Some of the patients' lymphoma cells strongly expressed the CD30 molecule, but in others the expression was less, and in some patients CD30 expression wasn't detected at all.
Surprisingly, the strength of CD30 expression by the patients' cancer bore no relationship to how they responded to the drug. "In fact, although the trend was not statistically significant, there was almost an inverse correlation. Some patients with the weakest CD30 expression had the most positive responses," said Jacobsen.
This is puzzling, he admitted: How did the antibody recognize and bind to the lymphoma cells that lacked the CD30 molecule? Possibilities include binding to another target, although preclinical tests suggested this was not the case. Other possibilities is that brentuximab vedotin binds more effectively to CD30 than the antibody used to detect CD30 in the lab or that different cells have differing abilities to ingest brentuximab once the antibody binds to the cell. There is no clear answer from the study but further laboratory tests are ongoing. Jacobsen said the trial is beginning to evaluate the drug's activity in a cohort of patients whose lymphomas have no measurable CD30 expression.
The drug caused an array of adverse events, leading to discontinuation in six patients. Among the toxicities were fatigue, nausea, low white blood counts, fever, diarrhea, peripheral sensory neuropathy, vomiting, anemia and constipation. The researchers said this profile was consistent with that seen previously with brentuximab vedotin.
Additional authors include Jeff P. Sharman, MD, Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR; Yasuhiro Oki, MD, MD Anderson Cancer Center, Houston, TX; Ranjana H. Advani, MD, Stanford University Medical Center, Stanford, CA; Celeste M. Bello, MD, H. Lee Moffitt Cancer Center, Tampa, FL; Jane N. Winter, MD, Northwestern University, Chicago, IL; Yin Yang, MS, and Dana A. Kennedy, PharmD, Seattle Genetics, Inc., Bothell, WA.
This study was supported by Seattle Genetics.
Teresa Herbert | EurekAlert!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine