Cancer Center experts present research at national conference

The Cancer Center’s John Byrd, MD, will present information on a Phase 1 trial testing a new treatment for patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) whose cancer has returned or stopped responding to treatment (relapsed/refractory).

On average, about a quarter of patients with NHL or CLL will relapse by 24 months. Each patient is unique, and the relapse can occur with different mutations, including a MALT mutation that promotes survival and proliferation of blood cancers.

Cancer cells can also sometimes develop resistance to currently-used drugs targeting other enzymes, creating the need for innovative new therapies. 

The trial drug, ONO-7018, targets a protein called MALT1. Preclinical data showed the drug inhibits MALT1 activity and exhibited an antitumor effect with a good safety profile, giving it therapeutic potential to be effective and overcome resistance.

In the trial, patients will be given ONO-7018 orally in 21-day treatment cycles. The first group of up to 48 patients will be enrolled to receive increasing doses until the maximum tolerated dose is identified. Once this occurs, a second group of up to 60 patients will be enrolled to receive the optimal dose identified.

“We are excited to have this exciting new agent, ONO-7018, available for our patients with NHL and CLL who have exhausted available effective therapies available for their disease,” said Byrd, Gordon and Helen Hughes Taylor Professor and Chair of the Department of Internal Medicine at the UC College of Medicine. “MALT1 is an exciting target across all B-cell malignancies and potentially for other types of cancer.” 

The trial, which is currently recruiting patients, will primarily assess the drug’s safety and tolerability.

Byrd will present the poster A phase I, first-in-human study of ONO-7018 in patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia June 3 from 9 a.m. to 12 p.m. Co-authors include Pierluigi Porcu, Thomas Sundermeier, Takashi Nakada, Takeyuki Iwata, Sergio Prados and Leo Gordon. 

For more information on this and other blood cancer clinical trials at the Cancer Center, contact Michelle Marcum at marcumma@ucmail.uc.edu or 513-584-6628.

Cancer-related cognitive impairment (CRCI), often called “chemo brain,” affects approximately 75% of individuals with cancer.

The Cancer Center’s cognitive clinical registry found that more than 83% of patients report experiencing sleep disturbances, leading researchers to ask the question of how sleep disturbances and sleep apnea contribute to CRCI.

“CRCI is complex and overlaps with risk factors associated with non-cancer cognitive impairment and neurodegenerative disease,” said Alique Topalian, PhD, a research scientist in Survivorship and Supportive Services at the Cancer Center. “Sleep is central to maintaining brain health. Understanding the relationship between sleep and cancer is important for mitigating CRCI and neurodegenerative disease.”  

In patients who do not have cancer, impaired sleep contributes to executive dysfunction and enlarged brain ventricles, which disrupt cerebral spinal fluid (CSF) flow and drainage of waste material from the brain, Topalian said. The team hypothesized this same process may be a contributing factor to CRCI.

“Reduced removal of toxic byproducts of normal brain metabolism and inflammation that is induced by cancer and its treatment could explain one mechanism of action for CRCI and the increased risk of neurodegenerative disease in cancer survivors,” Topalian said.

The research team analyzed data from 135 patients in the cognitive clinic’s clinical registry and found sleep apnea and sleep disturbances to be highly prevalent in CRCI. 

“There was a statistical trend toward a relationship between sleep disturbance severity in CRCI and enlarged ventricles,” Topalian said. “Sleep disturbances did not correlate with measures of cognitive impairment. However, ventricular size was significantly associated with impaired processing speed, sustained attention/inhibitory control and semantic fluency.”

Topalian said the novel finding of enlarged brain ventricles in these patients suggests treatment aimed at improving sleep disturbances may help regulate disrupted CSF flow, which could potentially improve CRCI cognitive symptoms.

“We are pursuing fundings for a CPAP and sleep health treatment trial for CRCI patients to investigate how treatment impacts cognitive, imaging and serum markers of CSF flow,” she said.

Additionally, the research team plans to form an ongoing translational working group to expand research on this topic.

Research assistant Sophie Kushman will present the poster “Sleep apnea and glymphatic dysfunction as a mediator of executive dysfunction and neurodegenerative risk in cancer related cognitive impairment (CRCI)” during the Symptom Science and Palliative Care session June 3 from 1:30 to 4:30 p.m. Abstract co-authors are Topalian and Rhonna Shatz, DO.

As the University of Cincinnati Cancer Center is tackling how to reduce the suffering and mortality of cancer in the community today, it is also testing unique ways to encourage the next generation of cancer researchers.

William Barrett, MD, co-director of the Cancer Center, professor and chair of Radiation Oncology in UC’s College of Medicine, and medical director of the Barrett Center for Cancer Prevention, Treatment and Research, said elementary students, particularly those in socially and financially disadvantaged settings, encounter barriers to effective scientific learning. 

With an aim to overcome these barriers, which include maintaining interest, concentration and focus, Barrett and his colleagues implemented a scientific educational program for children attending an urban community center’s after-school program. 

During the program’s activities, five students at a time complete three-minute sessions at tutoring stations on human physiology, astronomy, geography, geology and cancer led by medical students or residents. Meanwhile, another group of five students goes through three-minute basketball drills with a coach on the court. 

The groups alternate between basketball and tutoring until all students have participated in all five drills and tutoring stations. Then the kids are quizzed on what they learned, and an end-of-practice scrimmage begins with a score based on the quiz results.

“Within weeks, nearly every child could list the planets of the solar system in order; calculate their pulse and explain its importance; list the most common symptoms of the most prevalent cancers; correctly identify continents, oceans, countries and states on maps; and explain the origin of volcanoes, earthquakes, hurricanes and tsunamis,” Barrett and his coauthors wrote in the abstract.

The alternating of physical exertion with learning appears to maintain interest, focus and concentration, and the approach could be widely applied to students from diverse backgrounds.

Barrett is first author on the abstract Defeating cancer through education, prevention, and youth athletics. Sherwin Anderson, Andrew Frankart, Samuel Thompson and William Mackey are co-authors.

Featured photo at top of ovarian cancer cells. Photo/OGPhoto/iStock.