Study suggests lymphoma drug acalabrutinib might offer a potential therapeutic approach for severe COVID-19 infection

A group of researchers including investigators from John Theurer Cancer Center and Hackensack University Medical Center, made the recent observation that the lymphoma drug acalabrutinib might offer a potential therapeutic approach for severe COVID-19 infection.

Newswise — HACKENSACK, N.J., July 13, 2020 — A group of researchers including investigators from John Theurer Cancer Center and Hackensack University Medical Center, made the recent observation that the lymphoma drug acalabrutinib might offer a potential therapeutic approach for severe COVID-19 infection. This effort was led by investigators at the Center for Cancer Research at the National Cancer Institute (NCI), in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), both part of the National Institutes of Health, as well as the U.S. Department of Defense’s Walter Reed National Military Medical Center, and four other hospitals nationally. 

The mechanisms of action of acalabrutinib led to the hypothesis it might be effective in reducing the massive inflammatory response seen severe forms of COVID19. Indeed, it did provide clinical benefit in a small group of patients by reducing their inflammatory parameters and improving their oxygenation. This exploratory study was published on June 5 in Science Immunology. The 1,000th patient released from Hackensack University Medical Center after COVID-19 treatment in the intensive care unit had received and improved after receiving this promising therapy. John Theurer Cancer Center, a member of the Georgetown Lombardi Comprehensive Cancer Center Consortium, subsequently became the first center in the world to open the new CALAVI trial, a multicenter national prospective controlled clinical trial to further evaluate safety and efficacy in particular preventing respiratory failure in theseCOVID-19 patients. 

“Acalabrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). BTK is part of the B-cell receptor (BCR) signaling pathway, which plays a central role in B-cell proliferation and survival, making it an important therapeutic target in the treatment of B-cell malignancies. It is now approved in mantle cell lymphoma, a specialty of Andre Goy, M.D., M.S. — chairman and executive director of John Theurer Cancer Center and physician-in-chief of the Hackensack Meridian Health Oncology Care Transformation Service — who led John Theurer Cancer Center's participation in the original small series of patients. 

COVID19 disease is dividable into 3 clinical phases: the early phase (viral phase where the SARS-COV-2 virus multiplies extensively), followed by the pulmonary phase (pneumonia with early hypoxia) and then the hyperinflammation phase, characterized by a cytokines storm, macrophages activation and accumulation of macrophages in the lungs, leading often to ICU admission and other complications with then much higher mortality. 

”BTK inhibitors such as acalabrutinib may modulate this human inflammatory response particularly the innate immunity (i.e. “built-in” first defense type immunity by opposition to acquired immunity), dominated by macrophages reaction in response to the virus, but also reduce the cytokines storm through BTK-dependent suppression of NF-κB, a key factor in the production of multiple inflammatory cytokines and chemokines,” says Goy. 

In the report recently published, researchers gave acalabrutinib to 19 patients hospitalized with severe COVID-19 (11 receiving supplemental oxygen and 8 on ventilators). After starting acalabrutinib, key measurements of inflammation such as CRP, IL6 and ferritin for example, improved in the majority of patients following a very similar pattern as shown in the paper, and which preceded oxygenation improvement of as well as of patients’ blood lymphocytes count. Over a 10-14-day course of treatment, acalabrutinib improved blood oxygen levels in most patients, often within just one to three days, with no evidence of side effects. After acalabrutinib treatment was completed eight of the eleven of the supplemental oxygen patients were discharged on “room” air and half of the mechanical ventilation patients had been extubated. 

Overall patients did better if they were treated earlier in the course of their illness versus those who started acalabrutinib after they had been in the hospital for weeks on ventilator. This was the case for the 1,000th patient discharged from Hackensack University Medical Center. Based on these findings, the CALAVI study was initiated as a Phase II study of acalabrutinib in hospitalized patients who have COVID-19 and pneumonia, a blood oxygen level under 94% on room air, or need supplemental oxygen. Patients will be randomly assigned to receive standard care with or without acalabrutinib, and outcomes in the two groups will be compared. 

"These results suggest that targeting excessive host inflammation with a BTK inhibitor might be a therapeutic strategy in severe COVID-19” explained Goy. “We hope the larger randomized CALAVI clinical trial, will serve as potential new option for COVID19, particularly as we might experience a second wave of cases as seen already in other states." 

This work was funded by the National Institutes of Health and the CALAVI trial is sponsored by AstraZeneca.

 

For more information, please email Katherine Emmanouilidis, Director of Communications, Northern Region at Hackensack Meridian Health, ke@hackensackmeridian.org.

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About John Theurer Cancer Center at Hackensack University Medical Center

John Theurer Cancer Center at Hackensack University Medical Center is New Jersey’s largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancers. The 14 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. John Theurer Cancer Center is a member of the Georgetown Lombardi Comprehensive Cancer Center Consortium, one of just 16 NCI-approved cancer research consortia based at the nation’s most prestigious institutions. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of aftercare services that distinguish John Theurer Cancer Center from other facilities. 

For additional information, please visit www.jtcancercenter.org.

ABOUT HACKENSACK MERIDIAN HEALTH

Hackensack Meridian Health is a leading not-for-profit health care organization that is the largest, most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care. 

Hackensack Meridian Health comprises 17 hospitals from Bergen to Ocean counties, which includes three academic medical centers – Hackensack University Medical Center in Hackensack, Jersey Shore University Medical Center in Neptune, JFK Medical Center in Edison; two children’s hospitals - Joseph M. Sanzari Children’s Hospital in Hackensack, K. Hovnanian Children’s Hospital in Neptune; nine community hospitals – Bayshore Medical Center in Holmdel, Mountainside Medical Center in Montclair, Ocean Medical Center in Brick, Palisades Medical Center in North Bergen, Pascack Valley Medical Center in Westwood, Raritan Bay Medical Center in Old Bridge, Raritan Bay Medical Center in Perth Amboy, Riverview Medical Center in Red Bank, and Southern Ocean Medical Center in Manahawkin; a behavioral health hospital – Carrier Clinic in Belle Mead; and two rehabilitation hospitals - JFK Johnson Rehabilitation Institute in Edison and Shore Rehabilitation Institute in Brick. 

Additionally, the network has more than 500 patient care locations throughout the state which include ambulatory care centers, surgery centers, home health services, long-term care and assisted living communities, ambulance services, lifesaving air medical transportation, fitness and wellness centers, rehabilitation centers, urgent care centers and physician practice locations. Hackensack Meridian Health has more than 35,000 team members, and 7,000 physicians and is a distinguished leader in health care philanthropy, committed to the health and well-being of the communities it serves. 

The network’s notable distinctions include having four hospitals among the top in New Jersey by U.S. News and World Report. Other honors include consistently achieving Magnet recognition for nursing excellence from the American Nurses Credentialing Center and being named to Becker’s Healthcare’s “150 Top Places to Work in Healthcare/2019” list. 

The Hackensack Meridian School of Medicine at Seton Hall University opened in 2018, the first private medical school in New Jersey in more than 50 years, welcomed its second class of 96 students in 2019 to its ON3 campus in Nutley and Clifton. Additionally, the network partnered with Memorial Sloan Kettering Cancer Center to find more cures for cancer faster while ensuring that patients have access to the highest quality, most individualized cancer care when and where they need it. 

Hackensack Meridian Health is a member of AllSpire Health Partners, an interstate consortium of leading health systems, to focus on the sharing of best practices in clinical care and achieving efficiencies.

 

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