Promising local results of off-label use acalabrutinib are part of findings published national medical journal
NYOH is playing a role in new exploratory research, testing a cancer drug on several COVID-19 patients. The promising results are part of new research that appears in Science Immunology.
The research involves acalabrutinib, a member of a class of drugs known as Bruton’s tyrosine kinase (BTK) inhibitors, which are used to treat B-cell leukemias and lymphomas.
In March, Stephen Wrzesinski, MD, PhD, Director of Immunooncology and Cellular Therapy at New York Oncology Hematology (NYOH), reached out to colleagues at St. Peter’s Hospital to try testing the drug on local patients battling COVID-19.
“While acalabrutinib does not treat the coronavirus itself, it was suspected that it could decrease inflammation in the lungs in patients with severe COVID-19 infection,” said Dr. Wrzesinski, who led the local clinical team overseeing the study. He explains, “By improving the patient’s respiratory status, we believed the drug could spur a quicker recovery – and for the majority of patients, it did.”
Dr. Wrzesinski is co-author of the manuscript, Inhibition of Bruton Tyrosine Kinase in Patients with Severe COVID-19, being published today in Science Immunology. Results of the exploratory research summarize findings of 19 patients receiving acalabrutinib at five hospitals across the country, including three who were treated at St. Peter’s Hospital (two were included in the case series as they completed the full course of therapy). The research was conducted in collaboration with AstraZeneca (AZ) and the National Institutes of Health. Findings include:
- Nineteen patients with acute respiratory distress syndrome (ARDS) from COVID-19 were treated with acalabrutinib for 10-14 days. Most patients demonstrated measurable improvements in oxygenation, often within 1-3 days. Nine out of 11 (82%) patients who had been receiving supplemental oxygen at acalabrutinib treatment were discharged from the hospital and no longer required supplemental oxygen.
- In addition, four out of eight (50%) patients who were receiving invasive mechanical ventilation prior to acalabrutinib administration were extubated, four of whom were discharged without the need of supplemental oxygen. Improvement in key laboratory assessments measuring disease progression, including c-reactive protein level and lymphocyte levels, were also seen. There were no observed toxicities attributable to acalabrutinib, including those outlined in the product’s important safety information, such as cardiac arrhythmia, bleeding, diarrhea or opportunistic infection.
NYOH was asked to join the study because of its extensive clinical research program and affiliation with The US Oncology Network. As the region’s largest clinical research operation, NYOH currently offers 25 active trials across 10 types of cancers. Over the past 30 years, NYOH patients have participated in more than 500 trials, resulting in 50 new FDA approved cancer therapies.
“US Oncology Research partnered with AstraZeneca in developing targeted therapies including acalabrutinib,” explains Ira Zackon, MD, President of NYOH. “After two COVID-19 patients at Walter Reed National Military Medical Center responded well to early treatment with the drug, we were contacted to participate in further study.”
Dr. Zackon tapped Dr. Wrzesinski, who specializes in immunooncology, to lead the project. They reached out to St. Peter’s Hospital to partner in what is called ‘off label’ use of a drug. This refers to cases where a medication is approved by the FDA for a specific condition, but a physician uses medical judgement to try the therapy for an unapproved use or patient population. In the case of the COVID-19 pandemic, the entire research group followed World Health Organization guidelines for off label testing of the medication for severe COVID-19 patients, as outlined in the paper.
At St. Peter’s, Philip Palmieri, MD, Chief of Infectious Disease, selected three patients to receive the experimental treatment.
“We identified patients who were either approaching intubation or had been on a ventilator for less than 24 hours,” Dr. Palmieri explains. “The selected patients were also free of several key underlying medical conditions, including bleeding issues and prior cardiac disease.”
“Working with Dr. Wrzesinski and his clinical team, we explained how the experimental therapy works to the patient or their loved ones and received consent to proceed with the therapy,” Dr. Palmieri recounts. “The three patients received off label acalabrutinib twice a day for up to 14 days.”
The NYOH clinical team included Lawrence Garbo, MD; John Phelan, MD; and Qin Zen, MD, PhD. While clinical research can typically take several months, Dr. Wrzesinski says the findings published today in Science Immunology contribute to a global race to identify novel ways to treat COVID-19 patients.
“This collaboration of clinical researchers was able to quickly evaluate a repurposed drug with the hope of learning how to better treat severe COVID-19 patients during this pandemic,” he says.
Dr. Zackon says the next step is likely a broader clinical trial that builds on findings in the paper as well as other recent research. All four physicians are hopeful NYOH and St. Peter’s will participate in the next phase. Preliminary steps towards opening the Phase II CALAVI (CALquence Against the Virus) are underway.
“There is still so much to learn and prepare for with this pandemic,” Dr. Wrzesinski explains. “We want to do everything we can to help our local patients as well as the scientific and medical community.”