(Press-News.org) Nearly 90 percent of patients with an aggressive subtype of non-Hodgkin lymphoma had their cancer go into remission in a small phase 2 clinical trial testing a treatment aimed at making chemotherapy more effective, according to Weill Cornell Medicine and NewYork-Presbyterian investigators.
The clinical trial, whose results were published May 4 in Blood, included 17 patients with a type of blood cancer called peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH), also known as angioimmunoblastic T-cell lymphoma. Fifteen of them (88.2 percent) had complete responses after a several-month course of treatment, which combined a standard four-drug chemotherapy regimen known as CHOP with another drug called azaciditine. Patients with PTCL-TFH have tumors that typically bear excessive clusters of gene-silencing marks called methylations on their DNA—marks that azacitidine removes.
“The treatment shows promise for this T cell lymphoma subtype, and we look forward to seeing how it performs in a larger clinical trial,” said study lead author Dr. Jia Ruan, a professor of clinical medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The study was a collaboration involving multiple investigators at Weill Cornell Medicine, including Drs. Peter Martin, John Leonard, Leandro Cerchietti, Giorgio Inghirami, Olivier Elemento, and Ari Melnick. Investigators from Memorial Sloan Kettering, Washington University School of Medicine, Moffitt Cancer Center and BostonGene Corporation also contributed to the study.
Lymphomas arise from immune cells, mostly B cells and T cells, whose malignant overgrowth leads to the swelling of lymph nodes. These cancers are newly diagnosed in approximately 90,000 people in the United States annually. PTCLs, which account for several thousand of these cases, are relatively hard to treat successfully, and have an estimated five-year survival rate of only 20 to 30 percent.
A standard initial therapy for most lymphomas is a four-drug chemotherapy regimen (CHOP) that is usually delivered in six three-week cycles. Researchers have been looking for ways to enhance the effectiveness of this treatment for PTCL and other forms of lymphoma that tend to have poor outcomes.
Combining standard chemotherapy with azacitidine is a promising strategy that is now being tested in various settings. A small study led by Dr. Martin and published last year found that the combination therapy was effective in producing complete response rates in patients with certain aggressive B-cell lymphomas.
Azacitidine, which is currently approved by the U.S. Food & Drug Administration for the treatment of myelodysplastic syndrome and some leukemias, works to remove gene-regulating marks on DNA called methylations. Many aggressive cancers harbor dense patches of these DNA marks—hypermethylations—which are thought to enhance tumor survival by silencing growth-restraining and DNA-repair genes.
In the new study, Dr. Ruan and her colleagues examined the effectiveness of the combination in PTCL patients with the TFH subtype, since PTCL-TFH tumors typically show DNA excessive methylation marks as well as mutations in one or more methylation-regulating genes.
The study included 20 evaluable PTCL patients, 17 of whom had the TFH subtype based on genetic tests of their tumors. All but one had advanced PTCLs of stages III-IV. The rate of complete responses at the end of azacitidine-plus-standard chemotherapy treatment was very high: three-quarters (15/20) of the patients showed complete responses, and all were PTCL-TFH patients—implying a complete-response rate of 88.2 percent for this subgroup. Although there was no placebo or standard-treatment comparison group, end-of-treatment complete response rates for PTCL patients treated with standard chemotherapy-only, such as CHOP-based regimens, are usually in the 30-40 percent range, said Dr. Ruan.
The median follow-up time for the patients was 21 months, allowing the researchers to estimate two-year progression-free survival rates of 65.8 percent for all 20 patients, and 69.2 percent for the 17 PTCL-TFH patients. Side-effects were comparable to what is normally seen in standard chemotherapy treatment.
These results are consistent with the idea that adding azacitidine to standard chemotherapy is safe and more effective for PTCL-TFH patients, Dr. Ruan said.
The researchers are now working with colleagues across the country investigating azacitidine-plus-standard chemotherapy in a randomized clinical trial in a group of more than 150 PTCL patients of different subtypes, scheduled to be completed by 2026.
Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see profile for Drs. Jia Ruan, Peter Martin, John Leonard, Olivier Elemento, and Ari Melnick.
END
Adding epigenetic drug to standard chemotherapy was effective in pilot study for T-cell lymphoma
2023-05-04
ELSE PRESS RELEASES FROM THIS DATE:
What really killed COVID-19 patients: it wasn’t a cytokine storm
2023-05-04
· No evidence of cytokine storm in critically ill patients with COVID-19
· Nearly half of patients with COVID-19 develop a secondary bacterial pneumonia
· Crucial to find and aggressively treat secondary bacterial pneumonia in ICU patients
CHICAGO --- Secondary bacterial infection of the lung (pneumonia) was extremely common in patients with COVID-19, affecting almost half the patients who required support from mechanical ventilation. By applying machine learning to medical record data, scientists at Northwestern University Feinberg School of Medicine found that secondary bacterial pneumonia that does not resolve was a key ...
Many older adults take multiple medications; an updated AGS Beers Criteria® will help ensure they are appropriate
2023-05-04
New York (May 4, 2023) — Today, the American Geriatrics Society (AGS) released the 2023 update to the AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults (DOI: 10.1111/jgs.18372). The AGS Beers Criteria® serves as a comprehensive list of medications that older people should potentially avoid or consider using with caution because they often present unnecessary risks for this population. Given that, according to the National Center for Health Statistics, United States (NCHSUS), more than 88% of older people use at least one prescription and more than 66% use ...
Study presents new clues about the rise of earth’s continents
2023-05-04
Continents are part of what makes Earth uniquely habitable for life among the planets of the solar system, yet surprisingly little is understood about what gave rise to these huge pieces of the planet’s crust and their special properties. New research from Elizabeth Cottrell, research geologist and curator of rocks at the Smithsonian’s National Museum of Natural History, and lead study author Megan Holycross, formerly a Peter Buck Fellow and National Science Foundation Fellow at the museum and now an assistant professor at Cornell University, deepens the understanding of Earth’s crust by testing ...
Converging ocean currents bring floating life and garbage together
2023-05-04
The North Pacific “Garbage Patch” is home to an abundance of floating sea creatures, as well as the plastic waste it has become famous for, according to a study by Rebecca Helm from Georgetown University, US, and colleagues, publishing April 27th in the open access journal PLOS Biology.
There are five main oceanic gyres — vortexes of water where multiple ocean currents meet — of which the North Pacific Subtropical Gyre (NPSG) is the largest. It is also known as the North Pacific “Garbage Patch”, because converging ocean currents have concentrated large amounts ...
Gutless marine worms on a Mediterranean diet: Animals can synthesize phytosterols
2023-05-04
Cholesterol and phytosterol are sterols, fatty compounds essential for many biological processes such as the functioning of cell membranes. Up to now, it has been assumed that phytosterols are characteristic for plants, and cholesterol for animals, and that only plants can make phytosterols, while animals typically make cholesterol. Dolma Michellod, Nicole Dubilier and Manuel Liebeke from the Max Planck Institute for Marine Microbiology in Bremen, Germany, were therefore surprised when they discovered that a small marine worm called Olavius ...
Scientists begin to unravel global role of atmospheric dust in nourishing oceans
2023-05-04
CORVALLIS, Ore. – New research led by an Oregon State University scientist begins to unravel the role dust plays in nourishing global ocean ecosystems while helping regulate atmospheric carbon dioxide levels.
Researchers have long known that phytoplankton – plantlike organisms that live in the upper part of the ocean and are the foundation of the marine food web – rely on dust from land-based sources for key nutrients. But the extent and magnitude of the impact of the dust – ...
Chemical signal protects migratory locusts from cannibalism
2023-05-04
Huge swarms of migratory locusts take on the proportions of natural disasters and threaten the food supply of millions of people, especially in Africa and Asia. As the eighth of the ten biblical plagues, the Book of Moses in the Old Testament already describes how swarms of locusts darkened the sky and ate up everything that grew in the fields and on the trees. Scientists suspect that cannibalism among locusts contributes to their swarming behavior, and swarms therefore constantly move ...
Pheromone deters swarming migratory locusts from cannibalism
2023-05-04
Swarming migratory locusts – which threaten food security across the globe – avoid being eaten by other locusts by producing a smelly pheromone called phenylacetonitrile (PAN), according to a new study. The discovery of an anticannibalistic signaling pathway in locusts could provide a target for locust management strategies since cannibalistic interactions among locusts have been implicated in creation of swarms, which are highly destructive. A wide range of species practice cannibalism, mostly to supplement nutrition. This has led to the evolution of ...
Social-belonging intervention promotes college success, increasing proportion of students who complete first year
2023-05-04
A randomized controlled experiment featuring more than 26,000 students across 22 4-year U.S. universities shows that the effects of a low-cost, brief online intervention focused on social belonging can promote success and equity for college students. This finding was particularly apparent among those from groups that have historically achieved at lower rates. The likelihood of earning a university degree in the U.S. is highly unequal across racial-ethnic and socioeconomic groups. In most cases, programs designed to help, by promoting college persistence, work differently for different people. Understanding these heterogenous effects ...
Recycled gas feeds a massive galaxy in the early Universe
2023-05-04
Streams of intergalactic gas, enriched with elements heavier than helium, encircle and spiral into a massive galaxy observed at redshift 2.3, researchers report. The findings provide evidence of enriched gas recycling during galaxy formation in the early Universe. Galaxies form through the accretion of gas from the circumgalactic medium (CGM) and intergalactic medium (IGM), which subsequently condenses into stars. Simulations and observations have shown that cold stream accretion – the accumulation of pristine intergalactic gas that contains almost no elements heavier ...