Tag: 15/1/26

Categories : CancerTags :

Tec-Dara Combo More Effective for Relapsed or Refractory Multiple Myeloma

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Depiction of multiple myeloma. Credit: Scientific Animations

Patients with relapsed or refractory (R/R) multiple myeloma who received a combination of teclistamab, a bispecific monoclonal antibody, and daratumumab, a CD38-directed monoclonal antibody, were 83% more likely to be alive without disease progression compared with those who received standard second-line therapies at a median of nearly 35 months of follow-up, according to the results of a new trial presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.

The trial is the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment for multiple myeloma. Based on the findings, researchers suggest the combination of teclistamab and daratumumab, known as Tec-Dara, could represent a new standard of care for R/R multiple myeloma.

“We were surprised by the efficacy data because we didn’t expect such a magnitude of benefit,” said lead study author María-Victoria Mateos, MD, PhD, physician in the haematology department and professor of medicine at the University of Salamanca in Spain. “These are the best data we’ve seen in patients with R/R multiple myeloma after one line of therapy. Patients will live longer overall and with no worsening of quality of life.”

Multiple myeloma is a cancer that causes excessive production of plasma cells, crowding out the production of other types of blood cells and harming the body’s ability to fight infections. It is most common in older adults. Patients who relapse or experience an incomplete response to initial treatment often have their cancer return after subsequent therapies, pointing to a need for improved second-line treatments.

Teclistamab is approved by the U.S. Food and Drug Administration for R/R multiple myeloma after at least four prior lines of therapy. Daratumumab is a therapy targeting the CD38 protein that has been approved for use in combination with other therapies for newly diagnosed and R/R multiple myeloma. Laboratory studies have suggested that teclistamab and daratumumab may work synergistically to eradicate cancer to a greater extent than either agent individually.

To test this hypothesis, researchers randomized 587 patients with R/R multiple myeloma to receive either Tec-Dara or standard second-line therapies. For patients in the control arm, treating physicians chose between two standard three-agent combination therapies which included daratumumab with dexamethasone plus either pomalidomide or bortezomib (known as DPd or DVd, respectively).

Study participants had a median age of 64 with a range of 25-88, and all patients were R/R after one to three prior lines of therapy. Participants remained on their assigned treatment regimen unless they experienced intolerable adverse events, and were followed for a median of nearly 35 months.

The 36-month rate of progression-free survival, the study’s primary endpoint, was achieved in 83.4% of participants who received Tec-Dara and 29.7% of those receiving DPd/DVd, a substantial improvement in favor of Tec-Dara. This benefit was consistent across subgroups of patients by age, prior treatment, tumor genetics, and other factors.

In addition to being a highly efficacious treatment for R/R multiple myeloma as early as the first relapse, researchers noted that the Tec-Dara combination could be more accessible than other second-line therapies for multiple myeloma as it could be delivered in community settings, not just academic centers.

Tec-Dara outperformed DPd/DVd in terms of the trial’s secondary efficacy endpoints as well as quality of life outcomes and had a safety profile comparable to the control arm. Patients receiving Tec-Dara were significantly more likely to achieve a complete response or better, which occurred in 81.8% of patients receiving Tec-Dara and 32.1% among the control arm. They were also more likely to test negative for minimal residual disease (MRD), a sensitive test for remaining cancer cells, with 58.4% of those in the Tec-Dara arm achieving MRD-negativity compared with 17.1% in the control arm. Overall survival was also higher in the Tec-Dara arm, with 83.3% of patients in this group being alive at 36 months compared with 65.0% in the control arm.

The results showed comparable rates of treatment-emergent adverse events, with 95.1% of patients in the Tec-Dara arm and 96.6% of those in the control arm experiencing grade 3-4 adverse events. Rates of serious adverse events and discontinuations due to adverse events were also comparable between groups, researchers reported.

The rate of infections was higher among those receiving Tec-Dara, with 96.5% of patients in this group experiencing infections compared with 84.1% in the control group. The onset of higher-grade infections decreased over time, and researchers noted that strategies for managing infections also improved over the course of the study. Low-grade cytokine release syndrome (CRS) was also common, with grade 1-2 CRS occurring in 60.1% of those receiving Tec-Dara.

One limitation of the study is that patients refractory to daratumumab were not included in the trial. However, some patients (5%) had received daratumumab as part of their first-line therapy and benefited equally from the Tec-Dara combination.

Dr. Mateos noted that future studies could help clarify how doctors might select which patients would benefit most from the Tec-Dara combination in comparison to other therapies. Trials involving other bispecific antibody combinations are also underway and could shed additional light on the optimal use of such combinations as early as the first relapse.

Source: American Society of Hematology

Categories : Mental HealthTags :

New Study Radically Shifts Ideas About Psychosis and Delusions

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New paper challenges old notions of ‘glitched brain’ idea of delusions and instead focuses on physical experiences of strong and deeply held emotion.

Photo by Alex Green on Pexels

People experiencing delusions during an episode of psychosis may be ‘living out’ a deeply held emotion, according to new research that provides a ‘radically different perspective’ on one of the most puzzling elements of psychosis.

About 2–3% of the UK and Australian population will experience psychosis at some point in their lives, with people commonly experiencing their first psychotic episode between the ages of 16 and 30 years old. Delusions are often described as fixed or false beliefs, understood to be reasoning or cognitive deficits and usually portrayed as incomprehensible and bizarre in popular culture.

New research by the University of Birmingham, University of Melbourne, and the University of York, in collaboration with the Australian youth mental health research institute Orygen, offers the first-known study of how delusions in psychosis are shaped by emotions and language, leading those experiencing delusions to ‘live in metaphor.’

The study has been published in The Lancet Psychiatry.

Our research provides a radically different perspective on psychotic delusions, demonstrating how they emerge from the emotional, bodily, and linguistic fabric of people’s lives.Dr Rosa Ritunnano, University of Birmingham

Conducted with young adults receiving care from Early Intervention in Psychosis services, the research combines clinical assessment, phenomenological interviews, and life-story narratives to explore how people’s sense of self and their perception of reality change during psychosis.

Dr Rosa Ritunnano, from the Institute for Mental Health at the University of Birmingham, consultant psychiatrist and author of the study, said: “Our research provides a radically different perspective on psychotic delusions, demonstrating how they emerge from the emotional, bodily, and linguistic fabric of people’s lives.

“For a long time, clinicians have struggled to understand where delusions come from and how they take shape. Our research offers new insight by showing how delusions are grounded in emotional experiences that involve great bodily turmoil.”

Strong emotions

The findings reveal that delusions are not isolated ideas produced by ‘glitches in the brain,’ but they reflect distinctive patterns of the body reacting to strong emotions or experiences of dissociation.

Participants described alternating states of intense emotional embodiment, such as feeling exposed, powerful, or connected to God, and disembodiment, such as feeling unreal or detached from one’s body, other people, and the world.

Before the delusions started, people often went through upsetting or traumatic experiences that triggered the same intense feelings they later felt during the delusions, especially being shamed.

Repeated negative experiences such as being publicly mocked and shamed by bullies could induce the bodily perception of being surveilled by others when no one is present (so-called ‘reference delusions’). These turn into persecutory beliefs that others are out to get them, and that an audience can literally see what they are doing or hear what they are thinking at all times — leaving no space for privacy (delusions of ‘thought broadcasting’).

Importantly, delusional experiences were not always negative. For some participants, they involved powerful feelings of awe, love, and spiritual connection, fostering a positive sense of identity and a renewed sense of hope about the future.

Figurative language

A striking feature of participants’ accounts was their use of figurative and metonymic language (expressions linking bodily sensations with complex emotions or abstract ideas). This helps explain why delusional content can appear unusual or bizarre. For instance, feeling ‘exposed’ or ‘tainted’ might be expressed through the beliefs of being watched by cameras or being contaminated (as in delusions of parasitosis).

As a result of having endured strong (often negative) emotional experiences, which are then responded to by the body, and shaped by everyday language use, people experiencing psychotic delusions really are living in metaphor. People may feel delighted and say they are so happy they can ‘touch the sky’; this could lead them to experience the delusion of thinking they can fly.Professor Jeannette Littlemore, University of Birmingham

The language reflects how emotion concepts take shape in bodily experiences, establishing fundamental cognitive links between, for instance, the emotion of parental love and the physical sensation of warmth, or the emotion of shame and the physical sensation of being ‘seen’ by others.

Jeannette Littlemore, Professor of Linguistics and Communication at the University of Birmingham and co-author of the paper, said: “We all use metaphors and narratives to understand our experiences and make sense of our lives. But psychosis patients do so more intensely. As a result of having endured strong (often negative) emotional experiences, which are then responded to by the body, and shaped by everyday language use, people experiencing psychotic delusions really are living in metaphor. People may feel delighted and say they are so happy they can ‘touch the sky’; this could lead them to experience the delusion of thinking they can fly.”

The study argues that better insight into how delusions come about can be used to create more effective care for people experiencing psychosis. Participants felt that there was no space to talk about the meaning of their delusions in the context of their treatment and recovery from psychosis, which led to more shame and increased the sense of being dismissed and marginalised.

The researchers highlight the importance of attending to people’s bodily and emotional worlds, and how they express them, when developing compassionate, effective approaches to psychosis care.

The paper concludes that delusions are not simply beliefs gone wrong, but embodied attempts to restore meaning and emotional balance when life becomes overwhelming. The metaphors and narratives people use are keys to understanding their suffering and are not signs of irrationality.

Source: University of Birmingham

Categories : General InterestTags :

Hyundai Automotive South Africa Reaffirms Disability Inclusion and Mobility for All

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Photo by Ivan S

Hyundai Automotive South Africa reaffirmed its commitment towards embedding disability inclusion into its operations, through continuous  disability-related employee training, improving dealership layouts and vehicle modifications. 

The aim is to foster a culture that recognises disability as part of human diversity rather than a limitation.  “Mobility is not just about getting from one point to another, rather, about access and dignity,” said Stanley Anderson, CEO of Hyundai Automotive South Africa. 

“Our commitment is to ensure our vehicles and dealerships are adequately prepared to support the needs of all customers, including those with disabilities.  More importantly, we want to empower our customer-facing employees with deeper understanding of disability, dismantle misconceptions.  By so doing, we will ensure that customers with disabilities feel welcomed, respected and supported when visiting any Hyundai dealership.”

It has also implemented a range of practical measures to ensure its dealerships are physically accessible and welcoming to persons with disabilities.  This includes improving dealership layouts for ease of movement, ensuring wheelchair-friendly access points. 

The company works closely with a range of specialised suppliers who modify some of its vehicles to suit the mobility needs of persons with disabilities.  “These partnerships ensure that more South Africans can access safe, reliable and custom-adapted mobility solutions suited to their lifestyles and independence,” stated Christine Masinga, Human Resources Director at Hyundai Automotive South Africa.

The national disability prevalence rate in South Africa is estimated at around 7.5%.  Despite national government targets for 2% representation of persons with disabilities in workplaces, recent reports indicate that they comprise less than 1% of the total employees across both government and private companies.

According to the Department of Employment and Labour, eight out of ten disabled persons are unemployed nationally, which is significantly higher than the general unemployment rate.

Categories : Environmental EffectsTags :

Many BPA Replacements may be Even More Toxic

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McGill researchers studying printed stickers on packaged food find some chemicals now used instead of bisphenol A can disrupt human ovarian cell function, and warn that ‘BPA-free’ does not necessarily mean safe

Photo by Polina Tankilevitch

Chemicals used to replace bisphenol A (BPA) in food packaging can trigger potentially harmful effects in human ovarian cells, according to McGill University researchers.

A new study examined several chemicals commonly used in price stickers on packaged meat, fish, cheese and produce found early signs of potential toxicity.

The findings, published in the journal Toxicological Sciences, raise concerns about the safety of BPA-free packaging and whether current regulations go far enough to protect consumers.

BPA substitutes disrupt gene expression

The research began with the 2023 discovery by Stéphane Bayen, Associate Professor in McGill’s Department of Food Science and Agricultural Chemistry, that label-printing chemicals like bisphenol S (BPS), a BPA replacement, were leaching through plastic wrap into the food. He teamed up with colleagues in reproductive toxicology to investigate what these substances could be doing inside the body.

Lab-grown human ovarian cells were exposed to four commonly used BPA substitutes: TGSA, D-8, PF-201 and BPS. Several of the chemicals, particularly TGSA and D-8, caused a buildup of fat droplets in the cells and changed the activity of genes that help cells grow and repair their DNA.

“These are major cellular functions,” said Bernard Robaire, co-senior author of the study and James McGill Professor in McGill’s Departments of Pharmacology & Therapeutics and Obstetrics & Gynecology. “Disrupting them doesn’t prove harm in humans, but it gives us a strong signal that these chemicals should be further investigated.”

Unregulated replacements under the radar

BPA is a chemical that can interfere with the body’s hormones, and has been linked to problems with fertility, early development and metabolism. Because of these risks, it has been banned in baby bottles and restricted in some products in Canada.

Many of the chemicals used to replace BPA are not regulated or routinely tested, the researchers explained.

“‘BPA-free’ is an incredibly misleading label,” said Robaire. “It usually means one bisphenol has been swapped for another, and there are more than 200 of them. Some may be just as harmful, or even worse. We need to test these compounds before they’re widely adopted, not after.”

Health Canada has now added all four substances to a list of chemicals requiring further investigation.

For consumers looking to err on the side of caution, Robaire suggests removing labels and plastic wrap from fresh foods before storing. He also recommends choosing items from the top of store display piles rather than the bottom, where pressure from stacking may push chemicals more deeply into the packaging and food.

Source: McGill University

Categories : Cardiovascular DiseaseTags :

Calcium Leak is the Culprit Behind Statin Muscle Pains

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Photo by Kampus Production

Many people stop taking cholesterol-lowering statins because they experience muscle aches, weakness, and fatigue. A new study by Columbia researchers now suggests that at least for some people, the side effects arise when statins bind to a protein in muscle cells and cause a leak of calcium ions inside the cells.

“It is unlikely that this explanation applies to everyone who experiences muscular side effects with statins, but even if it explains a small subset, that’s a lot of people we could help if we can resolve the issue,” says Andrew Marks, chair of the Department of Physiology and Cellular Biophysics at the Vagelos College of Physicians and Surgeons.

About 10% of adults taking statins experience these muscular side effects.

“I’ve had patients who’ve been prescribed statins, and they refused to take them because of the side effects. It’s the most common reason patients quit statins, and it’s a very real problem that needs a solution,” says Marks.

Electron microscopy pinpoints statin-muscle interaction

Statins’ muscular side effects have puzzled researchers since the drugs hit the market in the late 80s. Statins are designed to lower cholesterol by binding to an enzyme involved in cholesterol synthesis. But statins also bind to other “off-target” molecules, and some previous studies have suggested that muscular side effects occur when statins bind to a specific protein in muscle.

With cryo-electron microscopy, a technique that can image molecules down to individual atoms, the researchers of the new study documented this binding and uncovered the precise details of the interaction.

Simvastatin molecules bind to two locations on a muscle protein, called the ryanodine receptor, which opens a channel in the receptor. The flow of calcium through the open channel could explain the muscular side effects of statins.

The images revealed two locations on the muscle protein, called the ryanodine receptor, where a statin called simvastatin binds, opening a channel in the receptor and allowing calcium to flow through.

The calcium leak could explain the muscular side effects of statins, Marks says, by weakening the muscle directly or by activating enzymes that degrade muscle tissue.

Building a better statin

The new images also suggest that statins could be redesigned so they do not bind the ryanodine receptor but retain their cholesterol-lowering ability.

Marks is now collaborating with chemists to create such a statin.

Plugging the calcium leak could be another option: Statin-induced calcium leaks in mice can be closed, the researchers showed, with an experimental drug developed in the Marks lab for other conditions involving calcium leaks.

These drugs are currently being tested in people with rare muscle diseases. If it shows efficacy in those patients, we can test it in statin-induced myopathies,” Marks says

Source: Columbia University Irving Medical Center