Conference Coverage

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. 

In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.

Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
 

Time to Rationalize Healthcare Resources?

People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.

Sara Freeman/Medscape Medical News

“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.

“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study. 

Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.

People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.

A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
 

Two Distinct Studies

ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.

Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.

ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.

“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.

The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).

TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).

This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.

TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.

SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.

The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. 
 

ReMonit Results

Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.

For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.

Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.

Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
 

TeleSpA Results

In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.

Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.

And more than 90% of participants in both groups reported having an overall good experience with their care.

Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”

In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. 

Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. 

Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.

“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”

ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.

A version of this article first appeared on Medscape.com.

Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. 

In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.

Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
 

Time to Rationalize Healthcare Resources?

People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.

Sara Freeman/Medscape Medical News

“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.

“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study. 

Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.

People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.

A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
 

Two Distinct Studies

ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.

Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.

ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.

“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.

The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).

TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).

This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.

TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.

SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.

The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. 
 

ReMonit Results

Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.

For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.

Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.

Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
 

TeleSpA Results

In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.

Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.

And more than 90% of participants in both groups reported having an overall good experience with their care.

Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”

In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. 

Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. 

Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.

“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”

ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.

A version of this article first appeared on Medscape.com.

Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. 

In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.

Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
 

Time to Rationalize Healthcare Resources?

People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.

Sara Freeman/Medscape Medical News

“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.

“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study. 

Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.

People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.

A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
 

Two Distinct Studies

ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.

Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.

ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.

“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.

The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).

TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).

This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.

TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.

SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.

The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. 
 

ReMonit Results

Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.

For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.

Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.

Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
 

TeleSpA Results

In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.

Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.

And more than 90% of participants in both groups reported having an overall good experience with their care.

Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”

In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. 

Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. 

Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.

“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”

ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.

A version of this article first appeared on Medscape.com.

Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.

“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.

“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.

Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
 

Study Methods and Results

Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.

Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.

The study’s primary endpoint was the residual cancer burden at the time of surgery.

Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.

While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.

In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).

The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”

The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).

Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
 

Ideas for Further Study of Tecemotide

“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.

Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”

Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.

The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.

“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.

“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.

Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
 

Study Methods and Results

Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.

Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.

The study’s primary endpoint was the residual cancer burden at the time of surgery.

Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.

While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.

In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).

The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”

The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).

Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
 

Ideas for Further Study of Tecemotide

“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.

Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”

Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.

The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.

“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.

“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.

Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
 

Study Methods and Results

Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.

Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.

The study’s primary endpoint was the residual cancer burden at the time of surgery.

Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.

While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.

In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).

The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”

The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).

Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
 

Ideas for Further Study of Tecemotide

“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.

Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”

Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.

Marstacimab, a novel, investigational monoclonal antibody, shows long-term safety and efficacy in the prevention of bleeding events in patients with hemophilia A as well as B without inhibitors, potentially adding to the toolbox for hemophilia A and representing a first of its kind therapy for hemophilia B.

“In the long-term extension study treatment with marstacimab demonstrates sustained or improved efficacy for treated and total annualized bleeding rates (ABR) in adults and adolescents with hemophilia A or hemophilia B in this data set of patients without inhibitors,” first author Shamsah Kazani, MD, of Pfizer, Cambridge, Massachusetts, said in presenting the findings at the 2024 annual meeting of the European Hematology Association (EHA) in Madrid.

“The majority of the patients from the pivotal study chose to transition into the long-term extension, and we are finding that these patients are highly compliant with their weekly marstacimab dose, with more than 98% compliance,” Dr. Kazani said.

Marstacimab targets the tissue factor pathway inhibitor, a natural anticoagulation protein that prevents the formation of blood clots, and is administered as a once-weekly subcutaneous injection.

The therapy has been granted fast-track and orphan drug status in the United States, in addition to orphan drug status in the European Union for the prevention of hemophilia bleeding episodes.

If approved, the therapy would become the first once-weekly subcutaneous therapy for either hemophilia A or B. Emicizumab, which also is administered subcutaneously, is only approved to prevent or reduce bleeding in hemophilia A.

The latest findings are from an interim analysis of a long-term extension study involving 107 of 116 patients who were in the non-inhibitor cohort in the pivotal BASIS trial. Data from that trial, involving patients aged 12-75 previously showed favorable outcomes in the non-inhibitor cohort receiving marstacimab, and a cohort of patients with inhibitors is ongoing.

Participants entering the extension study were continuing on 150-mg subcutaneous doses of marstacimab, which had been administered in the BASIS study for 12 months after a loading dose of 300 mg.

Of the patients, 89 (83%) were adult and 18 (17%) were adolescents. Overall, they had a mean age of 29 years; 83 (76%) patients had hemophilia A, while 24 (22.4%) had hemophilia B.

Prior to switching to marstacimab treatment, 32 patients had been treated with factor replacement therapy on demand, while 75 received the therapy as routine prophylaxis.

With a mean additional duration of follow-up of 12.5 months in the extension study (range, 1-23.1 months), the overall rate of compliance was very high, at 98.9%.

In the pivotal and extension studies combined, 21% of patients had their marstacimab dose increased from 150 mg to 300 mg weekly, which was an option if patients had 2 or more spontaneous bleeds in a major joint while on the 150-mg dose.

In the hemophilia A and B groups combined, those previously treated with on-demand factor replacement therapy (n = 33) had substantial reductions in estimated ABR for treated bleeds from the baseline of 38.0 prior to initiating marstacimab, to 3.2 after 12 months of the treatment in the trial (P < .001).That reduction was sustained at an ABR of 3.7 after the mean additional 12.5 months in the extension study.

The corresponding estimated ABR rates in the routine prophylaxis group (n = 83) were 7.9 at baseline, 5.1 at the end of the trial, and 2.8 in the extension study analysis interim cutoff.

The authors then further stratified the results based on hemophilia A or B groups: Among patients with hemophilia A (n = 26), the on-demand subgroup had a baseline ABR of 40.6, which dropped substantially to just 3.6 after 12 months on marstacimab in the pivotal trial and was sustained at 5.3 in the extension study.

Similar trends were observed in the hemophilia A group who received routine prophylaxis (n = 65), with an ABR of 9.2 at baseline; 5.3 after the trial, and 3.1 at the extension study interim.

The trends were similar among those with hemophilia B, albeit with lower numbers of patients, consistent with hemophilia B being more rare.

The mean ABR at baseline in the on-demand group of those patients (n = 7) was 28.7, which was reduced to just 1.7 after the 12-months of active marstacimab treatment and sustained at 1.8 by the interim analysis of the extension study.

Of hemophilia B patients previously on routine prophylaxis (n = 18), the mean ABR at baseline was 3.3 and was at 4.7 at the end of the trial. The rate declined to 2.3 in the extension phase.

“We see that these trends of improvement with marstacimab are sustained into the long-term extension study, both in the on-demand group and in the routine prophylaxis groups,” Dr. Kazani said.

Importantly, she noted that marstacimab continued to be well tolerated and safe in the long-term extension study, with no reports of thromboembolic events, which had been a concern with the drug.

Commenting on the study, Margaret Ragni, MD, MPH, a professor of medicine and clinical and translational research in the Division of Hematology/Oncology at the University of Pittsburgh, Pittsburgh, Pennsylvania, noted that marstacimab could represent an important addition in the prevention of bleeds in hemophilia. “[If marstacimab is approved], hemophilia B patients [will] have a drug that can be given subcutaneously weekly to rebalance hemostasis, reducing bleeds, just as hemophilia A patients have with emicizumab.”

Dr. Ragni underscored, however, that caveats include the important point that “neither [marstacimab nor emicizumab] treats bleeds. For that, standard factor replacement therapy or bypass for inhibitors, would be required.”

Also, “a limitation with marstacimab is the lack of weight-dependent dosing. All use one dose [however, in the studies they did use 150 mg or 300 mg]. ... Furthermore, emicizumab can be given weekly, biweekly, or monthly, while that [variation in dosing] is not yet studied with marstacimab.”

And while no thromboembolic events occurred during the trial, Dr. Ragni underscored that “longer-term follow-up is needed.”

The marstacimab long-term extension study is designed to extend to 7 years of follow-up.

The study was sponsored by Pfizer, and Dr. Kazani is an employee of Pfizer. Dr. Ragni reported no disclosures.

Marstacimab, a novel, investigational monoclonal antibody, shows long-term safety and efficacy in the prevention of bleeding events in patients with hemophilia A as well as B without inhibitors, potentially adding to the toolbox for hemophilia A and representing a first of its kind therapy for hemophilia B.

“In the long-term extension study treatment with marstacimab demonstrates sustained or improved efficacy for treated and total annualized bleeding rates (ABR) in adults and adolescents with hemophilia A or hemophilia B in this data set of patients without inhibitors,” first author Shamsah Kazani, MD, of Pfizer, Cambridge, Massachusetts, said in presenting the findings at the 2024 annual meeting of the European Hematology Association (EHA) in Madrid.

“The majority of the patients from the pivotal study chose to transition into the long-term extension, and we are finding that these patients are highly compliant with their weekly marstacimab dose, with more than 98% compliance,” Dr. Kazani said.

Marstacimab targets the tissue factor pathway inhibitor, a natural anticoagulation protein that prevents the formation of blood clots, and is administered as a once-weekly subcutaneous injection.

The therapy has been granted fast-track and orphan drug status in the United States, in addition to orphan drug status in the European Union for the prevention of hemophilia bleeding episodes.

If approved, the therapy would become the first once-weekly subcutaneous therapy for either hemophilia A or B. Emicizumab, which also is administered subcutaneously, is only approved to prevent or reduce bleeding in hemophilia A.

The latest findings are from an interim analysis of a long-term extension study involving 107 of 116 patients who were in the non-inhibitor cohort in the pivotal BASIS trial. Data from that trial, involving patients aged 12-75 previously showed favorable outcomes in the non-inhibitor cohort receiving marstacimab, and a cohort of patients with inhibitors is ongoing.

Participants entering the extension study were continuing on 150-mg subcutaneous doses of marstacimab, which had been administered in the BASIS study for 12 months after a loading dose of 300 mg.

Of the patients, 89 (83%) were adult and 18 (17%) were adolescents. Overall, they had a mean age of 29 years; 83 (76%) patients had hemophilia A, while 24 (22.4%) had hemophilia B.

Prior to switching to marstacimab treatment, 32 patients had been treated with factor replacement therapy on demand, while 75 received the therapy as routine prophylaxis.

With a mean additional duration of follow-up of 12.5 months in the extension study (range, 1-23.1 months), the overall rate of compliance was very high, at 98.9%.

In the pivotal and extension studies combined, 21% of patients had their marstacimab dose increased from 150 mg to 300 mg weekly, which was an option if patients had 2 or more spontaneous bleeds in a major joint while on the 150-mg dose.

In the hemophilia A and B groups combined, those previously treated with on-demand factor replacement therapy (n = 33) had substantial reductions in estimated ABR for treated bleeds from the baseline of 38.0 prior to initiating marstacimab, to 3.2 after 12 months of the treatment in the trial (P < .001).That reduction was sustained at an ABR of 3.7 after the mean additional 12.5 months in the extension study.

The corresponding estimated ABR rates in the routine prophylaxis group (n = 83) were 7.9 at baseline, 5.1 at the end of the trial, and 2.8 in the extension study analysis interim cutoff.

The authors then further stratified the results based on hemophilia A or B groups: Among patients with hemophilia A (n = 26), the on-demand subgroup had a baseline ABR of 40.6, which dropped substantially to just 3.6 after 12 months on marstacimab in the pivotal trial and was sustained at 5.3 in the extension study.

Similar trends were observed in the hemophilia A group who received routine prophylaxis (n = 65), with an ABR of 9.2 at baseline; 5.3 after the trial, and 3.1 at the extension study interim.

The trends were similar among those with hemophilia B, albeit with lower numbers of patients, consistent with hemophilia B being more rare.

The mean ABR at baseline in the on-demand group of those patients (n = 7) was 28.7, which was reduced to just 1.7 after the 12-months of active marstacimab treatment and sustained at 1.8 by the interim analysis of the extension study.

Of hemophilia B patients previously on routine prophylaxis (n = 18), the mean ABR at baseline was 3.3 and was at 4.7 at the end of the trial. The rate declined to 2.3 in the extension phase.

“We see that these trends of improvement with marstacimab are sustained into the long-term extension study, both in the on-demand group and in the routine prophylaxis groups,” Dr. Kazani said.

Importantly, she noted that marstacimab continued to be well tolerated and safe in the long-term extension study, with no reports of thromboembolic events, which had been a concern with the drug.

Commenting on the study, Margaret Ragni, MD, MPH, a professor of medicine and clinical and translational research in the Division of Hematology/Oncology at the University of Pittsburgh, Pittsburgh, Pennsylvania, noted that marstacimab could represent an important addition in the prevention of bleeds in hemophilia. “[If marstacimab is approved], hemophilia B patients [will] have a drug that can be given subcutaneously weekly to rebalance hemostasis, reducing bleeds, just as hemophilia A patients have with emicizumab.”

Dr. Ragni underscored, however, that caveats include the important point that “neither [marstacimab nor emicizumab] treats bleeds. For that, standard factor replacement therapy or bypass for inhibitors, would be required.”

Also, “a limitation with marstacimab is the lack of weight-dependent dosing. All use one dose [however, in the studies they did use 150 mg or 300 mg]. ... Furthermore, emicizumab can be given weekly, biweekly, or monthly, while that [variation in dosing] is not yet studied with marstacimab.”

And while no thromboembolic events occurred during the trial, Dr. Ragni underscored that “longer-term follow-up is needed.”

The marstacimab long-term extension study is designed to extend to 7 years of follow-up.

The study was sponsored by Pfizer, and Dr. Kazani is an employee of Pfizer. Dr. Ragni reported no disclosures.

Marstacimab, a novel, investigational monoclonal antibody, shows long-term safety and efficacy in the prevention of bleeding events in patients with hemophilia A as well as B without inhibitors, potentially adding to the toolbox for hemophilia A and representing a first of its kind therapy for hemophilia B.

“In the long-term extension study treatment with marstacimab demonstrates sustained or improved efficacy for treated and total annualized bleeding rates (ABR) in adults and adolescents with hemophilia A or hemophilia B in this data set of patients without inhibitors,” first author Shamsah Kazani, MD, of Pfizer, Cambridge, Massachusetts, said in presenting the findings at the 2024 annual meeting of the European Hematology Association (EHA) in Madrid.

“The majority of the patients from the pivotal study chose to transition into the long-term extension, and we are finding that these patients are highly compliant with their weekly marstacimab dose, with more than 98% compliance,” Dr. Kazani said.

Marstacimab targets the tissue factor pathway inhibitor, a natural anticoagulation protein that prevents the formation of blood clots, and is administered as a once-weekly subcutaneous injection.

The therapy has been granted fast-track and orphan drug status in the United States, in addition to orphan drug status in the European Union for the prevention of hemophilia bleeding episodes.

If approved, the therapy would become the first once-weekly subcutaneous therapy for either hemophilia A or B. Emicizumab, which also is administered subcutaneously, is only approved to prevent or reduce bleeding in hemophilia A.

The latest findings are from an interim analysis of a long-term extension study involving 107 of 116 patients who were in the non-inhibitor cohort in the pivotal BASIS trial. Data from that trial, involving patients aged 12-75 previously showed favorable outcomes in the non-inhibitor cohort receiving marstacimab, and a cohort of patients with inhibitors is ongoing.

Participants entering the extension study were continuing on 150-mg subcutaneous doses of marstacimab, which had been administered in the BASIS study for 12 months after a loading dose of 300 mg.

Of the patients, 89 (83%) were adult and 18 (17%) were adolescents. Overall, they had a mean age of 29 years; 83 (76%) patients had hemophilia A, while 24 (22.4%) had hemophilia B.

Prior to switching to marstacimab treatment, 32 patients had been treated with factor replacement therapy on demand, while 75 received the therapy as routine prophylaxis.

With a mean additional duration of follow-up of 12.5 months in the extension study (range, 1-23.1 months), the overall rate of compliance was very high, at 98.9%.

In the pivotal and extension studies combined, 21% of patients had their marstacimab dose increased from 150 mg to 300 mg weekly, which was an option if patients had 2 or more spontaneous bleeds in a major joint while on the 150-mg dose.

In the hemophilia A and B groups combined, those previously treated with on-demand factor replacement therapy (n = 33) had substantial reductions in estimated ABR for treated bleeds from the baseline of 38.0 prior to initiating marstacimab, to 3.2 after 12 months of the treatment in the trial (P < .001).That reduction was sustained at an ABR of 3.7 after the mean additional 12.5 months in the extension study.

The corresponding estimated ABR rates in the routine prophylaxis group (n = 83) were 7.9 at baseline, 5.1 at the end of the trial, and 2.8 in the extension study analysis interim cutoff.

The authors then further stratified the results based on hemophilia A or B groups: Among patients with hemophilia A (n = 26), the on-demand subgroup had a baseline ABR of 40.6, which dropped substantially to just 3.6 after 12 months on marstacimab in the pivotal trial and was sustained at 5.3 in the extension study.

Similar trends were observed in the hemophilia A group who received routine prophylaxis (n = 65), with an ABR of 9.2 at baseline; 5.3 after the trial, and 3.1 at the extension study interim.

The trends were similar among those with hemophilia B, albeit with lower numbers of patients, consistent with hemophilia B being more rare.

The mean ABR at baseline in the on-demand group of those patients (n = 7) was 28.7, which was reduced to just 1.7 after the 12-months of active marstacimab treatment and sustained at 1.8 by the interim analysis of the extension study.

Of hemophilia B patients previously on routine prophylaxis (n = 18), the mean ABR at baseline was 3.3 and was at 4.7 at the end of the trial. The rate declined to 2.3 in the extension phase.

“We see that these trends of improvement with marstacimab are sustained into the long-term extension study, both in the on-demand group and in the routine prophylaxis groups,” Dr. Kazani said.

Importantly, she noted that marstacimab continued to be well tolerated and safe in the long-term extension study, with no reports of thromboembolic events, which had been a concern with the drug.

Commenting on the study, Margaret Ragni, MD, MPH, a professor of medicine and clinical and translational research in the Division of Hematology/Oncology at the University of Pittsburgh, Pittsburgh, Pennsylvania, noted that marstacimab could represent an important addition in the prevention of bleeds in hemophilia. “[If marstacimab is approved], hemophilia B patients [will] have a drug that can be given subcutaneously weekly to rebalance hemostasis, reducing bleeds, just as hemophilia A patients have with emicizumab.”

Dr. Ragni underscored, however, that caveats include the important point that “neither [marstacimab nor emicizumab] treats bleeds. For that, standard factor replacement therapy or bypass for inhibitors, would be required.”

Also, “a limitation with marstacimab is the lack of weight-dependent dosing. All use one dose [however, in the studies they did use 150 mg or 300 mg]. ... Furthermore, emicizumab can be given weekly, biweekly, or monthly, while that [variation in dosing] is not yet studied with marstacimab.”

And while no thromboembolic events occurred during the trial, Dr. Ragni underscored that “longer-term follow-up is needed.”

The marstacimab long-term extension study is designed to extend to 7 years of follow-up.

The study was sponsored by Pfizer, and Dr. Kazani is an employee of Pfizer. Dr. Ragni reported no disclosures.

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

A version of this article first appeared on Medscape.com.

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

A version of this article first appeared on Medscape.com.

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

A version of this article first appeared on Medscape.com.

CHICAGO — Surgical resection is the standard of care for small colorectal liver metastases, but the results of a phase 3 trial reported at the American Society of Clinical Oncology (ASCO) 2024 annual meeting may prompt a change.

At nearly 30 months of follow-up, European investigators found no difference in overall and progression-free survival with thermal ablation instead of surgery, as well as better local control, fewer adverse events, shorter hospital stays, and no treatment-related deaths.

The benefit of thermal ablation was so substantial that the trial was stopped early with about 300 of the planned 600 patients randomized.

Numerous retrospective studies have compared the two approaches, and some have reported better survival with surgery. As a result, although a large number of lesions are amenable to either approach, “the majority of colorectal liver mets [are] still being” resected, said lead investigator and presenter Martijn R. Meijerink, MD, PhD, an interventional radiologist at the Amsterdam University Medical Center, Amsterdam, the Netherlands.

Dr. Meijerink said many of the previous reviews were unreliable due to selection bias because patients only had ablation if their lesions couldn’t be removed surgically. In contrast, all patients in the COLLISION trial were eligible for resection.

“Thermal ablation in experienced centers seems to be at least as good as surgical resection for small liver tumors.” Patients would benefit if it replaced surgery as the standard of care with no compromise in survival, Dr. Meijerink added.

The 296 COLLISION patients were treated at 14 centers in the Netherlands, Belgium, and Italy. They had no more than 12 liver lesions 3 cm or smaller with a median of two lesions. Participants were split equally between the ablation and surgical arms of the trial.

Almost half of the surgeries were laparoscopic, and nearly 60% of the ablations were percutaneous. Recent technological advances were used in the ablation cases, including software to confirm the complete eradication of targeted metastases.

At 28.8 months, there was no difference in overall survival between treatment arms (hazard ratio [HR], 1.051; P = .813) and no difference in local (HR, 0.817; P = .53) and distant (HR, 1.03; P = .836) progression-free survival. Local control — meaning treated lesions didn’t grow back — favored thermal ablation (HR, 0.092; P = .024).

The results held across number subgroup analyses, including by stage, molecular profile, and number of lesions.

“Interestingly, the majority of ablation site recurrences were somehow retreated, and most of them successfully, [while] the majority of resection plane recurrences were not retreated,” Dr. Meijerink said.

Patients with ablation vs surgery spent a median of 1 day vs 4 days in the hospital. Almost 20% of patients in the surgery group had grade 3/4 treatment-related adverse events vs 6% of those in the ablation group, which isn’t surprising, Dr. Meijerink said, because “the needle is less invasive than a knife.”

Three patients (2.1%) died of surgical complications, but there were no treatment-related deaths with ablation.

Major Kenneth Lee, MD, PhD, a gastrointestinal surgeon at the University of Pennsylvania, Philadelphia, who was the study discussant, emphasized the importance of gathering prospective data to compare the two approaches fairly.

“Ablation appears equivalent to resection for small, ideally located colorectal liver mets,” he said. Still, longer follow-up is needed to ensure that cure rates with ablation match those with surgery.

The study was funded by Medtronic-Covidien, a maker of thermal ablation equipment. Among other industry ties, Dr. Meijerink reported receiving honoraria and research funding from Medtronic and advising the company. Dr. Lee didn’t have any disclosures.

A version of this article appeared on Medscape.com.

CHICAGO — Surgical resection is the standard of care for small colorectal liver metastases, but the results of a phase 3 trial reported at the American Society of Clinical Oncology (ASCO) 2024 annual meeting may prompt a change.

At nearly 30 months of follow-up, European investigators found no difference in overall and progression-free survival with thermal ablation instead of surgery, as well as better local control, fewer adverse events, shorter hospital stays, and no treatment-related deaths.

The benefit of thermal ablation was so substantial that the trial was stopped early with about 300 of the planned 600 patients randomized.

Numerous retrospective studies have compared the two approaches, and some have reported better survival with surgery. As a result, although a large number of lesions are amenable to either approach, “the majority of colorectal liver mets [are] still being” resected, said lead investigator and presenter Martijn R. Meijerink, MD, PhD, an interventional radiologist at the Amsterdam University Medical Center, Amsterdam, the Netherlands.

Dr. Meijerink said many of the previous reviews were unreliable due to selection bias because patients only had ablation if their lesions couldn’t be removed surgically. In contrast, all patients in the COLLISION trial were eligible for resection.

“Thermal ablation in experienced centers seems to be at least as good as surgical resection for small liver tumors.” Patients would benefit if it replaced surgery as the standard of care with no compromise in survival, Dr. Meijerink added.

The 296 COLLISION patients were treated at 14 centers in the Netherlands, Belgium, and Italy. They had no more than 12 liver lesions 3 cm or smaller with a median of two lesions. Participants were split equally between the ablation and surgical arms of the trial.

Almost half of the surgeries were laparoscopic, and nearly 60% of the ablations were percutaneous. Recent technological advances were used in the ablation cases, including software to confirm the complete eradication of targeted metastases.

At 28.8 months, there was no difference in overall survival between treatment arms (hazard ratio [HR], 1.051; P = .813) and no difference in local (HR, 0.817; P = .53) and distant (HR, 1.03; P = .836) progression-free survival. Local control — meaning treated lesions didn’t grow back — favored thermal ablation (HR, 0.092; P = .024).

The results held across number subgroup analyses, including by stage, molecular profile, and number of lesions.

“Interestingly, the majority of ablation site recurrences were somehow retreated, and most of them successfully, [while] the majority of resection plane recurrences were not retreated,” Dr. Meijerink said.

Patients with ablation vs surgery spent a median of 1 day vs 4 days in the hospital. Almost 20% of patients in the surgery group had grade 3/4 treatment-related adverse events vs 6% of those in the ablation group, which isn’t surprising, Dr. Meijerink said, because “the needle is less invasive than a knife.”

Three patients (2.1%) died of surgical complications, but there were no treatment-related deaths with ablation.

Major Kenneth Lee, MD, PhD, a gastrointestinal surgeon at the University of Pennsylvania, Philadelphia, who was the study discussant, emphasized the importance of gathering prospective data to compare the two approaches fairly.

“Ablation appears equivalent to resection for small, ideally located colorectal liver mets,” he said. Still, longer follow-up is needed to ensure that cure rates with ablation match those with surgery.

The study was funded by Medtronic-Covidien, a maker of thermal ablation equipment. Among other industry ties, Dr. Meijerink reported receiving honoraria and research funding from Medtronic and advising the company. Dr. Lee didn’t have any disclosures.

A version of this article appeared on Medscape.com.

CHICAGO — Surgical resection is the standard of care for small colorectal liver metastases, but the results of a phase 3 trial reported at the American Society of Clinical Oncology (ASCO) 2024 annual meeting may prompt a change.

At nearly 30 months of follow-up, European investigators found no difference in overall and progression-free survival with thermal ablation instead of surgery, as well as better local control, fewer adverse events, shorter hospital stays, and no treatment-related deaths.

The benefit of thermal ablation was so substantial that the trial was stopped early with about 300 of the planned 600 patients randomized.

Numerous retrospective studies have compared the two approaches, and some have reported better survival with surgery. As a result, although a large number of lesions are amenable to either approach, “the majority of colorectal liver mets [are] still being” resected, said lead investigator and presenter Martijn R. Meijerink, MD, PhD, an interventional radiologist at the Amsterdam University Medical Center, Amsterdam, the Netherlands.

Dr. Meijerink said many of the previous reviews were unreliable due to selection bias because patients only had ablation if their lesions couldn’t be removed surgically. In contrast, all patients in the COLLISION trial were eligible for resection.

“Thermal ablation in experienced centers seems to be at least as good as surgical resection for small liver tumors.” Patients would benefit if it replaced surgery as the standard of care with no compromise in survival, Dr. Meijerink added.

The 296 COLLISION patients were treated at 14 centers in the Netherlands, Belgium, and Italy. They had no more than 12 liver lesions 3 cm or smaller with a median of two lesions. Participants were split equally between the ablation and surgical arms of the trial.

Almost half of the surgeries were laparoscopic, and nearly 60% of the ablations were percutaneous. Recent technological advances were used in the ablation cases, including software to confirm the complete eradication of targeted metastases.

At 28.8 months, there was no difference in overall survival between treatment arms (hazard ratio [HR], 1.051; P = .813) and no difference in local (HR, 0.817; P = .53) and distant (HR, 1.03; P = .836) progression-free survival. Local control — meaning treated lesions didn’t grow back — favored thermal ablation (HR, 0.092; P = .024).

The results held across number subgroup analyses, including by stage, molecular profile, and number of lesions.

“Interestingly, the majority of ablation site recurrences were somehow retreated, and most of them successfully, [while] the majority of resection plane recurrences were not retreated,” Dr. Meijerink said.

Patients with ablation vs surgery spent a median of 1 day vs 4 days in the hospital. Almost 20% of patients in the surgery group had grade 3/4 treatment-related adverse events vs 6% of those in the ablation group, which isn’t surprising, Dr. Meijerink said, because “the needle is less invasive than a knife.”

Three patients (2.1%) died of surgical complications, but there were no treatment-related deaths with ablation.

Major Kenneth Lee, MD, PhD, a gastrointestinal surgeon at the University of Pennsylvania, Philadelphia, who was the study discussant, emphasized the importance of gathering prospective data to compare the two approaches fairly.

“Ablation appears equivalent to resection for small, ideally located colorectal liver mets,” he said. Still, longer follow-up is needed to ensure that cure rates with ablation match those with surgery.

The study was funded by Medtronic-Covidien, a maker of thermal ablation equipment. Among other industry ties, Dr. Meijerink reported receiving honoraria and research funding from Medtronic and advising the company. Dr. Lee didn’t have any disclosures.

A version of this article appeared on Medscape.com.

MONTREAL – Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (CIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6-12 months post-treatment, suggesting the blood protein may provide an early CIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. She added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to CIPN.”

The findings were presented at the Peripheral Nerve Society (PNS) 2024 annual meeting.
 

Common, Burdensome Side Effect

A common side effect of chemotherapy, CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale, and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing, for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed CIPN, which was mild in 44% and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P < .001), “highlighting that nerve damage occurs from the very beginning of treatment,” senior investigator Susanna Park, PhD, told this news organization. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ .026], and higher TNS scores [P ≤ .00]),” added Dr. Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Dr. Park. 

“Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Dr. Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 
 

Promising Research

Commenting on the research for this news organization, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Dr. Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Dr. Lustberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

MONTREAL – Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (CIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6-12 months post-treatment, suggesting the blood protein may provide an early CIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. She added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to CIPN.”

The findings were presented at the Peripheral Nerve Society (PNS) 2024 annual meeting.
 

Common, Burdensome Side Effect

A common side effect of chemotherapy, CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale, and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing, for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed CIPN, which was mild in 44% and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P < .001), “highlighting that nerve damage occurs from the very beginning of treatment,” senior investigator Susanna Park, PhD, told this news organization. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ .026], and higher TNS scores [P ≤ .00]),” added Dr. Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Dr. Park. 

“Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Dr. Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 
 

Promising Research

Commenting on the research for this news organization, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Dr. Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Dr. Lustberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

MONTREAL – Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (CIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6-12 months post-treatment, suggesting the blood protein may provide an early CIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. She added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to CIPN.”

The findings were presented at the Peripheral Nerve Society (PNS) 2024 annual meeting.
 

Common, Burdensome Side Effect

A common side effect of chemotherapy, CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale, and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing, for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed CIPN, which was mild in 44% and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P < .001), “highlighting that nerve damage occurs from the very beginning of treatment,” senior investigator Susanna Park, PhD, told this news organization. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ .026], and higher TNS scores [P ≤ .00]),” added Dr. Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Dr. Park. 

“Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Dr. Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 
 

Promising Research

Commenting on the research for this news organization, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Dr. Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Dr. Lustberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.