Hematology News

Three cups of tea, two biscuit packs, and a Christmas study from the BMJ

Warning: The following content may contain excessive Britishness. Continue at your own risk.

It’s no secret that the world economy is in an … interesting spot right now. Belt tightening is occurring around the world despite the holiday season, and hospitals across the pond in Great Britain are no exception.

PxHere

It was a simple sign that prompted the study, published in the Christmas edition of the BMJ: “Please do not take excessive quantities of these refreshments.” And if we all know one thing, you do not get between Brits and their tea and biscuits. So the researchers behind the study drafted a survey and sent it around to nearly 2,000 British health care workers and asked what they considered to be excessive consumption of work-provided hot drinks and biscuits.

In the hot drinks department (tea and coffee, though we appreciate the two people who voiced a preference for free hot whiskey, if it was available) the survey participants decreed that 3.32 drinks was the maximum before consumption became excessive. That’s pretty close to the actual number of hot drinks respondents drank daily (3.04), so it’s pretty fair to say that British health care workers do a good job of self-limiting.

It’s much the same story with biscuits: Health care workers reported that consuming 2.25 packets of free biscuits would be excessive. Notably, doctors would take more than nondoctors (2.35 vs. 2.14 – typical doctor behavior), and those who had been in their role for less than 2 years would consume nearly 3 packets a day before calling it quits.

The study did not include an official cost analysis, but calculations conducted on a biscuit wrapper (that’s not a joke, by the way) estimated that the combined cost for providing every National Health Service employee with three free drinks and two free biscuit packages a day would be about 160 million pounds a year. Now, that’s a lot of money for tea and biscuits, but, they added, it’s a meager 0.1% of the NHS annual budget. They also noted that most employees consider free hot drinks a more valuable workplace perk than free support for mental health.

In conclusion, the authors wrote, “As a target for cost-saving initiatives, limiting free refreshment consumption is really scraping the biscuit barrel (although some limits on hot whiskey availability may be necessary), and implementing, or continuing, perks that improve staff morale seems justifiable. … Healthcare employers should allow biscuits and hot drinks to be freely available to staff, and they should leave these grateful recipients to judge for themselves what constitutes reasonable consumption.”

Now there’s a Christmas sentiment we can all get behind.
 

We come not to bury sugar, but to improve it

When we think about sugar, healthy isn’t the first thing that comes to mind. Research also shows that artificial sweeteners, as well as processed foods in general, are bad for your body and brain. People, however, love the stuff. That’s why one of the leading brands in processed foods, Kraft Heinz, partnered with the Wyss Institute for Biologically Inspired Engineering at Harvard to find a way to reduce consumers’ sugar consumption.

Vassiliy Vassilenko/thinkstockphotos.com

The question that Kraft Heinz presented to Wyss was this: How could it reduce the fructose in its products without losing the functionality of regular sugar.

The Wyss team’s approach seems pretty simple: Use a naturally occurring enzyme to convert sugar to fiber. The trick was to add the enzymes into the food so they could convert the sugar to fiber after being consumed. The enzymes also needed to be able to be added to existing food products without changing their existing recipes, Kraft Heinz insisted.

How does it work? The crafted enzyme is encapsulated to remain dormant in the food until exposed to an increased pH level, as is found in the GI tract between the stomach and the intestine. It reduces the amount of sugar absorbed in the bloodstream and creates a healthy prebiotic fiber, the institute explained.

This opens a whole new window for consumers. People with diabetes can enjoy their favorite cookies from time to time, while parents can feel less guilty about their children bathing their chicken nuggets in unholy amounts of ketchup.
 

New genes, or not new genes? That is the question

… and the police report that no capybaras were harmed in the incident. What a relief. Now Action News 8 brings you Carol Espinosa’s exclusive interview with legendary scientist and zombie, Charles Darwin.

Carol: Thanks, Daryl. Tell us, Prof. Darwin, what have you been up to lately?

Gio_tto/Thinkstock

Three cups of tea, two biscuit packs, and a Christmas study from the BMJ

Warning: The following content may contain excessive Britishness. Continue at your own risk.

It’s no secret that the world economy is in an … interesting spot right now. Belt tightening is occurring around the world despite the holiday season, and hospitals across the pond in Great Britain are no exception.

PxHere

It was a simple sign that prompted the study, published in the Christmas edition of the BMJ: “Please do not take excessive quantities of these refreshments.” And if we all know one thing, you do not get between Brits and their tea and biscuits. So the researchers behind the study drafted a survey and sent it around to nearly 2,000 British health care workers and asked what they considered to be excessive consumption of work-provided hot drinks and biscuits.

In the hot drinks department (tea and coffee, though we appreciate the two people who voiced a preference for free hot whiskey, if it was available) the survey participants decreed that 3.32 drinks was the maximum before consumption became excessive. That’s pretty close to the actual number of hot drinks respondents drank daily (3.04), so it’s pretty fair to say that British health care workers do a good job of self-limiting.

It’s much the same story with biscuits: Health care workers reported that consuming 2.25 packets of free biscuits would be excessive. Notably, doctors would take more than nondoctors (2.35 vs. 2.14 – typical doctor behavior), and those who had been in their role for less than 2 years would consume nearly 3 packets a day before calling it quits.

The study did not include an official cost analysis, but calculations conducted on a biscuit wrapper (that’s not a joke, by the way) estimated that the combined cost for providing every National Health Service employee with three free drinks and two free biscuit packages a day would be about 160 million pounds a year. Now, that’s a lot of money for tea and biscuits, but, they added, it’s a meager 0.1% of the NHS annual budget. They also noted that most employees consider free hot drinks a more valuable workplace perk than free support for mental health.

In conclusion, the authors wrote, “As a target for cost-saving initiatives, limiting free refreshment consumption is really scraping the biscuit barrel (although some limits on hot whiskey availability may be necessary), and implementing, or continuing, perks that improve staff morale seems justifiable. … Healthcare employers should allow biscuits and hot drinks to be freely available to staff, and they should leave these grateful recipients to judge for themselves what constitutes reasonable consumption.”

Now there’s a Christmas sentiment we can all get behind.
 

We come not to bury sugar, but to improve it

When we think about sugar, healthy isn’t the first thing that comes to mind. Research also shows that artificial sweeteners, as well as processed foods in general, are bad for your body and brain. People, however, love the stuff. That’s why one of the leading brands in processed foods, Kraft Heinz, partnered with the Wyss Institute for Biologically Inspired Engineering at Harvard to find a way to reduce consumers’ sugar consumption.

Vassiliy Vassilenko/thinkstockphotos.com

The question that Kraft Heinz presented to Wyss was this: How could it reduce the fructose in its products without losing the functionality of regular sugar.

The Wyss team’s approach seems pretty simple: Use a naturally occurring enzyme to convert sugar to fiber. The trick was to add the enzymes into the food so they could convert the sugar to fiber after being consumed. The enzymes also needed to be able to be added to existing food products without changing their existing recipes, Kraft Heinz insisted.

How does it work? The crafted enzyme is encapsulated to remain dormant in the food until exposed to an increased pH level, as is found in the GI tract between the stomach and the intestine. It reduces the amount of sugar absorbed in the bloodstream and creates a healthy prebiotic fiber, the institute explained.

This opens a whole new window for consumers. People with diabetes can enjoy their favorite cookies from time to time, while parents can feel less guilty about their children bathing their chicken nuggets in unholy amounts of ketchup.
 

New genes, or not new genes? That is the question

… and the police report that no capybaras were harmed in the incident. What a relief. Now Action News 8 brings you Carol Espinosa’s exclusive interview with legendary scientist and zombie, Charles Darwin.

Carol: Thanks, Daryl. Tell us, Prof. Darwin, what have you been up to lately?

Gio_tto/Thinkstock

Three cups of tea, two biscuit packs, and a Christmas study from the BMJ

Warning: The following content may contain excessive Britishness. Continue at your own risk.

It’s no secret that the world economy is in an … interesting spot right now. Belt tightening is occurring around the world despite the holiday season, and hospitals across the pond in Great Britain are no exception.

PxHere

It was a simple sign that prompted the study, published in the Christmas edition of the BMJ: “Please do not take excessive quantities of these refreshments.” And if we all know one thing, you do not get between Brits and their tea and biscuits. So the researchers behind the study drafted a survey and sent it around to nearly 2,000 British health care workers and asked what they considered to be excessive consumption of work-provided hot drinks and biscuits.

In the hot drinks department (tea and coffee, though we appreciate the two people who voiced a preference for free hot whiskey, if it was available) the survey participants decreed that 3.32 drinks was the maximum before consumption became excessive. That’s pretty close to the actual number of hot drinks respondents drank daily (3.04), so it’s pretty fair to say that British health care workers do a good job of self-limiting.

It’s much the same story with biscuits: Health care workers reported that consuming 2.25 packets of free biscuits would be excessive. Notably, doctors would take more than nondoctors (2.35 vs. 2.14 – typical doctor behavior), and those who had been in their role for less than 2 years would consume nearly 3 packets a day before calling it quits.

The study did not include an official cost analysis, but calculations conducted on a biscuit wrapper (that’s not a joke, by the way) estimated that the combined cost for providing every National Health Service employee with three free drinks and two free biscuit packages a day would be about 160 million pounds a year. Now, that’s a lot of money for tea and biscuits, but, they added, it’s a meager 0.1% of the NHS annual budget. They also noted that most employees consider free hot drinks a more valuable workplace perk than free support for mental health.

In conclusion, the authors wrote, “As a target for cost-saving initiatives, limiting free refreshment consumption is really scraping the biscuit barrel (although some limits on hot whiskey availability may be necessary), and implementing, or continuing, perks that improve staff morale seems justifiable. … Healthcare employers should allow biscuits and hot drinks to be freely available to staff, and they should leave these grateful recipients to judge for themselves what constitutes reasonable consumption.”

Now there’s a Christmas sentiment we can all get behind.
 

We come not to bury sugar, but to improve it

When we think about sugar, healthy isn’t the first thing that comes to mind. Research also shows that artificial sweeteners, as well as processed foods in general, are bad for your body and brain. People, however, love the stuff. That’s why one of the leading brands in processed foods, Kraft Heinz, partnered with the Wyss Institute for Biologically Inspired Engineering at Harvard to find a way to reduce consumers’ sugar consumption.

Vassiliy Vassilenko/thinkstockphotos.com

The question that Kraft Heinz presented to Wyss was this: How could it reduce the fructose in its products without losing the functionality of regular sugar.

The Wyss team’s approach seems pretty simple: Use a naturally occurring enzyme to convert sugar to fiber. The trick was to add the enzymes into the food so they could convert the sugar to fiber after being consumed. The enzymes also needed to be able to be added to existing food products without changing their existing recipes, Kraft Heinz insisted.

How does it work? The crafted enzyme is encapsulated to remain dormant in the food until exposed to an increased pH level, as is found in the GI tract between the stomach and the intestine. It reduces the amount of sugar absorbed in the bloodstream and creates a healthy prebiotic fiber, the institute explained.

This opens a whole new window for consumers. People with diabetes can enjoy their favorite cookies from time to time, while parents can feel less guilty about their children bathing their chicken nuggets in unholy amounts of ketchup.
 

New genes, or not new genes? That is the question

… and the police report that no capybaras were harmed in the incident. What a relief. Now Action News 8 brings you Carol Espinosa’s exclusive interview with legendary scientist and zombie, Charles Darwin.

Carol: Thanks, Daryl. Tell us, Prof. Darwin, what have you been up to lately?

Gio_tto/Thinkstock

The Food and Drug Administration has requested that Oncopeptides withdraw the U.S. marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.
 

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).

The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.

Now, the FDA has requested that the company withdraw its U.S. marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.

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

The Food and Drug Administration has requested that Oncopeptides withdraw the U.S. marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.
 

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).

The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.

Now, the FDA has requested that the company withdraw its U.S. marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.

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

The Food and Drug Administration has requested that Oncopeptides withdraw the U.S. marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.
 

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).

The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.

Now, the FDA has requested that the company withdraw its U.S. marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.

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

NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.

“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.

B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.

Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).

As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.

The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”

For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”

There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).

“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.

Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.

In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”

The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”

The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.

Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.

NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.

“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.

B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.

Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).

As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.

The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”

For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”

There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).

“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.

Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.

In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”

The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”

The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.

Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.

NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.

“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.

B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.

Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).

As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.

The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”

For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”

There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).

“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.

Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.

In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”

The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”

The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.

Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.

Key takeaway

Patients with multiple myeloma were diagnosed at a significantly higher rate through emergency care during the COVID-19 pandemic, compared with before.

Why this matters

While trying to avoid COVID-19 infection, patients ultimately diagnosed with multiple myeloma may have delayed interactions with healthcare professionals and consequently delayed their cancer diagnosis.

Study design

Researchers collected data on newly diagnosed patients with multiple myeloma from January 2019 until July 2021 across five institutions (three universities and two hospitals) in England. In total, 323 patients with multiple myeloma were identified.

Patients were divided into two groups: those diagnosed between Jan. 1, 2019, until Jan. 31, 2020, or pre-COVID, and those diagnosed from Feb. 1, 2020, to July 31, 2021, or post COVID.
 

Key results

Among all patients, 80 (24.8%) were diagnosed with smoldering multiple myeloma and 243 (75.2%) were diagnosed with multiple myeloma requiring treatment.

Significantly more patients in the post-COVID group were diagnosed with myeloma through the emergency route (45.5% post COVID vs. 32.7% pre-COVID; P = .03).

Clinical complications leading to emergency admission prior to a myeloma diagnosis also differed between the two cohorts: Acute kidney injury accounted for most emergency admissions in the pre-COVID cohort while skeletal-related events, including spinal cord compression, were the major causes for diagnosis through the emergency route in the post-COVID cohort.

Patients who were diagnosed with symptomatic myeloma pre-COVID were more likely to be treated with a triplet rather than doublet combination compared with those diagnosed in the post-COVID period (triplet pre-COVID 79.1%, post COVID 63.75%; P = .014).

Overall survival at 1 year was not significantly different between the pre-COVID and post-COVID groups: 88.2% pre-COVID, compared with 87.8% post COVID. 

Overall, the authors concluded that the COVID pandemic “resulted in a shift in the symptomatology, disease burden, and routes of diagnosis of patients presenting with myeloma” and “this may have significant consequences” over the long term.
 

Limitations

The study does not provide a clear time frame of delays in diagnosis.

Disclosures

The study authors did not report any conflicts of interest.

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

The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.

Key takeaway

Patients with multiple myeloma were diagnosed at a significantly higher rate through emergency care during the COVID-19 pandemic, compared with before.

Why this matters

While trying to avoid COVID-19 infection, patients ultimately diagnosed with multiple myeloma may have delayed interactions with healthcare professionals and consequently delayed their cancer diagnosis.

Study design

Researchers collected data on newly diagnosed patients with multiple myeloma from January 2019 until July 2021 across five institutions (three universities and two hospitals) in England. In total, 323 patients with multiple myeloma were identified.

Patients were divided into two groups: those diagnosed between Jan. 1, 2019, until Jan. 31, 2020, or pre-COVID, and those diagnosed from Feb. 1, 2020, to July 31, 2021, or post COVID.
 

Key results

Among all patients, 80 (24.8%) were diagnosed with smoldering multiple myeloma and 243 (75.2%) were diagnosed with multiple myeloma requiring treatment.

Significantly more patients in the post-COVID group were diagnosed with myeloma through the emergency route (45.5% post COVID vs. 32.7% pre-COVID; P = .03).

Clinical complications leading to emergency admission prior to a myeloma diagnosis also differed between the two cohorts: Acute kidney injury accounted for most emergency admissions in the pre-COVID cohort while skeletal-related events, including spinal cord compression, were the major causes for diagnosis through the emergency route in the post-COVID cohort.

Patients who were diagnosed with symptomatic myeloma pre-COVID were more likely to be treated with a triplet rather than doublet combination compared with those diagnosed in the post-COVID period (triplet pre-COVID 79.1%, post COVID 63.75%; P = .014).

Overall survival at 1 year was not significantly different between the pre-COVID and post-COVID groups: 88.2% pre-COVID, compared with 87.8% post COVID. 

Overall, the authors concluded that the COVID pandemic “resulted in a shift in the symptomatology, disease burden, and routes of diagnosis of patients presenting with myeloma” and “this may have significant consequences” over the long term.
 

Limitations

The study does not provide a clear time frame of delays in diagnosis.

Disclosures

The study authors did not report any conflicts of interest.

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

The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.

Key takeaway

Patients with multiple myeloma were diagnosed at a significantly higher rate through emergency care during the COVID-19 pandemic, compared with before.

Why this matters

While trying to avoid COVID-19 infection, patients ultimately diagnosed with multiple myeloma may have delayed interactions with healthcare professionals and consequently delayed their cancer diagnosis.

Study design

Researchers collected data on newly diagnosed patients with multiple myeloma from January 2019 until July 2021 across five institutions (three universities and two hospitals) in England. In total, 323 patients with multiple myeloma were identified.

Patients were divided into two groups: those diagnosed between Jan. 1, 2019, until Jan. 31, 2020, or pre-COVID, and those diagnosed from Feb. 1, 2020, to July 31, 2021, or post COVID.
 

Key results

Among all patients, 80 (24.8%) were diagnosed with smoldering multiple myeloma and 243 (75.2%) were diagnosed with multiple myeloma requiring treatment.

Significantly more patients in the post-COVID group were diagnosed with myeloma through the emergency route (45.5% post COVID vs. 32.7% pre-COVID; P = .03).

Clinical complications leading to emergency admission prior to a myeloma diagnosis also differed between the two cohorts: Acute kidney injury accounted for most emergency admissions in the pre-COVID cohort while skeletal-related events, including spinal cord compression, were the major causes for diagnosis through the emergency route in the post-COVID cohort.

Patients who were diagnosed with symptomatic myeloma pre-COVID were more likely to be treated with a triplet rather than doublet combination compared with those diagnosed in the post-COVID period (triplet pre-COVID 79.1%, post COVID 63.75%; P = .014).

Overall survival at 1 year was not significantly different between the pre-COVID and post-COVID groups: 88.2% pre-COVID, compared with 87.8% post COVID. 

Overall, the authors concluded that the COVID pandemic “resulted in a shift in the symptomatology, disease burden, and routes of diagnosis of patients presenting with myeloma” and “this may have significant consequences” over the long term.
 

Limitations

The study does not provide a clear time frame of delays in diagnosis.

Disclosures

The study authors did not report any conflicts of interest.

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

Zanubrutinib (Brukinsa) demonstrated superior efficacy and safety over ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to results of the randomized, phase 3 ALPINE study.

Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.

Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.

Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.

“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.

Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.

But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.

The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”

The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
 

Improved safety, efficacy

Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.

Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.

In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.

By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.

In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.

With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.

Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.

However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.

Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.

Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
 

Impressive benefit

The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.

“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview

However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.

In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.

“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”

Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.

Zanubrutinib (Brukinsa) demonstrated superior efficacy and safety over ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to results of the randomized, phase 3 ALPINE study.

Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.

Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.

Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.

“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.

Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.

But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.

The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”

The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
 

Improved safety, efficacy

Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.

Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.

In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.

By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.

In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.

With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.

Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.

However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.

Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.

Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
 

Impressive benefit

The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.

“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview

However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.

In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.

“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”

Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.

Zanubrutinib (Brukinsa) demonstrated superior efficacy and safety over ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to results of the randomized, phase 3 ALPINE study.

Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.

Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.

Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.

“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.

Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.

But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.

The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”

The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
 

Improved safety, efficacy

Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.

Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.

In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.

By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.

In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.

With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.

Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.

However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.

Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.

Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
 

Impressive benefit

The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.

“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview

However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.

In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.

“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”

Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

NEW ORLEANS – Patients with chronic immune thrombocytopenia (ITP) fared better on intravenous efgartigimod (Vyvgart) than a placebo, a new study found. Still, only 21.8% of subjects who received the biologic reached the primary endpoint of sustained platelet count response, an indication that most patients won’t benefit.

Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.

“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.

In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”

The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.

Treatment options include corticosteroids and intravenous immunoglobulin.

“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.

For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).

Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.

Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.

Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).

“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”

She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”

Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.

Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.

In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.

Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.

As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”

It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”

For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”

What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.

The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.

NEW ORLEANS – Patients with chronic immune thrombocytopenia (ITP) fared better on intravenous efgartigimod (Vyvgart) than a placebo, a new study found. Still, only 21.8% of subjects who received the biologic reached the primary endpoint of sustained platelet count response, an indication that most patients won’t benefit.

Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.

“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.

In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”

The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.

Treatment options include corticosteroids and intravenous immunoglobulin.

“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.

For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).

Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.

Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.

Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).

“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”

She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”

Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.

Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.

In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.

Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.

As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”

It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”

For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”

What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.

The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.

NEW ORLEANS – Patients with chronic immune thrombocytopenia (ITP) fared better on intravenous efgartigimod (Vyvgart) than a placebo, a new study found. Still, only 21.8% of subjects who received the biologic reached the primary endpoint of sustained platelet count response, an indication that most patients won’t benefit.

Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.

“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.

In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”

The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.

Treatment options include corticosteroids and intravenous immunoglobulin.

“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.

For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).

Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.

Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.

Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).

“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”

She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”

Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.

Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.

In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.

Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.

As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”

It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”

For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”

What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.

The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.