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ASH 2022: New clinical data challenge long-held assumptions
The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
“Feeding Our Patients Gruel”
Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).
“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”
He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”
Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
Practice-changing data
ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).
Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
Premature aging in HL survivors
ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).
“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”
Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
Inherited thrombophilia and miscarriage
Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).
“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.
Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.
Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).
“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”
A version of this article first appeared on Medscape.com.
The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
“Feeding Our Patients Gruel”
Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).
“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”
He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”
Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
Practice-changing data
ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).
Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
Premature aging in HL survivors
ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).
“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”
Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
Inherited thrombophilia and miscarriage
Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).
“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.
Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.
Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).
“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”
A version of this article first appeared on Medscape.com.
The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
“Feeding Our Patients Gruel”
Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).
“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”
He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”
Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
Practice-changing data
ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).
Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
Premature aging in HL survivors
ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).
“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”
Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
Inherited thrombophilia and miscarriage
Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).
“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.
Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.
Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).
“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”
A version of this article first appeared on Medscape.com.
FROM ASH 2022
FDA approves olutasidenib for some AML patients
Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.
The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.
Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.
About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.
“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.
This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.
Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).
The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).
Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”
The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.
Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.
In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.
In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.
Further details are available in the full prescribing information.
A version of this article first appeared on Medscape.com.
Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.
The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.
Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.
About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.
“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.
This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.
Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).
The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).
Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”
The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.
Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.
In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.
In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.
Further details are available in the full prescribing information.
A version of this article first appeared on Medscape.com.
Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.
The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.
Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.
About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.
“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.
This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.
Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).
The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).
Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”
The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.
Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.
In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.
In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.
Further details are available in the full prescribing information.
A version of this article first appeared on Medscape.com.
Worldwide trial seeks to revolutionize pediatric leukemia care
While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.
Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children.
“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”
The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).
The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.
“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”
In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”
In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.
“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”
Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.
The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”
In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”
In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”
In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.
What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”
As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.
”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”
Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.
While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.
Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children.
“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”
The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).
The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.
“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”
In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”
In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.
“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”
Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.
The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”
In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”
In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”
In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.
What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”
As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.
”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”
Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.
While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.
Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children.
“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”
The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).
The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.
“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”
In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”
In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.
“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”
Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.
The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”
In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”
In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”
In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.
What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”
As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.
”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”
Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.
Drug combo holds promise of better AML outcomes
Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.
“.
Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.
“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.
For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).
The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.
Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.
“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.
Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”
About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.
All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.
Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”
The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”
He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”
Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”
The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.
Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.
Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.
“.
Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.
“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.
For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).
The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.
Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.
“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.
Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”
About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.
All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.
Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”
The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”
He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”
Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”
The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.
Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.
Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.
“.
Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.
“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.
For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).
The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.
Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.
“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.
Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”
About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.
All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.
Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”
The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”
He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”
Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”
The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.
Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.
FROM JOURNAL OF CLINICAL ONCOLOGY
`Wonder Woman’ launches myelofibrosis research foundation
When Lynda Carter talks about her late husband Robert Altman, you can sense right away that this was a love affair for the ages.
“As I’ve often said, if you were a friend of Robert’s, you were one of the luckiest people in the world,” said Ms. Carter, the singer-songwriter and actor best known for her role as Wonder Woman in the 1970s TV series, who married Mr. Altman, an attorney, in 1984.
For Ms. Carter, Mr. Altman, and their children, Jessica and James, everything changed in 2017, when Mr. Altman was diagnosed with myelofibrosis, a rare bone marrow disorder – about one case is reported per 100,000 Americans each year – that was found during routine blood work.
“Robert was never sick a day in his life,” she said in an interview. “He skied and swam, and in many ways we were in the prime of our lives together. When he was initially diagnosed, we weren’t even clear what he had. The buzzword was that he had a rare blood disorder, not cancer.”
The family was told to wait and see if the disease would get worse, which it did, unfortunately, at the exact time COVID-19 hit.
This condition can progress from myelofibrosis to secondary acute myeloid leukemia, a rare blood cancer, said Michael Caligiuri, MD, a leading researcher in immunology, lymphoma, and leukemia and president of City of Hope National Medical Center, Duarte, Calif., one of the largest cancer research and treatment organizations in the United States.
“This disease is chronic and slow changing, but when it progresses more acutely to a form of leukemia, it can advance rapidly,” he said.
At the acute phase, there’s not much that can be done for the patient.
“This becomes very much a life-and-death situation,” he said. “You want to hope for the best, but there needs to be an expectation of the worst in terms of trying to prepare the patient and the family for what may come so that they can start to psychologically and legally put the person’s life in order.”
Despite every effort, Mr. Altman died in February 2021 at the age of 73.
The goal: To speed up critical research that will improve early detection and survival for this hard-to-treat blood cancer.
“I’m excited to be a part of this team and to know that I may play a small part in helping other families facing this same diagnosis,” Ms. Carter said. “It’s thrilling seeing the progress these scientists are making, from genomic research into a universe of trillions of codes that might actually become a drug therapy someday.”
With the creation of the foundation, there will be funding to develop better diagnostics and better treatments.
“In many instances, this research will shed light on other related disorders, too,” said Dr. Caligiuri. “Cancer is a disease of the genes, and in most cases, we’re not inheriting from our mothers or fathers, but the DNA gets switched around in one of the trillion cells in our body, the way a word is misspelled.”
What happens next is that the cell doesn’t die.
“Instead, it undergoes a nuclear reaction and grows and grows,” he said. “In this case, the first evidence of a problem was myelofibrosis. That ticking time bomb continued until it exploded into leukemia.”
Dr. Caligiuri said the goal of their research will be to develop a device that can rearrange that DNA or block the DNA changes so the disease doesn’t progress to leukemia or, if it does, so “that we can turn it into a chronic condition, not an acute one that’s life-threatening.”
For Ms. Carter, this foundation is one very heartfelt way that she can honor her husband’s legacy.
“When I lost Robert, I was left with so many questions,” she said. “I wanted to understand why rare cancers are so difficult to treat and what research or treatment advances were being made to change that. Robert was never one for self-aggrandizement, but I think he would like this. I think Robert would really be touched by this.”
A version of this article first appeared on WebMD.com.
When Lynda Carter talks about her late husband Robert Altman, you can sense right away that this was a love affair for the ages.
“As I’ve often said, if you were a friend of Robert’s, you were one of the luckiest people in the world,” said Ms. Carter, the singer-songwriter and actor best known for her role as Wonder Woman in the 1970s TV series, who married Mr. Altman, an attorney, in 1984.
For Ms. Carter, Mr. Altman, and their children, Jessica and James, everything changed in 2017, when Mr. Altman was diagnosed with myelofibrosis, a rare bone marrow disorder – about one case is reported per 100,000 Americans each year – that was found during routine blood work.
“Robert was never sick a day in his life,” she said in an interview. “He skied and swam, and in many ways we were in the prime of our lives together. When he was initially diagnosed, we weren’t even clear what he had. The buzzword was that he had a rare blood disorder, not cancer.”
The family was told to wait and see if the disease would get worse, which it did, unfortunately, at the exact time COVID-19 hit.
This condition can progress from myelofibrosis to secondary acute myeloid leukemia, a rare blood cancer, said Michael Caligiuri, MD, a leading researcher in immunology, lymphoma, and leukemia and president of City of Hope National Medical Center, Duarte, Calif., one of the largest cancer research and treatment organizations in the United States.
“This disease is chronic and slow changing, but when it progresses more acutely to a form of leukemia, it can advance rapidly,” he said.
At the acute phase, there’s not much that can be done for the patient.
“This becomes very much a life-and-death situation,” he said. “You want to hope for the best, but there needs to be an expectation of the worst in terms of trying to prepare the patient and the family for what may come so that they can start to psychologically and legally put the person’s life in order.”
Despite every effort, Mr. Altman died in February 2021 at the age of 73.
The goal: To speed up critical research that will improve early detection and survival for this hard-to-treat blood cancer.
“I’m excited to be a part of this team and to know that I may play a small part in helping other families facing this same diagnosis,” Ms. Carter said. “It’s thrilling seeing the progress these scientists are making, from genomic research into a universe of trillions of codes that might actually become a drug therapy someday.”
With the creation of the foundation, there will be funding to develop better diagnostics and better treatments.
“In many instances, this research will shed light on other related disorders, too,” said Dr. Caligiuri. “Cancer is a disease of the genes, and in most cases, we’re not inheriting from our mothers or fathers, but the DNA gets switched around in one of the trillion cells in our body, the way a word is misspelled.”
What happens next is that the cell doesn’t die.
“Instead, it undergoes a nuclear reaction and grows and grows,” he said. “In this case, the first evidence of a problem was myelofibrosis. That ticking time bomb continued until it exploded into leukemia.”
Dr. Caligiuri said the goal of their research will be to develop a device that can rearrange that DNA or block the DNA changes so the disease doesn’t progress to leukemia or, if it does, so “that we can turn it into a chronic condition, not an acute one that’s life-threatening.”
For Ms. Carter, this foundation is one very heartfelt way that she can honor her husband’s legacy.
“When I lost Robert, I was left with so many questions,” she said. “I wanted to understand why rare cancers are so difficult to treat and what research or treatment advances were being made to change that. Robert was never one for self-aggrandizement, but I think he would like this. I think Robert would really be touched by this.”
A version of this article first appeared on WebMD.com.
When Lynda Carter talks about her late husband Robert Altman, you can sense right away that this was a love affair for the ages.
“As I’ve often said, if you were a friend of Robert’s, you were one of the luckiest people in the world,” said Ms. Carter, the singer-songwriter and actor best known for her role as Wonder Woman in the 1970s TV series, who married Mr. Altman, an attorney, in 1984.
For Ms. Carter, Mr. Altman, and their children, Jessica and James, everything changed in 2017, when Mr. Altman was diagnosed with myelofibrosis, a rare bone marrow disorder – about one case is reported per 100,000 Americans each year – that was found during routine blood work.
“Robert was never sick a day in his life,” she said in an interview. “He skied and swam, and in many ways we were in the prime of our lives together. When he was initially diagnosed, we weren’t even clear what he had. The buzzword was that he had a rare blood disorder, not cancer.”
The family was told to wait and see if the disease would get worse, which it did, unfortunately, at the exact time COVID-19 hit.
This condition can progress from myelofibrosis to secondary acute myeloid leukemia, a rare blood cancer, said Michael Caligiuri, MD, a leading researcher in immunology, lymphoma, and leukemia and president of City of Hope National Medical Center, Duarte, Calif., one of the largest cancer research and treatment organizations in the United States.
“This disease is chronic and slow changing, but when it progresses more acutely to a form of leukemia, it can advance rapidly,” he said.
At the acute phase, there’s not much that can be done for the patient.
“This becomes very much a life-and-death situation,” he said. “You want to hope for the best, but there needs to be an expectation of the worst in terms of trying to prepare the patient and the family for what may come so that they can start to psychologically and legally put the person’s life in order.”
Despite every effort, Mr. Altman died in February 2021 at the age of 73.
The goal: To speed up critical research that will improve early detection and survival for this hard-to-treat blood cancer.
“I’m excited to be a part of this team and to know that I may play a small part in helping other families facing this same diagnosis,” Ms. Carter said. “It’s thrilling seeing the progress these scientists are making, from genomic research into a universe of trillions of codes that might actually become a drug therapy someday.”
With the creation of the foundation, there will be funding to develop better diagnostics and better treatments.
“In many instances, this research will shed light on other related disorders, too,” said Dr. Caligiuri. “Cancer is a disease of the genes, and in most cases, we’re not inheriting from our mothers or fathers, but the DNA gets switched around in one of the trillion cells in our body, the way a word is misspelled.”
What happens next is that the cell doesn’t die.
“Instead, it undergoes a nuclear reaction and grows and grows,” he said. “In this case, the first evidence of a problem was myelofibrosis. That ticking time bomb continued until it exploded into leukemia.”
Dr. Caligiuri said the goal of their research will be to develop a device that can rearrange that DNA or block the DNA changes so the disease doesn’t progress to leukemia or, if it does, so “that we can turn it into a chronic condition, not an acute one that’s life-threatening.”
For Ms. Carter, this foundation is one very heartfelt way that she can honor her husband’s legacy.
“When I lost Robert, I was left with so many questions,” she said. “I wanted to understand why rare cancers are so difficult to treat and what research or treatment advances were being made to change that. Robert was never one for self-aggrandizement, but I think he would like this. I think Robert would really be touched by this.”
A version of this article first appeared on WebMD.com.
Pivotal trials in blood cancers don’t mirror patient populations
, a new study concludes.
“Our analysis shows that, over the past 10 years, participation in pivotal clinical trials investigating therapies for leukemias and MM is unrepresentative of the U.S. population,” say the authors, led by Jorge E. Cortes, MD, of the Georgia Cancer Center at Augusta University, Ga. “Trials should represent the population with the disease,” they comment.
The study was published in the Journal of Clinical Oncology.
“This study confirms that the U.S. cancer population for select hematologic malignancies was inadequately racially and ethnically represented in studies leading to drug approval,” comment the authors of an accompanying editorial.
“The results from this study should lead to questions about the generalizability of drug safety and efficacy in populations we serve as medical hematologists and oncologists,” say Mikkael A. Sekeres, MD, along with Namrata S. Chandhok, MD, both of the division of hematology, Sylvester Comprehensive Cancer Center, University of Miami.
They pose the question, for instance, as physicians practicing in South Florida, where most of their patients are Hispanic, “can we apply the results of these pivotal studies – and drug labels – to them, without any sense of whether they metabolize the drug the same way as those included in the study or have the same biologic targets?”
Analysis of pivotal trials
For their study, Dr. Cortes and colleagues analyzed 61 pivotal trials for leukemia and MM leading to approval of the drugs from the U.S. Food and Drug Administration between 2011 and 2021.
They found that only two-thirds (67.2%) of these trials reported data pertaining to race, while about half (48.8%) reported on ethnicity.
The trials that did report data on race involved a total of 13,731 patients. The vast majority (81.6%) were White, and Black patients represented only 3.8%. Asian/Pacific Islanders made up 9.1%, and American Indians or Alaskan Natives made up just 0.12% of participants, with 1.5% categorized as other.
Among the trials reporting on ethnicity, 4.7% of patients were Hispanic, with 11.5% being Hispanic in acute lymphoblastic leukemia (ALL) trials and 7.6% Hispanic in chronic myeloid leukemia (CML) trials.
Slightly more than half (54.8%) of all trial participants were male, and patients’ average ages ranged from 41.7 to 67.3 years across all malignancies.
Of the minority groups, Asian/Pacific Islanders and Black people had the highest representation in trials involving CML, at 12.7% and 5.3%, respectively.
Their lowest representation was in chronic lymphocytic leukemia (CLL), at 3% and 1.1%, respectively.
Among the trials reporting ethnicity, Hispanic people were the highest representation, with percentages ranging from 3.8% of MM trials to 11.5% in ALL trials.
Inconsistent with patient populations
Next, the researchers compared the proportions of race/ethnic groups that were found among the participants of these pivotal trials with the proportions that would be expected in patient populations for each of these blood cancers (according to the U.S. Surveillance, Epidemiology, and End Results [SEER] database).
For example, White people made up 80.3% of participants in clinical trials of MM, whereas they represent 68.7% of patients with MM, a difference that was statistically significant (P < .0001).
The finding was similar for CML, with White people accounting for 90.5% of participants in clinical trials versus 82.5% of the patient population (P < .0001).
For AML, the difference was smaller, with respective percentages of 79.6 versus 77.3% (P = .0389).
For Black people, Asian/Pacific Islanders and Hispanic people, across all five cancer types that were analyzed, the proportion of participants in clinical trials was significantly lower than the proportion in the patient population.
The analysis also showed that females were overrepresented in clinical trials for two blood cancers. For MM, trial participation was 44.7%, while disease incidence was 41.7% (P < .0001), and for CML the proportions were 44.7% versus 39.5% (P = .0009). However, females were underrepresented in a third blood cancer: in AML, the proportions were 44.7% versus 60.5% (P < .0001).
Geographic location of trials often inaccessible
The study also highlighted an obstacle to minorities participating in clinical trials: geography.
For this analysis, the researchers looked at mortality rates for the various blood cancers.
For AML, they found mortality rates were high across the whole of the United States, but centers conducting AML clinical trials were primarily in the Northeast, with no centers in the Midwest.
Key regions with high rates of AML mortality, low access to trials, and high minority representation were notably clustered in areas including east of the Carolinas, South Georgia, Alabama, and Mississippi, the authors noted.
“In many instances, trials were absent in areas with high mortality,” they report. “This makes access to clinical trials difficult, if not impossible, to patients who do not have the financial means for travel.”
Further action needed
Racial and ethnic disparities in clinical trials have been widely reported in numerous previous studies, the authors note.
Various initiatives have been launched in recent years to tackle the problem, including the National Institutes of Health Revitalization Act, FDA race and ethnicity guidance, and the International Conference for Harmonization guidance.
For oncology, the American Society of Clinical Oncology has also taken steps with the release of the new Equity, Diversity, and Inclusion Action Plan in 2021 to improve representation of minorities in research.
Dr. Cortes and colleagues suggest another step that is needed is standardized reporting of demographics of clinical trial participants.
“More importantly, efforts to increase representation of minorities and disadvantaged populations in clinical trials should be prioritized,” they say.
Dr. Cortes reports a consulting role and receiving research funding from many pharmaceutical companies. No other coauthors have financial disclosures. Dr. Chandhok reports honoraria from Healio, Clinical Care Options, and a consulting role with Servier. Dr. Sekeres reports a consulting role with Celgene, Millennium, Pfizer, Novartis, Syros Pharmaceuticals, Kurome Therapeutics, and institutional research funding from Takeda, Pfizer, Bristol Myers Squibb, Actuate Therapeutics, Sellas Life Sciences, and Bio-Path Holdings.
A version of this article first appeared on Medscape.com.
, a new study concludes.
“Our analysis shows that, over the past 10 years, participation in pivotal clinical trials investigating therapies for leukemias and MM is unrepresentative of the U.S. population,” say the authors, led by Jorge E. Cortes, MD, of the Georgia Cancer Center at Augusta University, Ga. “Trials should represent the population with the disease,” they comment.
The study was published in the Journal of Clinical Oncology.
“This study confirms that the U.S. cancer population for select hematologic malignancies was inadequately racially and ethnically represented in studies leading to drug approval,” comment the authors of an accompanying editorial.
“The results from this study should lead to questions about the generalizability of drug safety and efficacy in populations we serve as medical hematologists and oncologists,” say Mikkael A. Sekeres, MD, along with Namrata S. Chandhok, MD, both of the division of hematology, Sylvester Comprehensive Cancer Center, University of Miami.
They pose the question, for instance, as physicians practicing in South Florida, where most of their patients are Hispanic, “can we apply the results of these pivotal studies – and drug labels – to them, without any sense of whether they metabolize the drug the same way as those included in the study or have the same biologic targets?”
Analysis of pivotal trials
For their study, Dr. Cortes and colleagues analyzed 61 pivotal trials for leukemia and MM leading to approval of the drugs from the U.S. Food and Drug Administration between 2011 and 2021.
They found that only two-thirds (67.2%) of these trials reported data pertaining to race, while about half (48.8%) reported on ethnicity.
The trials that did report data on race involved a total of 13,731 patients. The vast majority (81.6%) were White, and Black patients represented only 3.8%. Asian/Pacific Islanders made up 9.1%, and American Indians or Alaskan Natives made up just 0.12% of participants, with 1.5% categorized as other.
Among the trials reporting on ethnicity, 4.7% of patients were Hispanic, with 11.5% being Hispanic in acute lymphoblastic leukemia (ALL) trials and 7.6% Hispanic in chronic myeloid leukemia (CML) trials.
Slightly more than half (54.8%) of all trial participants were male, and patients’ average ages ranged from 41.7 to 67.3 years across all malignancies.
Of the minority groups, Asian/Pacific Islanders and Black people had the highest representation in trials involving CML, at 12.7% and 5.3%, respectively.
Their lowest representation was in chronic lymphocytic leukemia (CLL), at 3% and 1.1%, respectively.
Among the trials reporting ethnicity, Hispanic people were the highest representation, with percentages ranging from 3.8% of MM trials to 11.5% in ALL trials.
Inconsistent with patient populations
Next, the researchers compared the proportions of race/ethnic groups that were found among the participants of these pivotal trials with the proportions that would be expected in patient populations for each of these blood cancers (according to the U.S. Surveillance, Epidemiology, and End Results [SEER] database).
For example, White people made up 80.3% of participants in clinical trials of MM, whereas they represent 68.7% of patients with MM, a difference that was statistically significant (P < .0001).
The finding was similar for CML, with White people accounting for 90.5% of participants in clinical trials versus 82.5% of the patient population (P < .0001).
For AML, the difference was smaller, with respective percentages of 79.6 versus 77.3% (P = .0389).
For Black people, Asian/Pacific Islanders and Hispanic people, across all five cancer types that were analyzed, the proportion of participants in clinical trials was significantly lower than the proportion in the patient population.
The analysis also showed that females were overrepresented in clinical trials for two blood cancers. For MM, trial participation was 44.7%, while disease incidence was 41.7% (P < .0001), and for CML the proportions were 44.7% versus 39.5% (P = .0009). However, females were underrepresented in a third blood cancer: in AML, the proportions were 44.7% versus 60.5% (P < .0001).
Geographic location of trials often inaccessible
The study also highlighted an obstacle to minorities participating in clinical trials: geography.
For this analysis, the researchers looked at mortality rates for the various blood cancers.
For AML, they found mortality rates were high across the whole of the United States, but centers conducting AML clinical trials were primarily in the Northeast, with no centers in the Midwest.
Key regions with high rates of AML mortality, low access to trials, and high minority representation were notably clustered in areas including east of the Carolinas, South Georgia, Alabama, and Mississippi, the authors noted.
“In many instances, trials were absent in areas with high mortality,” they report. “This makes access to clinical trials difficult, if not impossible, to patients who do not have the financial means for travel.”
Further action needed
Racial and ethnic disparities in clinical trials have been widely reported in numerous previous studies, the authors note.
Various initiatives have been launched in recent years to tackle the problem, including the National Institutes of Health Revitalization Act, FDA race and ethnicity guidance, and the International Conference for Harmonization guidance.
For oncology, the American Society of Clinical Oncology has also taken steps with the release of the new Equity, Diversity, and Inclusion Action Plan in 2021 to improve representation of minorities in research.
Dr. Cortes and colleagues suggest another step that is needed is standardized reporting of demographics of clinical trial participants.
“More importantly, efforts to increase representation of minorities and disadvantaged populations in clinical trials should be prioritized,” they say.
Dr. Cortes reports a consulting role and receiving research funding from many pharmaceutical companies. No other coauthors have financial disclosures. Dr. Chandhok reports honoraria from Healio, Clinical Care Options, and a consulting role with Servier. Dr. Sekeres reports a consulting role with Celgene, Millennium, Pfizer, Novartis, Syros Pharmaceuticals, Kurome Therapeutics, and institutional research funding from Takeda, Pfizer, Bristol Myers Squibb, Actuate Therapeutics, Sellas Life Sciences, and Bio-Path Holdings.
A version of this article first appeared on Medscape.com.
, a new study concludes.
“Our analysis shows that, over the past 10 years, participation in pivotal clinical trials investigating therapies for leukemias and MM is unrepresentative of the U.S. population,” say the authors, led by Jorge E. Cortes, MD, of the Georgia Cancer Center at Augusta University, Ga. “Trials should represent the population with the disease,” they comment.
The study was published in the Journal of Clinical Oncology.
“This study confirms that the U.S. cancer population for select hematologic malignancies was inadequately racially and ethnically represented in studies leading to drug approval,” comment the authors of an accompanying editorial.
“The results from this study should lead to questions about the generalizability of drug safety and efficacy in populations we serve as medical hematologists and oncologists,” say Mikkael A. Sekeres, MD, along with Namrata S. Chandhok, MD, both of the division of hematology, Sylvester Comprehensive Cancer Center, University of Miami.
They pose the question, for instance, as physicians practicing in South Florida, where most of their patients are Hispanic, “can we apply the results of these pivotal studies – and drug labels – to them, without any sense of whether they metabolize the drug the same way as those included in the study or have the same biologic targets?”
Analysis of pivotal trials
For their study, Dr. Cortes and colleagues analyzed 61 pivotal trials for leukemia and MM leading to approval of the drugs from the U.S. Food and Drug Administration between 2011 and 2021.
They found that only two-thirds (67.2%) of these trials reported data pertaining to race, while about half (48.8%) reported on ethnicity.
The trials that did report data on race involved a total of 13,731 patients. The vast majority (81.6%) were White, and Black patients represented only 3.8%. Asian/Pacific Islanders made up 9.1%, and American Indians or Alaskan Natives made up just 0.12% of participants, with 1.5% categorized as other.
Among the trials reporting on ethnicity, 4.7% of patients were Hispanic, with 11.5% being Hispanic in acute lymphoblastic leukemia (ALL) trials and 7.6% Hispanic in chronic myeloid leukemia (CML) trials.
Slightly more than half (54.8%) of all trial participants were male, and patients’ average ages ranged from 41.7 to 67.3 years across all malignancies.
Of the minority groups, Asian/Pacific Islanders and Black people had the highest representation in trials involving CML, at 12.7% and 5.3%, respectively.
Their lowest representation was in chronic lymphocytic leukemia (CLL), at 3% and 1.1%, respectively.
Among the trials reporting ethnicity, Hispanic people were the highest representation, with percentages ranging from 3.8% of MM trials to 11.5% in ALL trials.
Inconsistent with patient populations
Next, the researchers compared the proportions of race/ethnic groups that were found among the participants of these pivotal trials with the proportions that would be expected in patient populations for each of these blood cancers (according to the U.S. Surveillance, Epidemiology, and End Results [SEER] database).
For example, White people made up 80.3% of participants in clinical trials of MM, whereas they represent 68.7% of patients with MM, a difference that was statistically significant (P < .0001).
The finding was similar for CML, with White people accounting for 90.5% of participants in clinical trials versus 82.5% of the patient population (P < .0001).
For AML, the difference was smaller, with respective percentages of 79.6 versus 77.3% (P = .0389).
For Black people, Asian/Pacific Islanders and Hispanic people, across all five cancer types that were analyzed, the proportion of participants in clinical trials was significantly lower than the proportion in the patient population.
The analysis also showed that females were overrepresented in clinical trials for two blood cancers. For MM, trial participation was 44.7%, while disease incidence was 41.7% (P < .0001), and for CML the proportions were 44.7% versus 39.5% (P = .0009). However, females were underrepresented in a third blood cancer: in AML, the proportions were 44.7% versus 60.5% (P < .0001).
Geographic location of trials often inaccessible
The study also highlighted an obstacle to minorities participating in clinical trials: geography.
For this analysis, the researchers looked at mortality rates for the various blood cancers.
For AML, they found mortality rates were high across the whole of the United States, but centers conducting AML clinical trials were primarily in the Northeast, with no centers in the Midwest.
Key regions with high rates of AML mortality, low access to trials, and high minority representation were notably clustered in areas including east of the Carolinas, South Georgia, Alabama, and Mississippi, the authors noted.
“In many instances, trials were absent in areas with high mortality,” they report. “This makes access to clinical trials difficult, if not impossible, to patients who do not have the financial means for travel.”
Further action needed
Racial and ethnic disparities in clinical trials have been widely reported in numerous previous studies, the authors note.
Various initiatives have been launched in recent years to tackle the problem, including the National Institutes of Health Revitalization Act, FDA race and ethnicity guidance, and the International Conference for Harmonization guidance.
For oncology, the American Society of Clinical Oncology has also taken steps with the release of the new Equity, Diversity, and Inclusion Action Plan in 2021 to improve representation of minorities in research.
Dr. Cortes and colleagues suggest another step that is needed is standardized reporting of demographics of clinical trial participants.
“More importantly, efforts to increase representation of minorities and disadvantaged populations in clinical trials should be prioritized,” they say.
Dr. Cortes reports a consulting role and receiving research funding from many pharmaceutical companies. No other coauthors have financial disclosures. Dr. Chandhok reports honoraria from Healio, Clinical Care Options, and a consulting role with Servier. Dr. Sekeres reports a consulting role with Celgene, Millennium, Pfizer, Novartis, Syros Pharmaceuticals, Kurome Therapeutics, and institutional research funding from Takeda, Pfizer, Bristol Myers Squibb, Actuate Therapeutics, Sellas Life Sciences, and Bio-Path Holdings.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Bias and other barriers to HSCT access
For example, at the June 5 plenary session of the American Society of Clinical Oncology, Paul Richardson, MD, presented results of the DETERMINATION trial. More than 40,000 attendees heard his message that, in patients with newly diagnosed multiple myeloma (MM), up-front high-dose melphalan with autologous hematopoietic stem cell transplant (HSCT) support is associated with a significantly longer median progression-free survival of 67 months, compared with 46 months for patients randomized to delayed transplantation. The 5-year overall survival is similar for both arms.
While I and many of my colleagues in the field of transplantation used this data to strongly encourage MM patients to undergo HSCT as consolidation of their initial remission, others – including many investigators on the DETERMINATION trial – reached a starkly different conclusion. They suggested that delaying transplant was a valid option, since no survival benefit was observed.
Bias, when defined as a prejudice in favor of or against a specific treatment on the part of physicians and patients, has not been carefully studied in the realm of cellular therapies. However, physician and patient perceptions or misperceptions about the value or toxicity of a specific therapy are probably major drivers of whether a patient is referred for and accepts a particular form of treatment. In my specialization, that would mean either a stem cell transplant or other forms of cell therapy.
As with other medical procedures, in my field there are significant disparities in the use of transplantation among patients of different racial, ethnic, and age groups. Rates of both auto- and allo-HSCT are significantly higher for Whites than for African Americans. Hispanic patients have the lowest rates of utilization of auto-HSCT. Patients over the age of 60 have an eightfold risk of nonreferral to an HSCT center. Obviously, these nonreferrals reduce access to HSCT for older patients, particularly if they are seen at nonacademic centers.
One must question whether these disparities are caused by the physicians not believing in the value of transplantation, or simply not understanding its value? Or do they just lack the time to refer patients to a transplant center?
Socioeconomic factors, insurance status, age, and psychosocial characteristics all impact access to HSCT, yet some older patients with fewer economic resources and less insurance coverage still undergo the procedure. Is that because their physicians spent time educating these patients about the potential value of this treatment? Is it because the physicians went the extra mile to get these patients access to HSCT?
Physician preference also plays a significant role in whether a patient receives an allo-HSCT for acute myeloid leukemia and myelodysplastic syndrome. In a large survey of hematologists and oncologists performed by Pidala and colleagues, half of those surveyed agreed with the statement: “I feel the risk (morbidity and mortality) after HSCT is very high.” Most indicated that they “feel outcomes of unrelated donor HCT are much worse than matched sibling HCT.”
More importantly, more than one-third of those surveyed agreed that, “because of the high risks of allogeneic HSCT, I refer only after failure of conventional chemotherapy.” They voiced this opinion despite the fact that mortality rates after HSCT have been reduced significantly. With modern techniques, outcomes of unrelated donors are as good as with sibling donor transplants, and national guidelines strongly recommend that patients get referred before they become refractory to chemotherapy.
What can we do about this problem? Obviously, physician and provider education is important, but primary care physicians and general oncologists are already bombarded daily with new information. Relatively rare conditions like those we treat simply may not get their attention.
Personally, I think one of the most effective ways to overcome bias among physicians would be to target patients through a direct advertising campaign and public service announcements. Only by getting the attention of patients can they be directed to current, accurate information.
This solution could reduce the impact of physician biases or misperceptions and provide patients with greater access to lifesaving cell therapies.
Dr. Giralt is deputy division head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center in New York.
For example, at the June 5 plenary session of the American Society of Clinical Oncology, Paul Richardson, MD, presented results of the DETERMINATION trial. More than 40,000 attendees heard his message that, in patients with newly diagnosed multiple myeloma (MM), up-front high-dose melphalan with autologous hematopoietic stem cell transplant (HSCT) support is associated with a significantly longer median progression-free survival of 67 months, compared with 46 months for patients randomized to delayed transplantation. The 5-year overall survival is similar for both arms.
While I and many of my colleagues in the field of transplantation used this data to strongly encourage MM patients to undergo HSCT as consolidation of their initial remission, others – including many investigators on the DETERMINATION trial – reached a starkly different conclusion. They suggested that delaying transplant was a valid option, since no survival benefit was observed.
Bias, when defined as a prejudice in favor of or against a specific treatment on the part of physicians and patients, has not been carefully studied in the realm of cellular therapies. However, physician and patient perceptions or misperceptions about the value or toxicity of a specific therapy are probably major drivers of whether a patient is referred for and accepts a particular form of treatment. In my specialization, that would mean either a stem cell transplant or other forms of cell therapy.
As with other medical procedures, in my field there are significant disparities in the use of transplantation among patients of different racial, ethnic, and age groups. Rates of both auto- and allo-HSCT are significantly higher for Whites than for African Americans. Hispanic patients have the lowest rates of utilization of auto-HSCT. Patients over the age of 60 have an eightfold risk of nonreferral to an HSCT center. Obviously, these nonreferrals reduce access to HSCT for older patients, particularly if they are seen at nonacademic centers.
One must question whether these disparities are caused by the physicians not believing in the value of transplantation, or simply not understanding its value? Or do they just lack the time to refer patients to a transplant center?
Socioeconomic factors, insurance status, age, and psychosocial characteristics all impact access to HSCT, yet some older patients with fewer economic resources and less insurance coverage still undergo the procedure. Is that because their physicians spent time educating these patients about the potential value of this treatment? Is it because the physicians went the extra mile to get these patients access to HSCT?
Physician preference also plays a significant role in whether a patient receives an allo-HSCT for acute myeloid leukemia and myelodysplastic syndrome. In a large survey of hematologists and oncologists performed by Pidala and colleagues, half of those surveyed agreed with the statement: “I feel the risk (morbidity and mortality) after HSCT is very high.” Most indicated that they “feel outcomes of unrelated donor HCT are much worse than matched sibling HCT.”
More importantly, more than one-third of those surveyed agreed that, “because of the high risks of allogeneic HSCT, I refer only after failure of conventional chemotherapy.” They voiced this opinion despite the fact that mortality rates after HSCT have been reduced significantly. With modern techniques, outcomes of unrelated donors are as good as with sibling donor transplants, and national guidelines strongly recommend that patients get referred before they become refractory to chemotherapy.
What can we do about this problem? Obviously, physician and provider education is important, but primary care physicians and general oncologists are already bombarded daily with new information. Relatively rare conditions like those we treat simply may not get their attention.
Personally, I think one of the most effective ways to overcome bias among physicians would be to target patients through a direct advertising campaign and public service announcements. Only by getting the attention of patients can they be directed to current, accurate information.
This solution could reduce the impact of physician biases or misperceptions and provide patients with greater access to lifesaving cell therapies.
Dr. Giralt is deputy division head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center in New York.
For example, at the June 5 plenary session of the American Society of Clinical Oncology, Paul Richardson, MD, presented results of the DETERMINATION trial. More than 40,000 attendees heard his message that, in patients with newly diagnosed multiple myeloma (MM), up-front high-dose melphalan with autologous hematopoietic stem cell transplant (HSCT) support is associated with a significantly longer median progression-free survival of 67 months, compared with 46 months for patients randomized to delayed transplantation. The 5-year overall survival is similar for both arms.
While I and many of my colleagues in the field of transplantation used this data to strongly encourage MM patients to undergo HSCT as consolidation of their initial remission, others – including many investigators on the DETERMINATION trial – reached a starkly different conclusion. They suggested that delaying transplant was a valid option, since no survival benefit was observed.
Bias, when defined as a prejudice in favor of or against a specific treatment on the part of physicians and patients, has not been carefully studied in the realm of cellular therapies. However, physician and patient perceptions or misperceptions about the value or toxicity of a specific therapy are probably major drivers of whether a patient is referred for and accepts a particular form of treatment. In my specialization, that would mean either a stem cell transplant or other forms of cell therapy.
As with other medical procedures, in my field there are significant disparities in the use of transplantation among patients of different racial, ethnic, and age groups. Rates of both auto- and allo-HSCT are significantly higher for Whites than for African Americans. Hispanic patients have the lowest rates of utilization of auto-HSCT. Patients over the age of 60 have an eightfold risk of nonreferral to an HSCT center. Obviously, these nonreferrals reduce access to HSCT for older patients, particularly if they are seen at nonacademic centers.
One must question whether these disparities are caused by the physicians not believing in the value of transplantation, or simply not understanding its value? Or do they just lack the time to refer patients to a transplant center?
Socioeconomic factors, insurance status, age, and psychosocial characteristics all impact access to HSCT, yet some older patients with fewer economic resources and less insurance coverage still undergo the procedure. Is that because their physicians spent time educating these patients about the potential value of this treatment? Is it because the physicians went the extra mile to get these patients access to HSCT?
Physician preference also plays a significant role in whether a patient receives an allo-HSCT for acute myeloid leukemia and myelodysplastic syndrome. In a large survey of hematologists and oncologists performed by Pidala and colleagues, half of those surveyed agreed with the statement: “I feel the risk (morbidity and mortality) after HSCT is very high.” Most indicated that they “feel outcomes of unrelated donor HCT are much worse than matched sibling HCT.”
More importantly, more than one-third of those surveyed agreed that, “because of the high risks of allogeneic HSCT, I refer only after failure of conventional chemotherapy.” They voiced this opinion despite the fact that mortality rates after HSCT have been reduced significantly. With modern techniques, outcomes of unrelated donors are as good as with sibling donor transplants, and national guidelines strongly recommend that patients get referred before they become refractory to chemotherapy.
What can we do about this problem? Obviously, physician and provider education is important, but primary care physicians and general oncologists are already bombarded daily with new information. Relatively rare conditions like those we treat simply may not get their attention.
Personally, I think one of the most effective ways to overcome bias among physicians would be to target patients through a direct advertising campaign and public service announcements. Only by getting the attention of patients can they be directed to current, accurate information.
This solution could reduce the impact of physician biases or misperceptions and provide patients with greater access to lifesaving cell therapies.
Dr. Giralt is deputy division head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center in New York.
First drug therapy approved for childhood GVHD
Specifically, the indication is for pediatric patients with cGVHD who have already been treated with one or more lines of systemic therapy. The manufacturers have also launched a new oral suspension formulation, in addition to capsules and tablets, which were already available.
Ibrutinib is already approved for use in adults with cGVHD.
The drug is also approved for use in several blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. All these approvals are for adult patients.
This is the first pediatric indication for the product and is “incredibly meaningful,” said Gauri Sunkersett, DO, associate medical director at AbbVie, which markets the drug together with Jansen. “As a pediatric oncologist, when my patients describe the physical pain they experience from simply hugging their parents, due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated.”
These children have already been through a lot, having been diagnosed with a leukemia or lymphoma and then undergoing chemotherapy and/or radiotherapy for a stem cell transplant. Just over half (52%-65%) of children who receive allogeneic transplants go on to develop cGVHD, in which the donor bone marrow or stem cells attack the recipient.
“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” commented Paul A. Carpenter, MD, attending physician at Seattle Children’s Hospital. “If these children were between 1 and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options – until now.”
The new indication was approved by the U.S. Food and Drug Administration on the basis of results from the iMAGINE trial, for which Dr. Carpenter was a principal investigator.
The phase 1/2 iMAGINE trial was an open-label, multicenter, single-arm trial conducted with 47 patients (mean age, 13 years; range, 1-19 years) with relapsed/refractory cGVHD who had received at least one prior systemic therapy. Ibrutinib was given at a dose of 420 mg orally once daily to patients aged 12 and older and at a dose of 240 mg/m2 orally once daily to patients who were younger than 12 years.
The overall response rate through week 25 was 60% (confidence interval, 95%, 44%-74%). The median duration of response was 5.3 months (95% CI, 2.8-8.8).
The safety profile was consistent with the established profile for ibrutinib. Observed adverse events in pediatric patients were consistent with those observed in adult patients with moderate to severe cGVHD, the companies noted.
The FDA noted that the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
Full prescribing information for ibrutinib is available here.
A version of this article first appeared on Medscape.com.
Specifically, the indication is for pediatric patients with cGVHD who have already been treated with one or more lines of systemic therapy. The manufacturers have also launched a new oral suspension formulation, in addition to capsules and tablets, which were already available.
Ibrutinib is already approved for use in adults with cGVHD.
The drug is also approved for use in several blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. All these approvals are for adult patients.
This is the first pediatric indication for the product and is “incredibly meaningful,” said Gauri Sunkersett, DO, associate medical director at AbbVie, which markets the drug together with Jansen. “As a pediatric oncologist, when my patients describe the physical pain they experience from simply hugging their parents, due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated.”
These children have already been through a lot, having been diagnosed with a leukemia or lymphoma and then undergoing chemotherapy and/or radiotherapy for a stem cell transplant. Just over half (52%-65%) of children who receive allogeneic transplants go on to develop cGVHD, in which the donor bone marrow or stem cells attack the recipient.
“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” commented Paul A. Carpenter, MD, attending physician at Seattle Children’s Hospital. “If these children were between 1 and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options – until now.”
The new indication was approved by the U.S. Food and Drug Administration on the basis of results from the iMAGINE trial, for which Dr. Carpenter was a principal investigator.
The phase 1/2 iMAGINE trial was an open-label, multicenter, single-arm trial conducted with 47 patients (mean age, 13 years; range, 1-19 years) with relapsed/refractory cGVHD who had received at least one prior systemic therapy. Ibrutinib was given at a dose of 420 mg orally once daily to patients aged 12 and older and at a dose of 240 mg/m2 orally once daily to patients who were younger than 12 years.
The overall response rate through week 25 was 60% (confidence interval, 95%, 44%-74%). The median duration of response was 5.3 months (95% CI, 2.8-8.8).
The safety profile was consistent with the established profile for ibrutinib. Observed adverse events in pediatric patients were consistent with those observed in adult patients with moderate to severe cGVHD, the companies noted.
The FDA noted that the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
Full prescribing information for ibrutinib is available here.
A version of this article first appeared on Medscape.com.
Specifically, the indication is for pediatric patients with cGVHD who have already been treated with one or more lines of systemic therapy. The manufacturers have also launched a new oral suspension formulation, in addition to capsules and tablets, which were already available.
Ibrutinib is already approved for use in adults with cGVHD.
The drug is also approved for use in several blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. All these approvals are for adult patients.
This is the first pediatric indication for the product and is “incredibly meaningful,” said Gauri Sunkersett, DO, associate medical director at AbbVie, which markets the drug together with Jansen. “As a pediatric oncologist, when my patients describe the physical pain they experience from simply hugging their parents, due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated.”
These children have already been through a lot, having been diagnosed with a leukemia or lymphoma and then undergoing chemotherapy and/or radiotherapy for a stem cell transplant. Just over half (52%-65%) of children who receive allogeneic transplants go on to develop cGVHD, in which the donor bone marrow or stem cells attack the recipient.
“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” commented Paul A. Carpenter, MD, attending physician at Seattle Children’s Hospital. “If these children were between 1 and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options – until now.”
The new indication was approved by the U.S. Food and Drug Administration on the basis of results from the iMAGINE trial, for which Dr. Carpenter was a principal investigator.
The phase 1/2 iMAGINE trial was an open-label, multicenter, single-arm trial conducted with 47 patients (mean age, 13 years; range, 1-19 years) with relapsed/refractory cGVHD who had received at least one prior systemic therapy. Ibrutinib was given at a dose of 420 mg orally once daily to patients aged 12 and older and at a dose of 240 mg/m2 orally once daily to patients who were younger than 12 years.
The overall response rate through week 25 was 60% (confidence interval, 95%, 44%-74%). The median duration of response was 5.3 months (95% CI, 2.8-8.8).
The safety profile was consistent with the established profile for ibrutinib. Observed adverse events in pediatric patients were consistent with those observed in adult patients with moderate to severe cGVHD, the companies noted.
The FDA noted that the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
Full prescribing information for ibrutinib is available here.
A version of this article first appeared on Medscape.com.
AML’s seasonal peak suggests viral or environmental etiology
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF HEMATOLOGY
Fourth patient cleared of HIV after stem cell transplant for blood cancer
MONTREAL – from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.
The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.
Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.
She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.
Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.
“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”
“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.
“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.
Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.
The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.
Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.
A version of this article first appeared on Medscape.com.
MONTREAL – from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.
The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.
Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.
She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.
Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.
“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”
“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.
“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.
Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.
The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.
Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.
A version of this article first appeared on Medscape.com.
MONTREAL – from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.
The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.
Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.
She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.
Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.
“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”
“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.
“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.
Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.
The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.
Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.
A version of this article first appeared on Medscape.com.
AT AIDS 2022