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FDA okays emergency use of convalescent plasma for seriously ill COVID-19 patients
As the proportion of patients infected with COVID-19 continues to rise in the United States, the Food and Drug Administration is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections.
While clinical trials are underway to evaluate the safety and efficacy of administering convalescent plasma to patients with COVID-19, the FDA is granting clinicians permission for use of investigational convalescent plasma under single-patient emergency Investigational New Drug Applications (INDs), since no known cure exists and a vaccine is more than 1 year away from becoming available.
This allows the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorization. This does not include the use of COVID-19 convalescent plasma for the prevention of infection, according to a statement issued by the agency on March 24.
“It is possible that convalescent plasma that contains antibodies to SARS-CoV-2 (the virus that causes COVID-19) might be effective against the infection,” the FDA statement reads. “Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and the 2012 MERS-CoV epidemic. Although promising, convalescent plasma has not been shown to be effective in every disease studied.”
“I think the FDA got caught initially a little flat-footed when it came to the development of COVID-19 tests, but they’re quickly catching up,” Peter J. Pitts, who was the FDA’s associate commissioner from 2002 to 2004, said in an interview. “I think that the attitude now is, ‘If it’s safe, let’s create a pathway to see how these things work in the real world.’ I think that’s going to be as true for treatments to lessen the symptoms and shorten the duration of the disease, as well as convalescent plasma as a potential alternative to a yet-to-be-developed vaccine.”
At the University of Washington School of Medicine, Seattle, Terry B. Gernsheimer, MD, and her colleagues are recruiting recovered COVID-19 patients to donate plasma for seriously ill patients affected with the virus. “The thought of using convalescent plasma makes total sense, because it’s immediately available, and it’s something that we can try to give people,” said Dr. Gernsheimer, a hematologist who is professor of medicine at the medical school. “It’s been used in China, and reports should be coming out shortly about their experience with this.”
In a case series that appeared in JAMA on March 27 (doi: 10.1001/jama.2020.4783), Chinese researchers led by Chenguang Shen, PhD, reported findings from five critically ill COVID-19 patients with acute respiratory distress syndrome who received a transfusion with convalescent plasma at Shenzhen Third People’s Hospital 10 and 22 days after hospital admission. The patients ranged in age from 36 to 73 years, three were men, and all were receiving mechanical ventilation at the time of treatment.
Dr. Shen and colleagues reported that viral loads decreased and became negative within 12 days following the transfusion. Three of the patients were discharged from the hospital after a length of stay that ranged from 51 to 55 days, and two remain in stable condition at 37 days after the transfusion. The researchers pointed out that all patients received antiviral agents, including interferon and lopinavir/ritonavir, during and following convalescent plasma treatment, “which also may have contributed to the viral clearance observed.”
Under the FDA policy on emergency IND use, COVID-19 convalescent plasma must only be collected from recovered individuals if they are eligible to donate blood, required testing must be performed, and the donation must be found suitable.
Potential donors “are going to be screened the way all blood donors are screened,” Dr. Gernsheimer said. “It’s not going to be any less safe than any unit of plasma that’s on the shelf that comes from our volunteer donors. There are always transfusion reactions that we have to worry about, [and] there are potentially unknown pathogens that we don’t yet know about that we are not yet testing for. It’s the regular risk we see with any unit of plasma.”
She added that COVID-19 survivors appear to start increasing their titer of the antibody around day 28. “We’ll be looking for recovered individuals who have had a documented infection, and whose symptoms started about 28 days before we collect,” she said.
The FDA advises clinicians to address several considerations for donor eligibility, including prior diagnosis of COVID-19 documented by a laboratory test; complete resolution of symptoms at least 14 days prior to donation; female donors negative for HLA antibodies or male donors, and negative results for COVID-19 either from one or more nasopharyngeal swab specimens or by a molecular diagnostic test from blood. [A partial list of available tests can be accessed on the FDA website.] The agency also advises that donors have defined SARS-CoV-2–neutralizing antibody titers, if testing can be conducted (optimally greater than 1:320).
Patients eligible to receive COVID-19 convalescent plasma must have a severe or immediately life-threatening infection with laboratory-confirmed COVID-19. The agency defines severe disease as dyspnea, respiratory frequency of 30 per minute or greater, blood oxygen saturation of 93% or less, partial pressure of arterial oxygen to fraction of inspired oxygen ratio of less than 300, and/or lung infiltrates of greater than 50% within 24-48 hours. Life-threatening disease is defined as respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Patients must provide informed consent.
The potential risks of receiving COVID-19 convalescent plasma remain unknown, according to Dr. Gernsheimer. “What some people have thought about is, could there be such an inflammatory response with the virus that we would initially see these patients get worse?” she said. “My understanding is that has not occurred in China yet, but we don’t have all those data. But we always worry if we have something that’s going to cause inflammation around an infection, for example, that could initially make it more difficult to breathe if it’s a lung infection. So far, my understanding is that has not been seen.”
For COVID-19 convalescent plasma authorization requests that require a response within 4-8 hours, requesting clinicians may complete form 3296 and submit it by email to [email protected].
For COVID-19 convalescent plasma authorization requests that require a response in less than 4 hours, or if the clinician is unable to complete and submit form 3926 because of extenuating circumstances, verbal authorization can be sought by calling the FDA’s Office of Emergency Operations at 1-866-300-4374.
The FDA is working with the National Institutes of Health, the Centers for Disease Control and Prevention, and other government partners to develop protocols for use by multiple investigators in order to coordinate the collection and use of COVID-19 convalescent plasma.
“It’s crucial that data be captured for every patient so that we really understand what safety and effectiveness looks like on as close to a real-world level as we can, as quickly as we can,” said Mr. Pitts, who is president and cofounder of the Center for Medicine in the Public Interest, and who also does consulting work for the FDA. “I understand that health care professionals are overworked and overburdened right now. I applaud them for their heroic work. But that doesn’t mean that we can shirk off collecting the data. When I was at the FDA, I helped address the SARS epidemic. The agency attitude at that point was, ‘Let’s get things that just might work through the process, as long as the cure isn’t going to be worse than the disease.’ I think that’s the attitude that’s leading the charge today.”
As the proportion of patients infected with COVID-19 continues to rise in the United States, the Food and Drug Administration is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections.
While clinical trials are underway to evaluate the safety and efficacy of administering convalescent plasma to patients with COVID-19, the FDA is granting clinicians permission for use of investigational convalescent plasma under single-patient emergency Investigational New Drug Applications (INDs), since no known cure exists and a vaccine is more than 1 year away from becoming available.
This allows the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorization. This does not include the use of COVID-19 convalescent plasma for the prevention of infection, according to a statement issued by the agency on March 24.
“It is possible that convalescent plasma that contains antibodies to SARS-CoV-2 (the virus that causes COVID-19) might be effective against the infection,” the FDA statement reads. “Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and the 2012 MERS-CoV epidemic. Although promising, convalescent plasma has not been shown to be effective in every disease studied.”
“I think the FDA got caught initially a little flat-footed when it came to the development of COVID-19 tests, but they’re quickly catching up,” Peter J. Pitts, who was the FDA’s associate commissioner from 2002 to 2004, said in an interview. “I think that the attitude now is, ‘If it’s safe, let’s create a pathway to see how these things work in the real world.’ I think that’s going to be as true for treatments to lessen the symptoms and shorten the duration of the disease, as well as convalescent plasma as a potential alternative to a yet-to-be-developed vaccine.”
At the University of Washington School of Medicine, Seattle, Terry B. Gernsheimer, MD, and her colleagues are recruiting recovered COVID-19 patients to donate plasma for seriously ill patients affected with the virus. “The thought of using convalescent plasma makes total sense, because it’s immediately available, and it’s something that we can try to give people,” said Dr. Gernsheimer, a hematologist who is professor of medicine at the medical school. “It’s been used in China, and reports should be coming out shortly about their experience with this.”
In a case series that appeared in JAMA on March 27 (doi: 10.1001/jama.2020.4783), Chinese researchers led by Chenguang Shen, PhD, reported findings from five critically ill COVID-19 patients with acute respiratory distress syndrome who received a transfusion with convalescent plasma at Shenzhen Third People’s Hospital 10 and 22 days after hospital admission. The patients ranged in age from 36 to 73 years, three were men, and all were receiving mechanical ventilation at the time of treatment.
Dr. Shen and colleagues reported that viral loads decreased and became negative within 12 days following the transfusion. Three of the patients were discharged from the hospital after a length of stay that ranged from 51 to 55 days, and two remain in stable condition at 37 days after the transfusion. The researchers pointed out that all patients received antiviral agents, including interferon and lopinavir/ritonavir, during and following convalescent plasma treatment, “which also may have contributed to the viral clearance observed.”
Under the FDA policy on emergency IND use, COVID-19 convalescent plasma must only be collected from recovered individuals if they are eligible to donate blood, required testing must be performed, and the donation must be found suitable.
Potential donors “are going to be screened the way all blood donors are screened,” Dr. Gernsheimer said. “It’s not going to be any less safe than any unit of plasma that’s on the shelf that comes from our volunteer donors. There are always transfusion reactions that we have to worry about, [and] there are potentially unknown pathogens that we don’t yet know about that we are not yet testing for. It’s the regular risk we see with any unit of plasma.”
She added that COVID-19 survivors appear to start increasing their titer of the antibody around day 28. “We’ll be looking for recovered individuals who have had a documented infection, and whose symptoms started about 28 days before we collect,” she said.
The FDA advises clinicians to address several considerations for donor eligibility, including prior diagnosis of COVID-19 documented by a laboratory test; complete resolution of symptoms at least 14 days prior to donation; female donors negative for HLA antibodies or male donors, and negative results for COVID-19 either from one or more nasopharyngeal swab specimens or by a molecular diagnostic test from blood. [A partial list of available tests can be accessed on the FDA website.] The agency also advises that donors have defined SARS-CoV-2–neutralizing antibody titers, if testing can be conducted (optimally greater than 1:320).
Patients eligible to receive COVID-19 convalescent plasma must have a severe or immediately life-threatening infection with laboratory-confirmed COVID-19. The agency defines severe disease as dyspnea, respiratory frequency of 30 per minute or greater, blood oxygen saturation of 93% or less, partial pressure of arterial oxygen to fraction of inspired oxygen ratio of less than 300, and/or lung infiltrates of greater than 50% within 24-48 hours. Life-threatening disease is defined as respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Patients must provide informed consent.
The potential risks of receiving COVID-19 convalescent plasma remain unknown, according to Dr. Gernsheimer. “What some people have thought about is, could there be such an inflammatory response with the virus that we would initially see these patients get worse?” she said. “My understanding is that has not occurred in China yet, but we don’t have all those data. But we always worry if we have something that’s going to cause inflammation around an infection, for example, that could initially make it more difficult to breathe if it’s a lung infection. So far, my understanding is that has not been seen.”
For COVID-19 convalescent plasma authorization requests that require a response within 4-8 hours, requesting clinicians may complete form 3296 and submit it by email to [email protected].
For COVID-19 convalescent plasma authorization requests that require a response in less than 4 hours, or if the clinician is unable to complete and submit form 3926 because of extenuating circumstances, verbal authorization can be sought by calling the FDA’s Office of Emergency Operations at 1-866-300-4374.
The FDA is working with the National Institutes of Health, the Centers for Disease Control and Prevention, and other government partners to develop protocols for use by multiple investigators in order to coordinate the collection and use of COVID-19 convalescent plasma.
“It’s crucial that data be captured for every patient so that we really understand what safety and effectiveness looks like on as close to a real-world level as we can, as quickly as we can,” said Mr. Pitts, who is president and cofounder of the Center for Medicine in the Public Interest, and who also does consulting work for the FDA. “I understand that health care professionals are overworked and overburdened right now. I applaud them for their heroic work. But that doesn’t mean that we can shirk off collecting the data. When I was at the FDA, I helped address the SARS epidemic. The agency attitude at that point was, ‘Let’s get things that just might work through the process, as long as the cure isn’t going to be worse than the disease.’ I think that’s the attitude that’s leading the charge today.”
As the proportion of patients infected with COVID-19 continues to rise in the United States, the Food and Drug Administration is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections.
While clinical trials are underway to evaluate the safety and efficacy of administering convalescent plasma to patients with COVID-19, the FDA is granting clinicians permission for use of investigational convalescent plasma under single-patient emergency Investigational New Drug Applications (INDs), since no known cure exists and a vaccine is more than 1 year away from becoming available.
This allows the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorization. This does not include the use of COVID-19 convalescent plasma for the prevention of infection, according to a statement issued by the agency on March 24.
“It is possible that convalescent plasma that contains antibodies to SARS-CoV-2 (the virus that causes COVID-19) might be effective against the infection,” the FDA statement reads. “Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and the 2012 MERS-CoV epidemic. Although promising, convalescent plasma has not been shown to be effective in every disease studied.”
“I think the FDA got caught initially a little flat-footed when it came to the development of COVID-19 tests, but they’re quickly catching up,” Peter J. Pitts, who was the FDA’s associate commissioner from 2002 to 2004, said in an interview. “I think that the attitude now is, ‘If it’s safe, let’s create a pathway to see how these things work in the real world.’ I think that’s going to be as true for treatments to lessen the symptoms and shorten the duration of the disease, as well as convalescent plasma as a potential alternative to a yet-to-be-developed vaccine.”
At the University of Washington School of Medicine, Seattle, Terry B. Gernsheimer, MD, and her colleagues are recruiting recovered COVID-19 patients to donate plasma for seriously ill patients affected with the virus. “The thought of using convalescent plasma makes total sense, because it’s immediately available, and it’s something that we can try to give people,” said Dr. Gernsheimer, a hematologist who is professor of medicine at the medical school. “It’s been used in China, and reports should be coming out shortly about their experience with this.”
In a case series that appeared in JAMA on March 27 (doi: 10.1001/jama.2020.4783), Chinese researchers led by Chenguang Shen, PhD, reported findings from five critically ill COVID-19 patients with acute respiratory distress syndrome who received a transfusion with convalescent plasma at Shenzhen Third People’s Hospital 10 and 22 days after hospital admission. The patients ranged in age from 36 to 73 years, three were men, and all were receiving mechanical ventilation at the time of treatment.
Dr. Shen and colleagues reported that viral loads decreased and became negative within 12 days following the transfusion. Three of the patients were discharged from the hospital after a length of stay that ranged from 51 to 55 days, and two remain in stable condition at 37 days after the transfusion. The researchers pointed out that all patients received antiviral agents, including interferon and lopinavir/ritonavir, during and following convalescent plasma treatment, “which also may have contributed to the viral clearance observed.”
Under the FDA policy on emergency IND use, COVID-19 convalescent plasma must only be collected from recovered individuals if they are eligible to donate blood, required testing must be performed, and the donation must be found suitable.
Potential donors “are going to be screened the way all blood donors are screened,” Dr. Gernsheimer said. “It’s not going to be any less safe than any unit of plasma that’s on the shelf that comes from our volunteer donors. There are always transfusion reactions that we have to worry about, [and] there are potentially unknown pathogens that we don’t yet know about that we are not yet testing for. It’s the regular risk we see with any unit of plasma.”
She added that COVID-19 survivors appear to start increasing their titer of the antibody around day 28. “We’ll be looking for recovered individuals who have had a documented infection, and whose symptoms started about 28 days before we collect,” she said.
The FDA advises clinicians to address several considerations for donor eligibility, including prior diagnosis of COVID-19 documented by a laboratory test; complete resolution of symptoms at least 14 days prior to donation; female donors negative for HLA antibodies or male donors, and negative results for COVID-19 either from one or more nasopharyngeal swab specimens or by a molecular diagnostic test from blood. [A partial list of available tests can be accessed on the FDA website.] The agency also advises that donors have defined SARS-CoV-2–neutralizing antibody titers, if testing can be conducted (optimally greater than 1:320).
Patients eligible to receive COVID-19 convalescent plasma must have a severe or immediately life-threatening infection with laboratory-confirmed COVID-19. The agency defines severe disease as dyspnea, respiratory frequency of 30 per minute or greater, blood oxygen saturation of 93% or less, partial pressure of arterial oxygen to fraction of inspired oxygen ratio of less than 300, and/or lung infiltrates of greater than 50% within 24-48 hours. Life-threatening disease is defined as respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Patients must provide informed consent.
The potential risks of receiving COVID-19 convalescent plasma remain unknown, according to Dr. Gernsheimer. “What some people have thought about is, could there be such an inflammatory response with the virus that we would initially see these patients get worse?” she said. “My understanding is that has not occurred in China yet, but we don’t have all those data. But we always worry if we have something that’s going to cause inflammation around an infection, for example, that could initially make it more difficult to breathe if it’s a lung infection. So far, my understanding is that has not been seen.”
For COVID-19 convalescent plasma authorization requests that require a response within 4-8 hours, requesting clinicians may complete form 3296 and submit it by email to [email protected].
For COVID-19 convalescent plasma authorization requests that require a response in less than 4 hours, or if the clinician is unable to complete and submit form 3926 because of extenuating circumstances, verbal authorization can be sought by calling the FDA’s Office of Emergency Operations at 1-866-300-4374.
The FDA is working with the National Institutes of Health, the Centers for Disease Control and Prevention, and other government partners to develop protocols for use by multiple investigators in order to coordinate the collection and use of COVID-19 convalescent plasma.
“It’s crucial that data be captured for every patient so that we really understand what safety and effectiveness looks like on as close to a real-world level as we can, as quickly as we can,” said Mr. Pitts, who is president and cofounder of the Center for Medicine in the Public Interest, and who also does consulting work for the FDA. “I understand that health care professionals are overworked and overburdened right now. I applaud them for their heroic work. But that doesn’t mean that we can shirk off collecting the data. When I was at the FDA, I helped address the SARS epidemic. The agency attitude at that point was, ‘Let’s get things that just might work through the process, as long as the cure isn’t going to be worse than the disease.’ I think that’s the attitude that’s leading the charge today.”
CLL and breast cancer differ in the expression of regulatory microRNAs
Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.
The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.
The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).
In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.
Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.
“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.
Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.
The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.
The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).
In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.
Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.
“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.
Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.
The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.
The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).
In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.
Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.
“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.
FROM MOLECULAR THERAPY ONCOLYTICS
Webinar confronts unique issues for the bleeding disorders community facing COVID-19
In a webinar conducted on March 20, Leonard Valentino, MD, president and CEO of the National Hemophilia Foundation (NHF), provided
Overall, the risk of comorbidities is no different in the bleeding disorders population than in the general population, and similar precautions should be maintained, Dr. Valentino stated. He listed some of the at-risk populations as designated by the Centers for Disease Control and Prevention.
In particular, he pointed out that, when the CDC referred to a greater risk of COVID-19 to individuals with bleeding disorders, the organization was referring to patients with HIV and sickle cell disease. The CDC was not referring to patients with other forms of bleeding disorders, such as hemophilia, Dr. Valentino stated.
All individuals should be following CDC and state and federal recommendations with regard to social distancing and hygiene. However, with regard to immunocompromised individuals, “the two populations we [in the bleeding disorders community] have to be concerned about are those in gene therapy clinical trials and those with inhibitors,” said Dr. Valentino.
Patients in a gene therapy clinical trial should exercise additional precautions because the use of steroids, common in these trials. “Steroids are an immunosuppressive drug, and this would increase one’s risk of infection, including COVID-19,” according to Dr. Valentino.
In addition, “I will say, if you have hemophilia and an inhibitor [an antibody to clotting factor treatment], that may alter the immune system, and we don’t know what the implication of that is in terms of coronavirus infection and COVID-19 disease. So people with an inhibitor should take special precautions to limit their exposures.”
Patients with a port should not need to have extra concerns regarding COVID-19, but they should continue to exercise the good hygiene that has always been essential, according to Dr. Valentino.
Dr. Valentino asked: Are patients with a bleeding disorder who become infected with COVID-19 more susceptible to a bleed? “You shouldn’t be more susceptible to bleeding except if you have severe cough, and that cough could result in bleeding to the head,” he answered.
If a patient needs to go to the emergency department for a bleed or possible COVID-19 infection, they should wear a face mask if they are sick to prevent spreading of disease. “This is really the only instance where a face mask may be beneficial” in that it limits other people’s exposure to your infection. It is especially important to call ahead before visiting the doctor or going to the emergency department. “Make sure that they’re aware that you’re coming.”
Of particular concern to patients is the amount of factor product they should have on hand. The current CDC recommendation is a 30-day supply of medicines, but that is misleading, because it refers to general medications, such as high-blood pressure medicine, and not factor products. “The current MASAC [NHF’s Medical and Scientific Advisory Council] recommendation is to have a 14-day supply of factor products available to you,” said Dr. Valentino, “and one should reorder when you have a 1-week supply.”
MASAC has issued a letter on the crisis on the NHF website.
These recommendations should not be exceeded in order to ensure that there is enough factor available to all patients, he added. Hoarding is discouraged, and there are no concerns as yet of factor running out. “We have had conversations with manufacturers and … the supply chain is robust.” The greater concern is with regard to ancillary supplies in the hospital that a hemophilia patient may require during treatment.
Patients and practitioners should consult the COVID-19 pages of both the NHF and Hemophilia Federation of America (HFA) websites. This includes a Health and Wellness update by Dr. Valentino.
With regard to financial issues, he and Sharon Meyers, CEO and president of the HFA, spoke, stating that both NHF and HFA have advocacy for patients seeking to deal with insurance issues or in paying for their products, urging people to go to the organizational websites and to also use their emails: [email protected] and [email protected].
She also announced that the annual meeting of the HFA was being postponed to Aug. 24-26 at the Hilton Inner Harbor Baltimore, Md.
Dr. Valentino and Ms. Meyers did not provide any disclosure information.
In a webinar conducted on March 20, Leonard Valentino, MD, president and CEO of the National Hemophilia Foundation (NHF), provided
Overall, the risk of comorbidities is no different in the bleeding disorders population than in the general population, and similar precautions should be maintained, Dr. Valentino stated. He listed some of the at-risk populations as designated by the Centers for Disease Control and Prevention.
In particular, he pointed out that, when the CDC referred to a greater risk of COVID-19 to individuals with bleeding disorders, the organization was referring to patients with HIV and sickle cell disease. The CDC was not referring to patients with other forms of bleeding disorders, such as hemophilia, Dr. Valentino stated.
All individuals should be following CDC and state and federal recommendations with regard to social distancing and hygiene. However, with regard to immunocompromised individuals, “the two populations we [in the bleeding disorders community] have to be concerned about are those in gene therapy clinical trials and those with inhibitors,” said Dr. Valentino.
Patients in a gene therapy clinical trial should exercise additional precautions because the use of steroids, common in these trials. “Steroids are an immunosuppressive drug, and this would increase one’s risk of infection, including COVID-19,” according to Dr. Valentino.
In addition, “I will say, if you have hemophilia and an inhibitor [an antibody to clotting factor treatment], that may alter the immune system, and we don’t know what the implication of that is in terms of coronavirus infection and COVID-19 disease. So people with an inhibitor should take special precautions to limit their exposures.”
Patients with a port should not need to have extra concerns regarding COVID-19, but they should continue to exercise the good hygiene that has always been essential, according to Dr. Valentino.
Dr. Valentino asked: Are patients with a bleeding disorder who become infected with COVID-19 more susceptible to a bleed? “You shouldn’t be more susceptible to bleeding except if you have severe cough, and that cough could result in bleeding to the head,” he answered.
If a patient needs to go to the emergency department for a bleed or possible COVID-19 infection, they should wear a face mask if they are sick to prevent spreading of disease. “This is really the only instance where a face mask may be beneficial” in that it limits other people’s exposure to your infection. It is especially important to call ahead before visiting the doctor or going to the emergency department. “Make sure that they’re aware that you’re coming.”
Of particular concern to patients is the amount of factor product they should have on hand. The current CDC recommendation is a 30-day supply of medicines, but that is misleading, because it refers to general medications, such as high-blood pressure medicine, and not factor products. “The current MASAC [NHF’s Medical and Scientific Advisory Council] recommendation is to have a 14-day supply of factor products available to you,” said Dr. Valentino, “and one should reorder when you have a 1-week supply.”
MASAC has issued a letter on the crisis on the NHF website.
These recommendations should not be exceeded in order to ensure that there is enough factor available to all patients, he added. Hoarding is discouraged, and there are no concerns as yet of factor running out. “We have had conversations with manufacturers and … the supply chain is robust.” The greater concern is with regard to ancillary supplies in the hospital that a hemophilia patient may require during treatment.
Patients and practitioners should consult the COVID-19 pages of both the NHF and Hemophilia Federation of America (HFA) websites. This includes a Health and Wellness update by Dr. Valentino.
With regard to financial issues, he and Sharon Meyers, CEO and president of the HFA, spoke, stating that both NHF and HFA have advocacy for patients seeking to deal with insurance issues or in paying for their products, urging people to go to the organizational websites and to also use their emails: [email protected] and [email protected].
She also announced that the annual meeting of the HFA was being postponed to Aug. 24-26 at the Hilton Inner Harbor Baltimore, Md.
Dr. Valentino and Ms. Meyers did not provide any disclosure information.
In a webinar conducted on March 20, Leonard Valentino, MD, president and CEO of the National Hemophilia Foundation (NHF), provided
Overall, the risk of comorbidities is no different in the bleeding disorders population than in the general population, and similar precautions should be maintained, Dr. Valentino stated. He listed some of the at-risk populations as designated by the Centers for Disease Control and Prevention.
In particular, he pointed out that, when the CDC referred to a greater risk of COVID-19 to individuals with bleeding disorders, the organization was referring to patients with HIV and sickle cell disease. The CDC was not referring to patients with other forms of bleeding disorders, such as hemophilia, Dr. Valentino stated.
All individuals should be following CDC and state and federal recommendations with regard to social distancing and hygiene. However, with regard to immunocompromised individuals, “the two populations we [in the bleeding disorders community] have to be concerned about are those in gene therapy clinical trials and those with inhibitors,” said Dr. Valentino.
Patients in a gene therapy clinical trial should exercise additional precautions because the use of steroids, common in these trials. “Steroids are an immunosuppressive drug, and this would increase one’s risk of infection, including COVID-19,” according to Dr. Valentino.
In addition, “I will say, if you have hemophilia and an inhibitor [an antibody to clotting factor treatment], that may alter the immune system, and we don’t know what the implication of that is in terms of coronavirus infection and COVID-19 disease. So people with an inhibitor should take special precautions to limit their exposures.”
Patients with a port should not need to have extra concerns regarding COVID-19, but they should continue to exercise the good hygiene that has always been essential, according to Dr. Valentino.
Dr. Valentino asked: Are patients with a bleeding disorder who become infected with COVID-19 more susceptible to a bleed? “You shouldn’t be more susceptible to bleeding except if you have severe cough, and that cough could result in bleeding to the head,” he answered.
If a patient needs to go to the emergency department for a bleed or possible COVID-19 infection, they should wear a face mask if they are sick to prevent spreading of disease. “This is really the only instance where a face mask may be beneficial” in that it limits other people’s exposure to your infection. It is especially important to call ahead before visiting the doctor or going to the emergency department. “Make sure that they’re aware that you’re coming.”
Of particular concern to patients is the amount of factor product they should have on hand. The current CDC recommendation is a 30-day supply of medicines, but that is misleading, because it refers to general medications, such as high-blood pressure medicine, and not factor products. “The current MASAC [NHF’s Medical and Scientific Advisory Council] recommendation is to have a 14-day supply of factor products available to you,” said Dr. Valentino, “and one should reorder when you have a 1-week supply.”
MASAC has issued a letter on the crisis on the NHF website.
These recommendations should not be exceeded in order to ensure that there is enough factor available to all patients, he added. Hoarding is discouraged, and there are no concerns as yet of factor running out. “We have had conversations with manufacturers and … the supply chain is robust.” The greater concern is with regard to ancillary supplies in the hospital that a hemophilia patient may require during treatment.
Patients and practitioners should consult the COVID-19 pages of both the NHF and Hemophilia Federation of America (HFA) websites. This includes a Health and Wellness update by Dr. Valentino.
With regard to financial issues, he and Sharon Meyers, CEO and president of the HFA, spoke, stating that both NHF and HFA have advocacy for patients seeking to deal with insurance issues or in paying for their products, urging people to go to the organizational websites and to also use their emails: [email protected] and [email protected].
She also announced that the annual meeting of the HFA was being postponed to Aug. 24-26 at the Hilton Inner Harbor Baltimore, Md.
Dr. Valentino and Ms. Meyers did not provide any disclosure information.
COVID-19: ASTCT provides interim guidelines for transplantation
The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.
The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.
The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
Diagnostic considerations
In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.
These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.
In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.
Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.
With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”
Treatment considerations
“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.
However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).
In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.
Evaluation prior to HCT or cellular therapy
“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.
If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.
In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”
Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.
In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”
Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”
In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”
In the updated ESBMT guidelines, this recommendation was made in reference to the greater spread of COVID-19: “It is therefore strongly recommended to have secured stem cell product access by freezing the product before start of conditioning and, in situations when this is not possible, to have an alternative donor as a backup. For low-risk patients, it is recommended to postpone the start of the transplant procedure if deemed to be safe to do so. This includes both allogeneic and autologous transplant procedures.”
In a recent webinar, Pavan Reddy, MD, of the University of Michigan, Ann Arbor, and ASTCT President; Alpana Waghmare, MD, of the Fred Hutchinson Cancer Research Center, Seattle; and Roy Chemaly, MD, of the MD Anderson Cancer Center, Houston, and chair of the ASTCT Transplant Infectious Disease Special Interest Group, discussed the guidelines and provided some updated information.
Dr. Reddy stated that, at the University of Michigan, they were delaying all nonurgent transplants, largely for myeloma, and are postponing even allotransplants. “The transplants we are not delaying are the high-risk AMLs … and in cases where we truly cannot delay transplants because of patient condition or, in some cases, the donor situation.”
Dr. Chemaly and Dr. Waghmare both agreed that their centers were following a similar approach.
With regard to patient testing, all three institution have recently moved to testing everyone a few days before transplant regardless of symptoms.
They also pointed out that essentially all clinical trials were being put on hold during the crisis, except for those few where patients would be put in danger if the trial were interrupted.
The guidelines discuss in depth the rationale, toxicity, and dosages for use of select agents, including remdesivir, chloroquine/hydroxychloroquine, ribavirin, and tocilizumab. There was some concern expressed about shortages developing in these drugs, which serve a number of other patient communities, in particular the possibility of a tocilizumab shortage was of concern.
Steroids and intravenous immunoglobulins are not are not recommended, according to the guidelines, which also stated that adjunctive therapies such as antibiotics should be considered.
Dr. Chemaly, Dr. Reddy, and Dr. Waghmare did not provide disclosure in the webinar.
The ASTCT recommends following the World Health Organization and CDC COVID-19 pages for continued updates and information on other aspects of the pandemic.
This article was updated 3/26/20.
SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.
There is emerging data regarding coinfection of SARS-CoV-2 with other viruses including infleunza. Immunocompromised hosts, especially transplantation and cellular therapy (TCT) recipients, are known to frequently have more than one pathogen present, especially in pulmonary infections. As the community spread increases, it would be reasonable to obtain concomitant testing for respiratory viruses along with SARS-CoV-2 as recommended. In addition, viral infection can cause secondary bacterial and fungal infections (especially Aspergillus). In the presence of SARS-CoV-2, where it is recommended to avoid bronchoalveolar lavage, we have to keep a high clinical suspicion based on patients’ risk factors.
Acute Respiratory Distress Syndrome (ARDS) caused by an intense inflammatory response is the main cause of death in COVID-19. Early reports on the use of tocilizumab (an IL-6 receptor blocker) for ARDS to block cytokine mediated injury to the lung should be a consideration early in the course of COVID-19 pneumonitis, especially in setting of high risk for ARDS mortality.
We are considering other IL-6–blocking agents like siltuximab in case of a shortage of tocilizumab while centers scramble to get these agents. It is important to note that any such usages for COVID-19 would be considered off-label.
TCT candidates should of course be practicing social distancing in days leading to transplant to reduce their risk of exposure regardless of state or federal recommendations. Household members of TCT candidates should practice similar caution because transmission has been reported by asymptomatic individuals.
Zainab Shahid, MD, is the medical director of Bone Marrow Transplant Infectious Diseases at the Levine Cancer Institute/Atrium Health and a clinical associate professor of medicine at University of North Carolina at Chapel Hill. She reported that she had no relevant disclosures.
There is emerging data regarding coinfection of SARS-CoV-2 with other viruses including infleunza. Immunocompromised hosts, especially transplantation and cellular therapy (TCT) recipients, are known to frequently have more than one pathogen present, especially in pulmonary infections. As the community spread increases, it would be reasonable to obtain concomitant testing for respiratory viruses along with SARS-CoV-2 as recommended. In addition, viral infection can cause secondary bacterial and fungal infections (especially Aspergillus). In the presence of SARS-CoV-2, where it is recommended to avoid bronchoalveolar lavage, we have to keep a high clinical suspicion based on patients’ risk factors.
Acute Respiratory Distress Syndrome (ARDS) caused by an intense inflammatory response is the main cause of death in COVID-19. Early reports on the use of tocilizumab (an IL-6 receptor blocker) for ARDS to block cytokine mediated injury to the lung should be a consideration early in the course of COVID-19 pneumonitis, especially in setting of high risk for ARDS mortality.
We are considering other IL-6–blocking agents like siltuximab in case of a shortage of tocilizumab while centers scramble to get these agents. It is important to note that any such usages for COVID-19 would be considered off-label.
TCT candidates should of course be practicing social distancing in days leading to transplant to reduce their risk of exposure regardless of state or federal recommendations. Household members of TCT candidates should practice similar caution because transmission has been reported by asymptomatic individuals.
Zainab Shahid, MD, is the medical director of Bone Marrow Transplant Infectious Diseases at the Levine Cancer Institute/Atrium Health and a clinical associate professor of medicine at University of North Carolina at Chapel Hill. She reported that she had no relevant disclosures.
There is emerging data regarding coinfection of SARS-CoV-2 with other viruses including infleunza. Immunocompromised hosts, especially transplantation and cellular therapy (TCT) recipients, are known to frequently have more than one pathogen present, especially in pulmonary infections. As the community spread increases, it would be reasonable to obtain concomitant testing for respiratory viruses along with SARS-CoV-2 as recommended. In addition, viral infection can cause secondary bacterial and fungal infections (especially Aspergillus). In the presence of SARS-CoV-2, where it is recommended to avoid bronchoalveolar lavage, we have to keep a high clinical suspicion based on patients’ risk factors.
Acute Respiratory Distress Syndrome (ARDS) caused by an intense inflammatory response is the main cause of death in COVID-19. Early reports on the use of tocilizumab (an IL-6 receptor blocker) for ARDS to block cytokine mediated injury to the lung should be a consideration early in the course of COVID-19 pneumonitis, especially in setting of high risk for ARDS mortality.
We are considering other IL-6–blocking agents like siltuximab in case of a shortage of tocilizumab while centers scramble to get these agents. It is important to note that any such usages for COVID-19 would be considered off-label.
TCT candidates should of course be practicing social distancing in days leading to transplant to reduce their risk of exposure regardless of state or federal recommendations. Household members of TCT candidates should practice similar caution because transmission has been reported by asymptomatic individuals.
Zainab Shahid, MD, is the medical director of Bone Marrow Transplant Infectious Diseases at the Levine Cancer Institute/Atrium Health and a clinical associate professor of medicine at University of North Carolina at Chapel Hill. She reported that she had no relevant disclosures.
The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.
The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.
The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
Diagnostic considerations
In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.
These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.
In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.
Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.
With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”
Treatment considerations
“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.
However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).
In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.
Evaluation prior to HCT or cellular therapy
“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.
If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.
In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”
Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.
In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”
Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”
In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”
In the updated ESBMT guidelines, this recommendation was made in reference to the greater spread of COVID-19: “It is therefore strongly recommended to have secured stem cell product access by freezing the product before start of conditioning and, in situations when this is not possible, to have an alternative donor as a backup. For low-risk patients, it is recommended to postpone the start of the transplant procedure if deemed to be safe to do so. This includes both allogeneic and autologous transplant procedures.”
In a recent webinar, Pavan Reddy, MD, of the University of Michigan, Ann Arbor, and ASTCT President; Alpana Waghmare, MD, of the Fred Hutchinson Cancer Research Center, Seattle; and Roy Chemaly, MD, of the MD Anderson Cancer Center, Houston, and chair of the ASTCT Transplant Infectious Disease Special Interest Group, discussed the guidelines and provided some updated information.
Dr. Reddy stated that, at the University of Michigan, they were delaying all nonurgent transplants, largely for myeloma, and are postponing even allotransplants. “The transplants we are not delaying are the high-risk AMLs … and in cases where we truly cannot delay transplants because of patient condition or, in some cases, the donor situation.”
Dr. Chemaly and Dr. Waghmare both agreed that their centers were following a similar approach.
With regard to patient testing, all three institution have recently moved to testing everyone a few days before transplant regardless of symptoms.
They also pointed out that essentially all clinical trials were being put on hold during the crisis, except for those few where patients would be put in danger if the trial were interrupted.
The guidelines discuss in depth the rationale, toxicity, and dosages for use of select agents, including remdesivir, chloroquine/hydroxychloroquine, ribavirin, and tocilizumab. There was some concern expressed about shortages developing in these drugs, which serve a number of other patient communities, in particular the possibility of a tocilizumab shortage was of concern.
Steroids and intravenous immunoglobulins are not are not recommended, according to the guidelines, which also stated that adjunctive therapies such as antibiotics should be considered.
Dr. Chemaly, Dr. Reddy, and Dr. Waghmare did not provide disclosure in the webinar.
The ASTCT recommends following the World Health Organization and CDC COVID-19 pages for continued updates and information on other aspects of the pandemic.
This article was updated 3/26/20.
SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.
The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.
The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.
The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
Diagnostic considerations
In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.
These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.
In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.
Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.
With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”
Treatment considerations
“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.
However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).
In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.
Evaluation prior to HCT or cellular therapy
“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.
If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.
In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”
Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.
In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”
Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”
In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”
In the updated ESBMT guidelines, this recommendation was made in reference to the greater spread of COVID-19: “It is therefore strongly recommended to have secured stem cell product access by freezing the product before start of conditioning and, in situations when this is not possible, to have an alternative donor as a backup. For low-risk patients, it is recommended to postpone the start of the transplant procedure if deemed to be safe to do so. This includes both allogeneic and autologous transplant procedures.”
In a recent webinar, Pavan Reddy, MD, of the University of Michigan, Ann Arbor, and ASTCT President; Alpana Waghmare, MD, of the Fred Hutchinson Cancer Research Center, Seattle; and Roy Chemaly, MD, of the MD Anderson Cancer Center, Houston, and chair of the ASTCT Transplant Infectious Disease Special Interest Group, discussed the guidelines and provided some updated information.
Dr. Reddy stated that, at the University of Michigan, they were delaying all nonurgent transplants, largely for myeloma, and are postponing even allotransplants. “The transplants we are not delaying are the high-risk AMLs … and in cases where we truly cannot delay transplants because of patient condition or, in some cases, the donor situation.”
Dr. Chemaly and Dr. Waghmare both agreed that their centers were following a similar approach.
With regard to patient testing, all three institution have recently moved to testing everyone a few days before transplant regardless of symptoms.
They also pointed out that essentially all clinical trials were being put on hold during the crisis, except for those few where patients would be put in danger if the trial were interrupted.
The guidelines discuss in depth the rationale, toxicity, and dosages for use of select agents, including remdesivir, chloroquine/hydroxychloroquine, ribavirin, and tocilizumab. There was some concern expressed about shortages developing in these drugs, which serve a number of other patient communities, in particular the possibility of a tocilizumab shortage was of concern.
Steroids and intravenous immunoglobulins are not are not recommended, according to the guidelines, which also stated that adjunctive therapies such as antibiotics should be considered.
Dr. Chemaly, Dr. Reddy, and Dr. Waghmare did not provide disclosure in the webinar.
The ASTCT recommends following the World Health Organization and CDC COVID-19 pages for continued updates and information on other aspects of the pandemic.
This article was updated 3/26/20.
SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.
Sickle cell patients with vitamin D deficiency prone to more ED visits, longer stays
Patients with sickle cell disease (SCD) plus vitamin D deficiency were found to have more hospitalization outcomes, including number of emergency department (ED) visits, the number of hospital admissions for pain crisis, and the length of hospital admission, according to a study published online by researchers from New York-Presbyterian Brooklyn Methodist Hospital.
The researchers performed a retrospective chart review of all 134 pediatric patients with SCD (aged 1-21 years) from January 2015 to January 2016 in an urban-based hospital setting. Ninety patients with at least one reported vitamin D level who maintained follow-up during the time studied were enrolled. Hospitalization rates were compared between vitamin D deficiency (< 20 ng/mL) and sufficiency (> 20 ng/mL) patients.
When compared to patients with SCD and sufficient vitamin D levels, patients with both SCD and vitamin D deficiency were more likely to have at least one ED visit (P < .01), at least one admission for pain crisis (P < .01), and a longer length of admission (P < .0001), the researchers found.
“Screening and treatment for vitamin D deficiency is generally cost effective and readily available, potentially having a significant impact on the quality of life for those living with sickle cell disease,” the researchers concluded.
The authors reported that there was no study funding and that they had no conflicts of interest.
SOURCE: Brown B et al. Blood Cells Mol Dis. 2020. doi: 10.1016/j.bcmd.2020.102415.
Patients with sickle cell disease (SCD) plus vitamin D deficiency were found to have more hospitalization outcomes, including number of emergency department (ED) visits, the number of hospital admissions for pain crisis, and the length of hospital admission, according to a study published online by researchers from New York-Presbyterian Brooklyn Methodist Hospital.
The researchers performed a retrospective chart review of all 134 pediatric patients with SCD (aged 1-21 years) from January 2015 to January 2016 in an urban-based hospital setting. Ninety patients with at least one reported vitamin D level who maintained follow-up during the time studied were enrolled. Hospitalization rates were compared between vitamin D deficiency (< 20 ng/mL) and sufficiency (> 20 ng/mL) patients.
When compared to patients with SCD and sufficient vitamin D levels, patients with both SCD and vitamin D deficiency were more likely to have at least one ED visit (P < .01), at least one admission for pain crisis (P < .01), and a longer length of admission (P < .0001), the researchers found.
“Screening and treatment for vitamin D deficiency is generally cost effective and readily available, potentially having a significant impact on the quality of life for those living with sickle cell disease,” the researchers concluded.
The authors reported that there was no study funding and that they had no conflicts of interest.
SOURCE: Brown B et al. Blood Cells Mol Dis. 2020. doi: 10.1016/j.bcmd.2020.102415.
Patients with sickle cell disease (SCD) plus vitamin D deficiency were found to have more hospitalization outcomes, including number of emergency department (ED) visits, the number of hospital admissions for pain crisis, and the length of hospital admission, according to a study published online by researchers from New York-Presbyterian Brooklyn Methodist Hospital.
The researchers performed a retrospective chart review of all 134 pediatric patients with SCD (aged 1-21 years) from January 2015 to January 2016 in an urban-based hospital setting. Ninety patients with at least one reported vitamin D level who maintained follow-up during the time studied were enrolled. Hospitalization rates were compared between vitamin D deficiency (< 20 ng/mL) and sufficiency (> 20 ng/mL) patients.
When compared to patients with SCD and sufficient vitamin D levels, patients with both SCD and vitamin D deficiency were more likely to have at least one ED visit (P < .01), at least one admission for pain crisis (P < .01), and a longer length of admission (P < .0001), the researchers found.
“Screening and treatment for vitamin D deficiency is generally cost effective and readily available, potentially having a significant impact on the quality of life for those living with sickle cell disease,” the researchers concluded.
The authors reported that there was no study funding and that they had no conflicts of interest.
SOURCE: Brown B et al. Blood Cells Mol Dis. 2020. doi: 10.1016/j.bcmd.2020.102415.
FROM BLOOD CELLS, MOLECULES, AND DISEASES
FDA approves new drug for relapsed/refractory multiple myeloma
The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.
“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.
The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.
In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.
The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.
Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).
The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.
The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.
The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
This article originally appeared on Medscape.com.
The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.
“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.
The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.
In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.
The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.
Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).
The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.
The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.
The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
This article originally appeared on Medscape.com.
The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.
“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.
The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.
In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.
The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.
Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).
The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.
The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.
The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
This article originally appeared on Medscape.com.
After PCI, stopping antiplatelet therapy for surgery appears safe
NATIONAL HARBOR, MD. – Following a percutaneous intervention with a second-generation drug-eluting stent, a judicious interruption of antiplatelet therapy for noncardiac surgery does not increase risk of net adverse clinical events, according to a large dataset presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Drawn from a multicenter registry in South Korea, it is likely that those in whom antiplatelet therapy was stopped during the perioperative period were at a lower relative risk, but the data remain reassuring, according to Jung-Sun Kim, MD, PhD, professor of medicine at Yonsei University, Seoul, South Korea.
In the registry of patients with a second-generation drug-eluting stent (DES) undergoing noncardiac surgery, “antiplatelet therapy was discontinued in almost half of the patients,” Dr. Kim reported. When these patients were compared with those who did not discontinue antiplatelet therapy, the data, called an “exploratory analysis,” suggested “no increased risk” of a composite of major adverse cardiac events (MACE) or major bleeding.
The retrospective analysis involved 3,582 percutaneous intervention (PCI) patients who had received a second-generation DES and subsequently underwent noncardiac surgery. In 1,750 of these patients, antiplatelet therapy was temporarily discontinued. The remaining 1,832 remained on some form of antiplatelet treatment, whether aspirin, a P2Y12 inhibitor, or dual-antiplatelet therapy.
There were no significant differences in crude rates between groups in rates at 30 days of a composite endpoint of MACE, major bleeding as defined by the International Society on Thrombosis and Haemostasis, or net adverse clinical events (NACE), a composite of adverse events that included MACE and major bleeding.
Relative risks for antiplatelet discontinuation remained generally low even after multiple stratifications performed to explore different variables, including the types of antiplatelet therapy being taken at the time of discontinuation, the types of noncardiac surgery performed, and the duration of discontinuation.
Of these variables, the interval of discontinuation appeared to be most relevant. Antiplatelet discontinuation of 3 days or less appeared to be associated with a higher risk of bleeding, although the difference did not reach significance. Discontinuations of 9 days or more were associated with increased risk of MACE, and this difference did reach statistical significance (hazard ratio, 3.38; 95% confidence interval, 1.36-8.38).
“Discontinuation of antiplatelet therapy for a period of 4-8 days appears to be optimal,” Dr. Kim said.
In general, risk of MACE, major bleeding, or NACE could not be linked to type of surgery, with the exception of intra-abdominal surgery. For this procedure, there appeared to be a lower risk of MACE in those who discontinued relative to those who remained on antiplatelet therapy, Dr. Kim reported.
Importantly, because of the fact that the decision to stop antiplatelet treatment was made by treating physicians, the characteristics of those who discontinued or remained on antiplatelet therapy differed meaningfully. Specifically, those in the discontinuation group were younger and were less likely to have additional risks for thrombotic events such as diabetes or chronic kidney disease. In those who discontinued antiplatelets, the average time since PCI was 23 months versus 16 months in the continuation group.
In addition, “more of the patients underwent higher-risk surgeries in the discontinuation group,” Dr. Kim added.
Relative rates of MACE and NACE remained similar even after risk adjustment, but Dr. Kim advised that the data should be “interpreted cautiously” because of the retrospective nature of the analysis.
A panel of experts invited to comment on the presentation agreed. These data were considered reassuring for clinicians considering an interruption of antiplatelet therapy following PCI with a second-generation DES, but there was uncertainty about their value for defining which patients are the best candidates.
The decision to discontinue antiplatelet drugs for noncardiac surgery is an important and common dilemma, but these data might be best characterized as “a testament to Korean cardiologists making good decisions,” said David J. Moliterno, MD, chairman of the department of medicine at University of Kentucky Health Care, Lexington.
Dr. Kim reported no potential financial conflicts of interest.
NATIONAL HARBOR, MD. – Following a percutaneous intervention with a second-generation drug-eluting stent, a judicious interruption of antiplatelet therapy for noncardiac surgery does not increase risk of net adverse clinical events, according to a large dataset presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Drawn from a multicenter registry in South Korea, it is likely that those in whom antiplatelet therapy was stopped during the perioperative period were at a lower relative risk, but the data remain reassuring, according to Jung-Sun Kim, MD, PhD, professor of medicine at Yonsei University, Seoul, South Korea.
In the registry of patients with a second-generation drug-eluting stent (DES) undergoing noncardiac surgery, “antiplatelet therapy was discontinued in almost half of the patients,” Dr. Kim reported. When these patients were compared with those who did not discontinue antiplatelet therapy, the data, called an “exploratory analysis,” suggested “no increased risk” of a composite of major adverse cardiac events (MACE) or major bleeding.
The retrospective analysis involved 3,582 percutaneous intervention (PCI) patients who had received a second-generation DES and subsequently underwent noncardiac surgery. In 1,750 of these patients, antiplatelet therapy was temporarily discontinued. The remaining 1,832 remained on some form of antiplatelet treatment, whether aspirin, a P2Y12 inhibitor, or dual-antiplatelet therapy.
There were no significant differences in crude rates between groups in rates at 30 days of a composite endpoint of MACE, major bleeding as defined by the International Society on Thrombosis and Haemostasis, or net adverse clinical events (NACE), a composite of adverse events that included MACE and major bleeding.
Relative risks for antiplatelet discontinuation remained generally low even after multiple stratifications performed to explore different variables, including the types of antiplatelet therapy being taken at the time of discontinuation, the types of noncardiac surgery performed, and the duration of discontinuation.
Of these variables, the interval of discontinuation appeared to be most relevant. Antiplatelet discontinuation of 3 days or less appeared to be associated with a higher risk of bleeding, although the difference did not reach significance. Discontinuations of 9 days or more were associated with increased risk of MACE, and this difference did reach statistical significance (hazard ratio, 3.38; 95% confidence interval, 1.36-8.38).
“Discontinuation of antiplatelet therapy for a period of 4-8 days appears to be optimal,” Dr. Kim said.
In general, risk of MACE, major bleeding, or NACE could not be linked to type of surgery, with the exception of intra-abdominal surgery. For this procedure, there appeared to be a lower risk of MACE in those who discontinued relative to those who remained on antiplatelet therapy, Dr. Kim reported.
Importantly, because of the fact that the decision to stop antiplatelet treatment was made by treating physicians, the characteristics of those who discontinued or remained on antiplatelet therapy differed meaningfully. Specifically, those in the discontinuation group were younger and were less likely to have additional risks for thrombotic events such as diabetes or chronic kidney disease. In those who discontinued antiplatelets, the average time since PCI was 23 months versus 16 months in the continuation group.
In addition, “more of the patients underwent higher-risk surgeries in the discontinuation group,” Dr. Kim added.
Relative rates of MACE and NACE remained similar even after risk adjustment, but Dr. Kim advised that the data should be “interpreted cautiously” because of the retrospective nature of the analysis.
A panel of experts invited to comment on the presentation agreed. These data were considered reassuring for clinicians considering an interruption of antiplatelet therapy following PCI with a second-generation DES, but there was uncertainty about their value for defining which patients are the best candidates.
The decision to discontinue antiplatelet drugs for noncardiac surgery is an important and common dilemma, but these data might be best characterized as “a testament to Korean cardiologists making good decisions,” said David J. Moliterno, MD, chairman of the department of medicine at University of Kentucky Health Care, Lexington.
Dr. Kim reported no potential financial conflicts of interest.
NATIONAL HARBOR, MD. – Following a percutaneous intervention with a second-generation drug-eluting stent, a judicious interruption of antiplatelet therapy for noncardiac surgery does not increase risk of net adverse clinical events, according to a large dataset presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Drawn from a multicenter registry in South Korea, it is likely that those in whom antiplatelet therapy was stopped during the perioperative period were at a lower relative risk, but the data remain reassuring, according to Jung-Sun Kim, MD, PhD, professor of medicine at Yonsei University, Seoul, South Korea.
In the registry of patients with a second-generation drug-eluting stent (DES) undergoing noncardiac surgery, “antiplatelet therapy was discontinued in almost half of the patients,” Dr. Kim reported. When these patients were compared with those who did not discontinue antiplatelet therapy, the data, called an “exploratory analysis,” suggested “no increased risk” of a composite of major adverse cardiac events (MACE) or major bleeding.
The retrospective analysis involved 3,582 percutaneous intervention (PCI) patients who had received a second-generation DES and subsequently underwent noncardiac surgery. In 1,750 of these patients, antiplatelet therapy was temporarily discontinued. The remaining 1,832 remained on some form of antiplatelet treatment, whether aspirin, a P2Y12 inhibitor, or dual-antiplatelet therapy.
There were no significant differences in crude rates between groups in rates at 30 days of a composite endpoint of MACE, major bleeding as defined by the International Society on Thrombosis and Haemostasis, or net adverse clinical events (NACE), a composite of adverse events that included MACE and major bleeding.
Relative risks for antiplatelet discontinuation remained generally low even after multiple stratifications performed to explore different variables, including the types of antiplatelet therapy being taken at the time of discontinuation, the types of noncardiac surgery performed, and the duration of discontinuation.
Of these variables, the interval of discontinuation appeared to be most relevant. Antiplatelet discontinuation of 3 days or less appeared to be associated with a higher risk of bleeding, although the difference did not reach significance. Discontinuations of 9 days or more were associated with increased risk of MACE, and this difference did reach statistical significance (hazard ratio, 3.38; 95% confidence interval, 1.36-8.38).
“Discontinuation of antiplatelet therapy for a period of 4-8 days appears to be optimal,” Dr. Kim said.
In general, risk of MACE, major bleeding, or NACE could not be linked to type of surgery, with the exception of intra-abdominal surgery. For this procedure, there appeared to be a lower risk of MACE in those who discontinued relative to those who remained on antiplatelet therapy, Dr. Kim reported.
Importantly, because of the fact that the decision to stop antiplatelet treatment was made by treating physicians, the characteristics of those who discontinued or remained on antiplatelet therapy differed meaningfully. Specifically, those in the discontinuation group were younger and were less likely to have additional risks for thrombotic events such as diabetes or chronic kidney disease. In those who discontinued antiplatelets, the average time since PCI was 23 months versus 16 months in the continuation group.
In addition, “more of the patients underwent higher-risk surgeries in the discontinuation group,” Dr. Kim added.
Relative rates of MACE and NACE remained similar even after risk adjustment, but Dr. Kim advised that the data should be “interpreted cautiously” because of the retrospective nature of the analysis.
A panel of experts invited to comment on the presentation agreed. These data were considered reassuring for clinicians considering an interruption of antiplatelet therapy following PCI with a second-generation DES, but there was uncertainty about their value for defining which patients are the best candidates.
The decision to discontinue antiplatelet drugs for noncardiac surgery is an important and common dilemma, but these data might be best characterized as “a testament to Korean cardiologists making good decisions,” said David J. Moliterno, MD, chairman of the department of medicine at University of Kentucky Health Care, Lexington.
Dr. Kim reported no potential financial conflicts of interest.
REPORTING FROM CRT 2020
New CAR T-cell therapy eliminates MM and tumor propagating cells without fratricide in lab study
These cells proved to be active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells, according to a report in Nature Communications.
This research is important because most MM patients eventually succumb to the disease and previously developed CAR T cells targeting B-cell maturation antigen (BCMA) on MM cells have shown high-response rates but limited durability.
Previous research showed that CD229/LY9 is a potential target for CAR T-cell therapy in MM because of its strong and homogeneous expression on the bulk of tumor cells, as well as chemotherapy-resistant myeloma progenitors; its absence from most normal cells; and dependence of MM cells on CD229 for their survival, according to Sabarinath V. Radhakrishnan, MD, of the University of Utah, Salt Lake City, and colleagues.
Using primary CD138+ tumor cells from three patients with plasma cell leukemia, a highly aggressive form of MM, which all showed high expression of CD229, the researchers found that CD229 CAR T cells exhibited high cytotoxic activity against these cells. In addition, when assessing two MM cell lines, U-266 and RPMI-8226, expressing different levels of CD229, they found that CD229 CAR T cells efficiently killed both cell lines in vitro.
“We do not observe fratricide during CD229 CAR T-cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM,” the authors concluded.
The study was funded by several nongovernmental organizations and the National Cancer Institute. Three of the authors are inventors on PCT application US2017/42840 “Antibodies and CAR T Cells for the Treatment of Multiple Myeloma” describing the therapeutic use of CD229 CAR T cells.
SOURCE: Radhakrishnan SV et al. Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.
These cells proved to be active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells, according to a report in Nature Communications.
This research is important because most MM patients eventually succumb to the disease and previously developed CAR T cells targeting B-cell maturation antigen (BCMA) on MM cells have shown high-response rates but limited durability.
Previous research showed that CD229/LY9 is a potential target for CAR T-cell therapy in MM because of its strong and homogeneous expression on the bulk of tumor cells, as well as chemotherapy-resistant myeloma progenitors; its absence from most normal cells; and dependence of MM cells on CD229 for their survival, according to Sabarinath V. Radhakrishnan, MD, of the University of Utah, Salt Lake City, and colleagues.
Using primary CD138+ tumor cells from three patients with plasma cell leukemia, a highly aggressive form of MM, which all showed high expression of CD229, the researchers found that CD229 CAR T cells exhibited high cytotoxic activity against these cells. In addition, when assessing two MM cell lines, U-266 and RPMI-8226, expressing different levels of CD229, they found that CD229 CAR T cells efficiently killed both cell lines in vitro.
“We do not observe fratricide during CD229 CAR T-cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM,” the authors concluded.
The study was funded by several nongovernmental organizations and the National Cancer Institute. Three of the authors are inventors on PCT application US2017/42840 “Antibodies and CAR T Cells for the Treatment of Multiple Myeloma” describing the therapeutic use of CD229 CAR T cells.
SOURCE: Radhakrishnan SV et al. Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.
These cells proved to be active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells, according to a report in Nature Communications.
This research is important because most MM patients eventually succumb to the disease and previously developed CAR T cells targeting B-cell maturation antigen (BCMA) on MM cells have shown high-response rates but limited durability.
Previous research showed that CD229/LY9 is a potential target for CAR T-cell therapy in MM because of its strong and homogeneous expression on the bulk of tumor cells, as well as chemotherapy-resistant myeloma progenitors; its absence from most normal cells; and dependence of MM cells on CD229 for their survival, according to Sabarinath V. Radhakrishnan, MD, of the University of Utah, Salt Lake City, and colleagues.
Using primary CD138+ tumor cells from three patients with plasma cell leukemia, a highly aggressive form of MM, which all showed high expression of CD229, the researchers found that CD229 CAR T cells exhibited high cytotoxic activity against these cells. In addition, when assessing two MM cell lines, U-266 and RPMI-8226, expressing different levels of CD229, they found that CD229 CAR T cells efficiently killed both cell lines in vitro.
“We do not observe fratricide during CD229 CAR T-cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM,” the authors concluded.
The study was funded by several nongovernmental organizations and the National Cancer Institute. Three of the authors are inventors on PCT application US2017/42840 “Antibodies and CAR T Cells for the Treatment of Multiple Myeloma” describing the therapeutic use of CD229 CAR T cells.
SOURCE: Radhakrishnan SV et al. Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.
FROM NATURE COMMUNICATIONS
Tumor neoantigenicity metric improves prediction of response to immunotherapy
A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.
The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.
“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.
The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.
The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.
In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).
Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).
In a cohort of patients with non–small cell lung cancer treated with checkpoint inhibitors, those with sustained responses were more likely to have higher CSiN scores than were patients with short-term progression (P = .015).
The investigators also compared the predictive power of CSiN with existing neoantigenicity metrics, ultimately concluding that CSiN was superior.
“Overall, the neoantigen load and neoantigen fitness models were not as strongly predictive of treatment response as CSiN,” the investigators wrote.
Again using data from patients with immunogenic cancers, the investigators looked for an association between CSiN score and overall survival. Indeed, patients with higher-than-average CSiN scores had significantly better survival than that of those with lower scores (P less than .001). This finding was maintained in a multivariate analysis that accounted for disease type, stage, sex, and age.
In contrast with the above findings, CSiN did not predict survival among patients with nonimmunogenic cancer types.
“Overall, our work offers a rigorous methodology of predicting response to immunotherapy and prognosis from routine patient samples and should be useful for personalizing medicine in the modern era of immunotherapy,” the investigators concluded.
The study was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society. The investigators reported no conflicts of interest.
SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.
A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.
The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.
“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.
The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.
The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.
In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).
Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).
In a cohort of patients with non–small cell lung cancer treated with checkpoint inhibitors, those with sustained responses were more likely to have higher CSiN scores than were patients with short-term progression (P = .015).
The investigators also compared the predictive power of CSiN with existing neoantigenicity metrics, ultimately concluding that CSiN was superior.
“Overall, the neoantigen load and neoantigen fitness models were not as strongly predictive of treatment response as CSiN,” the investigators wrote.
Again using data from patients with immunogenic cancers, the investigators looked for an association between CSiN score and overall survival. Indeed, patients with higher-than-average CSiN scores had significantly better survival than that of those with lower scores (P less than .001). This finding was maintained in a multivariate analysis that accounted for disease type, stage, sex, and age.
In contrast with the above findings, CSiN did not predict survival among patients with nonimmunogenic cancer types.
“Overall, our work offers a rigorous methodology of predicting response to immunotherapy and prognosis from routine patient samples and should be useful for personalizing medicine in the modern era of immunotherapy,” the investigators concluded.
The study was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society. The investigators reported no conflicts of interest.
SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.
A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.
The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.
“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.
The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.
The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.
In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).
Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).
In a cohort of patients with non–small cell lung cancer treated with checkpoint inhibitors, those with sustained responses were more likely to have higher CSiN scores than were patients with short-term progression (P = .015).
The investigators also compared the predictive power of CSiN with existing neoantigenicity metrics, ultimately concluding that CSiN was superior.
“Overall, the neoantigen load and neoantigen fitness models were not as strongly predictive of treatment response as CSiN,” the investigators wrote.
Again using data from patients with immunogenic cancers, the investigators looked for an association between CSiN score and overall survival. Indeed, patients with higher-than-average CSiN scores had significantly better survival than that of those with lower scores (P less than .001). This finding was maintained in a multivariate analysis that accounted for disease type, stage, sex, and age.
In contrast with the above findings, CSiN did not predict survival among patients with nonimmunogenic cancer types.
“Overall, our work offers a rigorous methodology of predicting response to immunotherapy and prognosis from routine patient samples and should be useful for personalizing medicine in the modern era of immunotherapy,” the investigators concluded.
The study was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society. The investigators reported no conflicts of interest.
SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.
FROM SCIENCE IMMUNOLOGY
Late effects in young cancer survivors underscore importance of high-risk screening
according to data from the Childhood Cancer Survivor Study.
At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.
Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.
The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.
For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).
These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”
In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”
Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.
This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.
SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.
according to data from the Childhood Cancer Survivor Study.
At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.
Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.
The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.
For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).
These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”
In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”
Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.
This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.
SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.
according to data from the Childhood Cancer Survivor Study.
At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.
Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.
The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.
For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).
These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”
In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”
Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.
This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.
SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.
FROM LANCET ONCOLOGY