Neil Osterweil

Gastroenterologists and other clinicians caring for patients with inflammatory bowel disease are being encouraged to report outcomes for pediatric and adult patients with IBD and COVID-19 infections to a new international registry.

The Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry is a repository for data on all cases of COVID-19 in patients with IBD, including those who are asymptomatic and detected only through public health screening.

The idea for the registry came from gastroenterologists at the University of North Carolina at Chapel Hill and at the Icahn School of Medicine at Mount Sinai, New York.

It was developed out of the recognition that, “with the emergence of this international health crisis, it would make sense to develop a registry to allow clinicians taking care of patients with inflammatory bowel disease to report on the specifics of their cases, so that we could then quickly define what the impact is of this disease on our patients, and determine how disease severity, medication, and specific demographics impact COVID-related outcomes in our population,” said registry cofounder Erica Brenner, MD, a pediatric gastroenterology fellow at UNC.

As of March 19, 2020, 14 cases of COVID-19 infections in patients with IBD had been reported to the registry: 6 from the United States, 3 from Spain, and 1 each from the United Kingdom, Switzerland, Ireland, Italy and the Netherlands. There were no patient deaths, and only two required hospitalization. Neither of the hospitalized patients required intensive care or ventilator support.

Dr. Brenner noted that it’s still early days, and that a clearer picture of the pandemic will begin to emerge as more cases are reported.

“We are planning at least weekly to update our ‘Updates and Data’ tab on the registry with summary data and aggregate information,” she said in an interview.

All data in the registry are deidentified in accordance with HIPAA Safe Harbor standards. The UNC–Chapel Hill Office for Human Research Ethics has determined that storage and analysis of deidentified data is exempt from institutional review board requirement because it does not constitute human subjects research as defined under federal regulations.

SECURE-IBD was the inspiration for a similarly designed COVID-19 registry for clinicians who treat patients with rheumatologic disorders, who often are treated with immunosuppressive agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and methotrexate.

“We’re in the process of talking to different leaders across specialties to leverage our blueprint to implement registries in all sorts of disease states, including cirrhosis, psoriasis, lupus, and sickle cell disease,” Dr. Brenner said.

The data entry process is estimated to take 5 minutes. Participating clinicians are requested to reported on confirmed COVID-19 cases only “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

“The success of this registry depends on international collaboration and buy-in from clinicians around the world, so we really encourage all clinicians who take care of patients with inflammatory bowel disease to go to our website and report a case,” Dr. Brenner said.

Gastroenterologists and other clinicians caring for patients with inflammatory bowel disease are being encouraged to report outcomes for pediatric and adult patients with IBD and COVID-19 infections to a new international registry.

The Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry is a repository for data on all cases of COVID-19 in patients with IBD, including those who are asymptomatic and detected only through public health screening.

The idea for the registry came from gastroenterologists at the University of North Carolina at Chapel Hill and at the Icahn School of Medicine at Mount Sinai, New York.

It was developed out of the recognition that, “with the emergence of this international health crisis, it would make sense to develop a registry to allow clinicians taking care of patients with inflammatory bowel disease to report on the specifics of their cases, so that we could then quickly define what the impact is of this disease on our patients, and determine how disease severity, medication, and specific demographics impact COVID-related outcomes in our population,” said registry cofounder Erica Brenner, MD, a pediatric gastroenterology fellow at UNC.

As of March 19, 2020, 14 cases of COVID-19 infections in patients with IBD had been reported to the registry: 6 from the United States, 3 from Spain, and 1 each from the United Kingdom, Switzerland, Ireland, Italy and the Netherlands. There were no patient deaths, and only two required hospitalization. Neither of the hospitalized patients required intensive care or ventilator support.

Dr. Brenner noted that it’s still early days, and that a clearer picture of the pandemic will begin to emerge as more cases are reported.

“We are planning at least weekly to update our ‘Updates and Data’ tab on the registry with summary data and aggregate information,” she said in an interview.

All data in the registry are deidentified in accordance with HIPAA Safe Harbor standards. The UNC–Chapel Hill Office for Human Research Ethics has determined that storage and analysis of deidentified data is exempt from institutional review board requirement because it does not constitute human subjects research as defined under federal regulations.

SECURE-IBD was the inspiration for a similarly designed COVID-19 registry for clinicians who treat patients with rheumatologic disorders, who often are treated with immunosuppressive agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and methotrexate.

“We’re in the process of talking to different leaders across specialties to leverage our blueprint to implement registries in all sorts of disease states, including cirrhosis, psoriasis, lupus, and sickle cell disease,” Dr. Brenner said.

The data entry process is estimated to take 5 minutes. Participating clinicians are requested to reported on confirmed COVID-19 cases only “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

“The success of this registry depends on international collaboration and buy-in from clinicians around the world, so we really encourage all clinicians who take care of patients with inflammatory bowel disease to go to our website and report a case,” Dr. Brenner said.

Gastroenterologists and other clinicians caring for patients with inflammatory bowel disease are being encouraged to report outcomes for pediatric and adult patients with IBD and COVID-19 infections to a new international registry.

The Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry is a repository for data on all cases of COVID-19 in patients with IBD, including those who are asymptomatic and detected only through public health screening.

The idea for the registry came from gastroenterologists at the University of North Carolina at Chapel Hill and at the Icahn School of Medicine at Mount Sinai, New York.

It was developed out of the recognition that, “with the emergence of this international health crisis, it would make sense to develop a registry to allow clinicians taking care of patients with inflammatory bowel disease to report on the specifics of their cases, so that we could then quickly define what the impact is of this disease on our patients, and determine how disease severity, medication, and specific demographics impact COVID-related outcomes in our population,” said registry cofounder Erica Brenner, MD, a pediatric gastroenterology fellow at UNC.

As of March 19, 2020, 14 cases of COVID-19 infections in patients with IBD had been reported to the registry: 6 from the United States, 3 from Spain, and 1 each from the United Kingdom, Switzerland, Ireland, Italy and the Netherlands. There were no patient deaths, and only two required hospitalization. Neither of the hospitalized patients required intensive care or ventilator support.

Dr. Brenner noted that it’s still early days, and that a clearer picture of the pandemic will begin to emerge as more cases are reported.

“We are planning at least weekly to update our ‘Updates and Data’ tab on the registry with summary data and aggregate information,” she said in an interview.

All data in the registry are deidentified in accordance with HIPAA Safe Harbor standards. The UNC–Chapel Hill Office for Human Research Ethics has determined that storage and analysis of deidentified data is exempt from institutional review board requirement because it does not constitute human subjects research as defined under federal regulations.

SECURE-IBD was the inspiration for a similarly designed COVID-19 registry for clinicians who treat patients with rheumatologic disorders, who often are treated with immunosuppressive agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and methotrexate.

“We’re in the process of talking to different leaders across specialties to leverage our blueprint to implement registries in all sorts of disease states, including cirrhosis, psoriasis, lupus, and sickle cell disease,” Dr. Brenner said.

The data entry process is estimated to take 5 minutes. Participating clinicians are requested to reported on confirmed COVID-19 cases only “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

“The success of this registry depends on international collaboration and buy-in from clinicians around the world, so we really encourage all clinicians who take care of patients with inflammatory bowel disease to go to our website and report a case,” Dr. Brenner said.

For patients age 75 and older with nonsquamous non–small cell lung cancer (NSCLC) not previously treated with chemotherapy, combination carboplatin and pemetrexed followed by pemetrexed maintenance is both effective and tolerable, suggest the results of a phase 3 trial.

The median overall survival was 18.7 months for patients randomized to carboplatin/pemetrexed and 15.5 months for patients randomized to docetaxel monotherapy.

The combination met the prespecified endpoint for noninferiority to docetaxel but was not shown to be superior in terms of overall survival, investigator Isamu Okamoto, MD, of Kyushu University in Fukuoka, Japan, and colleagues reported in JAMA Oncology.

Still, progression-free survival was significantly longer in the carboplatin/pemetrexed arm, and dose reductions were less frequent with the combination than with docetaxel.

“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance ... provides a clinically significant benefit with regard to its effectiveness and tolerability,” the investigators wrote. “This combination should therefore be considered as a standard option for treatment in this setting.”

Dr. Okamoto and colleagues noted that the lung cancer incidence in elderly patients – 75 years and older – is increasing, and cytotoxic chemotherapy remains the standard treatment for patients whose tumors do not carry targetable mutations or are resistant to immunotherapy.

“In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group,” the investigators wrote.

To that end, they conducted a phase 3 trial of carboplatin/pemetrexed in patients aged 75 and older with NSCLC who had not been exposed to cytotoxic chemotherapy.
 

Patients and treatment

There were 433 patients enrolled in the trial. Their median age was 78 years (range, 75-88 years), and 57.7% were men. All patients had Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were stratified by clinical stage (III, IV, or recurrence), sex, epidermal growth factor receptor variant status (wild-type, exon 19 deletion, L858R variant of exon 21, or unknown), and treatment center.

The patients were then randomly assigned on a 1:1 basis to receive either intravenous docetaxel at 60 mg/m² for 60 minutes on day 1 every 3 weeks or pemetrexed at 500 mg/m² for 10 minutes followed by an infusion of carboplatin at an area under the curve of 5 for 30 minutes on day 1 every 3 weeks. The combination therapy was repeated for up to four courses and followed by 3-week courses of maintenance therapy with the same dose of pemetrexed.

Both regimens were continued until disease progression or the development of unacceptable toxicities.
 

Efficacy and safety

All 433 randomized patients were included in the efficacy analysis, but the safety analysis included 428 patients. Three patients assigned to docetaxel and two assigned to carboplatin/pemetrexed did not receive protocol treatment.

The respective median overall survival for the docetaxel and carboplatin/pemetrexed arms was 15.5 months and 18.7 months, which translated to a stratified hazard ratio for death of 0.85, meeting the prespecified noninferiority endpoint (P = .003).

However, the upper limit of the 95% confidence interval was 1.056, exceeding the prespecified superiority margin of 1.000. Therefore, the combination could not be proven superior to docetaxel with regard to overall survival.

On the other hand, progression-free survival was significantly longer with carboplatin/pemetrexed. The median progression-free survival was 6.4 months in the combination arm and 4.3 months in the docetaxel arm (unstratified HR, 0.739; P < .001).

The overall response rate with carboplatin/pemetrexed was 36.8%, compared with 28.2% for docetaxel, but this difference was not statistically significant.

Adverse events that were more common in the docetaxel arm than in the combination arm included grade 3/4 decreases in white blood cell count (68.7% and 28%, respectively), grade 3/4 decreases in neutrophil count (86% and 46.3%, respectively), and febrile neutropenia (17.8% and 4.2%, respectively).

Adverse events more frequently seen with the combination than with docetaxel included anemia (29.4% and 1.9%, respectively) and decreased platelet counts (25.7% and 1.4%, respectively).

Two patients in each arm died from treatment-related causes. In the docetaxel arm, the deaths were caused by acute respiratory distress syndrome and pneumonitis. In the combination arm, the deaths were caused by dyspnea and pneumonitis.

Approximately 29% of patients in each arm reported improvement in quality of life at 18 weeks, compared with baseline.

Performance status is key

A lung cancer specialist who was not involved in the study agreed with the authors that age should not be the primary determinant for choice of a treatment regimen.

“There’s a convergence of data over the last decade or so that has really clearly shown that our treatment decisions should be based on performance status much more than chronologic age, certainly for our patients who are in their 70s, and even potentially into their early 80s,” Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview.

“The available data really say that patients with a good performance status who are in their 70s should be treated just like patients in their 60s and 50s,” he said.

He added, however, that for patients such as those in the study without targetable driver mutations, the best treatment would likely be immunotherapy or immunotherapy combined with chemotherapy.

“If there were a patient with a nonsquamous non–small cell lung cancer where we would be thinking about carboplatin and pemetrexed, I would go further than just carbo and pemetrexed; I would give carbo and pemetrexed with pembrolizumab for most of these patients,” he said.

Dr. West said the study primarily offers reassurances about the efficacy and tolerability of the carboplatin/pemetrexed combination in patients aged 75 years and older.

The study was funded by agencies of the Japanese government. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Eli Lilly Japan KK, and many other companies. Dr. West disclosed consulting for Merck.

SOURCE: Okamoto I et al. JAMA Oncol. 2020 Mar 12. doi: 10.1001/jamaoncol.2019.6828.

For patients age 75 and older with nonsquamous non–small cell lung cancer (NSCLC) not previously treated with chemotherapy, combination carboplatin and pemetrexed followed by pemetrexed maintenance is both effective and tolerable, suggest the results of a phase 3 trial.

The median overall survival was 18.7 months for patients randomized to carboplatin/pemetrexed and 15.5 months for patients randomized to docetaxel monotherapy.

The combination met the prespecified endpoint for noninferiority to docetaxel but was not shown to be superior in terms of overall survival, investigator Isamu Okamoto, MD, of Kyushu University in Fukuoka, Japan, and colleagues reported in JAMA Oncology.

Still, progression-free survival was significantly longer in the carboplatin/pemetrexed arm, and dose reductions were less frequent with the combination than with docetaxel.

“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance ... provides a clinically significant benefit with regard to its effectiveness and tolerability,” the investigators wrote. “This combination should therefore be considered as a standard option for treatment in this setting.”

Dr. Okamoto and colleagues noted that the lung cancer incidence in elderly patients – 75 years and older – is increasing, and cytotoxic chemotherapy remains the standard treatment for patients whose tumors do not carry targetable mutations or are resistant to immunotherapy.

“In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group,” the investigators wrote.

To that end, they conducted a phase 3 trial of carboplatin/pemetrexed in patients aged 75 and older with NSCLC who had not been exposed to cytotoxic chemotherapy.
 

Patients and treatment

There were 433 patients enrolled in the trial. Their median age was 78 years (range, 75-88 years), and 57.7% were men. All patients had Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were stratified by clinical stage (III, IV, or recurrence), sex, epidermal growth factor receptor variant status (wild-type, exon 19 deletion, L858R variant of exon 21, or unknown), and treatment center.

The patients were then randomly assigned on a 1:1 basis to receive either intravenous docetaxel at 60 mg/m² for 60 minutes on day 1 every 3 weeks or pemetrexed at 500 mg/m² for 10 minutes followed by an infusion of carboplatin at an area under the curve of 5 for 30 minutes on day 1 every 3 weeks. The combination therapy was repeated for up to four courses and followed by 3-week courses of maintenance therapy with the same dose of pemetrexed.

Both regimens were continued until disease progression or the development of unacceptable toxicities.
 

Efficacy and safety

All 433 randomized patients were included in the efficacy analysis, but the safety analysis included 428 patients. Three patients assigned to docetaxel and two assigned to carboplatin/pemetrexed did not receive protocol treatment.

The respective median overall survival for the docetaxel and carboplatin/pemetrexed arms was 15.5 months and 18.7 months, which translated to a stratified hazard ratio for death of 0.85, meeting the prespecified noninferiority endpoint (P = .003).

However, the upper limit of the 95% confidence interval was 1.056, exceeding the prespecified superiority margin of 1.000. Therefore, the combination could not be proven superior to docetaxel with regard to overall survival.

On the other hand, progression-free survival was significantly longer with carboplatin/pemetrexed. The median progression-free survival was 6.4 months in the combination arm and 4.3 months in the docetaxel arm (unstratified HR, 0.739; P < .001).

The overall response rate with carboplatin/pemetrexed was 36.8%, compared with 28.2% for docetaxel, but this difference was not statistically significant.

Adverse events that were more common in the docetaxel arm than in the combination arm included grade 3/4 decreases in white blood cell count (68.7% and 28%, respectively), grade 3/4 decreases in neutrophil count (86% and 46.3%, respectively), and febrile neutropenia (17.8% and 4.2%, respectively).

Adverse events more frequently seen with the combination than with docetaxel included anemia (29.4% and 1.9%, respectively) and decreased platelet counts (25.7% and 1.4%, respectively).

Two patients in each arm died from treatment-related causes. In the docetaxel arm, the deaths were caused by acute respiratory distress syndrome and pneumonitis. In the combination arm, the deaths were caused by dyspnea and pneumonitis.

Approximately 29% of patients in each arm reported improvement in quality of life at 18 weeks, compared with baseline.

Performance status is key

A lung cancer specialist who was not involved in the study agreed with the authors that age should not be the primary determinant for choice of a treatment regimen.

“There’s a convergence of data over the last decade or so that has really clearly shown that our treatment decisions should be based on performance status much more than chronologic age, certainly for our patients who are in their 70s, and even potentially into their early 80s,” Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview.

“The available data really say that patients with a good performance status who are in their 70s should be treated just like patients in their 60s and 50s,” he said.

He added, however, that for patients such as those in the study without targetable driver mutations, the best treatment would likely be immunotherapy or immunotherapy combined with chemotherapy.

“If there were a patient with a nonsquamous non–small cell lung cancer where we would be thinking about carboplatin and pemetrexed, I would go further than just carbo and pemetrexed; I would give carbo and pemetrexed with pembrolizumab for most of these patients,” he said.

Dr. West said the study primarily offers reassurances about the efficacy and tolerability of the carboplatin/pemetrexed combination in patients aged 75 years and older.

The study was funded by agencies of the Japanese government. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Eli Lilly Japan KK, and many other companies. Dr. West disclosed consulting for Merck.

SOURCE: Okamoto I et al. JAMA Oncol. 2020 Mar 12. doi: 10.1001/jamaoncol.2019.6828.

For patients age 75 and older with nonsquamous non–small cell lung cancer (NSCLC) not previously treated with chemotherapy, combination carboplatin and pemetrexed followed by pemetrexed maintenance is both effective and tolerable, suggest the results of a phase 3 trial.

The median overall survival was 18.7 months for patients randomized to carboplatin/pemetrexed and 15.5 months for patients randomized to docetaxel monotherapy.

The combination met the prespecified endpoint for noninferiority to docetaxel but was not shown to be superior in terms of overall survival, investigator Isamu Okamoto, MD, of Kyushu University in Fukuoka, Japan, and colleagues reported in JAMA Oncology.

Still, progression-free survival was significantly longer in the carboplatin/pemetrexed arm, and dose reductions were less frequent with the combination than with docetaxel.

“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance ... provides a clinically significant benefit with regard to its effectiveness and tolerability,” the investigators wrote. “This combination should therefore be considered as a standard option for treatment in this setting.”

Dr. Okamoto and colleagues noted that the lung cancer incidence in elderly patients – 75 years and older – is increasing, and cytotoxic chemotherapy remains the standard treatment for patients whose tumors do not carry targetable mutations or are resistant to immunotherapy.

“In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group,” the investigators wrote.

To that end, they conducted a phase 3 trial of carboplatin/pemetrexed in patients aged 75 and older with NSCLC who had not been exposed to cytotoxic chemotherapy.
 

Patients and treatment

There were 433 patients enrolled in the trial. Their median age was 78 years (range, 75-88 years), and 57.7% were men. All patients had Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were stratified by clinical stage (III, IV, or recurrence), sex, epidermal growth factor receptor variant status (wild-type, exon 19 deletion, L858R variant of exon 21, or unknown), and treatment center.

The patients were then randomly assigned on a 1:1 basis to receive either intravenous docetaxel at 60 mg/m² for 60 minutes on day 1 every 3 weeks or pemetrexed at 500 mg/m² for 10 minutes followed by an infusion of carboplatin at an area under the curve of 5 for 30 minutes on day 1 every 3 weeks. The combination therapy was repeated for up to four courses and followed by 3-week courses of maintenance therapy with the same dose of pemetrexed.

Both regimens were continued until disease progression or the development of unacceptable toxicities.
 

Efficacy and safety

All 433 randomized patients were included in the efficacy analysis, but the safety analysis included 428 patients. Three patients assigned to docetaxel and two assigned to carboplatin/pemetrexed did not receive protocol treatment.

The respective median overall survival for the docetaxel and carboplatin/pemetrexed arms was 15.5 months and 18.7 months, which translated to a stratified hazard ratio for death of 0.85, meeting the prespecified noninferiority endpoint (P = .003).

However, the upper limit of the 95% confidence interval was 1.056, exceeding the prespecified superiority margin of 1.000. Therefore, the combination could not be proven superior to docetaxel with regard to overall survival.

On the other hand, progression-free survival was significantly longer with carboplatin/pemetrexed. The median progression-free survival was 6.4 months in the combination arm and 4.3 months in the docetaxel arm (unstratified HR, 0.739; P < .001).

The overall response rate with carboplatin/pemetrexed was 36.8%, compared with 28.2% for docetaxel, but this difference was not statistically significant.

Adverse events that were more common in the docetaxel arm than in the combination arm included grade 3/4 decreases in white blood cell count (68.7% and 28%, respectively), grade 3/4 decreases in neutrophil count (86% and 46.3%, respectively), and febrile neutropenia (17.8% and 4.2%, respectively).

Adverse events more frequently seen with the combination than with docetaxel included anemia (29.4% and 1.9%, respectively) and decreased platelet counts (25.7% and 1.4%, respectively).

Two patients in each arm died from treatment-related causes. In the docetaxel arm, the deaths were caused by acute respiratory distress syndrome and pneumonitis. In the combination arm, the deaths were caused by dyspnea and pneumonitis.

Approximately 29% of patients in each arm reported improvement in quality of life at 18 weeks, compared with baseline.

Performance status is key

A lung cancer specialist who was not involved in the study agreed with the authors that age should not be the primary determinant for choice of a treatment regimen.

“There’s a convergence of data over the last decade or so that has really clearly shown that our treatment decisions should be based on performance status much more than chronologic age, certainly for our patients who are in their 70s, and even potentially into their early 80s,” Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview.

“The available data really say that patients with a good performance status who are in their 70s should be treated just like patients in their 60s and 50s,” he said.

He added, however, that for patients such as those in the study without targetable driver mutations, the best treatment would likely be immunotherapy or immunotherapy combined with chemotherapy.

“If there were a patient with a nonsquamous non–small cell lung cancer where we would be thinking about carboplatin and pemetrexed, I would go further than just carbo and pemetrexed; I would give carbo and pemetrexed with pembrolizumab for most of these patients,” he said.

Dr. West said the study primarily offers reassurances about the efficacy and tolerability of the carboplatin/pemetrexed combination in patients aged 75 years and older.

The study was funded by agencies of the Japanese government. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Eli Lilly Japan KK, and many other companies. Dr. West disclosed consulting for Merck.

SOURCE: Okamoto I et al. JAMA Oncol. 2020 Mar 12. doi: 10.1001/jamaoncol.2019.6828.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Clinicians across the United States are petitioning the federal government to follow the lead of South Korea, China, and other nations by imposing an immediate nationwide quarantine to slow the inevitable spread of COVID-19. Without federal action, the creators say, their lives and the lives of their colleagues, patients, and families are being put at increased risk.

In addition to the quarantine, the petition, posted on the website Change.org, calls on U.S. leaders to institute emergency production and distribution of personal protective equipment for healthcare workers and to rapidly increase access to testing.

The petition – which garnered more than 40,000 signatures in just 12 hours and as of this writing was approaching 94,000 – was started by an apolitical Facebook group to focus attention on what members see as the most critical issues for clinicians: slowing the spread of the virus through a coast-to-coast quarantine, protection of medical personnel with adequate supplies of essential equipment, and widespread testing.

“We started this group last Friday out of the realization that clinicians needed information about the outbreak and weren’t getting it,” said coadministrator Jessica McIntyre, MD, a pediatric hospitalist at Elliot Hospital in Manchester, N.H.

“We wanted to get ahead of it and connect with people before we were in the trenches experiencing it and to see what other programs were doing. From a local perspective, it has been really hard to see what people are doing in other states, especially when the protocols in our own states are changing every single day as we collect more information,” she said in an interview.
 

The Horse Has Bolted

A family medicine physician in Illinois helped launch the Facebook group. She asked that her name not be used but said in an interview that earlier actions may have prevented or at least delayed the need for the more draconian measures that her group is recommending.

“Clearly South Korea is one of the superstars as far as response has gone, but the concern we have in the United States is that we’re well beyond that point – we needed to be testing people over a month ago, in the hope of preventing a quarantine,” she said in an interview.

According to National Public Radio, as of March 13, South Korea had conducted 3,600 tests per million population, compared with five per million in the United States.

“I think the most concerning part is to see where Italy is now and where we are in comparison. Our ICUs have not yet overflowed, but I think we’re definitely looking at that in the next few weeks – hopefully longer, but I suspect that it will happen shortly,” she continued.

She cited work by Harvard University biostatistician Xihong Lin, PhD, that shows that when health authorities in Wuhan, China – widely cited as the epicenter of the global pandemic – cordoned off the city, the infection rate dropped from one person infecting 3.8 others to one infecting 1.25, thereby significantly slowing the rate of transmission.

“This is absolutely what we need to be doing,” she said.
 

Real News

Within 3 days of its creation, the online group had accrued more than 80,000 members with advanced medical training, including MDs, DOs, physician assistants, nurse practitioners, and certified registered nurse anesthetists.

“A lot of us were already very busy with our day-to-day work outside of COVID-19, and I think a lot of us felt unsure about where to get the best information,” said coadministrator David Janssen, MD, a family medicine physician in group practice in Sioux Center, Iowa,

“If you turn on the TV, there’s a lot of politicizing of the issue, and there’s a lot of good information, but also a lot of bad information. When health care providers talk to other health care providers, that’s often how we get our information and how we learn,” he said in an interview.

The COVID-19 U.S. Physicians/APP Facebook group includes 20 volunteer moderators who handle hundreds of posts per hour from persons seeking information on the novel coronavirus, what to tell patients, and how to protect themselves.

“It’s been wonderful to see how providers have been helping other providers sort through issues. Teaching hospitals have their hands on the latest research, but a lot of people like myself are at small community hospitals, critical-access hospitals, where we may have a lot of questions but don’t necessarily have the answers readily available to us,” Dr. Janssen said.

Dr. Janssen said that his community of about 8,000 residents initially had only four COVID-19 testing kits, or one for every 2,000 people. The situation has since improved, and more tests are now available, he added.

Dr. McIntyre, Dr. Janssen, and the Illinois family physician have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Clinicians across the United States are petitioning the federal government to follow the lead of South Korea, China, and other nations by imposing an immediate nationwide quarantine to slow the inevitable spread of COVID-19. Without federal action, the creators say, their lives and the lives of their colleagues, patients, and families are being put at increased risk.

In addition to the quarantine, the petition, posted on the website Change.org, calls on U.S. leaders to institute emergency production and distribution of personal protective equipment for healthcare workers and to rapidly increase access to testing.

The petition – which garnered more than 40,000 signatures in just 12 hours and as of this writing was approaching 94,000 – was started by an apolitical Facebook group to focus attention on what members see as the most critical issues for clinicians: slowing the spread of the virus through a coast-to-coast quarantine, protection of medical personnel with adequate supplies of essential equipment, and widespread testing.

“We started this group last Friday out of the realization that clinicians needed information about the outbreak and weren’t getting it,” said coadministrator Jessica McIntyre, MD, a pediatric hospitalist at Elliot Hospital in Manchester, N.H.

“We wanted to get ahead of it and connect with people before we were in the trenches experiencing it and to see what other programs were doing. From a local perspective, it has been really hard to see what people are doing in other states, especially when the protocols in our own states are changing every single day as we collect more information,” she said in an interview.
 

The Horse Has Bolted

A family medicine physician in Illinois helped launch the Facebook group. She asked that her name not be used but said in an interview that earlier actions may have prevented or at least delayed the need for the more draconian measures that her group is recommending.

“Clearly South Korea is one of the superstars as far as response has gone, but the concern we have in the United States is that we’re well beyond that point – we needed to be testing people over a month ago, in the hope of preventing a quarantine,” she said in an interview.

According to National Public Radio, as of March 13, South Korea had conducted 3,600 tests per million population, compared with five per million in the United States.

“I think the most concerning part is to see where Italy is now and where we are in comparison. Our ICUs have not yet overflowed, but I think we’re definitely looking at that in the next few weeks – hopefully longer, but I suspect that it will happen shortly,” she continued.

She cited work by Harvard University biostatistician Xihong Lin, PhD, that shows that when health authorities in Wuhan, China – widely cited as the epicenter of the global pandemic – cordoned off the city, the infection rate dropped from one person infecting 3.8 others to one infecting 1.25, thereby significantly slowing the rate of transmission.

“This is absolutely what we need to be doing,” she said.
 

Real News

Within 3 days of its creation, the online group had accrued more than 80,000 members with advanced medical training, including MDs, DOs, physician assistants, nurse practitioners, and certified registered nurse anesthetists.

“A lot of us were already very busy with our day-to-day work outside of COVID-19, and I think a lot of us felt unsure about where to get the best information,” said coadministrator David Janssen, MD, a family medicine physician in group practice in Sioux Center, Iowa,

“If you turn on the TV, there’s a lot of politicizing of the issue, and there’s a lot of good information, but also a lot of bad information. When health care providers talk to other health care providers, that’s often how we get our information and how we learn,” he said in an interview.

The COVID-19 U.S. Physicians/APP Facebook group includes 20 volunteer moderators who handle hundreds of posts per hour from persons seeking information on the novel coronavirus, what to tell patients, and how to protect themselves.

“It’s been wonderful to see how providers have been helping other providers sort through issues. Teaching hospitals have their hands on the latest research, but a lot of people like myself are at small community hospitals, critical-access hospitals, where we may have a lot of questions but don’t necessarily have the answers readily available to us,” Dr. Janssen said.

Dr. Janssen said that his community of about 8,000 residents initially had only four COVID-19 testing kits, or one for every 2,000 people. The situation has since improved, and more tests are now available, he added.

Dr. McIntyre, Dr. Janssen, and the Illinois family physician have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Clinicians across the United States are petitioning the federal government to follow the lead of South Korea, China, and other nations by imposing an immediate nationwide quarantine to slow the inevitable spread of COVID-19. Without federal action, the creators say, their lives and the lives of their colleagues, patients, and families are being put at increased risk.

In addition to the quarantine, the petition, posted on the website Change.org, calls on U.S. leaders to institute emergency production and distribution of personal protective equipment for healthcare workers and to rapidly increase access to testing.

The petition – which garnered more than 40,000 signatures in just 12 hours and as of this writing was approaching 94,000 – was started by an apolitical Facebook group to focus attention on what members see as the most critical issues for clinicians: slowing the spread of the virus through a coast-to-coast quarantine, protection of medical personnel with adequate supplies of essential equipment, and widespread testing.

“We started this group last Friday out of the realization that clinicians needed information about the outbreak and weren’t getting it,” said coadministrator Jessica McIntyre, MD, a pediatric hospitalist at Elliot Hospital in Manchester, N.H.

“We wanted to get ahead of it and connect with people before we were in the trenches experiencing it and to see what other programs were doing. From a local perspective, it has been really hard to see what people are doing in other states, especially when the protocols in our own states are changing every single day as we collect more information,” she said in an interview.
 

The Horse Has Bolted

A family medicine physician in Illinois helped launch the Facebook group. She asked that her name not be used but said in an interview that earlier actions may have prevented or at least delayed the need for the more draconian measures that her group is recommending.

“Clearly South Korea is one of the superstars as far as response has gone, but the concern we have in the United States is that we’re well beyond that point – we needed to be testing people over a month ago, in the hope of preventing a quarantine,” she said in an interview.

According to National Public Radio, as of March 13, South Korea had conducted 3,600 tests per million population, compared with five per million in the United States.

“I think the most concerning part is to see where Italy is now and where we are in comparison. Our ICUs have not yet overflowed, but I think we’re definitely looking at that in the next few weeks – hopefully longer, but I suspect that it will happen shortly,” she continued.

She cited work by Harvard University biostatistician Xihong Lin, PhD, that shows that when health authorities in Wuhan, China – widely cited as the epicenter of the global pandemic – cordoned off the city, the infection rate dropped from one person infecting 3.8 others to one infecting 1.25, thereby significantly slowing the rate of transmission.

“This is absolutely what we need to be doing,” she said.
 

Real News

Within 3 days of its creation, the online group had accrued more than 80,000 members with advanced medical training, including MDs, DOs, physician assistants, nurse practitioners, and certified registered nurse anesthetists.

“A lot of us were already very busy with our day-to-day work outside of COVID-19, and I think a lot of us felt unsure about where to get the best information,” said coadministrator David Janssen, MD, a family medicine physician in group practice in Sioux Center, Iowa,

“If you turn on the TV, there’s a lot of politicizing of the issue, and there’s a lot of good information, but also a lot of bad information. When health care providers talk to other health care providers, that’s often how we get our information and how we learn,” he said in an interview.

The COVID-19 U.S. Physicians/APP Facebook group includes 20 volunteer moderators who handle hundreds of posts per hour from persons seeking information on the novel coronavirus, what to tell patients, and how to protect themselves.

“It’s been wonderful to see how providers have been helping other providers sort through issues. Teaching hospitals have their hands on the latest research, but a lot of people like myself are at small community hospitals, critical-access hospitals, where we may have a lot of questions but don’t necessarily have the answers readily available to us,” Dr. Janssen said.

Dr. Janssen said that his community of about 8,000 residents initially had only four COVID-19 testing kits, or one for every 2,000 people. The situation has since improved, and more tests are now available, he added.

Dr. McIntyre, Dr. Janssen, and the Illinois family physician have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Ideally, all cases of colorectal cancer would be detected at an early and curable stage, but, as new guidelines for late-stage colorectal cancer suggest, the world is far from perfect.

“Different regions of the world, both among and within countries, differ with respect to access to early detection,” the guideline authors wrote in JCO Global Oncology. “Many regions do not have mass or even opportunistic screening, and even within regions with mass screening, subpopulations may not have access to screening.”

The guidelines were developed by the American Society of Clinical Oncology’s Resource-Stratified Guidelines Advisory Group. Based on and adapted from existing guidelines developed by four international agencies, the ASCO guidelines take into account economic and social realities and offer recommendations for diagnosis, staging, and treatment by resource level: basic, limited, enhanced, or maximal.

“We made these guidelines to apply to countries or regions that have basic resources,” lead author E. Gabriela Chiorean, MD, of the University of Washington, Seattle, and the Seattle Cancer Care Alliance, said in an interview.

“We decided what should be the most basic resources – diagnostics, imaging, and treatment – that should be available to patients, and we make recommendations for the use of limited resources and supplies,” she added.

The guidelines pose and answer seven questions about optimal initial symptom management, diagnosis, and staging; optimal first and later lines of therapy; liver-directed therapy options for patients with late-stage colorectal cancer and liver metastases; and optimal on-treatment surveillance and follow-up strategies for patients treated for metastatic colorectal cancer.

For each question, the document offers guidance based on the availability of resources. As defined by the authors, the recommendations are stratified according to the following categories:

• Basic resources – “Core resources or fundamental services that are absolutely necessary for any cancer health care system to function.”
• Limited resources – “Second-tier resources or services that are intended to produce major improvements in outcome, such as increased survival and cost effectiveness, and are attainable with limited financial means and modest infrastructure.”
• Enhanced resources – “Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of options and patient choice.”
• Maximal resources – “High-level/state-of-the art resources or services that may be used/available in some high-resource regions and/or may be recommended by high-resource setting guidelines that do not adapt to resource constraints but that nonetheless should be considered a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for broad use in a resource-limited environment.”

The guidelines address common elements of symptom management for patients with acute disease, such as diagnosis involving the primary tumor, endoscopy when possible, and staging to include digital rectal exam and/or imaging when possible. The guidelines also include information tailored to resource level about chemotherapy and surgical resection.

“If, for example, a patient presents with bleeding and you suspect it to be of colorectal origin, we make recommendations that if the patient has symptoms of obstruction and bleeding and is resectable, they should undergo surgery, which should be available in countries of all resource levels,” Dr. Chiorean said.

The guidelines also recommend following the ASCO palliative care guidelines (J Clin Oncol. 2017 Jan;35[1]:96-112) for those patients who present with clinically unstable disease because of bowel obstruction, uncontrolled bleeding, or uncontrolled pain. Patients with clinically stable disease and ongoing bleeding from the primary tumor site are recommended to undergo transfusion and primary-site resection if only basic resources are available or transfusion plus multidisciplinary specialized evaluation when higher-level resources are available.

The ASCO guidelines are adapted from guidelines developed by Cancer Council Australia; the European Society for Medical Oncology; the National Institute for Health and Care Excellence, including separate recommendation for therapy combinations (https://www.nice.org.uk/guidance/ta212, https://www.nice.org.uk/guidance/ta439); and the National Comprehensive Cancer Network. Some of these guidelines have been updated since the creation of the ASCO guidelines.

ASCO funds the guideline development process. Dr. Chiorean and other authors disclosed relationships with multiple companies.

SOURCE: Chiorean EG et al. JCO Glob Oncol. 2020 Mar;6:414-38.

Ideally, all cases of colorectal cancer would be detected at an early and curable stage, but, as new guidelines for late-stage colorectal cancer suggest, the world is far from perfect.

“Different regions of the world, both among and within countries, differ with respect to access to early detection,” the guideline authors wrote in JCO Global Oncology. “Many regions do not have mass or even opportunistic screening, and even within regions with mass screening, subpopulations may not have access to screening.”

The guidelines were developed by the American Society of Clinical Oncology’s Resource-Stratified Guidelines Advisory Group. Based on and adapted from existing guidelines developed by four international agencies, the ASCO guidelines take into account economic and social realities and offer recommendations for diagnosis, staging, and treatment by resource level: basic, limited, enhanced, or maximal.

“We made these guidelines to apply to countries or regions that have basic resources,” lead author E. Gabriela Chiorean, MD, of the University of Washington, Seattle, and the Seattle Cancer Care Alliance, said in an interview.

“We decided what should be the most basic resources – diagnostics, imaging, and treatment – that should be available to patients, and we make recommendations for the use of limited resources and supplies,” she added.

The guidelines pose and answer seven questions about optimal initial symptom management, diagnosis, and staging; optimal first and later lines of therapy; liver-directed therapy options for patients with late-stage colorectal cancer and liver metastases; and optimal on-treatment surveillance and follow-up strategies for patients treated for metastatic colorectal cancer.

For each question, the document offers guidance based on the availability of resources. As defined by the authors, the recommendations are stratified according to the following categories:

• Basic resources – “Core resources or fundamental services that are absolutely necessary for any cancer health care system to function.”
• Limited resources – “Second-tier resources or services that are intended to produce major improvements in outcome, such as increased survival and cost effectiveness, and are attainable with limited financial means and modest infrastructure.”
• Enhanced resources – “Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of options and patient choice.”
• Maximal resources – “High-level/state-of-the art resources or services that may be used/available in some high-resource regions and/or may be recommended by high-resource setting guidelines that do not adapt to resource constraints but that nonetheless should be considered a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for broad use in a resource-limited environment.”

The guidelines address common elements of symptom management for patients with acute disease, such as diagnosis involving the primary tumor, endoscopy when possible, and staging to include digital rectal exam and/or imaging when possible. The guidelines also include information tailored to resource level about chemotherapy and surgical resection.

“If, for example, a patient presents with bleeding and you suspect it to be of colorectal origin, we make recommendations that if the patient has symptoms of obstruction and bleeding and is resectable, they should undergo surgery, which should be available in countries of all resource levels,” Dr. Chiorean said.

The guidelines also recommend following the ASCO palliative care guidelines (J Clin Oncol. 2017 Jan;35[1]:96-112) for those patients who present with clinically unstable disease because of bowel obstruction, uncontrolled bleeding, or uncontrolled pain. Patients with clinically stable disease and ongoing bleeding from the primary tumor site are recommended to undergo transfusion and primary-site resection if only basic resources are available or transfusion plus multidisciplinary specialized evaluation when higher-level resources are available.

The ASCO guidelines are adapted from guidelines developed by Cancer Council Australia; the European Society for Medical Oncology; the National Institute for Health and Care Excellence, including separate recommendation for therapy combinations (https://www.nice.org.uk/guidance/ta212, https://www.nice.org.uk/guidance/ta439); and the National Comprehensive Cancer Network. Some of these guidelines have been updated since the creation of the ASCO guidelines.

ASCO funds the guideline development process. Dr. Chiorean and other authors disclosed relationships with multiple companies.

SOURCE: Chiorean EG et al. JCO Glob Oncol. 2020 Mar;6:414-38.

Ideally, all cases of colorectal cancer would be detected at an early and curable stage, but, as new guidelines for late-stage colorectal cancer suggest, the world is far from perfect.

“Different regions of the world, both among and within countries, differ with respect to access to early detection,” the guideline authors wrote in JCO Global Oncology. “Many regions do not have mass or even opportunistic screening, and even within regions with mass screening, subpopulations may not have access to screening.”

The guidelines were developed by the American Society of Clinical Oncology’s Resource-Stratified Guidelines Advisory Group. Based on and adapted from existing guidelines developed by four international agencies, the ASCO guidelines take into account economic and social realities and offer recommendations for diagnosis, staging, and treatment by resource level: basic, limited, enhanced, or maximal.

“We made these guidelines to apply to countries or regions that have basic resources,” lead author E. Gabriela Chiorean, MD, of the University of Washington, Seattle, and the Seattle Cancer Care Alliance, said in an interview.

“We decided what should be the most basic resources – diagnostics, imaging, and treatment – that should be available to patients, and we make recommendations for the use of limited resources and supplies,” she added.

The guidelines pose and answer seven questions about optimal initial symptom management, diagnosis, and staging; optimal first and later lines of therapy; liver-directed therapy options for patients with late-stage colorectal cancer and liver metastases; and optimal on-treatment surveillance and follow-up strategies for patients treated for metastatic colorectal cancer.

For each question, the document offers guidance based on the availability of resources. As defined by the authors, the recommendations are stratified according to the following categories:

• Basic resources – “Core resources or fundamental services that are absolutely necessary for any cancer health care system to function.”
• Limited resources – “Second-tier resources or services that are intended to produce major improvements in outcome, such as increased survival and cost effectiveness, and are attainable with limited financial means and modest infrastructure.”
• Enhanced resources – “Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of options and patient choice.”
• Maximal resources – “High-level/state-of-the art resources or services that may be used/available in some high-resource regions and/or may be recommended by high-resource setting guidelines that do not adapt to resource constraints but that nonetheless should be considered a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for broad use in a resource-limited environment.”

The guidelines address common elements of symptom management for patients with acute disease, such as diagnosis involving the primary tumor, endoscopy when possible, and staging to include digital rectal exam and/or imaging when possible. The guidelines also include information tailored to resource level about chemotherapy and surgical resection.

“If, for example, a patient presents with bleeding and you suspect it to be of colorectal origin, we make recommendations that if the patient has symptoms of obstruction and bleeding and is resectable, they should undergo surgery, which should be available in countries of all resource levels,” Dr. Chiorean said.

The guidelines also recommend following the ASCO palliative care guidelines (J Clin Oncol. 2017 Jan;35[1]:96-112) for those patients who present with clinically unstable disease because of bowel obstruction, uncontrolled bleeding, or uncontrolled pain. Patients with clinically stable disease and ongoing bleeding from the primary tumor site are recommended to undergo transfusion and primary-site resection if only basic resources are available or transfusion plus multidisciplinary specialized evaluation when higher-level resources are available.

The ASCO guidelines are adapted from guidelines developed by Cancer Council Australia; the European Society for Medical Oncology; the National Institute for Health and Care Excellence, including separate recommendation for therapy combinations (https://www.nice.org.uk/guidance/ta212, https://www.nice.org.uk/guidance/ta439); and the National Comprehensive Cancer Network. Some of these guidelines have been updated since the creation of the ASCO guidelines.

ASCO funds the guideline development process. Dr. Chiorean and other authors disclosed relationships with multiple companies.

SOURCE: Chiorean EG et al. JCO Glob Oncol. 2020 Mar;6:414-38.

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

ORLANDO – A second hematopoietic stem cell transplant can be a successful salvage therapy for a child who has experienced a relapse following a first allogeneic transplant, investigators report.

Neil Osterweil/MDedge News

A retrospective study of 221 children who experienced a relapse after a first hematopoietic stem cell transplant (HSCT) showed that 3-year overall survival (OS) was six times higher among those who had second HSCT, compared with those who did not, reported Akshay Sharma, MBBS, from St. Jude’s Children’s Research Hospital in Memphis.

“We found that factors that are typically associated with poor outcomes after transplant such as disease status at the time of first transplantation – being in remission or not, type of transplant – myeloablative or reduced intensity, and choice of donor were generally not significantly predictive of outcomes following posttransplant relapse in our multivariable model,” he said at the Transplantation and Cellular Therapy Meetings.

Relapse is the most common cause of death after HSCT, and 20%-30% of children who undergo allogeneic HSCT will experience a relapse.

To study this issue, Dr. Sharma and colleagues took a retrospective look at 703 patients 21 and younger who received a first alloHSCT at St. Jude’s for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome from 1990 through 2018. Of this cohort, 211 patients (31%) experienced a relapse after transplant.

There were no significant differences between patients who had a relapse and those who did not in sex, race, conditioning-regimen intensity, performance status, donor type, or graft type (peripheral blood stem cell, umbilical cord blood, bone marrow), or in the incidence of acute graft-versus-host disease GVHD.

The investigators found that, as expected, outcomes were poor for patients who experienced a posttransplant relapse, with 3-year overall survival from relapse for the 221 patients of just 10%.

In multivariable analysis controlling for sex, disease status at the time of first transplant, interval from first transplant to relapse, management after relapse, chronic GVHD and year of relapse, factors significantly associated with worse overall survival were relapse within 6 months of transplant vs. later than 6 months (hazard ratio, 4.6; P < .001) and decade of transplant (HR, 2.6 for 1990-2000 and 1.6 for 2001-2010 vs. 2011-2018; P < .001).

In contrast, both second HSCT and donor lymphocyte infusion were associated with better overall survival, compared with postrelapse chemotherapy or supportive care (HR, 0.04 and 0.6, respectively; P < .001 for both comparisons).

A longer interval from first transplant to relapse was the strongest predictor of long-term survival, Dr. Sharma said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Among the 221 patients who had a relapse, 61 (28%) had a second HSCT, 28 (13%) received only donor lymphocyte infusions, without second transplant, and 132 (62%) received either chemotherapy or supportive care.

The 3-year overall survival rate for patients who received a second transplant was 28%, compared with 4% for those who did not have a repeat HSCT. The most important independent predictors for getting a second transplant were longer time to relapse after first transplant, first transplantation from a matched sibling donor instead of from a haploidentical donor, some degree of acute GVHD, and decade of first transplant (current decade vs. earlier decades).

The investigators also looked at guideline recommendations from both the American Society of Hematology and UK National Health Service regarding second allogenenic transplant after relapse.

ASH guidelines say that “patients with chemo-sensitive disease in remission who had a long initial remission (> 6-12 months) after first transplant and who never developed any GVHD” are most likely to benefit from a second transplant.

NHS guidelines say that a second transplant can be considered for patients who experience relapse more than 12 months after first alloHSCT. But as Dr. Sharma and colleagues discovered, patients who had a second transplant had better overall survival regardless of time from first to second transplant, compared with patients who had later relapses but no second transplant.

“With these data in mind, we submit that these ASH and NHS guidelines, which are based on older data from the 1900s and 2000 and are mostly based on adult data and do not include much pediatric data should be reconsidered, at least in the context of pediatric patients as we approach them,” he said.

Jaap-Jan Boelens, MD, PhD, a pediatric transplant specialist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study, said that the use of second transplant as salvage therapy is becoming more common at his center.

“But there is a little nuance,” he said in an interview. “If someone relapses a month after transplant, let’s say, it doesn’t make sense to go for another allo transplant. But if the interval between transplant is longer, more than half a year, we usually consider going for a second allo transplant.”

The decision to attempt a second transplant may also hinge on the disease the patient is being treated for, and on the depth of remission prior to relapse, he said.

Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago, said that trying to replicate the conditions of the first transplant may not work.

“It’s also a function of who was the donor for the first transplant – was it a matched sibling? And then for the second one do you go to an unrelated donor, or a half-matched relative, banking on the fact that the donor’s immune system for the second transplant is going to be able to mediate some kind of graft-versus-leukemia effect that wasn’t there the first time around?” he said.

Dr. Duerst, who was not involved in the study, noted that, for some patients with lymphoid malignancies, chimeric antigen receptor (CAR) T-cell therapy may be a more effective salvage strategy than second transplant, but added that it’s still too soon to know which strategy will be more effective.

The study was supported by St. Jude’s, the American Society of Hematology, and the American Society for Transplantation and Cellular Therapy. Dr. Sharma, Dr. Boelens, and Dr. Duerst reported having no relevant disclosures.

SOURCE: Sharma A et al. TCT 2020, Abstract 116.

ORLANDO – A second hematopoietic stem cell transplant can be a successful salvage therapy for a child who has experienced a relapse following a first allogeneic transplant, investigators report.

Neil Osterweil/MDedge News

A retrospective study of 221 children who experienced a relapse after a first hematopoietic stem cell transplant (HSCT) showed that 3-year overall survival (OS) was six times higher among those who had second HSCT, compared with those who did not, reported Akshay Sharma, MBBS, from St. Jude’s Children’s Research Hospital in Memphis.

“We found that factors that are typically associated with poor outcomes after transplant such as disease status at the time of first transplantation – being in remission or not, type of transplant – myeloablative or reduced intensity, and choice of donor were generally not significantly predictive of outcomes following posttransplant relapse in our multivariable model,” he said at the Transplantation and Cellular Therapy Meetings.

Relapse is the most common cause of death after HSCT, and 20%-30% of children who undergo allogeneic HSCT will experience a relapse.

To study this issue, Dr. Sharma and colleagues took a retrospective look at 703 patients 21 and younger who received a first alloHSCT at St. Jude’s for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome from 1990 through 2018. Of this cohort, 211 patients (31%) experienced a relapse after transplant.

There were no significant differences between patients who had a relapse and those who did not in sex, race, conditioning-regimen intensity, performance status, donor type, or graft type (peripheral blood stem cell, umbilical cord blood, bone marrow), or in the incidence of acute graft-versus-host disease GVHD.

The investigators found that, as expected, outcomes were poor for patients who experienced a posttransplant relapse, with 3-year overall survival from relapse for the 221 patients of just 10%.

In multivariable analysis controlling for sex, disease status at the time of first transplant, interval from first transplant to relapse, management after relapse, chronic GVHD and year of relapse, factors significantly associated with worse overall survival were relapse within 6 months of transplant vs. later than 6 months (hazard ratio, 4.6; P < .001) and decade of transplant (HR, 2.6 for 1990-2000 and 1.6 for 2001-2010 vs. 2011-2018; P < .001).

In contrast, both second HSCT and donor lymphocyte infusion were associated with better overall survival, compared with postrelapse chemotherapy or supportive care (HR, 0.04 and 0.6, respectively; P < .001 for both comparisons).

A longer interval from first transplant to relapse was the strongest predictor of long-term survival, Dr. Sharma said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Among the 221 patients who had a relapse, 61 (28%) had a second HSCT, 28 (13%) received only donor lymphocyte infusions, without second transplant, and 132 (62%) received either chemotherapy or supportive care.

The 3-year overall survival rate for patients who received a second transplant was 28%, compared with 4% for those who did not have a repeat HSCT. The most important independent predictors for getting a second transplant were longer time to relapse after first transplant, first transplantation from a matched sibling donor instead of from a haploidentical donor, some degree of acute GVHD, and decade of first transplant (current decade vs. earlier decades).

The investigators also looked at guideline recommendations from both the American Society of Hematology and UK National Health Service regarding second allogenenic transplant after relapse.

ASH guidelines say that “patients with chemo-sensitive disease in remission who had a long initial remission (> 6-12 months) after first transplant and who never developed any GVHD” are most likely to benefit from a second transplant.

NHS guidelines say that a second transplant can be considered for patients who experience relapse more than 12 months after first alloHSCT. But as Dr. Sharma and colleagues discovered, patients who had a second transplant had better overall survival regardless of time from first to second transplant, compared with patients who had later relapses but no second transplant.

“With these data in mind, we submit that these ASH and NHS guidelines, which are based on older data from the 1900s and 2000 and are mostly based on adult data and do not include much pediatric data should be reconsidered, at least in the context of pediatric patients as we approach them,” he said.

Jaap-Jan Boelens, MD, PhD, a pediatric transplant specialist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study, said that the use of second transplant as salvage therapy is becoming more common at his center.

“But there is a little nuance,” he said in an interview. “If someone relapses a month after transplant, let’s say, it doesn’t make sense to go for another allo transplant. But if the interval between transplant is longer, more than half a year, we usually consider going for a second allo transplant.”

The decision to attempt a second transplant may also hinge on the disease the patient is being treated for, and on the depth of remission prior to relapse, he said.

Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago, said that trying to replicate the conditions of the first transplant may not work.

“It’s also a function of who was the donor for the first transplant – was it a matched sibling? And then for the second one do you go to an unrelated donor, or a half-matched relative, banking on the fact that the donor’s immune system for the second transplant is going to be able to mediate some kind of graft-versus-leukemia effect that wasn’t there the first time around?” he said.

Dr. Duerst, who was not involved in the study, noted that, for some patients with lymphoid malignancies, chimeric antigen receptor (CAR) T-cell therapy may be a more effective salvage strategy than second transplant, but added that it’s still too soon to know which strategy will be more effective.

The study was supported by St. Jude’s, the American Society of Hematology, and the American Society for Transplantation and Cellular Therapy. Dr. Sharma, Dr. Boelens, and Dr. Duerst reported having no relevant disclosures.

SOURCE: Sharma A et al. TCT 2020, Abstract 116.

ORLANDO – A second hematopoietic stem cell transplant can be a successful salvage therapy for a child who has experienced a relapse following a first allogeneic transplant, investigators report.

Neil Osterweil/MDedge News

A retrospective study of 221 children who experienced a relapse after a first hematopoietic stem cell transplant (HSCT) showed that 3-year overall survival (OS) was six times higher among those who had second HSCT, compared with those who did not, reported Akshay Sharma, MBBS, from St. Jude’s Children’s Research Hospital in Memphis.

“We found that factors that are typically associated with poor outcomes after transplant such as disease status at the time of first transplantation – being in remission or not, type of transplant – myeloablative or reduced intensity, and choice of donor were generally not significantly predictive of outcomes following posttransplant relapse in our multivariable model,” he said at the Transplantation and Cellular Therapy Meetings.

Relapse is the most common cause of death after HSCT, and 20%-30% of children who undergo allogeneic HSCT will experience a relapse.

To study this issue, Dr. Sharma and colleagues took a retrospective look at 703 patients 21 and younger who received a first alloHSCT at St. Jude’s for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome from 1990 through 2018. Of this cohort, 211 patients (31%) experienced a relapse after transplant.

There were no significant differences between patients who had a relapse and those who did not in sex, race, conditioning-regimen intensity, performance status, donor type, or graft type (peripheral blood stem cell, umbilical cord blood, bone marrow), or in the incidence of acute graft-versus-host disease GVHD.

The investigators found that, as expected, outcomes were poor for patients who experienced a posttransplant relapse, with 3-year overall survival from relapse for the 221 patients of just 10%.

In multivariable analysis controlling for sex, disease status at the time of first transplant, interval from first transplant to relapse, management after relapse, chronic GVHD and year of relapse, factors significantly associated with worse overall survival were relapse within 6 months of transplant vs. later than 6 months (hazard ratio, 4.6; P < .001) and decade of transplant (HR, 2.6 for 1990-2000 and 1.6 for 2001-2010 vs. 2011-2018; P < .001).

In contrast, both second HSCT and donor lymphocyte infusion were associated with better overall survival, compared with postrelapse chemotherapy or supportive care (HR, 0.04 and 0.6, respectively; P < .001 for both comparisons).

A longer interval from first transplant to relapse was the strongest predictor of long-term survival, Dr. Sharma said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Among the 221 patients who had a relapse, 61 (28%) had a second HSCT, 28 (13%) received only donor lymphocyte infusions, without second transplant, and 132 (62%) received either chemotherapy or supportive care.

The 3-year overall survival rate for patients who received a second transplant was 28%, compared with 4% for those who did not have a repeat HSCT. The most important independent predictors for getting a second transplant were longer time to relapse after first transplant, first transplantation from a matched sibling donor instead of from a haploidentical donor, some degree of acute GVHD, and decade of first transplant (current decade vs. earlier decades).

The investigators also looked at guideline recommendations from both the American Society of Hematology and UK National Health Service regarding second allogenenic transplant after relapse.

ASH guidelines say that “patients with chemo-sensitive disease in remission who had a long initial remission (> 6-12 months) after first transplant and who never developed any GVHD” are most likely to benefit from a second transplant.

NHS guidelines say that a second transplant can be considered for patients who experience relapse more than 12 months after first alloHSCT. But as Dr. Sharma and colleagues discovered, patients who had a second transplant had better overall survival regardless of time from first to second transplant, compared with patients who had later relapses but no second transplant.

“With these data in mind, we submit that these ASH and NHS guidelines, which are based on older data from the 1900s and 2000 and are mostly based on adult data and do not include much pediatric data should be reconsidered, at least in the context of pediatric patients as we approach them,” he said.

Jaap-Jan Boelens, MD, PhD, a pediatric transplant specialist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study, said that the use of second transplant as salvage therapy is becoming more common at his center.

“But there is a little nuance,” he said in an interview. “If someone relapses a month after transplant, let’s say, it doesn’t make sense to go for another allo transplant. But if the interval between transplant is longer, more than half a year, we usually consider going for a second allo transplant.”

The decision to attempt a second transplant may also hinge on the disease the patient is being treated for, and on the depth of remission prior to relapse, he said.

Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago, said that trying to replicate the conditions of the first transplant may not work.

“It’s also a function of who was the donor for the first transplant – was it a matched sibling? And then for the second one do you go to an unrelated donor, or a half-matched relative, banking on the fact that the donor’s immune system for the second transplant is going to be able to mediate some kind of graft-versus-leukemia effect that wasn’t there the first time around?” he said.

Dr. Duerst, who was not involved in the study, noted that, for some patients with lymphoid malignancies, chimeric antigen receptor (CAR) T-cell therapy may be a more effective salvage strategy than second transplant, but added that it’s still too soon to know which strategy will be more effective.

The study was supported by St. Jude’s, the American Society of Hematology, and the American Society for Transplantation and Cellular Therapy. Dr. Sharma, Dr. Boelens, and Dr. Duerst reported having no relevant disclosures.

SOURCE: Sharma A et al. TCT 2020, Abstract 116.

ORLANDO – For visits to hematopoietic stem cell transplant recipients, the kids are alright – assuming that they’re not sniffling, coughing, or running a fever, that is.

Neil Osterweill/MDedge News

Since their blood and marrow transplant (BMT) unit began allowing child visits to patients in 2018, there have been no increases in either health care–associated infections or average length of stay, and patient satisfaction has markedly improved, reported Mylene R. de Vera, RN, and colleagues from the Greenbaum Cancer Center at the University of Maryland Medical Center in Baltimore.

Although her center had previously had a policy restricting child visitors out of concerns about transmission of infections, “we did a literature search and found that child visitor restriction is really neither evidence based nor recommended by any professional organization,” she said in an interview at the annual Transplantation & Cellular Therapy Meetings.

“At the same time, I also informally surveyed 10 hospitals and BMT centers nationally, and found that 70% of them allow child visitation,” she added at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

An informal survey by this reporter found wide variations in practice. For example, Massachusetts General Hospital Cancer Center policy allows only children 12 and older to visit, but other hospitals have somewhat less stringent policies.

“Our policy is that for children under 12, they need to A) be screened, and B) need to get approval from the attending stem-cell physician,” said Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago.

Dr. Duerst, who was not involved in the study, said in an interview seeking objective commentary that his center doesn’t especially encourage visits from younger children, on the understanding that, as every parent knows, the odds are higher that children under 12 may be carrying a respiratory virus, compared with adolescents.

He added that visits from children might be beneficial for patients who are more critically ill or at high risk for dying, but again, only if the child has been carefully screened.

At Memorial Sloan Kettering Cancer Center in New York, children are allowed to visit transplant recipients strictly on a case-by-case basis, and only after consultation with and approval from transplant unit staff, an MSKCC spokesman said.

In an interview, Ms. de Vera cited a 2016 study in the American Journal of Critical Care by Mini Jacob, RN, and colleagues from Emory University in Atlanta, who reported that, among family members visiting patients in an intensive care unit with a continuous visitation policy, open visitation was ranked as the second-most important need.

Beginning in 2018, Ms. de Vera and colleagues sought to promote a patient-centered policy by implementing guidelines that would allow safe visitation by children to BMT recipients.

The process included the aforementioned literature search, survey of other centers, and a staff survey, which showed that 70% of staff said they believed that allowing child visitation would support the goal of patient-centered care. The survey also showed, however, that 40% of staff thought that healthy children presented a higher risk of infection to immunocompromised patients, and 50% agreed with the statement that having children on the unit would be disruptive to care.

In August of 2019, all BMT unit staff members took part in an in-service training session designed “to align perception with evidence-based practice.” The training included detailed information and procedures for screening would-be child visitors for potential risks prior to allowing them on the unit.

The one-page screening tool asks about current or recent infections; coughing, sneezing, etc.; and other health-related issues, including whether the child is up to date on vaccinations.

The following month, the BMT unit implemented its new child visitation policy, and by the end of 2019 the unit had logged a total of 71 child visits.

As noted, there were no increases in either health care–associated infections or in the average length of stay, In fact, from April to September 2019 the average length of stay was 13 days, compared with 18 days during the 6-month period in 2018, before child visits were allowed.

In addition, a Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient-satisfaction survey showed that the scores on “taking preferences into account” increased to 92% during October through December 2018, compared with 33% from July through September of the same year.

Interestingly, patient-reported satisfaction also fell by half from January to March 2019, when child visits were suspended as part of hospital-wide restrictions during the influenza season.

A survey of staff conducted a year after the child visitation policy was implemented showed a relative 37% increase in reported awareness that the visits promote patient-centered care, a 35% drop in the reported belief that healthy child visitors pose higher risk of infection, and a more than 100% relative decline in the perception that child visitors would upset BMT unit routine.

“I just wanted to prove to my coworkers that child visitation really did not affect length of stay or health care–associated infections, and at the same time may have a positive effect on patient satisfaction,” Ms. de Vera said.

The study was internally supported. All persons interviewed reported no conflicts of interest to disclose.

SOURCE: de Vera MR et al. TCT 2020, Abstract 588.

ORLANDO – For visits to hematopoietic stem cell transplant recipients, the kids are alright – assuming that they’re not sniffling, coughing, or running a fever, that is.

Neil Osterweill/MDedge News

Since their blood and marrow transplant (BMT) unit began allowing child visits to patients in 2018, there have been no increases in either health care–associated infections or average length of stay, and patient satisfaction has markedly improved, reported Mylene R. de Vera, RN, and colleagues from the Greenbaum Cancer Center at the University of Maryland Medical Center in Baltimore.

Although her center had previously had a policy restricting child visitors out of concerns about transmission of infections, “we did a literature search and found that child visitor restriction is really neither evidence based nor recommended by any professional organization,” she said in an interview at the annual Transplantation & Cellular Therapy Meetings.

“At the same time, I also informally surveyed 10 hospitals and BMT centers nationally, and found that 70% of them allow child visitation,” she added at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

An informal survey by this reporter found wide variations in practice. For example, Massachusetts General Hospital Cancer Center policy allows only children 12 and older to visit, but other hospitals have somewhat less stringent policies.

“Our policy is that for children under 12, they need to A) be screened, and B) need to get approval from the attending stem-cell physician,” said Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago.

Dr. Duerst, who was not involved in the study, said in an interview seeking objective commentary that his center doesn’t especially encourage visits from younger children, on the understanding that, as every parent knows, the odds are higher that children under 12 may be carrying a respiratory virus, compared with adolescents.

He added that visits from children might be beneficial for patients who are more critically ill or at high risk for dying, but again, only if the child has been carefully screened.

At Memorial Sloan Kettering Cancer Center in New York, children are allowed to visit transplant recipients strictly on a case-by-case basis, and only after consultation with and approval from transplant unit staff, an MSKCC spokesman said.

In an interview, Ms. de Vera cited a 2016 study in the American Journal of Critical Care by Mini Jacob, RN, and colleagues from Emory University in Atlanta, who reported that, among family members visiting patients in an intensive care unit with a continuous visitation policy, open visitation was ranked as the second-most important need.

Beginning in 2018, Ms. de Vera and colleagues sought to promote a patient-centered policy by implementing guidelines that would allow safe visitation by children to BMT recipients.

The process included the aforementioned literature search, survey of other centers, and a staff survey, which showed that 70% of staff said they believed that allowing child visitation would support the goal of patient-centered care. The survey also showed, however, that 40% of staff thought that healthy children presented a higher risk of infection to immunocompromised patients, and 50% agreed with the statement that having children on the unit would be disruptive to care.

In August of 2019, all BMT unit staff members took part in an in-service training session designed “to align perception with evidence-based practice.” The training included detailed information and procedures for screening would-be child visitors for potential risks prior to allowing them on the unit.

The one-page screening tool asks about current or recent infections; coughing, sneezing, etc.; and other health-related issues, including whether the child is up to date on vaccinations.

The following month, the BMT unit implemented its new child visitation policy, and by the end of 2019 the unit had logged a total of 71 child visits.

As noted, there were no increases in either health care–associated infections or in the average length of stay, In fact, from April to September 2019 the average length of stay was 13 days, compared with 18 days during the 6-month period in 2018, before child visits were allowed.

In addition, a Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient-satisfaction survey showed that the scores on “taking preferences into account” increased to 92% during October through December 2018, compared with 33% from July through September of the same year.

Interestingly, patient-reported satisfaction also fell by half from January to March 2019, when child visits were suspended as part of hospital-wide restrictions during the influenza season.

A survey of staff conducted a year after the child visitation policy was implemented showed a relative 37% increase in reported awareness that the visits promote patient-centered care, a 35% drop in the reported belief that healthy child visitors pose higher risk of infection, and a more than 100% relative decline in the perception that child visitors would upset BMT unit routine.

“I just wanted to prove to my coworkers that child visitation really did not affect length of stay or health care–associated infections, and at the same time may have a positive effect on patient satisfaction,” Ms. de Vera said.

The study was internally supported. All persons interviewed reported no conflicts of interest to disclose.

SOURCE: de Vera MR et al. TCT 2020, Abstract 588.

ORLANDO – For visits to hematopoietic stem cell transplant recipients, the kids are alright – assuming that they’re not sniffling, coughing, or running a fever, that is.

Neil Osterweill/MDedge News

Since their blood and marrow transplant (BMT) unit began allowing child visits to patients in 2018, there have been no increases in either health care–associated infections or average length of stay, and patient satisfaction has markedly improved, reported Mylene R. de Vera, RN, and colleagues from the Greenbaum Cancer Center at the University of Maryland Medical Center in Baltimore.

Although her center had previously had a policy restricting child visitors out of concerns about transmission of infections, “we did a literature search and found that child visitor restriction is really neither evidence based nor recommended by any professional organization,” she said in an interview at the annual Transplantation & Cellular Therapy Meetings.

“At the same time, I also informally surveyed 10 hospitals and BMT centers nationally, and found that 70% of them allow child visitation,” she added at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

An informal survey by this reporter found wide variations in practice. For example, Massachusetts General Hospital Cancer Center policy allows only children 12 and older to visit, but other hospitals have somewhat less stringent policies.

“Our policy is that for children under 12, they need to A) be screened, and B) need to get approval from the attending stem-cell physician,” said Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago.

Dr. Duerst, who was not involved in the study, said in an interview seeking objective commentary that his center doesn’t especially encourage visits from younger children, on the understanding that, as every parent knows, the odds are higher that children under 12 may be carrying a respiratory virus, compared with adolescents.

He added that visits from children might be beneficial for patients who are more critically ill or at high risk for dying, but again, only if the child has been carefully screened.

At Memorial Sloan Kettering Cancer Center in New York, children are allowed to visit transplant recipients strictly on a case-by-case basis, and only after consultation with and approval from transplant unit staff, an MSKCC spokesman said.

In an interview, Ms. de Vera cited a 2016 study in the American Journal of Critical Care by Mini Jacob, RN, and colleagues from Emory University in Atlanta, who reported that, among family members visiting patients in an intensive care unit with a continuous visitation policy, open visitation was ranked as the second-most important need.

Beginning in 2018, Ms. de Vera and colleagues sought to promote a patient-centered policy by implementing guidelines that would allow safe visitation by children to BMT recipients.

The process included the aforementioned literature search, survey of other centers, and a staff survey, which showed that 70% of staff said they believed that allowing child visitation would support the goal of patient-centered care. The survey also showed, however, that 40% of staff thought that healthy children presented a higher risk of infection to immunocompromised patients, and 50% agreed with the statement that having children on the unit would be disruptive to care.

In August of 2019, all BMT unit staff members took part in an in-service training session designed “to align perception with evidence-based practice.” The training included detailed information and procedures for screening would-be child visitors for potential risks prior to allowing them on the unit.

The one-page screening tool asks about current or recent infections; coughing, sneezing, etc.; and other health-related issues, including whether the child is up to date on vaccinations.

The following month, the BMT unit implemented its new child visitation policy, and by the end of 2019 the unit had logged a total of 71 child visits.

As noted, there were no increases in either health care–associated infections or in the average length of stay, In fact, from April to September 2019 the average length of stay was 13 days, compared with 18 days during the 6-month period in 2018, before child visits were allowed.

In addition, a Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient-satisfaction survey showed that the scores on “taking preferences into account” increased to 92% during October through December 2018, compared with 33% from July through September of the same year.

Interestingly, patient-reported satisfaction also fell by half from January to March 2019, when child visits were suspended as part of hospital-wide restrictions during the influenza season.

A survey of staff conducted a year after the child visitation policy was implemented showed a relative 37% increase in reported awareness that the visits promote patient-centered care, a 35% drop in the reported belief that healthy child visitors pose higher risk of infection, and a more than 100% relative decline in the perception that child visitors would upset BMT unit routine.

“I just wanted to prove to my coworkers that child visitation really did not affect length of stay or health care–associated infections, and at the same time may have a positive effect on patient satisfaction,” Ms. de Vera said.

The study was internally supported. All persons interviewed reported no conflicts of interest to disclose.

SOURCE: de Vera MR et al. TCT 2020, Abstract 588.

ORLANDO – Collecting and storing extra stem cells on the off chance that a patient with multiple myeloma will need a salvage autologous stem cell transplant may not be worth the money or effort, investigators say.

Neil Osterweil/MDedge News

Among patients with multiple myeloma who had adequate collection of mobilized and stored cells, only 3 of 146 eligible patients were given the stored cells in a second autologous stem cell transplant (ASCT), reported Nausheen Ahmed, MD, from the Case Western Reserve Cancer Center and University Hospitals Seidman Cancer Center, both in Cleveland.

“We found overall low utilization of salvage transplants and storage stem cells at our institution, which may not justify the strategy of early collection for all patients fit for transplant,” she said at the Transplantation and Cellular Therapy Meetings.

But Sergio Giralt, MD, a transplant specialist from Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study, warned against changing practice “for the wrong reason, because it’s just a financial reason.”
 

Get them while they’re fresh

The rationale for collecting and storing extra cells is the risk that mobilization will fail in the future following prolonged maintenance with immunomodulatory agents such as lenalidomide (Revlimid), and the risk for genetic or epigenetic damage to cells from high-dose melphalan used in transplant-conditioning regimens, Dr. Ahmed noted at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

“However, there are potential issues with early mobilization and storage, including cost, resources, apheresis scheduling, uncertainty of cell viability, and liability. There’s also risk of side effects with filgrastim and plerixafor use [for mobilization],” she said.

Dr. Ahmed and colleagues conducted a study to determine how stored stem cells for second ASCT were used, describe how second ASCTs are used in patients who meet the Mayo Consensus Stratification for Myeloma & Risk-Adapted Therapy (mSMART) criteria, and the costs of mobilizing and storing stem cells for a second ASCT.

They took a retrospective look at all adults aged 18 years and older with a diagnosis of multiple myeloma who received a first ASCT at their institution from 2009 to 2017. They excluded patients who had amyloidosis without myeloma or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) syndrome.

Patients were considered eligible for a second ASCT based on mSMART recommendations if they had a relapse either 18 or more months without maintenance therapy or after at least 36 months on maintenance. The investigators defined an extra day of collection as an additional day of apheresis to obtain 2 million or more CD34 cells/kg for storage only.

They estimated costs from the institution’s charge master as the sum of cell processing, leukapheresis costs, additional plerixafor costs, and storage costs, and calculated the total duration of storage as months from the date of collection until the last follow-up.

The median age of the total study population of 179 patients was 61 years, with a majority of male and white patients. Of this group, 98% had an Eastern Cooperative Oncology Group performance score of 0-1. In all, 63.7% of the patients had standard-risk cytogenetics, 22.4% had high-risk disease, and the remainder had unknown cytogenetic risk.

At a median follow-up of 56.5 months, 95 patients (53.1%) had experienced a relapse after transplant with a median time to progression of 47.5 months. The majority of patients (166; 92.7%) had received a single transplant, 10 (5.6%) had received tandem transplants, and only 3 (1.6%) had a second transplant at relapse.

Looking at the use of second transplant in patients who met the criteria for salvage transplant based on mSMART (excluding patients who had undergone tandem transplant) and whose maintenance status was known, they identified 61 patients on maintenance therapy and 24 with no maintenance. A total of 31 patients (18 in the maintenance group and 13 in the no-maintenance group) met mSMART criteria for salvage ASCT.

Dr. Ahmed and colleagues next looked at the 146 patients who had at least 2 million stored cells/kg, and found that the stored cells were used for only three patients. Of the 146 patients, 66 had 1 extra collection day, 17 had 2 extra days, and 4 had 3 extra days, for an average additional cost per patient of $16,859.
 

‘Woefully underutilized’

Discussing the study, Dr. Giralt asked: “How valid are the SMART criteria of 36 months? And the answer is there is no data to support it, and if we actually go back to our oncology, any patient who has had more than 18 months without exposure to a drug can continue to have sensitivity to that drug, and that’s why if we used the ASBMT criteria of greater than 18 months you’d have a larger population” of patients eligible for salvage transplant.

He stated that, “we know these patients exist, we know they have cells in the freezer, but we’re not using those cells. Second transplant is woefully underutilized in myeloma patients,” and he added that stored cells could also be used to support those patients who develop cytopenias following chimeric antigen receptor (CAR) T-cell therapy.

Yago Nieto, MD, from the University of Texas MD Anderson Cancer Center, Houston, who comoderated the session where the data were presented, agreed with Dr. Giralt that stored stem cells are underutilized in the treatment of patients with multiple myeloma.

“I don’t think that the experience from Case Western, where the percentage of patients who are eligible for salvage transplant and actually got it was less than 10%, can be extrapolated to many other centers. I think that in most centers the actual percentage is higher than that,” he said in an interview.

“There are going to be therapies like CAR T that will compete with salvage transplants, but I think more patients should be considered for this salvage procedure,” he added.

No funding source for the story was disclosed. Dr. Ahmed reported no financial disclosures. Dr. Giralt reported consulting/advisory activities and receiving research funding from multiple companies. Dr. Nieto disclosed research funding from, and consultancy for, several companies.

SOURCE: Ahmed N et al. TCT 2020, Abstract 28.

ORLANDO – Collecting and storing extra stem cells on the off chance that a patient with multiple myeloma will need a salvage autologous stem cell transplant may not be worth the money or effort, investigators say.

Neil Osterweil/MDedge News

Among patients with multiple myeloma who had adequate collection of mobilized and stored cells, only 3 of 146 eligible patients were given the stored cells in a second autologous stem cell transplant (ASCT), reported Nausheen Ahmed, MD, from the Case Western Reserve Cancer Center and University Hospitals Seidman Cancer Center, both in Cleveland.

“We found overall low utilization of salvage transplants and storage stem cells at our institution, which may not justify the strategy of early collection for all patients fit for transplant,” she said at the Transplantation and Cellular Therapy Meetings.

But Sergio Giralt, MD, a transplant specialist from Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study, warned against changing practice “for the wrong reason, because it’s just a financial reason.”
 

Get them while they’re fresh

The rationale for collecting and storing extra cells is the risk that mobilization will fail in the future following prolonged maintenance with immunomodulatory agents such as lenalidomide (Revlimid), and the risk for genetic or epigenetic damage to cells from high-dose melphalan used in transplant-conditioning regimens, Dr. Ahmed noted at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

“However, there are potential issues with early mobilization and storage, including cost, resources, apheresis scheduling, uncertainty of cell viability, and liability. There’s also risk of side effects with filgrastim and plerixafor use [for mobilization],” she said.

Dr. Ahmed and colleagues conducted a study to determine how stored stem cells for second ASCT were used, describe how second ASCTs are used in patients who meet the Mayo Consensus Stratification for Myeloma & Risk-Adapted Therapy (mSMART) criteria, and the costs of mobilizing and storing stem cells for a second ASCT.

They took a retrospective look at all adults aged 18 years and older with a diagnosis of multiple myeloma who received a first ASCT at their institution from 2009 to 2017. They excluded patients who had amyloidosis without myeloma or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) syndrome.

Patients were considered eligible for a second ASCT based on mSMART recommendations if they had a relapse either 18 or more months without maintenance therapy or after at least 36 months on maintenance. The investigators defined an extra day of collection as an additional day of apheresis to obtain 2 million or more CD34 cells/kg for storage only.

They estimated costs from the institution’s charge master as the sum of cell processing, leukapheresis costs, additional plerixafor costs, and storage costs, and calculated the total duration of storage as months from the date of collection until the last follow-up.

The median age of the total study population of 179 patients was 61 years, with a majority of male and white patients. Of this group, 98% had an Eastern Cooperative Oncology Group performance score of 0-1. In all, 63.7% of the patients had standard-risk cytogenetics, 22.4% had high-risk disease, and the remainder had unknown cytogenetic risk.

At a median follow-up of 56.5 months, 95 patients (53.1%) had experienced a relapse after transplant with a median time to progression of 47.5 months. The majority of patients (166; 92.7%) had received a single transplant, 10 (5.6%) had received tandem transplants, and only 3 (1.6%) had a second transplant at relapse.

Looking at the use of second transplant in patients who met the criteria for salvage transplant based on mSMART (excluding patients who had undergone tandem transplant) and whose maintenance status was known, they identified 61 patients on maintenance therapy and 24 with no maintenance. A total of 31 patients (18 in the maintenance group and 13 in the no-maintenance group) met mSMART criteria for salvage ASCT.

Dr. Ahmed and colleagues next looked at the 146 patients who had at least 2 million stored cells/kg, and found that the stored cells were used for only three patients. Of the 146 patients, 66 had 1 extra collection day, 17 had 2 extra days, and 4 had 3 extra days, for an average additional cost per patient of $16,859.
 

‘Woefully underutilized’

Discussing the study, Dr. Giralt asked: “How valid are the SMART criteria of 36 months? And the answer is there is no data to support it, and if we actually go back to our oncology, any patient who has had more than 18 months without exposure to a drug can continue to have sensitivity to that drug, and that’s why if we used the ASBMT criteria of greater than 18 months you’d have a larger population” of patients eligible for salvage transplant.

He stated that, “we know these patients exist, we know they have cells in the freezer, but we’re not using those cells. Second transplant is woefully underutilized in myeloma patients,” and he added that stored cells could also be used to support those patients who develop cytopenias following chimeric antigen receptor (CAR) T-cell therapy.

Yago Nieto, MD, from the University of Texas MD Anderson Cancer Center, Houston, who comoderated the session where the data were presented, agreed with Dr. Giralt that stored stem cells are underutilized in the treatment of patients with multiple myeloma.

“I don’t think that the experience from Case Western, where the percentage of patients who are eligible for salvage transplant and actually got it was less than 10%, can be extrapolated to many other centers. I think that in most centers the actual percentage is higher than that,” he said in an interview.

“There are going to be therapies like CAR T that will compete with salvage transplants, but I think more patients should be considered for this salvage procedure,” he added.

No funding source for the story was disclosed. Dr. Ahmed reported no financial disclosures. Dr. Giralt reported consulting/advisory activities and receiving research funding from multiple companies. Dr. Nieto disclosed research funding from, and consultancy for, several companies.

SOURCE: Ahmed N et al. TCT 2020, Abstract 28.

ORLANDO – Collecting and storing extra stem cells on the off chance that a patient with multiple myeloma will need a salvage autologous stem cell transplant may not be worth the money or effort, investigators say.

Neil Osterweil/MDedge News

Among patients with multiple myeloma who had adequate collection of mobilized and stored cells, only 3 of 146 eligible patients were given the stored cells in a second autologous stem cell transplant (ASCT), reported Nausheen Ahmed, MD, from the Case Western Reserve Cancer Center and University Hospitals Seidman Cancer Center, both in Cleveland.

“We found overall low utilization of salvage transplants and storage stem cells at our institution, which may not justify the strategy of early collection for all patients fit for transplant,” she said at the Transplantation and Cellular Therapy Meetings.

But Sergio Giralt, MD, a transplant specialist from Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study, warned against changing practice “for the wrong reason, because it’s just a financial reason.”
 

Get them while they’re fresh

The rationale for collecting and storing extra cells is the risk that mobilization will fail in the future following prolonged maintenance with immunomodulatory agents such as lenalidomide (Revlimid), and the risk for genetic or epigenetic damage to cells from high-dose melphalan used in transplant-conditioning regimens, Dr. Ahmed noted at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

“However, there are potential issues with early mobilization and storage, including cost, resources, apheresis scheduling, uncertainty of cell viability, and liability. There’s also risk of side effects with filgrastim and plerixafor use [for mobilization],” she said.

Dr. Ahmed and colleagues conducted a study to determine how stored stem cells for second ASCT were used, describe how second ASCTs are used in patients who meet the Mayo Consensus Stratification for Myeloma & Risk-Adapted Therapy (mSMART) criteria, and the costs of mobilizing and storing stem cells for a second ASCT.

They took a retrospective look at all adults aged 18 years and older with a diagnosis of multiple myeloma who received a first ASCT at their institution from 2009 to 2017. They excluded patients who had amyloidosis without myeloma or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) syndrome.

Patients were considered eligible for a second ASCT based on mSMART recommendations if they had a relapse either 18 or more months without maintenance therapy or after at least 36 months on maintenance. The investigators defined an extra day of collection as an additional day of apheresis to obtain 2 million or more CD34 cells/kg for storage only.

They estimated costs from the institution’s charge master as the sum of cell processing, leukapheresis costs, additional plerixafor costs, and storage costs, and calculated the total duration of storage as months from the date of collection until the last follow-up.

The median age of the total study population of 179 patients was 61 years, with a majority of male and white patients. Of this group, 98% had an Eastern Cooperative Oncology Group performance score of 0-1. In all, 63.7% of the patients had standard-risk cytogenetics, 22.4% had high-risk disease, and the remainder had unknown cytogenetic risk.

At a median follow-up of 56.5 months, 95 patients (53.1%) had experienced a relapse after transplant with a median time to progression of 47.5 months. The majority of patients (166; 92.7%) had received a single transplant, 10 (5.6%) had received tandem transplants, and only 3 (1.6%) had a second transplant at relapse.

Looking at the use of second transplant in patients who met the criteria for salvage transplant based on mSMART (excluding patients who had undergone tandem transplant) and whose maintenance status was known, they identified 61 patients on maintenance therapy and 24 with no maintenance. A total of 31 patients (18 in the maintenance group and 13 in the no-maintenance group) met mSMART criteria for salvage ASCT.

Dr. Ahmed and colleagues next looked at the 146 patients who had at least 2 million stored cells/kg, and found that the stored cells were used for only three patients. Of the 146 patients, 66 had 1 extra collection day, 17 had 2 extra days, and 4 had 3 extra days, for an average additional cost per patient of $16,859.
 

‘Woefully underutilized’

Discussing the study, Dr. Giralt asked: “How valid are the SMART criteria of 36 months? And the answer is there is no data to support it, and if we actually go back to our oncology, any patient who has had more than 18 months without exposure to a drug can continue to have sensitivity to that drug, and that’s why if we used the ASBMT criteria of greater than 18 months you’d have a larger population” of patients eligible for salvage transplant.

He stated that, “we know these patients exist, we know they have cells in the freezer, but we’re not using those cells. Second transplant is woefully underutilized in myeloma patients,” and he added that stored cells could also be used to support those patients who develop cytopenias following chimeric antigen receptor (CAR) T-cell therapy.

Yago Nieto, MD, from the University of Texas MD Anderson Cancer Center, Houston, who comoderated the session where the data were presented, agreed with Dr. Giralt that stored stem cells are underutilized in the treatment of patients with multiple myeloma.

“I don’t think that the experience from Case Western, where the percentage of patients who are eligible for salvage transplant and actually got it was less than 10%, can be extrapolated to many other centers. I think that in most centers the actual percentage is higher than that,” he said in an interview.

“There are going to be therapies like CAR T that will compete with salvage transplants, but I think more patients should be considered for this salvage procedure,” he added.

No funding source for the story was disclosed. Dr. Ahmed reported no financial disclosures. Dr. Giralt reported consulting/advisory activities and receiving research funding from multiple companies. Dr. Nieto disclosed research funding from, and consultancy for, several companies.

SOURCE: Ahmed N et al. TCT 2020, Abstract 28.

ORLANDO – Folinic acid does not prevent oral mucositis in patients who are receiving a calcineurin inhibitor and methotrexate for graft-vs.-host disease prophylaxis, results of a multicenter study from Israel suggest.

A randomized clinical trial to determine whether folinic acid rescue 24 hours after a methotrexate dose protects patients against severe oral mucositis was halted for futility after an interim analysis showed no advantage to adding folinic acid, reported Moshe Yeshrun, MD, of Rabin Medical Center at Tel Aviv University, Israel.

“Regarding the primary and secondary endpoints, we observed identical rates and duration of severe oral mucositis, as well as identical rates of oral mucositis of any grade in the folinic acid and placebo groups,” he said at the annual Transplantation and Cellular Therapy Meetings.

There were also no significant differences between the folinic acid and placebo control groups in time to neutrophil and platelet engraftment, rates of febrile neutropenia and bloodstream infections, veno-occlusive disease, need for opiates or total parenteral nutrition (TPN), or time from transplant to discharge, Dr. Yeshrun added at the meeting, held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Folinic acid therapy did not, however, appear to abrogate or interfere with the effects of methotrexate on prevention of either acute or chronic graft-vs-host disease (GVHD).
 

Severe adverse event

Oral mucositis can be a serious complication of therapy, associated with increased morbidity and mortality; significant pain; difficulty with eating or speaking; difficulty swallowing water, food, and medications; prolonged hospitalizations; and increased costs of care, Dr. Yeshrun noted.

The presence of oral mucositis sometimes leads clinicians to reduce or even skip methotrexate doses, thereby increasing risk for GVHD.

There are limited data from nonrandomized studies indicating that folinic acid (also called leucovorin) may reduce methotrexate-associated toxicities, and both the European Society for Blood and Marrow Transplantation and European LeukemiaNet working group recommend the use of folinic-acid rescue 24 hours following each methotrexate dose, Dr. Yeshrun said.

To see whether folinic acid rescue actually reduces the rate of methotrexate-induced toxicity and affects outcomes for patients who receive methotrexate post transplant for GVHD prophylaxis, Dr. Yeshrun and colleagues in three Israeli medical centers conducted a randomized, placebo-controlled trial.

The eligible study population included patients 18 and older with hematological malignancies in complete remission or minimal residual disease who underwent myeloablative conditioning and allogeneic transplant from HLA-matched or 1-antigen mismatched siblings or unrelated donors.

The patients were stratified by treatment center and intensity of the conditioning regimen, and then randomized on a 1:1 basis to receive folinic acid or placebo beginning 24 hours after each methotrexate dose, with the assigned medication given at a dose of 15 mg three times daily on the first day, and once daily on days 3 and 6.

Patients who received a transplant from an unrelated donor were also given anti-thymocyte globulin at a total dose of 15 mg/kg.

Supportive care included filgrastim (Neupogen) 5 mcg/kg from day 7 until neutrophil engraftment, infection prophylaxis, and ursodeoxycholic acid for prevention of veno-occlusive disease.
 

Trial stopped

Although the study was designed to enroll 116 patients to have a power of 80% to detect a 50% reduction in the rate of severe oral mucositis from an anticipated 50% in the placebo arm, a planned interim analysis conducted after approximately half of the target events occurred showed no difference in the rates of severe oral mucositis, and the trial was halted.

A total of 28 patients in the folinic acid group and 24 in the placebo group were available for the analysis.

The rate of grade 3 or 4 mucositis, the primary endpoint, was 46.6% in the folinic acid group, and 45.8% in the placebo group.

Respectively, the median duration of severe oral mucositis was 4 days in each group, days to neutrophil engraftment were a median of 12 and to platelet engraftment were a median of 13 days in each group, rates of febrile neutropenia were 57.1% and 58.3%, rates of bloodstream infections were 10.7% and 16.6%, rates of veno-occlusive disease were 7% and 12.5%, need for TPN occurred in 14.2% vs. 25%, need for opiates occurred in 78.5% vs. 66.6%, and median time to discharge was 18 and 19 days. As noted, none of the differences were statistically significant.

“These unequivocal interim results led to our decision to discontinue the study,” Dr. Yeshrun said.

Arnon Nagler, MD, MSc, from Sheba Medical Center Tel HaShomer at Tel Aviv University in Israel, who was not involved in the study, said in an interview “I think this is a very practical and important study, because we need evidence-based data such as this.”

Ted Bosworth/MDedge News

Ted Bosworth/MDedge News

His comoderator, Maria Gilleece, MD, director of the Yorkshire (England) Blood and Marrow Transplant Program, noted in an interview that folinic acid is frequently used in the United Kingdom for patients receiving high-dose methotrexate, ”and certainly, this study suggests that may be inappropriate.”

Rabin Medical Center sponsored the trial. Dr. Yeshrun, Dr. Nagler, and Dr. Gilleece reported no relevant conflicts of interest.

SOURCE: Yeshrun M. et al. TCT 2020. Abstract 61.

ORLANDO – Folinic acid does not prevent oral mucositis in patients who are receiving a calcineurin inhibitor and methotrexate for graft-vs.-host disease prophylaxis, results of a multicenter study from Israel suggest.

A randomized clinical trial to determine whether folinic acid rescue 24 hours after a methotrexate dose protects patients against severe oral mucositis was halted for futility after an interim analysis showed no advantage to adding folinic acid, reported Moshe Yeshrun, MD, of Rabin Medical Center at Tel Aviv University, Israel.

“Regarding the primary and secondary endpoints, we observed identical rates and duration of severe oral mucositis, as well as identical rates of oral mucositis of any grade in the folinic acid and placebo groups,” he said at the annual Transplantation and Cellular Therapy Meetings.

There were also no significant differences between the folinic acid and placebo control groups in time to neutrophil and platelet engraftment, rates of febrile neutropenia and bloodstream infections, veno-occlusive disease, need for opiates or total parenteral nutrition (TPN), or time from transplant to discharge, Dr. Yeshrun added at the meeting, held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Folinic acid therapy did not, however, appear to abrogate or interfere with the effects of methotrexate on prevention of either acute or chronic graft-vs-host disease (GVHD).
 

Severe adverse event

Oral mucositis can be a serious complication of therapy, associated with increased morbidity and mortality; significant pain; difficulty with eating or speaking; difficulty swallowing water, food, and medications; prolonged hospitalizations; and increased costs of care, Dr. Yeshrun noted.

The presence of oral mucositis sometimes leads clinicians to reduce or even skip methotrexate doses, thereby increasing risk for GVHD.

There are limited data from nonrandomized studies indicating that folinic acid (also called leucovorin) may reduce methotrexate-associated toxicities, and both the European Society for Blood and Marrow Transplantation and European LeukemiaNet working group recommend the use of folinic-acid rescue 24 hours following each methotrexate dose, Dr. Yeshrun said.

To see whether folinic acid rescue actually reduces the rate of methotrexate-induced toxicity and affects outcomes for patients who receive methotrexate post transplant for GVHD prophylaxis, Dr. Yeshrun and colleagues in three Israeli medical centers conducted a randomized, placebo-controlled trial.

The eligible study population included patients 18 and older with hematological malignancies in complete remission or minimal residual disease who underwent myeloablative conditioning and allogeneic transplant from HLA-matched or 1-antigen mismatched siblings or unrelated donors.

The patients were stratified by treatment center and intensity of the conditioning regimen, and then randomized on a 1:1 basis to receive folinic acid or placebo beginning 24 hours after each methotrexate dose, with the assigned medication given at a dose of 15 mg three times daily on the first day, and once daily on days 3 and 6.

Patients who received a transplant from an unrelated donor were also given anti-thymocyte globulin at a total dose of 15 mg/kg.

Supportive care included filgrastim (Neupogen) 5 mcg/kg from day 7 until neutrophil engraftment, infection prophylaxis, and ursodeoxycholic acid for prevention of veno-occlusive disease.
 

Trial stopped

Although the study was designed to enroll 116 patients to have a power of 80% to detect a 50% reduction in the rate of severe oral mucositis from an anticipated 50% in the placebo arm, a planned interim analysis conducted after approximately half of the target events occurred showed no difference in the rates of severe oral mucositis, and the trial was halted.

A total of 28 patients in the folinic acid group and 24 in the placebo group were available for the analysis.

The rate of grade 3 or 4 mucositis, the primary endpoint, was 46.6% in the folinic acid group, and 45.8% in the placebo group.

Respectively, the median duration of severe oral mucositis was 4 days in each group, days to neutrophil engraftment were a median of 12 and to platelet engraftment were a median of 13 days in each group, rates of febrile neutropenia were 57.1% and 58.3%, rates of bloodstream infections were 10.7% and 16.6%, rates of veno-occlusive disease were 7% and 12.5%, need for TPN occurred in 14.2% vs. 25%, need for opiates occurred in 78.5% vs. 66.6%, and median time to discharge was 18 and 19 days. As noted, none of the differences were statistically significant.

“These unequivocal interim results led to our decision to discontinue the study,” Dr. Yeshrun said.

Arnon Nagler, MD, MSc, from Sheba Medical Center Tel HaShomer at Tel Aviv University in Israel, who was not involved in the study, said in an interview “I think this is a very practical and important study, because we need evidence-based data such as this.”

Ted Bosworth/MDedge News

Ted Bosworth/MDedge News

His comoderator, Maria Gilleece, MD, director of the Yorkshire (England) Blood and Marrow Transplant Program, noted in an interview that folinic acid is frequently used in the United Kingdom for patients receiving high-dose methotrexate, ”and certainly, this study suggests that may be inappropriate.”

Rabin Medical Center sponsored the trial. Dr. Yeshrun, Dr. Nagler, and Dr. Gilleece reported no relevant conflicts of interest.

SOURCE: Yeshrun M. et al. TCT 2020. Abstract 61.

ORLANDO – Folinic acid does not prevent oral mucositis in patients who are receiving a calcineurin inhibitor and methotrexate for graft-vs.-host disease prophylaxis, results of a multicenter study from Israel suggest.

A randomized clinical trial to determine whether folinic acid rescue 24 hours after a methotrexate dose protects patients against severe oral mucositis was halted for futility after an interim analysis showed no advantage to adding folinic acid, reported Moshe Yeshrun, MD, of Rabin Medical Center at Tel Aviv University, Israel.

“Regarding the primary and secondary endpoints, we observed identical rates and duration of severe oral mucositis, as well as identical rates of oral mucositis of any grade in the folinic acid and placebo groups,” he said at the annual Transplantation and Cellular Therapy Meetings.

There were also no significant differences between the folinic acid and placebo control groups in time to neutrophil and platelet engraftment, rates of febrile neutropenia and bloodstream infections, veno-occlusive disease, need for opiates or total parenteral nutrition (TPN), or time from transplant to discharge, Dr. Yeshrun added at the meeting, held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Folinic acid therapy did not, however, appear to abrogate or interfere with the effects of methotrexate on prevention of either acute or chronic graft-vs-host disease (GVHD).
 

Severe adverse event

Oral mucositis can be a serious complication of therapy, associated with increased morbidity and mortality; significant pain; difficulty with eating or speaking; difficulty swallowing water, food, and medications; prolonged hospitalizations; and increased costs of care, Dr. Yeshrun noted.

The presence of oral mucositis sometimes leads clinicians to reduce or even skip methotrexate doses, thereby increasing risk for GVHD.

There are limited data from nonrandomized studies indicating that folinic acid (also called leucovorin) may reduce methotrexate-associated toxicities, and both the European Society for Blood and Marrow Transplantation and European LeukemiaNet working group recommend the use of folinic-acid rescue 24 hours following each methotrexate dose, Dr. Yeshrun said.

To see whether folinic acid rescue actually reduces the rate of methotrexate-induced toxicity and affects outcomes for patients who receive methotrexate post transplant for GVHD prophylaxis, Dr. Yeshrun and colleagues in three Israeli medical centers conducted a randomized, placebo-controlled trial.

The eligible study population included patients 18 and older with hematological malignancies in complete remission or minimal residual disease who underwent myeloablative conditioning and allogeneic transplant from HLA-matched or 1-antigen mismatched siblings or unrelated donors.

The patients were stratified by treatment center and intensity of the conditioning regimen, and then randomized on a 1:1 basis to receive folinic acid or placebo beginning 24 hours after each methotrexate dose, with the assigned medication given at a dose of 15 mg three times daily on the first day, and once daily on days 3 and 6.

Patients who received a transplant from an unrelated donor were also given anti-thymocyte globulin at a total dose of 15 mg/kg.

Supportive care included filgrastim (Neupogen) 5 mcg/kg from day 7 until neutrophil engraftment, infection prophylaxis, and ursodeoxycholic acid for prevention of veno-occlusive disease.
 

Trial stopped

Although the study was designed to enroll 116 patients to have a power of 80% to detect a 50% reduction in the rate of severe oral mucositis from an anticipated 50% in the placebo arm, a planned interim analysis conducted after approximately half of the target events occurred showed no difference in the rates of severe oral mucositis, and the trial was halted.

A total of 28 patients in the folinic acid group and 24 in the placebo group were available for the analysis.

The rate of grade 3 or 4 mucositis, the primary endpoint, was 46.6% in the folinic acid group, and 45.8% in the placebo group.

Respectively, the median duration of severe oral mucositis was 4 days in each group, days to neutrophil engraftment were a median of 12 and to platelet engraftment were a median of 13 days in each group, rates of febrile neutropenia were 57.1% and 58.3%, rates of bloodstream infections were 10.7% and 16.6%, rates of veno-occlusive disease were 7% and 12.5%, need for TPN occurred in 14.2% vs. 25%, need for opiates occurred in 78.5% vs. 66.6%, and median time to discharge was 18 and 19 days. As noted, none of the differences were statistically significant.

“These unequivocal interim results led to our decision to discontinue the study,” Dr. Yeshrun said.

Arnon Nagler, MD, MSc, from Sheba Medical Center Tel HaShomer at Tel Aviv University in Israel, who was not involved in the study, said in an interview “I think this is a very practical and important study, because we need evidence-based data such as this.”

Ted Bosworth/MDedge News

Ted Bosworth/MDedge News

His comoderator, Maria Gilleece, MD, director of the Yorkshire (England) Blood and Marrow Transplant Program, noted in an interview that folinic acid is frequently used in the United Kingdom for patients receiving high-dose methotrexate, ”and certainly, this study suggests that may be inappropriate.”

Rabin Medical Center sponsored the trial. Dr. Yeshrun, Dr. Nagler, and Dr. Gilleece reported no relevant conflicts of interest.

SOURCE: Yeshrun M. et al. TCT 2020. Abstract 61.