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Tom Collins is a freelance writer in South Florida who has written about medical topics from nasty infections to ethical dilemmas, runaway tumors to tornado-chasing doctors. He travels the globe gathering conference health news and lives in West Palm Beach.
Minimal residual disease measures not yet impactful for AML patients
SAN FRANCISCO – Routine testing for minimal residual disease is probably not of value in acute myeloid leukemia, as there is no evidence that changing treatment based on MRD status currently makes a difference in patient outcomes, experts said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.
“If we find minimal residual disease, we don’t always have a better therapy to offer our patients,” Jessica Altman, MD, associate professor of hematology and oncology at the Northwestern University Feinberg School of Medicine, said.
Beyond that therapeutic reality, there are no clear guidelines and standards for MRD testing. The optimal timing for MRD testing and a standard threshold for an MRD classification are not yet established, she said.
“Having MRD is bad, not having it is better,” Richard Stone, MD, PhD, clinical director of the adult leukemia program at the Dana-Farber Cancer Institute, said. The problem in AML, he said, is, “So?” There is no reliable “MRD eraser” in AML, he said. Until then, there is not much point in knowing whether a patient is MRD positive or not.
A recent survey conducted by researchers at Moffitt Cancer Center, Tampa, addressed MRD testing at 13 major cancer centers. While most centers reported that they test for MRD, many physicians said that they are unsure about what to do with the results.
A 2013 study by the HOVON group found that patients who were in complete remission but MRD positive after their first course of therapy, subsequently became MRD negative after their second course of therapy. But the second regimen would not have been different based on knowledge of MRD status, according to the HOVON/SAKK AML 42A study (J Clin Oncol. 2013; 31:3889-97).
The AML community is awaiting guidelines on MRD use from the NCCN and other groups, Dr. Altman said. An option for using NPM1 mutations to assess MRD should be available soon, and could be an improvement on existing options (N Engl J Med 2016; 374:422-33).
Given the treatment limitations, knowing about MRD status can have a negative mental toll on patients, Dr. Stone said. “I would not underplay the psychological burden.” Nevertheless, MRD should be measured in clinical trials, and it could be a valuable surrogate marker by which to compare drug efficacy.
One of the biggest hopes is that MRD status could eventually be useful in determining the need for allogeneic stem cell transplant in patients deemed intermediate risk, Dr. Altman said. “I think we are finally on the brink of this being actionable.”
Dr. Altman reports financial relationships with Astellas, Bristol-Myers Squibb, Celgene, Janssen, Novartis, and Syros. Dr. Stone reports financial relationships with AbbVie, Actinium, Agios, Amgen and many other companies.
SAN FRANCISCO – Routine testing for minimal residual disease is probably not of value in acute myeloid leukemia, as there is no evidence that changing treatment based on MRD status currently makes a difference in patient outcomes, experts said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.
“If we find minimal residual disease, we don’t always have a better therapy to offer our patients,” Jessica Altman, MD, associate professor of hematology and oncology at the Northwestern University Feinberg School of Medicine, said.
Beyond that therapeutic reality, there are no clear guidelines and standards for MRD testing. The optimal timing for MRD testing and a standard threshold for an MRD classification are not yet established, she said.
“Having MRD is bad, not having it is better,” Richard Stone, MD, PhD, clinical director of the adult leukemia program at the Dana-Farber Cancer Institute, said. The problem in AML, he said, is, “So?” There is no reliable “MRD eraser” in AML, he said. Until then, there is not much point in knowing whether a patient is MRD positive or not.
A recent survey conducted by researchers at Moffitt Cancer Center, Tampa, addressed MRD testing at 13 major cancer centers. While most centers reported that they test for MRD, many physicians said that they are unsure about what to do with the results.
A 2013 study by the HOVON group found that patients who were in complete remission but MRD positive after their first course of therapy, subsequently became MRD negative after their second course of therapy. But the second regimen would not have been different based on knowledge of MRD status, according to the HOVON/SAKK AML 42A study (J Clin Oncol. 2013; 31:3889-97).
The AML community is awaiting guidelines on MRD use from the NCCN and other groups, Dr. Altman said. An option for using NPM1 mutations to assess MRD should be available soon, and could be an improvement on existing options (N Engl J Med 2016; 374:422-33).
Given the treatment limitations, knowing about MRD status can have a negative mental toll on patients, Dr. Stone said. “I would not underplay the psychological burden.” Nevertheless, MRD should be measured in clinical trials, and it could be a valuable surrogate marker by which to compare drug efficacy.
One of the biggest hopes is that MRD status could eventually be useful in determining the need for allogeneic stem cell transplant in patients deemed intermediate risk, Dr. Altman said. “I think we are finally on the brink of this being actionable.”
Dr. Altman reports financial relationships with Astellas, Bristol-Myers Squibb, Celgene, Janssen, Novartis, and Syros. Dr. Stone reports financial relationships with AbbVie, Actinium, Agios, Amgen and many other companies.
SAN FRANCISCO – Routine testing for minimal residual disease is probably not of value in acute myeloid leukemia, as there is no evidence that changing treatment based on MRD status currently makes a difference in patient outcomes, experts said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.
“If we find minimal residual disease, we don’t always have a better therapy to offer our patients,” Jessica Altman, MD, associate professor of hematology and oncology at the Northwestern University Feinberg School of Medicine, said.
Beyond that therapeutic reality, there are no clear guidelines and standards for MRD testing. The optimal timing for MRD testing and a standard threshold for an MRD classification are not yet established, she said.
“Having MRD is bad, not having it is better,” Richard Stone, MD, PhD, clinical director of the adult leukemia program at the Dana-Farber Cancer Institute, said. The problem in AML, he said, is, “So?” There is no reliable “MRD eraser” in AML, he said. Until then, there is not much point in knowing whether a patient is MRD positive or not.
A recent survey conducted by researchers at Moffitt Cancer Center, Tampa, addressed MRD testing at 13 major cancer centers. While most centers reported that they test for MRD, many physicians said that they are unsure about what to do with the results.
A 2013 study by the HOVON group found that patients who were in complete remission but MRD positive after their first course of therapy, subsequently became MRD negative after their second course of therapy. But the second regimen would not have been different based on knowledge of MRD status, according to the HOVON/SAKK AML 42A study (J Clin Oncol. 2013; 31:3889-97).
The AML community is awaiting guidelines on MRD use from the NCCN and other groups, Dr. Altman said. An option for using NPM1 mutations to assess MRD should be available soon, and could be an improvement on existing options (N Engl J Med 2016; 374:422-33).
Given the treatment limitations, knowing about MRD status can have a negative mental toll on patients, Dr. Stone said. “I would not underplay the psychological burden.” Nevertheless, MRD should be measured in clinical trials, and it could be a valuable surrogate marker by which to compare drug efficacy.
One of the biggest hopes is that MRD status could eventually be useful in determining the need for allogeneic stem cell transplant in patients deemed intermediate risk, Dr. Altman said. “I think we are finally on the brink of this being actionable.”
Dr. Altman reports financial relationships with Astellas, Bristol-Myers Squibb, Celgene, Janssen, Novartis, and Syros. Dr. Stone reports financial relationships with AbbVie, Actinium, Agios, Amgen and many other companies.
EXPERT ANALYSIS AT NCCN HEMATOLOGIC MALIGNANCIES CONGRESS
ALL therapies grow, so do the complexities of choosing the order of treatments
SAN FRANCISCO – A growing number of immunotherapy options for adults with acute lymphocytic leukemia (ALL) – rituximab, inotuzumab ozogamicin, blinatumomab and chimeric antigen receptor (CAR) T-cell therapy – have improved remission rates, but their collective effects on patient outcomes remain to be seen, David Maloney, MD, PhD, said at the National Comprehensive Cancer Network Annual Congress: Hematologic Malignancies.
The main challenge for the field is deciding when and how to use a variety of therapies, he said. “How are we going to put these together? What’s the order?” he asked. “Are we going to be able to decrease the need for allogeneic stem cell transplant? And, obviously, that’s the goal.”
About 30%-50% of adults with ALL exhibit CD20-positive cells, making them potentially treatable with rituximab. Data show a better event-free survival rate and a reduced relapse rate when rituximab is added to standard chemotherapy as compared with standard chemotherapy alone, Dr. Maloney of the clinical research division at the Fred Hutchinson Cancer Research Center, Seattle, noted (N Engl J Med. 2016 Sep 15;375[11]:1044-53). But the improvement was only “modest,” he said.
The anti-CD22 antibody inotuzumab ozogamicin has produced complete remission in 81% of relapsed or refractory ALL patients, compared with those getting standard therapy (N Engl J Med. 2016 Aug 25;375:740-53). Dr. Maloney said it seems well tolerated, but there is concern about an increase in veno-occlusive disease in patients who have undergone or will undergo an allogeneic stem cell transplant.
Blinatumomab produces moderate response rates and minimal residual disease–negative remissions, but delivery of the drug is “cumbersome,” requiring a 4-week continuous infusion, he said. The drug seems to be more effective in those with a lower burden of disease, he noted.
CAR T-cell therapy has produced MRD-negative complete responses in 94% of patients, based on results from a clinical trial at Fred Hutchinson. And using the chemotherapy drug fludarabine in combination with this therapy “dramatically” boosts the peak number of the CAR T cells and how long they persist, Dr. Maloney said. Still, CAR T-cell therapy is a work-intensive treatment requiring cells harvested from the patient, and the procedure often brings on cytokine-release syndrome and neurotoxicity, though both adverse events are typically reversible, he said.
It may be that using fewer CAR T cells can reduce toxicity without compromising treatment response, he said.
Questions remain over whether to transplant patients who are in remission after CAR T-cell therapy. “This is a hot debate,” he said. The decision will likely depend on their prior therapy, whether they’ve had a prior transplant, and the how robust the CAR T-cell expansion has been, he said.
Dr. Maloney reports financial relationships with Celgene, Gilead Sciences, Kite Pharma, and Roche.
SAN FRANCISCO – A growing number of immunotherapy options for adults with acute lymphocytic leukemia (ALL) – rituximab, inotuzumab ozogamicin, blinatumomab and chimeric antigen receptor (CAR) T-cell therapy – have improved remission rates, but their collective effects on patient outcomes remain to be seen, David Maloney, MD, PhD, said at the National Comprehensive Cancer Network Annual Congress: Hematologic Malignancies.
The main challenge for the field is deciding when and how to use a variety of therapies, he said. “How are we going to put these together? What’s the order?” he asked. “Are we going to be able to decrease the need for allogeneic stem cell transplant? And, obviously, that’s the goal.”
About 30%-50% of adults with ALL exhibit CD20-positive cells, making them potentially treatable with rituximab. Data show a better event-free survival rate and a reduced relapse rate when rituximab is added to standard chemotherapy as compared with standard chemotherapy alone, Dr. Maloney of the clinical research division at the Fred Hutchinson Cancer Research Center, Seattle, noted (N Engl J Med. 2016 Sep 15;375[11]:1044-53). But the improvement was only “modest,” he said.
The anti-CD22 antibody inotuzumab ozogamicin has produced complete remission in 81% of relapsed or refractory ALL patients, compared with those getting standard therapy (N Engl J Med. 2016 Aug 25;375:740-53). Dr. Maloney said it seems well tolerated, but there is concern about an increase in veno-occlusive disease in patients who have undergone or will undergo an allogeneic stem cell transplant.
Blinatumomab produces moderate response rates and minimal residual disease–negative remissions, but delivery of the drug is “cumbersome,” requiring a 4-week continuous infusion, he said. The drug seems to be more effective in those with a lower burden of disease, he noted.
CAR T-cell therapy has produced MRD-negative complete responses in 94% of patients, based on results from a clinical trial at Fred Hutchinson. And using the chemotherapy drug fludarabine in combination with this therapy “dramatically” boosts the peak number of the CAR T cells and how long they persist, Dr. Maloney said. Still, CAR T-cell therapy is a work-intensive treatment requiring cells harvested from the patient, and the procedure often brings on cytokine-release syndrome and neurotoxicity, though both adverse events are typically reversible, he said.
It may be that using fewer CAR T cells can reduce toxicity without compromising treatment response, he said.
Questions remain over whether to transplant patients who are in remission after CAR T-cell therapy. “This is a hot debate,” he said. The decision will likely depend on their prior therapy, whether they’ve had a prior transplant, and the how robust the CAR T-cell expansion has been, he said.
Dr. Maloney reports financial relationships with Celgene, Gilead Sciences, Kite Pharma, and Roche.
SAN FRANCISCO – A growing number of immunotherapy options for adults with acute lymphocytic leukemia (ALL) – rituximab, inotuzumab ozogamicin, blinatumomab and chimeric antigen receptor (CAR) T-cell therapy – have improved remission rates, but their collective effects on patient outcomes remain to be seen, David Maloney, MD, PhD, said at the National Comprehensive Cancer Network Annual Congress: Hematologic Malignancies.
The main challenge for the field is deciding when and how to use a variety of therapies, he said. “How are we going to put these together? What’s the order?” he asked. “Are we going to be able to decrease the need for allogeneic stem cell transplant? And, obviously, that’s the goal.”
About 30%-50% of adults with ALL exhibit CD20-positive cells, making them potentially treatable with rituximab. Data show a better event-free survival rate and a reduced relapse rate when rituximab is added to standard chemotherapy as compared with standard chemotherapy alone, Dr. Maloney of the clinical research division at the Fred Hutchinson Cancer Research Center, Seattle, noted (N Engl J Med. 2016 Sep 15;375[11]:1044-53). But the improvement was only “modest,” he said.
The anti-CD22 antibody inotuzumab ozogamicin has produced complete remission in 81% of relapsed or refractory ALL patients, compared with those getting standard therapy (N Engl J Med. 2016 Aug 25;375:740-53). Dr. Maloney said it seems well tolerated, but there is concern about an increase in veno-occlusive disease in patients who have undergone or will undergo an allogeneic stem cell transplant.
Blinatumomab produces moderate response rates and minimal residual disease–negative remissions, but delivery of the drug is “cumbersome,” requiring a 4-week continuous infusion, he said. The drug seems to be more effective in those with a lower burden of disease, he noted.
CAR T-cell therapy has produced MRD-negative complete responses in 94% of patients, based on results from a clinical trial at Fred Hutchinson. And using the chemotherapy drug fludarabine in combination with this therapy “dramatically” boosts the peak number of the CAR T cells and how long they persist, Dr. Maloney said. Still, CAR T-cell therapy is a work-intensive treatment requiring cells harvested from the patient, and the procedure often brings on cytokine-release syndrome and neurotoxicity, though both adverse events are typically reversible, he said.
It may be that using fewer CAR T cells can reduce toxicity without compromising treatment response, he said.
Questions remain over whether to transplant patients who are in remission after CAR T-cell therapy. “This is a hot debate,” he said. The decision will likely depend on their prior therapy, whether they’ve had a prior transplant, and the how robust the CAR T-cell expansion has been, he said.
Dr. Maloney reports financial relationships with Celgene, Gilead Sciences, Kite Pharma, and Roche.
EXPERT ANALYSIS FROM THE NCCN ANNUAL CONGRESS: HEMATOLOGIC MALIGNANCIES
High rate of cannabis use among cancer patients
A survey has found that 24% of cancer patients at an ambulatory cancer center in Seattle report being active cannabis users.
Respondents said that the legalization of both medical and recreational marijuana increased the likelihood that they’d use the drug, and with most having a strong interest in learning about cannabis during treatment, according to findings published online Sept. 25 in Cancer (doi: 10.1002/cncr.30879).
A total of 926 of 2,737 possible patients – or 34% – filled out the survey.
Twenty-four percent had used cannabis in the last year, and 21% in the last month, with about half smoking cannabis and half consuming edibles.
About half of the respondents reported using cannabis for pain, the top physical symptom for use, with nausea a close second. About 30 to 50% of patients reported using cannabis for nonphysical symptoms such as depression and mood problems. But the researchers noted that the evidence of benefit is mixed at best for all of these symptoms.
“There is a need to better understand methods of cannabis use,” Dr. Pergam said, “to maximize benefit and limit risk because patients are already using a wide variety of products.”
Researchers reported receiving consulting fees from Merck Sharp & Dohme, Optimer/Cubist Pharmaceuticals, Gilead Sciences, and Quartet Health.
A survey has found that 24% of cancer patients at an ambulatory cancer center in Seattle report being active cannabis users.
Respondents said that the legalization of both medical and recreational marijuana increased the likelihood that they’d use the drug, and with most having a strong interest in learning about cannabis during treatment, according to findings published online Sept. 25 in Cancer (doi: 10.1002/cncr.30879).
A total of 926 of 2,737 possible patients – or 34% – filled out the survey.
Twenty-four percent had used cannabis in the last year, and 21% in the last month, with about half smoking cannabis and half consuming edibles.
About half of the respondents reported using cannabis for pain, the top physical symptom for use, with nausea a close second. About 30 to 50% of patients reported using cannabis for nonphysical symptoms such as depression and mood problems. But the researchers noted that the evidence of benefit is mixed at best for all of these symptoms.
“There is a need to better understand methods of cannabis use,” Dr. Pergam said, “to maximize benefit and limit risk because patients are already using a wide variety of products.”
Researchers reported receiving consulting fees from Merck Sharp & Dohme, Optimer/Cubist Pharmaceuticals, Gilead Sciences, and Quartet Health.
A survey has found that 24% of cancer patients at an ambulatory cancer center in Seattle report being active cannabis users.
Respondents said that the legalization of both medical and recreational marijuana increased the likelihood that they’d use the drug, and with most having a strong interest in learning about cannabis during treatment, according to findings published online Sept. 25 in Cancer (doi: 10.1002/cncr.30879).
A total of 926 of 2,737 possible patients – or 34% – filled out the survey.
Twenty-four percent had used cannabis in the last year, and 21% in the last month, with about half smoking cannabis and half consuming edibles.
About half of the respondents reported using cannabis for pain, the top physical symptom for use, with nausea a close second. About 30 to 50% of patients reported using cannabis for nonphysical symptoms such as depression and mood problems. But the researchers noted that the evidence of benefit is mixed at best for all of these symptoms.
“There is a need to better understand methods of cannabis use,” Dr. Pergam said, “to maximize benefit and limit risk because patients are already using a wide variety of products.”
Researchers reported receiving consulting fees from Merck Sharp & Dohme, Optimer/Cubist Pharmaceuticals, Gilead Sciences, and Quartet Health.
FROM CANCER
Key clinical point:
Major finding: Twenty-four percent of patients reported using cannabis in the past year, mostly for pain and nausea.
Data source: A survey of patients at an ambulatory cancer center in Seattle, where cannabis is legal for medical and recreational use.
Disclosures: Researchers reported receiving consulting fees from Merck Sharp & Dohme, Optimer/Cubist Pharmaceuticals, Gilead Sciences, and Quartet Health.
Primary care deficient in cancer survivor care
Even advanced primary care practices are not providing comprehensive cancer survivorship care, with deficiencies in how cancer survivors are categorized, how they’re transitioned to primary care, and in the information systems used in their care, according to a new study published online September 25 in JAMA Internal Medicine.
The analysis came from data gathered by investigators at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., who performed case studies on 12 advanced primary care centers across a variety of practice types and geographic settings. The centers were chosen using a national registry of “workforce innovators” compiled by the Robert Wood Johnson Foundation in 2011 and 2012. All but three of the centers were designated patient-centered medical homes (JAMA Intern Med. 2017. doi: 10.1001/jamainternmed.2017.4747).
Researchers noted the tremendous importance of primary care to cancer survivors. Only about a third of cancer survivors continue to be seen by a cancer specialist 5 years after their diagnosis, but 75% are seen in primary care. The importance of preventive screening, surveillance for recurrence, interventions for long-term effects, and care coordination between specialty and primary care were noted in an Institute of Medicine report in 2006.
Researchers found that the primary care clinicians don’t treat cancer survivors as a distinct population; they get limited information or follow-up guidance on cancer care; and information systems aren’t good at supporting survivorship care.
“Codifying survivorship as a distinct clinical category that belongs on problem lists with payment-linked – fee, value-based, or capitated – care services is a critical first step toward bringing comprehensive cancer survivorship services to primary care,” Dr. Rubinstein said.
Researchers described what they called “cancer exceptionalism,” in which a cancer diagnosis follows a different clinical norm and patients are referred to oncology and then become disengaged with primary care.
On transition of care, one primary care physician told an interviewer that it seems that patients’ cancer treatment “kind of happens in a black box” and that they feel “a little intimidated” in providing the needed follow-up care.
Another said that while a patient’s cancer history could be seen “at a glance” in old paper charts, their electronic health record requires searching multiple screens and “sometimes it’s a needle in a haystack.”
“Despite the push from national organizations to enhance cancer survivorship care capacity in primary care,” Dr. Rubinstein said, “findings from this study suggest that cancer survivorship care does not integrate easily into advanced primary care.”
The researchers reported no conflicts of interest.
Even advanced primary care practices are not providing comprehensive cancer survivorship care, with deficiencies in how cancer survivors are categorized, how they’re transitioned to primary care, and in the information systems used in their care, according to a new study published online September 25 in JAMA Internal Medicine.
The analysis came from data gathered by investigators at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., who performed case studies on 12 advanced primary care centers across a variety of practice types and geographic settings. The centers were chosen using a national registry of “workforce innovators” compiled by the Robert Wood Johnson Foundation in 2011 and 2012. All but three of the centers were designated patient-centered medical homes (JAMA Intern Med. 2017. doi: 10.1001/jamainternmed.2017.4747).
Researchers noted the tremendous importance of primary care to cancer survivors. Only about a third of cancer survivors continue to be seen by a cancer specialist 5 years after their diagnosis, but 75% are seen in primary care. The importance of preventive screening, surveillance for recurrence, interventions for long-term effects, and care coordination between specialty and primary care were noted in an Institute of Medicine report in 2006.
Researchers found that the primary care clinicians don’t treat cancer survivors as a distinct population; they get limited information or follow-up guidance on cancer care; and information systems aren’t good at supporting survivorship care.
“Codifying survivorship as a distinct clinical category that belongs on problem lists with payment-linked – fee, value-based, or capitated – care services is a critical first step toward bringing comprehensive cancer survivorship services to primary care,” Dr. Rubinstein said.
Researchers described what they called “cancer exceptionalism,” in which a cancer diagnosis follows a different clinical norm and patients are referred to oncology and then become disengaged with primary care.
On transition of care, one primary care physician told an interviewer that it seems that patients’ cancer treatment “kind of happens in a black box” and that they feel “a little intimidated” in providing the needed follow-up care.
Another said that while a patient’s cancer history could be seen “at a glance” in old paper charts, their electronic health record requires searching multiple screens and “sometimes it’s a needle in a haystack.”
“Despite the push from national organizations to enhance cancer survivorship care capacity in primary care,” Dr. Rubinstein said, “findings from this study suggest that cancer survivorship care does not integrate easily into advanced primary care.”
The researchers reported no conflicts of interest.
Even advanced primary care practices are not providing comprehensive cancer survivorship care, with deficiencies in how cancer survivors are categorized, how they’re transitioned to primary care, and in the information systems used in their care, according to a new study published online September 25 in JAMA Internal Medicine.
The analysis came from data gathered by investigators at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., who performed case studies on 12 advanced primary care centers across a variety of practice types and geographic settings. The centers were chosen using a national registry of “workforce innovators” compiled by the Robert Wood Johnson Foundation in 2011 and 2012. All but three of the centers were designated patient-centered medical homes (JAMA Intern Med. 2017. doi: 10.1001/jamainternmed.2017.4747).
Researchers noted the tremendous importance of primary care to cancer survivors. Only about a third of cancer survivors continue to be seen by a cancer specialist 5 years after their diagnosis, but 75% are seen in primary care. The importance of preventive screening, surveillance for recurrence, interventions for long-term effects, and care coordination between specialty and primary care were noted in an Institute of Medicine report in 2006.
Researchers found that the primary care clinicians don’t treat cancer survivors as a distinct population; they get limited information or follow-up guidance on cancer care; and information systems aren’t good at supporting survivorship care.
“Codifying survivorship as a distinct clinical category that belongs on problem lists with payment-linked – fee, value-based, or capitated – care services is a critical first step toward bringing comprehensive cancer survivorship services to primary care,” Dr. Rubinstein said.
Researchers described what they called “cancer exceptionalism,” in which a cancer diagnosis follows a different clinical norm and patients are referred to oncology and then become disengaged with primary care.
On transition of care, one primary care physician told an interviewer that it seems that patients’ cancer treatment “kind of happens in a black box” and that they feel “a little intimidated” in providing the needed follow-up care.
Another said that while a patient’s cancer history could be seen “at a glance” in old paper charts, their electronic health record requires searching multiple screens and “sometimes it’s a needle in a haystack.”
“Despite the push from national organizations to enhance cancer survivorship care capacity in primary care,” Dr. Rubinstein said, “findings from this study suggest that cancer survivorship care does not integrate easily into advanced primary care.”
The researchers reported no conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Advanced primary care practices are not providing comprehensive cancer survivorship care.
Major finding: Primary care clinicians don’t treat cancer survivors as a distinct population; they get limited information or follow-up guidance on cancer care; and information systems aren’t good at supporting survivorship care.
Data source: A comparative case study of 12 primary care practices compiled using a national registry of “workforce innovators.”
Disclosures: None reported.
No overall survival benefit from early SIRT for liver metastases from colorectal cancer
Combining first-line chemotherapy with selective internal radiotherapy (SIRT) using Y-90 resin microspheres in patients with liver metastases from colorectal cancer does not result in greater overall survival compared with first-line chemotherapy alone, according to an analysis of three randomized trials.
The liver is the most common site of metastases in colorectal cancer, and liver metastases are the most common cause of death in these patients. Data from previous trials suggest SIRT has a clinical benefit as a third-line or subsequent therapy in patients with colorectal liver metastases with liver-dominant disease after chemotherapy.
In the current analysis, the largest so far to look at first-line SIRT plus chemotherapy’s effects on overall survival in these patients, researchers assessed data from FOXFIRE, SIRFLOX, and FOXFIRE-Global – phase 3 trials conducted in 14 countries. Patients were randomized to either the oxaliplatin-based chemotherapy FOLFOX (leucovorin, fluorouracil, and oxaliplatin) plus SIRT, or FOLFOX alone. In SIRFLOX and FOXFIRE-Global the chemotherapy regimen was modified, compared with FOXFIRE. (The Lancet. 2017 Aug 3. doi: 10.1016/S1470-2045[17]30457-6).
The randomizing was tweaked using the “minimization” technique to keep the treatment groups balanced for liver-only versus liver plus extrahepatic involvement, the extent of tumor involvement, anticipated use of a biologic agent, and the investigational center.
With a median follow-up of 43 months, there was no difference in overall survival, with a median survival time of 22.6 months in the FOLFOX plus SIRT group and 23.3 months in the FOLFOX alone group, said Harpreet Wasan, MBBS, MRCP, head of the gastrointestinal clinical research program at Imperial College London.
Serious adverse events occurred in 54% of the FOLFOX plus SIRT group and 43% of the FOLFOX alone group. There were eight treatment-related deaths in the FOLFOX plus SIRT group and three in the FOLFOX alone group.
Dr. Wasan said the lack of a benefit from SIRT could be partially explained by a high proportion of patients who developed first progression at an extrahepatic site.
“The absence of an overall survival benefit,” he said, “suggests that early use of SIRT in combination with first-line oxaliplatin-based chemotherapy cannot be recommended in unselected patients with metastatic colorectal cancer.”
SIRFLOX and FOXFIRE-Global were sponsored by Sirtex, the manufacturer of the resin microspheres used for the SIRT therapy in the trials that were analyzed. Study authors reported receiving grants, personal fees, speakers fees, and other financial relationships with Sirtex, Merck, Pfizer, Roche, and other companies.
Combining first-line chemotherapy with selective internal radiotherapy (SIRT) using Y-90 resin microspheres in patients with liver metastases from colorectal cancer does not result in greater overall survival compared with first-line chemotherapy alone, according to an analysis of three randomized trials.
The liver is the most common site of metastases in colorectal cancer, and liver metastases are the most common cause of death in these patients. Data from previous trials suggest SIRT has a clinical benefit as a third-line or subsequent therapy in patients with colorectal liver metastases with liver-dominant disease after chemotherapy.
In the current analysis, the largest so far to look at first-line SIRT plus chemotherapy’s effects on overall survival in these patients, researchers assessed data from FOXFIRE, SIRFLOX, and FOXFIRE-Global – phase 3 trials conducted in 14 countries. Patients were randomized to either the oxaliplatin-based chemotherapy FOLFOX (leucovorin, fluorouracil, and oxaliplatin) plus SIRT, or FOLFOX alone. In SIRFLOX and FOXFIRE-Global the chemotherapy regimen was modified, compared with FOXFIRE. (The Lancet. 2017 Aug 3. doi: 10.1016/S1470-2045[17]30457-6).
The randomizing was tweaked using the “minimization” technique to keep the treatment groups balanced for liver-only versus liver plus extrahepatic involvement, the extent of tumor involvement, anticipated use of a biologic agent, and the investigational center.
With a median follow-up of 43 months, there was no difference in overall survival, with a median survival time of 22.6 months in the FOLFOX plus SIRT group and 23.3 months in the FOLFOX alone group, said Harpreet Wasan, MBBS, MRCP, head of the gastrointestinal clinical research program at Imperial College London.
Serious adverse events occurred in 54% of the FOLFOX plus SIRT group and 43% of the FOLFOX alone group. There were eight treatment-related deaths in the FOLFOX plus SIRT group and three in the FOLFOX alone group.
Dr. Wasan said the lack of a benefit from SIRT could be partially explained by a high proportion of patients who developed first progression at an extrahepatic site.
“The absence of an overall survival benefit,” he said, “suggests that early use of SIRT in combination with first-line oxaliplatin-based chemotherapy cannot be recommended in unselected patients with metastatic colorectal cancer.”
SIRFLOX and FOXFIRE-Global were sponsored by Sirtex, the manufacturer of the resin microspheres used for the SIRT therapy in the trials that were analyzed. Study authors reported receiving grants, personal fees, speakers fees, and other financial relationships with Sirtex, Merck, Pfizer, Roche, and other companies.
Combining first-line chemotherapy with selective internal radiotherapy (SIRT) using Y-90 resin microspheres in patients with liver metastases from colorectal cancer does not result in greater overall survival compared with first-line chemotherapy alone, according to an analysis of three randomized trials.
The liver is the most common site of metastases in colorectal cancer, and liver metastases are the most common cause of death in these patients. Data from previous trials suggest SIRT has a clinical benefit as a third-line or subsequent therapy in patients with colorectal liver metastases with liver-dominant disease after chemotherapy.
In the current analysis, the largest so far to look at first-line SIRT plus chemotherapy’s effects on overall survival in these patients, researchers assessed data from FOXFIRE, SIRFLOX, and FOXFIRE-Global – phase 3 trials conducted in 14 countries. Patients were randomized to either the oxaliplatin-based chemotherapy FOLFOX (leucovorin, fluorouracil, and oxaliplatin) plus SIRT, or FOLFOX alone. In SIRFLOX and FOXFIRE-Global the chemotherapy regimen was modified, compared with FOXFIRE. (The Lancet. 2017 Aug 3. doi: 10.1016/S1470-2045[17]30457-6).
The randomizing was tweaked using the “minimization” technique to keep the treatment groups balanced for liver-only versus liver plus extrahepatic involvement, the extent of tumor involvement, anticipated use of a biologic agent, and the investigational center.
With a median follow-up of 43 months, there was no difference in overall survival, with a median survival time of 22.6 months in the FOLFOX plus SIRT group and 23.3 months in the FOLFOX alone group, said Harpreet Wasan, MBBS, MRCP, head of the gastrointestinal clinical research program at Imperial College London.
Serious adverse events occurred in 54% of the FOLFOX plus SIRT group and 43% of the FOLFOX alone group. There were eight treatment-related deaths in the FOLFOX plus SIRT group and three in the FOLFOX alone group.
Dr. Wasan said the lack of a benefit from SIRT could be partially explained by a high proportion of patients who developed first progression at an extrahepatic site.
“The absence of an overall survival benefit,” he said, “suggests that early use of SIRT in combination with first-line oxaliplatin-based chemotherapy cannot be recommended in unselected patients with metastatic colorectal cancer.”
SIRFLOX and FOXFIRE-Global were sponsored by Sirtex, the manufacturer of the resin microspheres used for the SIRT therapy in the trials that were analyzed. Study authors reported receiving grants, personal fees, speakers fees, and other financial relationships with Sirtex, Merck, Pfizer, Roche, and other companies.
FROM THE LANCET
Key clinical point:
Major finding: There was a median survival time of 22.6 months in the FOLFOX plus SIRT group and 23.3 months in the FOLFOX alone group, which was not a significant difference, after a median follow-up of 43 months.
Data source: An analysis of three phase 3 randomized trials across 14 countries from 2006 to 2014.
Disclosures: SIRFLOX and FOXFIRE-Global were sponsored by Sirtex, the manufacturer of the resin microspheres used for the SIRT therapy in the trials that were analyzed. Study authors reported receiving grants, personal fees, speakers fees, and other financial relationships with Sirtex, Merck, Pfizer, Roche, and other companies.
ASCO issues new guideline on stage IV NSCLC
The American Society of Clinical Oncology has updated its clinical practice guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC), incorporating recommendations on using checkpoint inhibitors in these patients.
The guideline was published recently on the Journal of Clinical Oncology website (J Clin Oncol. 2017 Aug 14. doi: 10.1200/JCO.2017.74.6065).
Among the recommendations is that, for patients with non–squamous cell carcinoma or squamous cell carcinoma without positive markers such as epidermal growth factor receptor who have high programmed death ligand 1 (PD-L1) expression, first-line treatment should be pembrolizumab alone. For those with low PD-L1 expression, standard chemotherapy should be used.
For second-line treatment in patients who received first-line chemotherapy without prior immune checkpoint treatment, if the NSCLC tumor is positive for PD-L1 expression, single-agent nivolumab, pembrolizumab, or atezolizumab should be used.
The guideline is an update of its 2015 recommendations. An expert panel made the changes after a systematic review of randomized controlled trials from February 2014 to December 2016.
Panelists said that there’s still a lot to learn about the use of checkpoint inhibitors in these patients.
“Cancer immunotherapy allows some patients to live longer with a better quality of life than chemotherapy; however, not all patients respond to this treatment,” panelists wrote. “Many factors remain unknown in the understanding of optimal sequencing of immune checkpoint therapy and other agents previously recommended in ASCO guidelines. Contraindications to receiving immune checkpoint therapy are not yet well defined.”
Several panelists report receiving research funding and/or consulting fees from Merck, Bristol-Meyers Squibb, Peloton Therapeutics, Genentech, and other companies.
The American Society of Clinical Oncology has updated its clinical practice guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC), incorporating recommendations on using checkpoint inhibitors in these patients.
The guideline was published recently on the Journal of Clinical Oncology website (J Clin Oncol. 2017 Aug 14. doi: 10.1200/JCO.2017.74.6065).
Among the recommendations is that, for patients with non–squamous cell carcinoma or squamous cell carcinoma without positive markers such as epidermal growth factor receptor who have high programmed death ligand 1 (PD-L1) expression, first-line treatment should be pembrolizumab alone. For those with low PD-L1 expression, standard chemotherapy should be used.
For second-line treatment in patients who received first-line chemotherapy without prior immune checkpoint treatment, if the NSCLC tumor is positive for PD-L1 expression, single-agent nivolumab, pembrolizumab, or atezolizumab should be used.
The guideline is an update of its 2015 recommendations. An expert panel made the changes after a systematic review of randomized controlled trials from February 2014 to December 2016.
Panelists said that there’s still a lot to learn about the use of checkpoint inhibitors in these patients.
“Cancer immunotherapy allows some patients to live longer with a better quality of life than chemotherapy; however, not all patients respond to this treatment,” panelists wrote. “Many factors remain unknown in the understanding of optimal sequencing of immune checkpoint therapy and other agents previously recommended in ASCO guidelines. Contraindications to receiving immune checkpoint therapy are not yet well defined.”
Several panelists report receiving research funding and/or consulting fees from Merck, Bristol-Meyers Squibb, Peloton Therapeutics, Genentech, and other companies.
The American Society of Clinical Oncology has updated its clinical practice guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC), incorporating recommendations on using checkpoint inhibitors in these patients.
The guideline was published recently on the Journal of Clinical Oncology website (J Clin Oncol. 2017 Aug 14. doi: 10.1200/JCO.2017.74.6065).
Among the recommendations is that, for patients with non–squamous cell carcinoma or squamous cell carcinoma without positive markers such as epidermal growth factor receptor who have high programmed death ligand 1 (PD-L1) expression, first-line treatment should be pembrolizumab alone. For those with low PD-L1 expression, standard chemotherapy should be used.
For second-line treatment in patients who received first-line chemotherapy without prior immune checkpoint treatment, if the NSCLC tumor is positive for PD-L1 expression, single-agent nivolumab, pembrolizumab, or atezolizumab should be used.
The guideline is an update of its 2015 recommendations. An expert panel made the changes after a systematic review of randomized controlled trials from February 2014 to December 2016.
Panelists said that there’s still a lot to learn about the use of checkpoint inhibitors in these patients.
“Cancer immunotherapy allows some patients to live longer with a better quality of life than chemotherapy; however, not all patients respond to this treatment,” panelists wrote. “Many factors remain unknown in the understanding of optimal sequencing of immune checkpoint therapy and other agents previously recommended in ASCO guidelines. Contraindications to receiving immune checkpoint therapy are not yet well defined.”
Several panelists report receiving research funding and/or consulting fees from Merck, Bristol-Meyers Squibb, Peloton Therapeutics, Genentech, and other companies.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The American Society of Clinical Oncology has issued its latest clinical practice guideline on the systemic treatment of non–small-cell lung cancer, an update of its 2015 guideline.
Major finding: For patients with non–squamous cell carcinoma or squamous cell carcinoma without positive markers such as epidermal growth factor receptor (EGFR), if a patient has high programmed death ligand 1 (PD-L1) expression, first-line treatment should be pembrolizumab alone. For those with low PD-L1 expression, standard chemotherapy should be used.
Data source: A systematic review of randomized controlled trials from February 2014 to December 2016.
Disclosures: Several panelists report receiving research funding and/or consulting fees from Merck, Bristol-Meyers Squibb, Peloton Therapeutics, Genentech, and other companies.
Study findings cast doubt on community-acquired pneumonia diagnostic practices
New studies raise doubts on the reliability of physical exam findings in suspected pediatric community-acquired pneumonia cases and on the value of blood cultures in hospitalized pediatric CAP cases.
In one study, 128 cases of suspected CAP in children aged 3 months to 18 years presenting to an ED from July 2013 to May 2016 underwent paired assessments within 20 minutes of each other. Only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability, with the lower end of the 95% confidential interval at a Fleiss’ kappa value of 0.4 or higher.
“The reliability of these findings must be considered in the clinical management and research of children with CAP,” said lead author Todd Florin, MD, associate research director in emergency medicine at Cincinnati Children’s Hospital Medical Center and his associates. (Pediatrics. 2017;140[3]:e20170310)
In a retrospective cohort analysis, researchers found that just 2.5% of 2,568 hospitalized children with CAP who had a blood culture performed actually grew a pathogen. And of the detected pathogens, 82% were susceptible to penicillin. Streptococcus pneumoniae accounted for 78% of all the pathogens that were found; it was detected in only 2% of all children who had blood cultures taken.
Just 11 children – or 0.43% of the children with a blood culture performed – had growth of a pathogen that was not treatable with penicillin, said lead author Mark Neuman, MD, director of research at Boston Children’s Hospital and his associates (Pediatrics. 2017;140[3]:e20171013).
The analysis was drawn from a cohort of 7,509 children hospitalized from 2007 to 2011, with children with complex chronic conditions excluded. Data for the analysis came from the Pediatric Health Information System Plus database, in which administrative, billing, laboratory, and radiographic information is stored from six tertiary children’s hospitals.
The investigators said that one challenge is that when blood cultures are drawn early in the course of evaluation and treatment, the severity of the child’s CAP might not be apparent, which makes it difficult to know which children would benefit from a blood culture.
“The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when identifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, narrow-spectrum antibiotics.”
Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, individual researchers received funding from the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relationships with BioFire Diagnostics.
New studies raise doubts on the reliability of physical exam findings in suspected pediatric community-acquired pneumonia cases and on the value of blood cultures in hospitalized pediatric CAP cases.
In one study, 128 cases of suspected CAP in children aged 3 months to 18 years presenting to an ED from July 2013 to May 2016 underwent paired assessments within 20 minutes of each other. Only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability, with the lower end of the 95% confidential interval at a Fleiss’ kappa value of 0.4 or higher.
“The reliability of these findings must be considered in the clinical management and research of children with CAP,” said lead author Todd Florin, MD, associate research director in emergency medicine at Cincinnati Children’s Hospital Medical Center and his associates. (Pediatrics. 2017;140[3]:e20170310)
In a retrospective cohort analysis, researchers found that just 2.5% of 2,568 hospitalized children with CAP who had a blood culture performed actually grew a pathogen. And of the detected pathogens, 82% were susceptible to penicillin. Streptococcus pneumoniae accounted for 78% of all the pathogens that were found; it was detected in only 2% of all children who had blood cultures taken.
Just 11 children – or 0.43% of the children with a blood culture performed – had growth of a pathogen that was not treatable with penicillin, said lead author Mark Neuman, MD, director of research at Boston Children’s Hospital and his associates (Pediatrics. 2017;140[3]:e20171013).
The analysis was drawn from a cohort of 7,509 children hospitalized from 2007 to 2011, with children with complex chronic conditions excluded. Data for the analysis came from the Pediatric Health Information System Plus database, in which administrative, billing, laboratory, and radiographic information is stored from six tertiary children’s hospitals.
The investigators said that one challenge is that when blood cultures are drawn early in the course of evaluation and treatment, the severity of the child’s CAP might not be apparent, which makes it difficult to know which children would benefit from a blood culture.
“The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when identifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, narrow-spectrum antibiotics.”
Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, individual researchers received funding from the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relationships with BioFire Diagnostics.
New studies raise doubts on the reliability of physical exam findings in suspected pediatric community-acquired pneumonia cases and on the value of blood cultures in hospitalized pediatric CAP cases.
In one study, 128 cases of suspected CAP in children aged 3 months to 18 years presenting to an ED from July 2013 to May 2016 underwent paired assessments within 20 minutes of each other. Only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability, with the lower end of the 95% confidential interval at a Fleiss’ kappa value of 0.4 or higher.
“The reliability of these findings must be considered in the clinical management and research of children with CAP,” said lead author Todd Florin, MD, associate research director in emergency medicine at Cincinnati Children’s Hospital Medical Center and his associates. (Pediatrics. 2017;140[3]:e20170310)
In a retrospective cohort analysis, researchers found that just 2.5% of 2,568 hospitalized children with CAP who had a blood culture performed actually grew a pathogen. And of the detected pathogens, 82% were susceptible to penicillin. Streptococcus pneumoniae accounted for 78% of all the pathogens that were found; it was detected in only 2% of all children who had blood cultures taken.
Just 11 children – or 0.43% of the children with a blood culture performed – had growth of a pathogen that was not treatable with penicillin, said lead author Mark Neuman, MD, director of research at Boston Children’s Hospital and his associates (Pediatrics. 2017;140[3]:e20171013).
The analysis was drawn from a cohort of 7,509 children hospitalized from 2007 to 2011, with children with complex chronic conditions excluded. Data for the analysis came from the Pediatric Health Information System Plus database, in which administrative, billing, laboratory, and radiographic information is stored from six tertiary children’s hospitals.
The investigators said that one challenge is that when blood cultures are drawn early in the course of evaluation and treatment, the severity of the child’s CAP might not be apparent, which makes it difficult to know which children would benefit from a blood culture.
“The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when identifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, narrow-spectrum antibiotics.”
Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, individual researchers received funding from the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relationships with BioFire Diagnostics.
FROM PEDIATRICS
Key clinical point:
Major finding: In one study, only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability in cases in which paired assessments were done 20 minutes apart after patients presented to the ED with suspected CAP. In another study, just 2.5% of hospitalized children with CAP who had a blood culture performed actually grew a pathogen.
Data source: An ongoing prospective cohort study of 128 pediatric patients presenting to an emergency room with suspected CAP, and a retrospective analysis of data collected on hospitalizations from 2007 to 2011 at six tertiary children’s hospitals.
Disclosures: The studies were funded by the National Institutes of Health and by other grants to individual researchers. For the physician exam study, no relevant financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reports receiving research funding from and other financial relationships with BioFire Diagnostics.
Obinutuzumab-CHOP not superior to rituximab-CHOP in new DLBCL
Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)
The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.
The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.
“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”
The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.
Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)
The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.
The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.
“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”
The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.
Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)
The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.
The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.
“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”
The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Obinutuzumab with CHOP therapy did not improve progression-free survival for diffuse large B-cell lymphoma, compared with standard treatment with rituximab used with CHOP.
Major finding: The estimated PFS was 69.6% for obinutuzumab-CHOP and 66.9% for rituximab-CHOP, an insignificant difference.
Data source: A randomized phase 3 trial of 1,418 patients at 207 centers in 29 countries.
Disclosures: The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi..
Crizotinib shows responses in pediatric ALCL and IMT
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The ALK-inhibitor crizotinib produced good responses in pediatric, relapsed/refractory ALK-positive anaplastic large cell lymphoma and unresectable inflammatory myofibroblastic tumors.
Major finding: Eighty percent of ALCL patients in the high-dose group had a complete response, along with 83% given the lower dose. In the IMT group, 36%, had a complete response.
Data source: A 26-patient trial with a two-stage design, including phase 2 results as well as some data from phase 1, conducted across four U.S. centers.
Disclosures: Several study authors reported financial conflicts, including stock or other ownership, speaking fees, or institutional research funding from Pfizer, Novartis, Johnson & Johnson and other companies.
Allele-matching in cord blood transplant yields better survival
Matching down to the allele level in umbilical cord blood transplantation between unrelated donors results in greater overall survival for those with nonmalignant diseases, such as aplastic anemia, researchers found in a retrospective study published in the Lancet Haematology.
The review (Lancet Haematol. 2017 Jul;4[7]:e325-33), the largest published on the topic, indicates that clinicians should change practice from the current standard of antigen-level matching, said Mary Eapen, MD, director of the Center for International Blood and Marrow Transplant Research (CIBMTR) in Wauwatosa, Wisconsin.
“Our findings,” Dr. Eapen wrote, “support a change in clinical practice to prioritization of units on allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.”
Data were pulled from cases reported to the Center for International Blood and Marrow Transplant Research or the European Group for Blood and Marrow Transplant. Researchers looked at 1,199 donor-recipient matches of cord blood transplantation for diseases, such as severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency, inborn errors of metabolism, severe aplastic anemia, and Fanconi anemia. Recipients could be as old as age 16, but most were age 5 or younger.
After adjustment for factors, including cytomegalovirus serostatus, the intensity of the conditioning regimen, and the total nucleated cell dose, the 5-year overall survival was 79% for transplants that were matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1. These results compare with 76% after transplants with one mismatch, 70% with two mismatches, 62% with three mismatches, and 49% with 4 or more mismatches.
Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched. There was no difference statistically between full matches and one mismatch, but the findings suggest that the mortality risk might prove significant with a larger sample size.
Researchers cautioned that, because most patients were age 5 or younger, the results might not be generalizable to older children.
Although HLA typing is available at CIBMTR for most blood cord transplants for nonmalignant diseases, full allele matches or just one mismatch are not the norm, Dr. Eapen wrote. Researchers said that they suspect this is because of difficulties finding matches or because a high total nucleated cell count is prioritized above HLA matching. They suggest clinicians change their decision making in this regard.
Matching down to the allele level in umbilical cord blood transplantation between unrelated donors results in greater overall survival for those with nonmalignant diseases, such as aplastic anemia, researchers found in a retrospective study published in the Lancet Haematology.
The review (Lancet Haematol. 2017 Jul;4[7]:e325-33), the largest published on the topic, indicates that clinicians should change practice from the current standard of antigen-level matching, said Mary Eapen, MD, director of the Center for International Blood and Marrow Transplant Research (CIBMTR) in Wauwatosa, Wisconsin.
“Our findings,” Dr. Eapen wrote, “support a change in clinical practice to prioritization of units on allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.”
Data were pulled from cases reported to the Center for International Blood and Marrow Transplant Research or the European Group for Blood and Marrow Transplant. Researchers looked at 1,199 donor-recipient matches of cord blood transplantation for diseases, such as severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency, inborn errors of metabolism, severe aplastic anemia, and Fanconi anemia. Recipients could be as old as age 16, but most were age 5 or younger.
After adjustment for factors, including cytomegalovirus serostatus, the intensity of the conditioning regimen, and the total nucleated cell dose, the 5-year overall survival was 79% for transplants that were matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1. These results compare with 76% after transplants with one mismatch, 70% with two mismatches, 62% with three mismatches, and 49% with 4 or more mismatches.
Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched. There was no difference statistically between full matches and one mismatch, but the findings suggest that the mortality risk might prove significant with a larger sample size.
Researchers cautioned that, because most patients were age 5 or younger, the results might not be generalizable to older children.
Although HLA typing is available at CIBMTR for most blood cord transplants for nonmalignant diseases, full allele matches or just one mismatch are not the norm, Dr. Eapen wrote. Researchers said that they suspect this is because of difficulties finding matches or because a high total nucleated cell count is prioritized above HLA matching. They suggest clinicians change their decision making in this regard.
Matching down to the allele level in umbilical cord blood transplantation between unrelated donors results in greater overall survival for those with nonmalignant diseases, such as aplastic anemia, researchers found in a retrospective study published in the Lancet Haematology.
The review (Lancet Haematol. 2017 Jul;4[7]:e325-33), the largest published on the topic, indicates that clinicians should change practice from the current standard of antigen-level matching, said Mary Eapen, MD, director of the Center for International Blood and Marrow Transplant Research (CIBMTR) in Wauwatosa, Wisconsin.
“Our findings,” Dr. Eapen wrote, “support a change in clinical practice to prioritization of units on allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.”
Data were pulled from cases reported to the Center for International Blood and Marrow Transplant Research or the European Group for Blood and Marrow Transplant. Researchers looked at 1,199 donor-recipient matches of cord blood transplantation for diseases, such as severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency, inborn errors of metabolism, severe aplastic anemia, and Fanconi anemia. Recipients could be as old as age 16, but most were age 5 or younger.
After adjustment for factors, including cytomegalovirus serostatus, the intensity of the conditioning regimen, and the total nucleated cell dose, the 5-year overall survival was 79% for transplants that were matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1. These results compare with 76% after transplants with one mismatch, 70% with two mismatches, 62% with three mismatches, and 49% with 4 or more mismatches.
Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched. There was no difference statistically between full matches and one mismatch, but the findings suggest that the mortality risk might prove significant with a larger sample size.
Researchers cautioned that, because most patients were age 5 or younger, the results might not be generalizable to older children.
Although HLA typing is available at CIBMTR for most blood cord transplants for nonmalignant diseases, full allele matches or just one mismatch are not the norm, Dr. Eapen wrote. Researchers said that they suspect this is because of difficulties finding matches or because a high total nucleated cell count is prioritized above HLA matching. They suggest clinicians change their decision making in this regard.
FROM THE LANCET HAEMATOLOGY
Key clinical point: HLA matching at the allele-level produces better survival in umbilical cord blood transplantation for nonmalignant diseases.
Major finding: Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1.
Data source: A retrospective review of 1,199 cases reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) or the European Group for Blood and Marrow Transplant (EGBMT).
Disclosures: The authors reported no conflicts of interest.