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EMA recommends authorization of T-cell product
Image courtesy of NIAID
The European Medicines Agency (EMA) has recommended granting conditional marketing authorization for a T-cell product known as Zalmoxis.
Zalmoxis is intended for use as an adjunctive therapy to aid immune reconstitution and help treat graft-versus-host disease (GVHD) in adults receiving a haploidentical hematopoietic stem cell transplant to treat hematologic malignancy.
Zalmoxis consists of allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2).
This modification makes the T cells susceptible to treatment with the drug ganciclovir. So if a patient develops GVHD, he can be treated with ganciclovir, which should kill the modified T cells and prevent further development of the disease.
Zalmoxis is being developed by MolMed S.p.A.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended conditional approval for Zalmoxis. Conditional approval is one of the agency’s main mechanisms to facilitate earlier access to medicines that fulfill unmet medical needs.
Conditional approval allows the EMA to recommend a medicine for marketing authorization before the availability of confirmatory clinical trial data, if the benefits of making this medicine available to patients immediately outweigh the risks inherent in the lack of comprehensive data.
Zalmoxis was also assessed by the Committee on Advanced Therapies (CAT), the EMA’s specialized scientific committee for advanced therapy medicinal products, such as gene or cell therapies.
At its June 2016 meeting, the CAT recommended a conditional marketing authorization for Zalmoxis. The CHMP then considered the CAT’s recommendation and agreed with it.
The recommendation has been sent to the European Commission, which will adopt a decision on marketing authorization that will apply to the European Economic Area.
If Zalmoxis is granted conditional marketing authorization, MolMed S.p.A. must provide the EMA with results from an ongoing phase 3 trial (TK008; NCT00914628).
Until the complete data from this trial are available, the CAT and the CHMP will review the benefits and risks of Zalmoxis annually to determine whether the conditional marketing authorization can be maintained.
Zalmoxis was designated as an orphan medicinal product in 2003. Orphan designation gives drug developers access to incentives such as fee reductions for scientific advice and the opportunity to obtain 10 years of market exclusivity for an authorized orphan-designated medicine. 
Image courtesy of NIAID
The European Medicines Agency (EMA) has recommended granting conditional marketing authorization for a T-cell product known as Zalmoxis.
Zalmoxis is intended for use as an adjunctive therapy to aid immune reconstitution and help treat graft-versus-host disease (GVHD) in adults receiving a haploidentical hematopoietic stem cell transplant to treat hematologic malignancy.
Zalmoxis consists of allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2).
This modification makes the T cells susceptible to treatment with the drug ganciclovir. So if a patient develops GVHD, he can be treated with ganciclovir, which should kill the modified T cells and prevent further development of the disease.
Zalmoxis is being developed by MolMed S.p.A.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended conditional approval for Zalmoxis. Conditional approval is one of the agency’s main mechanisms to facilitate earlier access to medicines that fulfill unmet medical needs.
Conditional approval allows the EMA to recommend a medicine for marketing authorization before the availability of confirmatory clinical trial data, if the benefits of making this medicine available to patients immediately outweigh the risks inherent in the lack of comprehensive data.
Zalmoxis was also assessed by the Committee on Advanced Therapies (CAT), the EMA’s specialized scientific committee for advanced therapy medicinal products, such as gene or cell therapies.
At its June 2016 meeting, the CAT recommended a conditional marketing authorization for Zalmoxis. The CHMP then considered the CAT’s recommendation and agreed with it.
The recommendation has been sent to the European Commission, which will adopt a decision on marketing authorization that will apply to the European Economic Area.
If Zalmoxis is granted conditional marketing authorization, MolMed S.p.A. must provide the EMA with results from an ongoing phase 3 trial (TK008; NCT00914628).
Until the complete data from this trial are available, the CAT and the CHMP will review the benefits and risks of Zalmoxis annually to determine whether the conditional marketing authorization can be maintained.
Zalmoxis was designated as an orphan medicinal product in 2003. Orphan designation gives drug developers access to incentives such as fee reductions for scientific advice and the opportunity to obtain 10 years of market exclusivity for an authorized orphan-designated medicine.
Image courtesy of NIAID
The European Medicines Agency (EMA) has recommended granting conditional marketing authorization for a T-cell product known as Zalmoxis.
Zalmoxis is intended for use as an adjunctive therapy to aid immune reconstitution and help treat graft-versus-host disease (GVHD) in adults receiving a haploidentical hematopoietic stem cell transplant to treat hematologic malignancy.
Zalmoxis consists of allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2).
This modification makes the T cells susceptible to treatment with the drug ganciclovir. So if a patient develops GVHD, he can be treated with ganciclovir, which should kill the modified T cells and prevent further development of the disease.
Zalmoxis is being developed by MolMed S.p.A.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended conditional approval for Zalmoxis. Conditional approval is one of the agency’s main mechanisms to facilitate earlier access to medicines that fulfill unmet medical needs.
Conditional approval allows the EMA to recommend a medicine for marketing authorization before the availability of confirmatory clinical trial data, if the benefits of making this medicine available to patients immediately outweigh the risks inherent in the lack of comprehensive data.
Zalmoxis was also assessed by the Committee on Advanced Therapies (CAT), the EMA’s specialized scientific committee for advanced therapy medicinal products, such as gene or cell therapies.
At its June 2016 meeting, the CAT recommended a conditional marketing authorization for Zalmoxis. The CHMP then considered the CAT’s recommendation and agreed with it.
The recommendation has been sent to the European Commission, which will adopt a decision on marketing authorization that will apply to the European Economic Area.
If Zalmoxis is granted conditional marketing authorization, MolMed S.p.A. must provide the EMA with results from an ongoing phase 3 trial (TK008; NCT00914628).
Until the complete data from this trial are available, the CAT and the CHMP will review the benefits and risks of Zalmoxis annually to determine whether the conditional marketing authorization can be maintained.
Zalmoxis was designated as an orphan medicinal product in 2003. Orphan designation gives drug developers access to incentives such as fee reductions for scientific advice and the opportunity to obtain 10 years of market exclusivity for an authorized orphan-designated medicine.
CHMP rejects ofatumumab as maintenance
Photo courtesy of GSK
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended against expanding the approved indication for ofatumumab (Arzerra).
Novartis, which is developing ofatumumab in cooperation with Genmab, had submitted an application requesting that ofatumumab be authorized as maintenance therapy for patients with relapsed chronic lymphocytic leukemia (CLL).
But the CHMP has advised the European Commission (EC) not to grant this authorization.
The CHMP noted that, in the phase 3 PROLONG trial, ofatumumab maintenance improved progression-free survival (PFS) in CLL patients.
However, the committee said the importance of this improvement is not clear because the PFS results were not supported by other measures, such as overall survival or a significant improvement in patients’ quality of life.
The CHMP also said the use of ofatumumab for maintenance treatment should be seen in the context of its side effects. Common side effects of ofatumumab in the PROLONG trial were infusion reactions, neutropenia, and upper respiratory tract infections.
In the end, the CHMP decided that the PROLONG data were not sufficient to conclude that maintenance treatment with ofatumumab is of more benefit than no treatment. So the committee recommended against expanding the drug’s marketing authorization.
This decision does not have any impact on ongoing clinical trials with ofatumumab.
About ofatumumab
Ofatumumab has been authorized for use in the European Union since April 2010.
The EC first granted ofatumumab conditional approval to treat CLL patients who are refractory to fludarabine and alemtuzumab.
Then, in 2014, the EC granted ofatumumab conditional approval for use in combination with chlorambucil or bendamustine in CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy.
Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses in the aforementioned indications. Ofatumumab will not receive full approval until the drug’s developers submit results of additional research to the EC.
About the PROLONG trial
The PROLONG trial was designed to compare ofatumumab maintenance to no further treatment in patients with a complete or partial response after second- or third-line treatment for CLL. Interim results of the study were presented at ASH 2014.
These results—in 474 patients—suggested that ofatumumab can significantly improve PFS. The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance therapy (P<0.0001).
There was no significant difference in the median overall survival, which was not reached in either treatment arm.
The researchers said there were no unexpected safety findings. The most common adverse events (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection.
Photo courtesy of GSK
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended against expanding the approved indication for ofatumumab (Arzerra).
Novartis, which is developing ofatumumab in cooperation with Genmab, had submitted an application requesting that ofatumumab be authorized as maintenance therapy for patients with relapsed chronic lymphocytic leukemia (CLL).
But the CHMP has advised the European Commission (EC) not to grant this authorization.
The CHMP noted that, in the phase 3 PROLONG trial, ofatumumab maintenance improved progression-free survival (PFS) in CLL patients.
However, the committee said the importance of this improvement is not clear because the PFS results were not supported by other measures, such as overall survival or a significant improvement in patients’ quality of life.
The CHMP also said the use of ofatumumab for maintenance treatment should be seen in the context of its side effects. Common side effects of ofatumumab in the PROLONG trial were infusion reactions, neutropenia, and upper respiratory tract infections.
In the end, the CHMP decided that the PROLONG data were not sufficient to conclude that maintenance treatment with ofatumumab is of more benefit than no treatment. So the committee recommended against expanding the drug’s marketing authorization.
This decision does not have any impact on ongoing clinical trials with ofatumumab.
About ofatumumab
Ofatumumab has been authorized for use in the European Union since April 2010.
The EC first granted ofatumumab conditional approval to treat CLL patients who are refractory to fludarabine and alemtuzumab.
Then, in 2014, the EC granted ofatumumab conditional approval for use in combination with chlorambucil or bendamustine in CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy.
Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses in the aforementioned indications. Ofatumumab will not receive full approval until the drug’s developers submit results of additional research to the EC.
About the PROLONG trial
The PROLONG trial was designed to compare ofatumumab maintenance to no further treatment in patients with a complete or partial response after second- or third-line treatment for CLL. Interim results of the study were presented at ASH 2014.
These results—in 474 patients—suggested that ofatumumab can significantly improve PFS. The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance therapy (P<0.0001).
There was no significant difference in the median overall survival, which was not reached in either treatment arm.
The researchers said there were no unexpected safety findings. The most common adverse events (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection.
Photo courtesy of GSK
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended against expanding the approved indication for ofatumumab (Arzerra).
Novartis, which is developing ofatumumab in cooperation with Genmab, had submitted an application requesting that ofatumumab be authorized as maintenance therapy for patients with relapsed chronic lymphocytic leukemia (CLL).
But the CHMP has advised the European Commission (EC) not to grant this authorization.
The CHMP noted that, in the phase 3 PROLONG trial, ofatumumab maintenance improved progression-free survival (PFS) in CLL patients.
However, the committee said the importance of this improvement is not clear because the PFS results were not supported by other measures, such as overall survival or a significant improvement in patients’ quality of life.
The CHMP also said the use of ofatumumab for maintenance treatment should be seen in the context of its side effects. Common side effects of ofatumumab in the PROLONG trial were infusion reactions, neutropenia, and upper respiratory tract infections.
In the end, the CHMP decided that the PROLONG data were not sufficient to conclude that maintenance treatment with ofatumumab is of more benefit than no treatment. So the committee recommended against expanding the drug’s marketing authorization.
This decision does not have any impact on ongoing clinical trials with ofatumumab.
About ofatumumab
Ofatumumab has been authorized for use in the European Union since April 2010.
The EC first granted ofatumumab conditional approval to treat CLL patients who are refractory to fludarabine and alemtuzumab.
Then, in 2014, the EC granted ofatumumab conditional approval for use in combination with chlorambucil or bendamustine in CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy.
Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses in the aforementioned indications. Ofatumumab will not receive full approval until the drug’s developers submit results of additional research to the EC.
About the PROLONG trial
The PROLONG trial was designed to compare ofatumumab maintenance to no further treatment in patients with a complete or partial response after second- or third-line treatment for CLL. Interim results of the study were presented at ASH 2014.
These results—in 474 patients—suggested that ofatumumab can significantly improve PFS. The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance therapy (P<0.0001).
There was no significant difference in the median overall survival, which was not reached in either treatment arm.
The researchers said there were no unexpected safety findings. The most common adverse events (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection.
HCPs may underestimate cancer risk from CT scans
Photo by Angela Mary Butler
Healthcare professionals (HCPs) may not be fully aware of a CT scan’s effect on lifetime malignancy risk, according to a study published in the Journal of Medical Imaging and Radiation Sciences.
Researchers surveyed a group of HCPs on radiation exposure from CT.
And although most of the respondents recognized that CT scans confer an increased risk of cancer, many underestimated the actual dose of radiation a person receives from a CT scan.
The survey was given to 308 HCPs—including physicians, radiologists, and technologists—in Saskatchewan, Canada.
Seventy-three percent of physicians, 97% of radiologists, and 76% of technologists correctly reported that there is an increased cancer risk from one abdominal-pelvic CT.
However, only 18% of physicians, 28% of radiologists, and 22% of technologists were able to correctly identify the dose in relation to chest X-rays.
In fact, 14% of physicians and 12% of technologists (but 0% of radiologists) “vastly” underestimated the dose as less than 10 chest X-ray equivalents, according to researchers.
The average radiation dose from an abdominal-pelvic CT is 10 millisieverts (mSv), compared to 0.02 mSv to 0.2 mSv from one chest X-ray, meaning that a radiation dose from a CT scan is equivalent to the dose from 100 to 250 chest radiographs.
“Underestimating radiation dose from a CT scan is more concerning than knowing the exact dose level, particularly when it is a vast underestimation, as this may lead to minimization of the risk estimate when considering a test,” said study author David Leswick, MD, of the University of Saskatchewan in Saskatoon.
“Although [cancer] risk from radiation dose levels in the range of medical imaging procedures is small, it is real, as evidenced from atomic bomb survivors and nuclear industry workers showing significantly increased risk of malignancy after exposure to doses in the range of diagnostic CT.”
“The risk of fatal malignancy may be as high as 1 in 1000 for a 10-mSv exposure. This risk is significant on a population basis, with up to 2% of cancers in the United States population possibly attributable to CT.”
Another aspect highlighted by the survey was some confusion regarding radiation exposure from MRIs and ultrasounds.
MRIs and ultrasounds do not employ ionizing radiation. However, 20% of physicians, 6% of radiologists, and 7% of technologists attributed radiation exposure to MRIs. Eleven percent of physicians, 0% of radiologists, and 7% of technologists believed an ultrasound used radiation.
“Belief that ionizing radiation is utilized by ultrasound and MRI is troubling, as it may result in underutilization of these imaging modalities because of unfounded radiation concerns,” Dr Leswick said.
“It is important for healthcare professionals (including referring physicians, radiologists, and technologists) to be aware of radiation dose levels and risks from imaging tests for several reasons, including the ability to weigh the risks and benefits of tests, counsel patients on relevant risks, optimize protocols to minimize radiation dose, and select appropriate protocols to minimize radiation dose.”
Photo by Angela Mary Butler
Healthcare professionals (HCPs) may not be fully aware of a CT scan’s effect on lifetime malignancy risk, according to a study published in the Journal of Medical Imaging and Radiation Sciences.
Researchers surveyed a group of HCPs on radiation exposure from CT.
And although most of the respondents recognized that CT scans confer an increased risk of cancer, many underestimated the actual dose of radiation a person receives from a CT scan.
The survey was given to 308 HCPs—including physicians, radiologists, and technologists—in Saskatchewan, Canada.
Seventy-three percent of physicians, 97% of radiologists, and 76% of technologists correctly reported that there is an increased cancer risk from one abdominal-pelvic CT.
However, only 18% of physicians, 28% of radiologists, and 22% of technologists were able to correctly identify the dose in relation to chest X-rays.
In fact, 14% of physicians and 12% of technologists (but 0% of radiologists) “vastly” underestimated the dose as less than 10 chest X-ray equivalents, according to researchers.
The average radiation dose from an abdominal-pelvic CT is 10 millisieverts (mSv), compared to 0.02 mSv to 0.2 mSv from one chest X-ray, meaning that a radiation dose from a CT scan is equivalent to the dose from 100 to 250 chest radiographs.
“Underestimating radiation dose from a CT scan is more concerning than knowing the exact dose level, particularly when it is a vast underestimation, as this may lead to minimization of the risk estimate when considering a test,” said study author David Leswick, MD, of the University of Saskatchewan in Saskatoon.
“Although [cancer] risk from radiation dose levels in the range of medical imaging procedures is small, it is real, as evidenced from atomic bomb survivors and nuclear industry workers showing significantly increased risk of malignancy after exposure to doses in the range of diagnostic CT.”
“The risk of fatal malignancy may be as high as 1 in 1000 for a 10-mSv exposure. This risk is significant on a population basis, with up to 2% of cancers in the United States population possibly attributable to CT.”
Another aspect highlighted by the survey was some confusion regarding radiation exposure from MRIs and ultrasounds.
MRIs and ultrasounds do not employ ionizing radiation. However, 20% of physicians, 6% of radiologists, and 7% of technologists attributed radiation exposure to MRIs. Eleven percent of physicians, 0% of radiologists, and 7% of technologists believed an ultrasound used radiation.
“Belief that ionizing radiation is utilized by ultrasound and MRI is troubling, as it may result in underutilization of these imaging modalities because of unfounded radiation concerns,” Dr Leswick said.
“It is important for healthcare professionals (including referring physicians, radiologists, and technologists) to be aware of radiation dose levels and risks from imaging tests for several reasons, including the ability to weigh the risks and benefits of tests, counsel patients on relevant risks, optimize protocols to minimize radiation dose, and select appropriate protocols to minimize radiation dose.”
Photo by Angela Mary Butler
Healthcare professionals (HCPs) may not be fully aware of a CT scan’s effect on lifetime malignancy risk, according to a study published in the Journal of Medical Imaging and Radiation Sciences.
Researchers surveyed a group of HCPs on radiation exposure from CT.
And although most of the respondents recognized that CT scans confer an increased risk of cancer, many underestimated the actual dose of radiation a person receives from a CT scan.
The survey was given to 308 HCPs—including physicians, radiologists, and technologists—in Saskatchewan, Canada.
Seventy-three percent of physicians, 97% of radiologists, and 76% of technologists correctly reported that there is an increased cancer risk from one abdominal-pelvic CT.
However, only 18% of physicians, 28% of radiologists, and 22% of technologists were able to correctly identify the dose in relation to chest X-rays.
In fact, 14% of physicians and 12% of technologists (but 0% of radiologists) “vastly” underestimated the dose as less than 10 chest X-ray equivalents, according to researchers.
The average radiation dose from an abdominal-pelvic CT is 10 millisieverts (mSv), compared to 0.02 mSv to 0.2 mSv from one chest X-ray, meaning that a radiation dose from a CT scan is equivalent to the dose from 100 to 250 chest radiographs.
“Underestimating radiation dose from a CT scan is more concerning than knowing the exact dose level, particularly when it is a vast underestimation, as this may lead to minimization of the risk estimate when considering a test,” said study author David Leswick, MD, of the University of Saskatchewan in Saskatoon.
“Although [cancer] risk from radiation dose levels in the range of medical imaging procedures is small, it is real, as evidenced from atomic bomb survivors and nuclear industry workers showing significantly increased risk of malignancy after exposure to doses in the range of diagnostic CT.”
“The risk of fatal malignancy may be as high as 1 in 1000 for a 10-mSv exposure. This risk is significant on a population basis, with up to 2% of cancers in the United States population possibly attributable to CT.”
Another aspect highlighted by the survey was some confusion regarding radiation exposure from MRIs and ultrasounds.
MRIs and ultrasounds do not employ ionizing radiation. However, 20% of physicians, 6% of radiologists, and 7% of technologists attributed radiation exposure to MRIs. Eleven percent of physicians, 0% of radiologists, and 7% of technologists believed an ultrasound used radiation.
“Belief that ionizing radiation is utilized by ultrasound and MRI is troubling, as it may result in underutilization of these imaging modalities because of unfounded radiation concerns,” Dr Leswick said.
“It is important for healthcare professionals (including referring physicians, radiologists, and technologists) to be aware of radiation dose levels and risks from imaging tests for several reasons, including the ability to weigh the risks and benefits of tests, counsel patients on relevant risks, optimize protocols to minimize radiation dose, and select appropriate protocols to minimize radiation dose.”
Drug enables transfusion independence in lower-risk MDS
COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).
In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.
In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.
The majority of adverse events in both trials were grade 1 and 2.
Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.
Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.
The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.
In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.
Base study
This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).
In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).
Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).
The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.
In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.
Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.
Extension study
This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.
In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).
In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.
At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).
Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.
Safety
There were three grade 3 adverse events that were possibly or probably related to luspatercept—an increase in blast cell count, myalgia, and worsening of general condition.
Adverse events that were possibly or probably related to luspatercept and occurred in at least 2 patients were fatigue (7%, n=4), bone pain (5%, n=3), diarrhea (5%, n=3), myalgia (5%, n=3), headache (3%, n=2), hypertension (3%, n=2), and injection site erythema (3%, n=2).
Dr Platzbecker said luspatercept was generally safe and well-tolerated in these studies. And the results of these trials supported the initiation of a phase 3 study (MEDALIST, NCT02631070) in patients with lower-risk MDS.
*Data in the abstract differ from data presented at the meeting.
COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).
In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.
In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.
The majority of adverse events in both trials were grade 1 and 2.
Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.
Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.
The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.
In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.
Base study
This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).
In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).
Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).
The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.
In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.
Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.
Extension study
This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.
In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).
In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.
At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).
Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.
Safety
There were three grade 3 adverse events that were possibly or probably related to luspatercept—an increase in blast cell count, myalgia, and worsening of general condition.
Adverse events that were possibly or probably related to luspatercept and occurred in at least 2 patients were fatigue (7%, n=4), bone pain (5%, n=3), diarrhea (5%, n=3), myalgia (5%, n=3), headache (3%, n=2), hypertension (3%, n=2), and injection site erythema (3%, n=2).
Dr Platzbecker said luspatercept was generally safe and well-tolerated in these studies. And the results of these trials supported the initiation of a phase 3 study (MEDALIST, NCT02631070) in patients with lower-risk MDS.
*Data in the abstract differ from data presented at the meeting.
COPENHAGEN—Results from a pair of phase 2 trials suggest luspatercept can produce erythroid responses and enable transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS).
In a 3-month base study, 51% of patients treated with luspatercept had an erythroid response, and 35% achieved transfusion independence.
In an ongoing extension study, 81% of luspatercept-treated patients have had an erythroid response, and 50% have achieved transfusion independence.
The majority of adverse events in both trials were grade 1 and 2.
Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented these results at the 21st Congress of the European Hematology Association (abstract S131*). The studies were sponsored by Acceleron Pharma, Inc.
Luspatercept (formerly ACE-536) is a modified activin receptor type IIB fusion protein that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron and Celgene are developing luspatercept to treat anemia in patients with rare blood disorders.
The phase 2 base study was a dose-escalation trial in which MDS patients received luspatercept for 3 months. In the ongoing extension study, patients from the base study are receiving luspatercept for an additional 24 months.
In both studies, patients with high transfusion burden (≥4 RBC units/8 weeks) and those with low transfusion burden (<4 RBC units/8 weeks) received luspatercept once every 3 weeks.
Base study
This study included 58 patients with a median age of 71.5 (range, 27-90). Their median time since diagnosis was 2.4 years (range, 0-14). Seventeen percent of patients had prior lenalidomide treatment, and 66% had previously received erythropoiesis-stimulating agents (ESAs).
In patients with low transfusion burden (n=19), the median hemoglobin at baseline was 8.7 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=39), the median number of RBC units transfused per 8 weeks was 6 (range, 4-18).
Patients received luspatercept subcutaneously every 3 weeks for up to 5 doses. The study included 7 dose-escalation cohorts (n=27, 0.125 to 1.75 mg/kg) and an expansion cohort (n=31, 1.0 to 1.75 mg/kg).
The primary outcome measure was the proportion of patients who had an erythroid response. In non-transfusion-dependent patients, an erythroid response was defined as a hemoglobin increase of at least 1.5 g/dL from baseline for at least 14 days.
In transfusion-dependent patients, an erythroid response was defined as a reduction of at least 4 RBC units transfused or a reduction of at least 50% of RBC units transfused compared to pretreatment.
Fifty-one percent (25/49) of patients treated at the higher dose levels had an erythroid response. And 35% (14/40) of transfused patients treated at the higher dose levels were transfusion independent for at least 8 weeks.
Extension study
This study includes 32 patients with a median age of 71.5 (range, 29-90). Their median time since diagnosis was 2.9 years (range, 0-14). Nineteen percent of patients had prior lenalidomide treatment, and 59% had previously received ESAs.
In patients with low transfusion burden (n=13), the median hemoglobin at baseline was 8.5 g/dL (range, 6.4-10.1). In patients with high transfusion burden (n=19), the median number of RBC units transfused per 8 weeks was 6 (range, 4-14).
In this ongoing study, patients are receiving luspatercept (1.0 to 1.75 mg/kg) subcutaneously every 3 weeks for an additional 24 months.
At last follow-up (March 4, 2016), 81% (26/32) of patients had an erythroid response. And 50% (11/22) of patients who were transfused prior to study initiation achieved transfusion independence for at least 8 weeks (range, 9-80+ weeks).
Dr Platzbecker noted that, in both studies, erythroid responses were observed whether or not patients previously received ESAs and regardless of patients’ baseline erythropoietin levels.
Safety
There were three grade 3 adverse events that were possibly or probably related to luspatercept—an increase in blast cell count, myalgia, and worsening of general condition.
Adverse events that were possibly or probably related to luspatercept and occurred in at least 2 patients were fatigue (7%, n=4), bone pain (5%, n=3), diarrhea (5%, n=3), myalgia (5%, n=3), headache (3%, n=2), hypertension (3%, n=2), and injection site erythema (3%, n=2).
Dr Platzbecker said luspatercept was generally safe and well-tolerated in these studies. And the results of these trials supported the initiation of a phase 3 study (MEDALIST, NCT02631070) in patients with lower-risk MDS.
*Data in the abstract differ from data presented at the meeting.
Team describes method of targeting LSCs in BC-CML
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UC San Diego Health
New research has revealed a method of targeting leukemia stem cells (LSCs) in blast crisis chronic myeloid leukemia (BC-CML).
For this study, investigators used human cells and mouse models to define the role of ADAR1, an RNA editing enzyme, in BC-CML.
The team discovered how ADAR1 promotes LSC generation and identified a small molecule that can disrupt this process to fight BC-CML.
Catriona Jamieson, MD, PhD, of the University of California, San Diego, and her colleagues described this work in Cell Stem Cell.
“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves,” Dr Jamieson said. “What’s more, we found a method to dial it down.”
The investigators knew that ADAR1 can edit the sequence of microRNAs. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.
ADAR1 is also known to promote cancer progression and resistance to therapy. But Dr Jamieson’s team wanted to determine ADAR1’s role in governing LSCs.
The investigators conducted experiments with human BC-CML cells and mouse models of BC-CML. And they found that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1 in BC-CML cells. Then, hyper-ADAR1 editing slows down microRNAs known as let-7.
Ultimately, this activity increases cellular regeneration, turning white blood cell precursors into LSCs. And LSCs promote BC-CML.
After learning how the ADAR1 system works, Dr Jamieson and her colleagues looked for a way to stop it.
By inhibiting ADAR1 with a small-molecule compound known as 8-Aza, the investigators were able to counter ADAR1’s effect on LSC self-renewal and restore let-7.
Treatment with 8-Aza reduced self-renewal of BC-CML cells by approximately 40%, when compared to untreated cells.
“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression,” Dr Jamieson said.
“In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”
Photo courtesy of
UC San Diego Health
New research has revealed a method of targeting leukemia stem cells (LSCs) in blast crisis chronic myeloid leukemia (BC-CML).
For this study, investigators used human cells and mouse models to define the role of ADAR1, an RNA editing enzyme, in BC-CML.
The team discovered how ADAR1 promotes LSC generation and identified a small molecule that can disrupt this process to fight BC-CML.
Catriona Jamieson, MD, PhD, of the University of California, San Diego, and her colleagues described this work in Cell Stem Cell.
“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves,” Dr Jamieson said. “What’s more, we found a method to dial it down.”
The investigators knew that ADAR1 can edit the sequence of microRNAs. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.
ADAR1 is also known to promote cancer progression and resistance to therapy. But Dr Jamieson’s team wanted to determine ADAR1’s role in governing LSCs.
The investigators conducted experiments with human BC-CML cells and mouse models of BC-CML. And they found that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1 in BC-CML cells. Then, hyper-ADAR1 editing slows down microRNAs known as let-7.
Ultimately, this activity increases cellular regeneration, turning white blood cell precursors into LSCs. And LSCs promote BC-CML.
After learning how the ADAR1 system works, Dr Jamieson and her colleagues looked for a way to stop it.
By inhibiting ADAR1 with a small-molecule compound known as 8-Aza, the investigators were able to counter ADAR1’s effect on LSC self-renewal and restore let-7.
Treatment with 8-Aza reduced self-renewal of BC-CML cells by approximately 40%, when compared to untreated cells.
“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression,” Dr Jamieson said.
“In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”
Photo courtesy of
UC San Diego Health
New research has revealed a method of targeting leukemia stem cells (LSCs) in blast crisis chronic myeloid leukemia (BC-CML).
For this study, investigators used human cells and mouse models to define the role of ADAR1, an RNA editing enzyme, in BC-CML.
The team discovered how ADAR1 promotes LSC generation and identified a small molecule that can disrupt this process to fight BC-CML.
Catriona Jamieson, MD, PhD, of the University of California, San Diego, and her colleagues described this work in Cell Stem Cell.
“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves,” Dr Jamieson said. “What’s more, we found a method to dial it down.”
The investigators knew that ADAR1 can edit the sequence of microRNAs. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.
ADAR1 is also known to promote cancer progression and resistance to therapy. But Dr Jamieson’s team wanted to determine ADAR1’s role in governing LSCs.
The investigators conducted experiments with human BC-CML cells and mouse models of BC-CML. And they found that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1 in BC-CML cells. Then, hyper-ADAR1 editing slows down microRNAs known as let-7.
Ultimately, this activity increases cellular regeneration, turning white blood cell precursors into LSCs. And LSCs promote BC-CML.
After learning how the ADAR1 system works, Dr Jamieson and her colleagues looked for a way to stop it.
By inhibiting ADAR1 with a small-molecule compound known as 8-Aza, the investigators were able to counter ADAR1’s effect on LSC self-renewal and restore let-7.
Treatment with 8-Aza reduced self-renewal of BC-CML cells by approximately 40%, when compared to untreated cells.
“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression,” Dr Jamieson said.
“In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”
FDA grants drug breakthrough designation to treat GVHD
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The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for ruxolitinib (Jakafi) for the treatment of patients with acute graft-versus-host disease (GVHD).
Ruxolitinib is a JAK1/2 inhibitor that is already FDA-approved to treat patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
The drug is also approved to treat patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.
Ruxolitinib is marketed as Jakafi by Incyte in the US and as Jakavi by Novartis outside the US.
“Receiving breakthrough therapy designation from the FDA recognizes the severe nature of acute GVHD, the clear unmet medical need of these patients, and the potential, based on clinical evidence to date, for ruxolitinib to address the urgent needs of patients with this life-threatening disease,” said Steven Stein, MD, Incyte’s chief medical officer.
The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
Photo from Business Wire
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for ruxolitinib (Jakafi) for the treatment of patients with acute graft-versus-host disease (GVHD).
Ruxolitinib is a JAK1/2 inhibitor that is already FDA-approved to treat patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
The drug is also approved to treat patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.
Ruxolitinib is marketed as Jakafi by Incyte in the US and as Jakavi by Novartis outside the US.
“Receiving breakthrough therapy designation from the FDA recognizes the severe nature of acute GVHD, the clear unmet medical need of these patients, and the potential, based on clinical evidence to date, for ruxolitinib to address the urgent needs of patients with this life-threatening disease,” said Steven Stein, MD, Incyte’s chief medical officer.
The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
Photo from Business Wire
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for ruxolitinib (Jakafi) for the treatment of patients with acute graft-versus-host disease (GVHD).
Ruxolitinib is a JAK1/2 inhibitor that is already FDA-approved to treat patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
The drug is also approved to treat patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.
Ruxolitinib is marketed as Jakafi by Incyte in the US and as Jakavi by Novartis outside the US.
“Receiving breakthrough therapy designation from the FDA recognizes the severe nature of acute GVHD, the clear unmet medical need of these patients, and the potential, based on clinical evidence to date, for ruxolitinib to address the urgent needs of patients with this life-threatening disease,” said Steven Stein, MD, Incyte’s chief medical officer.
The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
Company recalls blood collection system
Photo by Charles Haymond
Haemonetics Corporation is recalling all lots of the Leukotrap RC System with RC2D Filter (re-order numbers 129-62 and 129-63) distributed since April 14, 2016.
The company says using these lots of the blood collection system may result in a higher-than-expected level of leukocytes in transfused blood.
Earlier this month, Haemonetics recalled 3 lots of the Leukotrap RC System with RC2D Filter due to reports of higher-than-expected residual white blood cells.
Since then, the company has received additional reports related to other lots.
Blood products that have been processed with the lots distributed since April 14, 2016, should not be re-filtered and should be labeled as non-leukoreduced, unless individual units have been tested and found suitable to be labeled as leukoreduced.
Continued use of these lots will require customers to verify that each unit labeled as leukoreduced was tested and meets standards for residual white blood cells acceptable to the US Food and Drug Administration.
Customers who want to return unused product to Haemonetics should contact their local customer service representative.
Photo by Charles Haymond
Haemonetics Corporation is recalling all lots of the Leukotrap RC System with RC2D Filter (re-order numbers 129-62 and 129-63) distributed since April 14, 2016.
The company says using these lots of the blood collection system may result in a higher-than-expected level of leukocytes in transfused blood.
Earlier this month, Haemonetics recalled 3 lots of the Leukotrap RC System with RC2D Filter due to reports of higher-than-expected residual white blood cells.
Since then, the company has received additional reports related to other lots.
Blood products that have been processed with the lots distributed since April 14, 2016, should not be re-filtered and should be labeled as non-leukoreduced, unless individual units have been tested and found suitable to be labeled as leukoreduced.
Continued use of these lots will require customers to verify that each unit labeled as leukoreduced was tested and meets standards for residual white blood cells acceptable to the US Food and Drug Administration.
Customers who want to return unused product to Haemonetics should contact their local customer service representative.
Photo by Charles Haymond
Haemonetics Corporation is recalling all lots of the Leukotrap RC System with RC2D Filter (re-order numbers 129-62 and 129-63) distributed since April 14, 2016.
The company says using these lots of the blood collection system may result in a higher-than-expected level of leukocytes in transfused blood.
Earlier this month, Haemonetics recalled 3 lots of the Leukotrap RC System with RC2D Filter due to reports of higher-than-expected residual white blood cells.
Since then, the company has received additional reports related to other lots.
Blood products that have been processed with the lots distributed since April 14, 2016, should not be re-filtered and should be labeled as non-leukoreduced, unless individual units have been tested and found suitable to be labeled as leukoreduced.
Continued use of these lots will require customers to verify that each unit labeled as leukoreduced was tested and meets standards for residual white blood cells acceptable to the US Food and Drug Administration.
Customers who want to return unused product to Haemonetics should contact their local customer service representative.
Interim PET-CT can spare HL patients intensive chemo
The use of interim PET-CT scans can spare some advanced Hodgkin lymphoma (HL) patients the toxicity associated with bleomycin, according to researchers.
The team found that patients with negative PET-CT scans after 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) could go on to receive AVD (doxorubicin, vinblastine, and dacarbazine) without experiencing a significant decrease in progression-free survival (PFS) or overall survival (OS).
Peter Johnson, MD, of the University of Southampton in the UK, and his colleagues reported these findings in NEJM.
“The good news is that the majority of people diagnosed with Hodgkin lymphoma can be cured,” Dr Johnson said. “In this trial, more than 95% of patients are alive after 3 years.”
“But we worry about the long-term side effects from the treatments we use. As we’ve done in this trial, personalizing treatment based on how well it works is a major development for patients with Hodgkin lymphoma and sets a new standard of care.”
Patients and treatment
For this study, Dr Johnson and his colleagues enrolled 1214 patients with newly diagnosed, advanced, classic HL. The patients’ median age was 33 (range, 18 to 79), and 54.5% were male. More patients had stage II disease (41.6%) than stage III (30.2%) or IV (28.3%).
A total of 1119 patients underwent a baseline PET-CT scan, received 2 cycles of ABVD, and underwent an interim PET-CT scan.
The patients with negative interim scans were then randomized to continue treatment with ABVD (n=470) or with AVD (n=465) in cycles 3 through 6.
Patients with positive interim scans (n=182) went on to receive BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, n=172), salvage treatments (n=6), or ABVD (n=4).
Results
The study’s primary outcome was the difference in 3-year PFS between the randomized groups of PET-CT-negative patients.
With a median follow-up of 41 months, the 3-year PFS was 85.7% in the ABVD group and 84.4% in the AVD group. The hazard ratio was 1.13 (95% CI, 0.81 to 1.57; P=0.48) in the intention-to-treat analysis and 1.10 (95% CI, 0.79 to 1.53; P=0.58) in the per-protocol analysis.
The absolute difference in 3-year PFS (ABVD minus AVD) was 1.6 percentage points (95% CI, −3.2 to 5.3).
The OS rates were 97.2% in the ABVD group and 97.6% in the AVD group. The hazard ratio in the intention-to-treat analysis was 0.90 (95% CI, 0.47 to 1.74; P=0.76).
Patients in the ABVD group had a significantly higher rate of clinical adverse events than patients in the AVD group—31% and 21%, respectively (P<0.005).
Patients in the ABVD group also had significantly (P<0.05) higher rates of fatigue (3% vs 1%), febrile neutropenia (5% vs 2%), pulmonary/upper respiratory events (3% vs 1%), and dyspnea (2% vs <0.5%). But patients in the AVD group had a significantly higher rate of thrombocytopenia (3% vs 1%).
For patients who had positive interim PET-CT scans, the 3-year PFS was 67.5%, and the OS was 87.8%. Among the 172 patients who went on to receive BEACOPP, 74.4% had negative findings on a third PET-CT scan.
Overall, 62 patients died during the trial—24 from HL. So, for the entire study cohort, the 3-year PFS was 82.6%, and the OS was 95.8%.
The use of interim PET-CT scans can spare some advanced Hodgkin lymphoma (HL) patients the toxicity associated with bleomycin, according to researchers.
The team found that patients with negative PET-CT scans after 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) could go on to receive AVD (doxorubicin, vinblastine, and dacarbazine) without experiencing a significant decrease in progression-free survival (PFS) or overall survival (OS).
Peter Johnson, MD, of the University of Southampton in the UK, and his colleagues reported these findings in NEJM.
“The good news is that the majority of people diagnosed with Hodgkin lymphoma can be cured,” Dr Johnson said. “In this trial, more than 95% of patients are alive after 3 years.”
“But we worry about the long-term side effects from the treatments we use. As we’ve done in this trial, personalizing treatment based on how well it works is a major development for patients with Hodgkin lymphoma and sets a new standard of care.”
Patients and treatment
For this study, Dr Johnson and his colleagues enrolled 1214 patients with newly diagnosed, advanced, classic HL. The patients’ median age was 33 (range, 18 to 79), and 54.5% were male. More patients had stage II disease (41.6%) than stage III (30.2%) or IV (28.3%).
A total of 1119 patients underwent a baseline PET-CT scan, received 2 cycles of ABVD, and underwent an interim PET-CT scan.
The patients with negative interim scans were then randomized to continue treatment with ABVD (n=470) or with AVD (n=465) in cycles 3 through 6.
Patients with positive interim scans (n=182) went on to receive BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, n=172), salvage treatments (n=6), or ABVD (n=4).
Results
The study’s primary outcome was the difference in 3-year PFS between the randomized groups of PET-CT-negative patients.
With a median follow-up of 41 months, the 3-year PFS was 85.7% in the ABVD group and 84.4% in the AVD group. The hazard ratio was 1.13 (95% CI, 0.81 to 1.57; P=0.48) in the intention-to-treat analysis and 1.10 (95% CI, 0.79 to 1.53; P=0.58) in the per-protocol analysis.
The absolute difference in 3-year PFS (ABVD minus AVD) was 1.6 percentage points (95% CI, −3.2 to 5.3).
The OS rates were 97.2% in the ABVD group and 97.6% in the AVD group. The hazard ratio in the intention-to-treat analysis was 0.90 (95% CI, 0.47 to 1.74; P=0.76).
Patients in the ABVD group had a significantly higher rate of clinical adverse events than patients in the AVD group—31% and 21%, respectively (P<0.005).
Patients in the ABVD group also had significantly (P<0.05) higher rates of fatigue (3% vs 1%), febrile neutropenia (5% vs 2%), pulmonary/upper respiratory events (3% vs 1%), and dyspnea (2% vs <0.5%). But patients in the AVD group had a significantly higher rate of thrombocytopenia (3% vs 1%).
For patients who had positive interim PET-CT scans, the 3-year PFS was 67.5%, and the OS was 87.8%. Among the 172 patients who went on to receive BEACOPP, 74.4% had negative findings on a third PET-CT scan.
Overall, 62 patients died during the trial—24 from HL. So, for the entire study cohort, the 3-year PFS was 82.6%, and the OS was 95.8%.
The use of interim PET-CT scans can spare some advanced Hodgkin lymphoma (HL) patients the toxicity associated with bleomycin, according to researchers.
The team found that patients with negative PET-CT scans after 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) could go on to receive AVD (doxorubicin, vinblastine, and dacarbazine) without experiencing a significant decrease in progression-free survival (PFS) or overall survival (OS).
Peter Johnson, MD, of the University of Southampton in the UK, and his colleagues reported these findings in NEJM.
“The good news is that the majority of people diagnosed with Hodgkin lymphoma can be cured,” Dr Johnson said. “In this trial, more than 95% of patients are alive after 3 years.”
“But we worry about the long-term side effects from the treatments we use. As we’ve done in this trial, personalizing treatment based on how well it works is a major development for patients with Hodgkin lymphoma and sets a new standard of care.”
Patients and treatment
For this study, Dr Johnson and his colleagues enrolled 1214 patients with newly diagnosed, advanced, classic HL. The patients’ median age was 33 (range, 18 to 79), and 54.5% were male. More patients had stage II disease (41.6%) than stage III (30.2%) or IV (28.3%).
A total of 1119 patients underwent a baseline PET-CT scan, received 2 cycles of ABVD, and underwent an interim PET-CT scan.
The patients with negative interim scans were then randomized to continue treatment with ABVD (n=470) or with AVD (n=465) in cycles 3 through 6.
Patients with positive interim scans (n=182) went on to receive BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, n=172), salvage treatments (n=6), or ABVD (n=4).
Results
The study’s primary outcome was the difference in 3-year PFS between the randomized groups of PET-CT-negative patients.
With a median follow-up of 41 months, the 3-year PFS was 85.7% in the ABVD group and 84.4% in the AVD group. The hazard ratio was 1.13 (95% CI, 0.81 to 1.57; P=0.48) in the intention-to-treat analysis and 1.10 (95% CI, 0.79 to 1.53; P=0.58) in the per-protocol analysis.
The absolute difference in 3-year PFS (ABVD minus AVD) was 1.6 percentage points (95% CI, −3.2 to 5.3).
The OS rates were 97.2% in the ABVD group and 97.6% in the AVD group. The hazard ratio in the intention-to-treat analysis was 0.90 (95% CI, 0.47 to 1.74; P=0.76).
Patients in the ABVD group had a significantly higher rate of clinical adverse events than patients in the AVD group—31% and 21%, respectively (P<0.005).
Patients in the ABVD group also had significantly (P<0.05) higher rates of fatigue (3% vs 1%), febrile neutropenia (5% vs 2%), pulmonary/upper respiratory events (3% vs 1%), and dyspnea (2% vs <0.5%). But patients in the AVD group had a significantly higher rate of thrombocytopenia (3% vs 1%).
For patients who had positive interim PET-CT scans, the 3-year PFS was 67.5%, and the OS was 87.8%. Among the 172 patients who went on to receive BEACOPP, 74.4% had negative findings on a third PET-CT scan.
Overall, 62 patients died during the trial—24 from HL. So, for the entire study cohort, the 3-year PFS was 82.6%, and the OS was 95.8%.
Stopping TKI therapy can be safe, study suggests
COPENHAGEN—Results of a large study suggest that stopping treatment with tyrosine kinase inhibitors (TKIs) can be safe for patients with chronic myeloid leukemia (CML) in deep molecular response (MR4).
Six months after patients stopped receiving a TKI, the relapse-free survival was 62%. At 12 months, it was 56%.
Havinga longer duration of TKI treatment and a longer duration of deep molecular response were both associated with a higher likelihood of relapse-free survival.
These results, from the EURO-SKI trial, were presented at the 21st Congress of the European Hematology Association (abstract S145*) by Johan Richter, MD, PhD, of Skåne University Hospital in Lund, Sweden.
The goal of the EURO-SKI study was to define prognostic markers to increase the proportion of patients in durable deep molecular response after stopping TKI treatment.
The trial included 760 adults with chronic phase CML who were on TKI treatment for at least 3 years. Patients were either on their first TKI or on their second TKI due to toxicity with their first. (None had failed TKI treatment.)
Patients had been in MR4 (BCR/ABL <0.01%) for at least a year, which was confirmed by 3 consecutive polymerase chain reaction (PCR) results during the last 12 months. The final MR4 confirmation was performed in a EUTOS standardized laboratory.
After the final MR4 confirmation, patients stopped TKI treatment. They underwent real-time quantitative PCR (RQ-PCR) every 4 weeks for the first 6 months and every 6 weeks for the next 6 months. In years 2 and 3, they underwent RQ-PCR every third month.
The patients had a median age at diagnosis of 52 (range, 11.2-85.5) and a median age at TKI stop of 60.3 (range, 19.5-89.9). The median duration of TKI therapy was 7.6 years (range, 3.0-14.2), and the median duration of MR4 before TKI stop was 4.7 years (range, 1.0-13.3).
Most patients had received imatinib (n=710) as first-line TKI treatment, though some received nilotinib (n=35) or dasatinib (n=14). The type of first-line TKI was unknown in 1 patient. Second-line TKI treatment included imatinib (n=7), nilotinib (n=47), and dasatinib (n=57).
Relapse, survival, and safety
Six months after stopping TKI treatment, the cumulative incidence of molecular relapse was 37%. It was 43% at 12 months, 47% at 24 months, and 50% at 36 months.
In all, 347 patients had a molecular relapse. Seventy-two patients had BCR/ABL >1%, and 11 lost their complete cytogenetic response. None of the patients progressed to accelerated phase or blast crisis.
Among patients who restarted TKI treatment, the median time to restart was 4.1 months. Fourteen patients restarted treatment without a loss of major molecular response.
Dr Richter noted that the study is still ongoing, but, thus far, more than 80% of patients who restarted TKI therapy have achieved MR4 again.
The molecular relapse-free survival was 62% at 6 months after TKI stop, 56% at 12 months, 52% at 24 months, and 49% at 36 months.
There were 9 on-trial deaths, none of which were related to CML. Five patients died while in remission.
Previous studies revealed a TKI withdrawal syndrome that consists of (mostly transient) musculoskeletal pain or discomfort. In this study, 30.9% of patients (n=235) reported musculoskeletal symptoms, 226 with grade 1-2 events and 9 with grade 3 events.
Prognostic factors
The researchers performed prognostic modeling in 448 patients who previously received imatinib. Univariate analysis revealed no significant association between molecular relapse-free survival at 6 months and age, gender, depth of molecular response, Sokal score, EURO score, EUTOS score, or ELTS score.
However, TKI treatment duration and MR4 duration were both significantly (P<0.001) associated with major molecular response status at 6 months.
The odds ratio for treatment duration was 1.16 (95% CI, 1.08-1.25), which means that an additional year of imatinib treatment increases a patient’s odds of staying in major molecular response at 6 months by 16%.
The odds ratio for MR4 duration was also 1.16 (95% CI, 1.076-1.253), which means that an additional year in MR4 before TKI stop increases a patient’s odds of staying in major molecular response at 6 months by 16%.
Dr Richter noted that treatment duration and MR4 duration were highly correlated, which prevented a significant multiple model including both variables. He said the researchers will conduct further analyses to overcome the correlation between the 2 variables and determine an optimal cutoff for MR4 duration.
The team also plans to collect more data on pretreatment with interferon, as there is reason to suspect it has an influence on major molecular response duration after TKI discontinuation.
*Data in the abstract differ from data presented at the meeting.
COPENHAGEN—Results of a large study suggest that stopping treatment with tyrosine kinase inhibitors (TKIs) can be safe for patients with chronic myeloid leukemia (CML) in deep molecular response (MR4).
Six months after patients stopped receiving a TKI, the relapse-free survival was 62%. At 12 months, it was 56%.
Havinga longer duration of TKI treatment and a longer duration of deep molecular response were both associated with a higher likelihood of relapse-free survival.
These results, from the EURO-SKI trial, were presented at the 21st Congress of the European Hematology Association (abstract S145*) by Johan Richter, MD, PhD, of Skåne University Hospital in Lund, Sweden.
The goal of the EURO-SKI study was to define prognostic markers to increase the proportion of patients in durable deep molecular response after stopping TKI treatment.
The trial included 760 adults with chronic phase CML who were on TKI treatment for at least 3 years. Patients were either on their first TKI or on their second TKI due to toxicity with their first. (None had failed TKI treatment.)
Patients had been in MR4 (BCR/ABL <0.01%) for at least a year, which was confirmed by 3 consecutive polymerase chain reaction (PCR) results during the last 12 months. The final MR4 confirmation was performed in a EUTOS standardized laboratory.
After the final MR4 confirmation, patients stopped TKI treatment. They underwent real-time quantitative PCR (RQ-PCR) every 4 weeks for the first 6 months and every 6 weeks for the next 6 months. In years 2 and 3, they underwent RQ-PCR every third month.
The patients had a median age at diagnosis of 52 (range, 11.2-85.5) and a median age at TKI stop of 60.3 (range, 19.5-89.9). The median duration of TKI therapy was 7.6 years (range, 3.0-14.2), and the median duration of MR4 before TKI stop was 4.7 years (range, 1.0-13.3).
Most patients had received imatinib (n=710) as first-line TKI treatment, though some received nilotinib (n=35) or dasatinib (n=14). The type of first-line TKI was unknown in 1 patient. Second-line TKI treatment included imatinib (n=7), nilotinib (n=47), and dasatinib (n=57).
Relapse, survival, and safety
Six months after stopping TKI treatment, the cumulative incidence of molecular relapse was 37%. It was 43% at 12 months, 47% at 24 months, and 50% at 36 months.
In all, 347 patients had a molecular relapse. Seventy-two patients had BCR/ABL >1%, and 11 lost their complete cytogenetic response. None of the patients progressed to accelerated phase or blast crisis.
Among patients who restarted TKI treatment, the median time to restart was 4.1 months. Fourteen patients restarted treatment without a loss of major molecular response.
Dr Richter noted that the study is still ongoing, but, thus far, more than 80% of patients who restarted TKI therapy have achieved MR4 again.
The molecular relapse-free survival was 62% at 6 months after TKI stop, 56% at 12 months, 52% at 24 months, and 49% at 36 months.
There were 9 on-trial deaths, none of which were related to CML. Five patients died while in remission.
Previous studies revealed a TKI withdrawal syndrome that consists of (mostly transient) musculoskeletal pain or discomfort. In this study, 30.9% of patients (n=235) reported musculoskeletal symptoms, 226 with grade 1-2 events and 9 with grade 3 events.
Prognostic factors
The researchers performed prognostic modeling in 448 patients who previously received imatinib. Univariate analysis revealed no significant association between molecular relapse-free survival at 6 months and age, gender, depth of molecular response, Sokal score, EURO score, EUTOS score, or ELTS score.
However, TKI treatment duration and MR4 duration were both significantly (P<0.001) associated with major molecular response status at 6 months.
The odds ratio for treatment duration was 1.16 (95% CI, 1.08-1.25), which means that an additional year of imatinib treatment increases a patient’s odds of staying in major molecular response at 6 months by 16%.
The odds ratio for MR4 duration was also 1.16 (95% CI, 1.076-1.253), which means that an additional year in MR4 before TKI stop increases a patient’s odds of staying in major molecular response at 6 months by 16%.
Dr Richter noted that treatment duration and MR4 duration were highly correlated, which prevented a significant multiple model including both variables. He said the researchers will conduct further analyses to overcome the correlation between the 2 variables and determine an optimal cutoff for MR4 duration.
The team also plans to collect more data on pretreatment with interferon, as there is reason to suspect it has an influence on major molecular response duration after TKI discontinuation.
*Data in the abstract differ from data presented at the meeting.
COPENHAGEN—Results of a large study suggest that stopping treatment with tyrosine kinase inhibitors (TKIs) can be safe for patients with chronic myeloid leukemia (CML) in deep molecular response (MR4).
Six months after patients stopped receiving a TKI, the relapse-free survival was 62%. At 12 months, it was 56%.
Havinga longer duration of TKI treatment and a longer duration of deep molecular response were both associated with a higher likelihood of relapse-free survival.
These results, from the EURO-SKI trial, were presented at the 21st Congress of the European Hematology Association (abstract S145*) by Johan Richter, MD, PhD, of Skåne University Hospital in Lund, Sweden.
The goal of the EURO-SKI study was to define prognostic markers to increase the proportion of patients in durable deep molecular response after stopping TKI treatment.
The trial included 760 adults with chronic phase CML who were on TKI treatment for at least 3 years. Patients were either on their first TKI or on their second TKI due to toxicity with their first. (None had failed TKI treatment.)
Patients had been in MR4 (BCR/ABL <0.01%) for at least a year, which was confirmed by 3 consecutive polymerase chain reaction (PCR) results during the last 12 months. The final MR4 confirmation was performed in a EUTOS standardized laboratory.
After the final MR4 confirmation, patients stopped TKI treatment. They underwent real-time quantitative PCR (RQ-PCR) every 4 weeks for the first 6 months and every 6 weeks for the next 6 months. In years 2 and 3, they underwent RQ-PCR every third month.
The patients had a median age at diagnosis of 52 (range, 11.2-85.5) and a median age at TKI stop of 60.3 (range, 19.5-89.9). The median duration of TKI therapy was 7.6 years (range, 3.0-14.2), and the median duration of MR4 before TKI stop was 4.7 years (range, 1.0-13.3).
Most patients had received imatinib (n=710) as first-line TKI treatment, though some received nilotinib (n=35) or dasatinib (n=14). The type of first-line TKI was unknown in 1 patient. Second-line TKI treatment included imatinib (n=7), nilotinib (n=47), and dasatinib (n=57).
Relapse, survival, and safety
Six months after stopping TKI treatment, the cumulative incidence of molecular relapse was 37%. It was 43% at 12 months, 47% at 24 months, and 50% at 36 months.
In all, 347 patients had a molecular relapse. Seventy-two patients had BCR/ABL >1%, and 11 lost their complete cytogenetic response. None of the patients progressed to accelerated phase or blast crisis.
Among patients who restarted TKI treatment, the median time to restart was 4.1 months. Fourteen patients restarted treatment without a loss of major molecular response.
Dr Richter noted that the study is still ongoing, but, thus far, more than 80% of patients who restarted TKI therapy have achieved MR4 again.
The molecular relapse-free survival was 62% at 6 months after TKI stop, 56% at 12 months, 52% at 24 months, and 49% at 36 months.
There were 9 on-trial deaths, none of which were related to CML. Five patients died while in remission.
Previous studies revealed a TKI withdrawal syndrome that consists of (mostly transient) musculoskeletal pain or discomfort. In this study, 30.9% of patients (n=235) reported musculoskeletal symptoms, 226 with grade 1-2 events and 9 with grade 3 events.
Prognostic factors
The researchers performed prognostic modeling in 448 patients who previously received imatinib. Univariate analysis revealed no significant association between molecular relapse-free survival at 6 months and age, gender, depth of molecular response, Sokal score, EURO score, EUTOS score, or ELTS score.
However, TKI treatment duration and MR4 duration were both significantly (P<0.001) associated with major molecular response status at 6 months.
The odds ratio for treatment duration was 1.16 (95% CI, 1.08-1.25), which means that an additional year of imatinib treatment increases a patient’s odds of staying in major molecular response at 6 months by 16%.
The odds ratio for MR4 duration was also 1.16 (95% CI, 1.076-1.253), which means that an additional year in MR4 before TKI stop increases a patient’s odds of staying in major molecular response at 6 months by 16%.
Dr Richter noted that treatment duration and MR4 duration were highly correlated, which prevented a significant multiple model including both variables. He said the researchers will conduct further analyses to overcome the correlation between the 2 variables and determine an optimal cutoff for MR4 duration.
The team also plans to collect more data on pretreatment with interferon, as there is reason to suspect it has an influence on major molecular response duration after TKI discontinuation.
*Data in the abstract differ from data presented at the meeting.
Therapy granted fast track designation to treat GVHD
Photo by Chad McNeeley
The US Food and Drug Administration (FDA) has granted fast track designation for ProTmune™, a programmed cellular immunotherapy, to reduce the incidence and severity of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT).
ProTmune is produced by modulating a donor-sourced, mobilized peripheral blood (mPB) graft ex vivo with 2 small molecules (FT1050 and FT4145) to enhance the biological properties and therapeutic function of the graft’s immune cells.
The programmed mPB graft is adoptively transferred and administered to a patient as a one-time intravenous infusion.
ProTmune is being developed by Fate Therapeutics, Inc.
The company is conducting a phase 1/2 trial testing ProTmune for the prevention of acute GVHD and cytomegalovirus infection in adults with hematologic malignancies who are undergoing HSCT.
The trial design consists of an initial 10-subject, phase 1 stage, during which all subjects undergoing allogeneic mPB HSCT will receive ProTmune.
Following an independent data monitoring committee safety review, a 60-subject, randomized, controlled phase 2 stage is expected to begin. In this stage, subjects undergoing allogeneic mPB HSCT will be assigned to receive either ProTmune or a conventional mPB cell graft in a 1:1 ratio.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Photo by Chad McNeeley
The US Food and Drug Administration (FDA) has granted fast track designation for ProTmune™, a programmed cellular immunotherapy, to reduce the incidence and severity of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT).
ProTmune is produced by modulating a donor-sourced, mobilized peripheral blood (mPB) graft ex vivo with 2 small molecules (FT1050 and FT4145) to enhance the biological properties and therapeutic function of the graft’s immune cells.
The programmed mPB graft is adoptively transferred and administered to a patient as a one-time intravenous infusion.
ProTmune is being developed by Fate Therapeutics, Inc.
The company is conducting a phase 1/2 trial testing ProTmune for the prevention of acute GVHD and cytomegalovirus infection in adults with hematologic malignancies who are undergoing HSCT.
The trial design consists of an initial 10-subject, phase 1 stage, during which all subjects undergoing allogeneic mPB HSCT will receive ProTmune.
Following an independent data monitoring committee safety review, a 60-subject, randomized, controlled phase 2 stage is expected to begin. In this stage, subjects undergoing allogeneic mPB HSCT will be assigned to receive either ProTmune or a conventional mPB cell graft in a 1:1 ratio.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Photo by Chad McNeeley
The US Food and Drug Administration (FDA) has granted fast track designation for ProTmune™, a programmed cellular immunotherapy, to reduce the incidence and severity of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT).
ProTmune is produced by modulating a donor-sourced, mobilized peripheral blood (mPB) graft ex vivo with 2 small molecules (FT1050 and FT4145) to enhance the biological properties and therapeutic function of the graft’s immune cells.
The programmed mPB graft is adoptively transferred and administered to a patient as a one-time intravenous infusion.
ProTmune is being developed by Fate Therapeutics, Inc.
The company is conducting a phase 1/2 trial testing ProTmune for the prevention of acute GVHD and cytomegalovirus infection in adults with hematologic malignancies who are undergoing HSCT.
The trial design consists of an initial 10-subject, phase 1 stage, during which all subjects undergoing allogeneic mPB HSCT will receive ProTmune.
Following an independent data monitoring committee safety review, a 60-subject, randomized, controlled phase 2 stage is expected to begin. In this stage, subjects undergoing allogeneic mPB HSCT will be assigned to receive either ProTmune or a conventional mPB cell graft in a 1:1 ratio.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.