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Ofatumumab to be pulled from non-US markets
Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.
The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.
Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.
And Novartis will continue to market ofatumumab for CLL in the US.
“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.
Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.
The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.
About ofatumumab
Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.
In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.
Other approved indications for ofatumumab in the European Union include:
- In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
- In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.
Other approved indications for ofatumumab in the US include:
- In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
- In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
- For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.
The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.
Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.
And Novartis will continue to market ofatumumab for CLL in the US.
“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.
Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.
The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.
About ofatumumab
Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.
In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.
Other approved indications for ofatumumab in the European Union include:
- In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
- In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.
Other approved indications for ofatumumab in the US include:
- In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
- In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
- For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.
The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.
Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.
And Novartis will continue to market ofatumumab for CLL in the US.
“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.
Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.
The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.
About ofatumumab
Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.
In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.
Other approved indications for ofatumumab in the European Union include:
- In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
- In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.
Other approved indications for ofatumumab in the US include:
- In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
- In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
- For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
Bright light therapy improves sleep in cancer survivors
Results of a pilot study suggest that systematic bright light exposure can improve sleep in fatigued cancer survivors.
Subjects who were exposed to bright light every morning for 4 weeks had a significantly greater improvement in sleep efficiency than those who were exposed to dim light over the same period.
In fact, subjects in the bright light group were able to achieve clinically normal levels of sleep efficiency, and subjects in the dim light group were not.
Sleep efficiency is the percentage of time in bed that subjects spent sleeping.
Lisa M. Wu, PhD, of Northwestern University in Chicago, Illinois, and her colleagues reported these results in the Journal of Clinical Sleep Medicine.
The team noted that cancer patients report sleep disturbances at a significantly higher rate than the general population. Between 23% and 44% of cancer patients experience insomnia symptoms even years after treatment.
With this in mind, the researchers studied 44 individuals who had completed cancer treatment and met criteria for clinically significant fatigue at screening.
The subjects had an average age of 53.6, and 75% percent were female. Roughly 55% (n=24) had been diagnosed with a hematologic malignancy.
The subjects were randomized to a bright white light intervention or a dim red light intervention. Subjects in both treatment arms were provided with a light box and instructed to use it every morning for 30 minutes for 4 weeks. Sleep was evaluated using wrist actigraphy and the Pittsburgh Sleep Quality Index.
At baseline, 52.6% of subjects in the dim light group and 60% in the bright light group exceeded the clinical cutoff for poor sleep efficiency (≤ 85%). The mean sleep efficiency was 81.8% and 82.8%, respectively.
During the study period, sleep efficiency improved significantly more among subjects exposed to the bright light than those exposed to the dim light (P=0.003).
The mean sleep efficiency was in the clinically normal range for subjects in the bright light group at the end of the intervention (86.06%) and 3 weeks after (85.77%).
However, the cutoff for poor sleep efficiency was not reached in the dim light group, either at the end of the intervention (mean=79.35%) or 3 weeks after (mean=80.88%).
Total sleep time tended to increase over the study period for subjects in the bright light group, but there was no significant difference in total sleep time between the bright light and dim light groups.
Likewise, there was no significant between-group difference in waking after sleep onset, although this outcome tended to decrease over the study period for subjects in the bright light group.
“Systematic light exposure using bright white light is a low-cost and easily disseminated intervention that offers a feasible and potentially effective alternative to improve sleep in cancer survivors,” Dr Wu said.
However, she and her colleagues noted that larger-scale studies are needed.
Results of a pilot study suggest that systematic bright light exposure can improve sleep in fatigued cancer survivors.
Subjects who were exposed to bright light every morning for 4 weeks had a significantly greater improvement in sleep efficiency than those who were exposed to dim light over the same period.
In fact, subjects in the bright light group were able to achieve clinically normal levels of sleep efficiency, and subjects in the dim light group were not.
Sleep efficiency is the percentage of time in bed that subjects spent sleeping.
Lisa M. Wu, PhD, of Northwestern University in Chicago, Illinois, and her colleagues reported these results in the Journal of Clinical Sleep Medicine.
The team noted that cancer patients report sleep disturbances at a significantly higher rate than the general population. Between 23% and 44% of cancer patients experience insomnia symptoms even years after treatment.
With this in mind, the researchers studied 44 individuals who had completed cancer treatment and met criteria for clinically significant fatigue at screening.
The subjects had an average age of 53.6, and 75% percent were female. Roughly 55% (n=24) had been diagnosed with a hematologic malignancy.
The subjects were randomized to a bright white light intervention or a dim red light intervention. Subjects in both treatment arms were provided with a light box and instructed to use it every morning for 30 minutes for 4 weeks. Sleep was evaluated using wrist actigraphy and the Pittsburgh Sleep Quality Index.
At baseline, 52.6% of subjects in the dim light group and 60% in the bright light group exceeded the clinical cutoff for poor sleep efficiency (≤ 85%). The mean sleep efficiency was 81.8% and 82.8%, respectively.
During the study period, sleep efficiency improved significantly more among subjects exposed to the bright light than those exposed to the dim light (P=0.003).
The mean sleep efficiency was in the clinically normal range for subjects in the bright light group at the end of the intervention (86.06%) and 3 weeks after (85.77%).
However, the cutoff for poor sleep efficiency was not reached in the dim light group, either at the end of the intervention (mean=79.35%) or 3 weeks after (mean=80.88%).
Total sleep time tended to increase over the study period for subjects in the bright light group, but there was no significant difference in total sleep time between the bright light and dim light groups.
Likewise, there was no significant between-group difference in waking after sleep onset, although this outcome tended to decrease over the study period for subjects in the bright light group.
“Systematic light exposure using bright white light is a low-cost and easily disseminated intervention that offers a feasible and potentially effective alternative to improve sleep in cancer survivors,” Dr Wu said.
However, she and her colleagues noted that larger-scale studies are needed.
Results of a pilot study suggest that systematic bright light exposure can improve sleep in fatigued cancer survivors.
Subjects who were exposed to bright light every morning for 4 weeks had a significantly greater improvement in sleep efficiency than those who were exposed to dim light over the same period.
In fact, subjects in the bright light group were able to achieve clinically normal levels of sleep efficiency, and subjects in the dim light group were not.
Sleep efficiency is the percentage of time in bed that subjects spent sleeping.
Lisa M. Wu, PhD, of Northwestern University in Chicago, Illinois, and her colleagues reported these results in the Journal of Clinical Sleep Medicine.
The team noted that cancer patients report sleep disturbances at a significantly higher rate than the general population. Between 23% and 44% of cancer patients experience insomnia symptoms even years after treatment.
With this in mind, the researchers studied 44 individuals who had completed cancer treatment and met criteria for clinically significant fatigue at screening.
The subjects had an average age of 53.6, and 75% percent were female. Roughly 55% (n=24) had been diagnosed with a hematologic malignancy.
The subjects were randomized to a bright white light intervention or a dim red light intervention. Subjects in both treatment arms were provided with a light box and instructed to use it every morning for 30 minutes for 4 weeks. Sleep was evaluated using wrist actigraphy and the Pittsburgh Sleep Quality Index.
At baseline, 52.6% of subjects in the dim light group and 60% in the bright light group exceeded the clinical cutoff for poor sleep efficiency (≤ 85%). The mean sleep efficiency was 81.8% and 82.8%, respectively.
During the study period, sleep efficiency improved significantly more among subjects exposed to the bright light than those exposed to the dim light (P=0.003).
The mean sleep efficiency was in the clinically normal range for subjects in the bright light group at the end of the intervention (86.06%) and 3 weeks after (85.77%).
However, the cutoff for poor sleep efficiency was not reached in the dim light group, either at the end of the intervention (mean=79.35%) or 3 weeks after (mean=80.88%).
Total sleep time tended to increase over the study period for subjects in the bright light group, but there was no significant difference in total sleep time between the bright light and dim light groups.
Likewise, there was no significant between-group difference in waking after sleep onset, although this outcome tended to decrease over the study period for subjects in the bright light group.
“Systematic light exposure using bright white light is a low-cost and easily disseminated intervention that offers a feasible and potentially effective alternative to improve sleep in cancer survivors,” Dr Wu said.
However, she and her colleagues noted that larger-scale studies are needed.
Risks of MGUS persist beyond 30 years
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
CAR T-cell therapy on fast track in US, EU
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
FDA grants priority review to CAR T-cell therapy for DLBCL
The Food and Drug Administration has granted a priority review for the CAR T-cell therapy tisagenlecleucel suspension, formerly CTL019, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for or relapsed after autologous stem cell transplant.
The current application is based on a 6-month primary analysis from the single-arm, phase 2 JULIET clinical trial in adult patients with relapsed or refractory diffuse large B-cell lymphoma. According to results presented at ASH 2017, among 81 patients followed for at least 3 months before data cutoff, best overall response rate was 53%, and 40% had a complete response. Cytokine release syndrome (all grades) occurred in 58% of infused patients. Other grade 3 or 4 adverse events included neurologic toxicities, cytopenias lasting more than 28 days, infections, and febrile neutropenia.
Tisagenlecleucel suspension is marketed as Kymriah by Novartis.
The Food and Drug Administration has granted a priority review for the CAR T-cell therapy tisagenlecleucel suspension, formerly CTL019, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for or relapsed after autologous stem cell transplant.
The current application is based on a 6-month primary analysis from the single-arm, phase 2 JULIET clinical trial in adult patients with relapsed or refractory diffuse large B-cell lymphoma. According to results presented at ASH 2017, among 81 patients followed for at least 3 months before data cutoff, best overall response rate was 53%, and 40% had a complete response. Cytokine release syndrome (all grades) occurred in 58% of infused patients. Other grade 3 or 4 adverse events included neurologic toxicities, cytopenias lasting more than 28 days, infections, and febrile neutropenia.
Tisagenlecleucel suspension is marketed as Kymriah by Novartis.
The Food and Drug Administration has granted a priority review for the CAR T-cell therapy tisagenlecleucel suspension, formerly CTL019, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for or relapsed after autologous stem cell transplant.
The current application is based on a 6-month primary analysis from the single-arm, phase 2 JULIET clinical trial in adult patients with relapsed or refractory diffuse large B-cell lymphoma. According to results presented at ASH 2017, among 81 patients followed for at least 3 months before data cutoff, best overall response rate was 53%, and 40% had a complete response. Cytokine release syndrome (all grades) occurred in 58% of infused patients. Other grade 3 or 4 adverse events included neurologic toxicities, cytopenias lasting more than 28 days, infections, and febrile neutropenia.
Tisagenlecleucel suspension is marketed as Kymriah by Novartis.
Drug’s label updated to include risk of allergic reactions
The US Food and Drug Administration (FDA) and Tesaro, Inc., have updated the prescribing information for Varubi® (rolapitant) injectable emulsion to include a new warning about the risk of allergic reactions.
Varubi injectable emulsion is a substance P/neurokinin receptor antagonist approved to prevent delayed nausea and vomiting associated with chemotherapy in adults.
Since Varubi injectable emulsion gained FDA approval, there have been reports of anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions to the drug, some of which required hospitalization.
Now, the labeling for Varubi injectable emulsion has been changed to include information about these events. The changes include modifications to the CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, and ADVERSE REACTIONS sections of the label.
Since Varubi injectable emulsion was introduced to the US market in late November 2017, at least 7000 doses of the drug have been administered to patients receiving emetogenic chemotherapy in the US, according to Tesaro.
Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have occurred during or soon after the infusion of Varubi. Most reactions have occurred within the first few minutes of administration.
The FDA has advised that patients who are hypersensitive to any component of Varubi injectable emulsion (including soybean oil) do not receive the drug. And patients with known allergies to legumes or other related allergens should be monitored closely.
The FDA said healthcare professionals should be vigilant for signs of hypersensitivity or anaphylaxis in all patients receiving Varubi injectable emulsion, both during administration and afterward.
Symptoms of anaphylaxis can include wheezing, difficulty breathing, swelling of the face or throat, hives, flushing, itching, abdominal cramping, abdominal pain, vomiting, back pain, chest pain, hypotension, and shock.
If anaphylaxis or any other serious hypersensitivity/infusion reaction occurs, Varubi injectable emulsion should be stopped immediately and permanently. The patient should receive appropriate medical management, including epinephrine and/or antihistamines.
To ensure patients and healthcare professionals are aware of the label update to Varubi injectable emulsion, Tesaro has issued a Dear Healthcare Professional letter. In addition, the updated prescribing information has been posted on the Varubi website.
For any questions about the use of Varubi injectable emulsion or to report adverse events related to the drug, contact Tesaro’s medical information department at 1-844-4-TESARO (1-844-483-7276).
Adverse events related to Varubi should also be reported to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
The US Food and Drug Administration (FDA) and Tesaro, Inc., have updated the prescribing information for Varubi® (rolapitant) injectable emulsion to include a new warning about the risk of allergic reactions.
Varubi injectable emulsion is a substance P/neurokinin receptor antagonist approved to prevent delayed nausea and vomiting associated with chemotherapy in adults.
Since Varubi injectable emulsion gained FDA approval, there have been reports of anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions to the drug, some of which required hospitalization.
Now, the labeling for Varubi injectable emulsion has been changed to include information about these events. The changes include modifications to the CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, and ADVERSE REACTIONS sections of the label.
Since Varubi injectable emulsion was introduced to the US market in late November 2017, at least 7000 doses of the drug have been administered to patients receiving emetogenic chemotherapy in the US, according to Tesaro.
Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have occurred during or soon after the infusion of Varubi. Most reactions have occurred within the first few minutes of administration.
The FDA has advised that patients who are hypersensitive to any component of Varubi injectable emulsion (including soybean oil) do not receive the drug. And patients with known allergies to legumes or other related allergens should be monitored closely.
The FDA said healthcare professionals should be vigilant for signs of hypersensitivity or anaphylaxis in all patients receiving Varubi injectable emulsion, both during administration and afterward.
Symptoms of anaphylaxis can include wheezing, difficulty breathing, swelling of the face or throat, hives, flushing, itching, abdominal cramping, abdominal pain, vomiting, back pain, chest pain, hypotension, and shock.
If anaphylaxis or any other serious hypersensitivity/infusion reaction occurs, Varubi injectable emulsion should be stopped immediately and permanently. The patient should receive appropriate medical management, including epinephrine and/or antihistamines.
To ensure patients and healthcare professionals are aware of the label update to Varubi injectable emulsion, Tesaro has issued a Dear Healthcare Professional letter. In addition, the updated prescribing information has been posted on the Varubi website.
For any questions about the use of Varubi injectable emulsion or to report adverse events related to the drug, contact Tesaro’s medical information department at 1-844-4-TESARO (1-844-483-7276).
Adverse events related to Varubi should also be reported to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
The US Food and Drug Administration (FDA) and Tesaro, Inc., have updated the prescribing information for Varubi® (rolapitant) injectable emulsion to include a new warning about the risk of allergic reactions.
Varubi injectable emulsion is a substance P/neurokinin receptor antagonist approved to prevent delayed nausea and vomiting associated with chemotherapy in adults.
Since Varubi injectable emulsion gained FDA approval, there have been reports of anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions to the drug, some of which required hospitalization.
Now, the labeling for Varubi injectable emulsion has been changed to include information about these events. The changes include modifications to the CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, and ADVERSE REACTIONS sections of the label.
Since Varubi injectable emulsion was introduced to the US market in late November 2017, at least 7000 doses of the drug have been administered to patients receiving emetogenic chemotherapy in the US, according to Tesaro.
Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have occurred during or soon after the infusion of Varubi. Most reactions have occurred within the first few minutes of administration.
The FDA has advised that patients who are hypersensitive to any component of Varubi injectable emulsion (including soybean oil) do not receive the drug. And patients with known allergies to legumes or other related allergens should be monitored closely.
The FDA said healthcare professionals should be vigilant for signs of hypersensitivity or anaphylaxis in all patients receiving Varubi injectable emulsion, both during administration and afterward.
Symptoms of anaphylaxis can include wheezing, difficulty breathing, swelling of the face or throat, hives, flushing, itching, abdominal cramping, abdominal pain, vomiting, back pain, chest pain, hypotension, and shock.
If anaphylaxis or any other serious hypersensitivity/infusion reaction occurs, Varubi injectable emulsion should be stopped immediately and permanently. The patient should receive appropriate medical management, including epinephrine and/or antihistamines.
To ensure patients and healthcare professionals are aware of the label update to Varubi injectable emulsion, Tesaro has issued a Dear Healthcare Professional letter. In addition, the updated prescribing information has been posted on the Varubi website.
For any questions about the use of Varubi injectable emulsion or to report adverse events related to the drug, contact Tesaro’s medical information department at 1-844-4-TESARO (1-844-483-7276).
Adverse events related to Varubi should also be reported to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Generic bortezomib available in US
Fresenius Kabi has introduced its generic version of Velcade, Bortezomib for Injection, to the US market.
This is the first intravenous alternative to Velcade available in the US.
Bortezomib for Injection is available as a single dose vial containing 3.5 mg of lyophilized powder.
The product is approved to treat patients with multiple myeloma and patients with mantle cell lymphoma who have received at least 1 prior therapy.
For details, see the prescribing information for Bortezomib for Injection.
Velcade is a registered trademark of Millennium Pharmaceuticals, Inc.
Fresenius Kabi has introduced its generic version of Velcade, Bortezomib for Injection, to the US market.
This is the first intravenous alternative to Velcade available in the US.
Bortezomib for Injection is available as a single dose vial containing 3.5 mg of lyophilized powder.
The product is approved to treat patients with multiple myeloma and patients with mantle cell lymphoma who have received at least 1 prior therapy.
For details, see the prescribing information for Bortezomib for Injection.
Velcade is a registered trademark of Millennium Pharmaceuticals, Inc.
Fresenius Kabi has introduced its generic version of Velcade, Bortezomib for Injection, to the US market.
This is the first intravenous alternative to Velcade available in the US.
Bortezomib for Injection is available as a single dose vial containing 3.5 mg of lyophilized powder.
The product is approved to treat patients with multiple myeloma and patients with mantle cell lymphoma who have received at least 1 prior therapy.
For details, see the prescribing information for Bortezomib for Injection.
Velcade is a registered trademark of Millennium Pharmaceuticals, Inc.
Survival differences among AYAs with blood cancers
A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.
The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.
The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).
For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).
For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.
“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.
That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”
According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.
Survival data for patients with hematologic malignancies were as follows.
Acute lymphoblastic leukemia
There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.
Five-year survival was similar between males (43%) and females (41%).
Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).
Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).
Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).
Acute myeloid leukemia
There were 1195 cases of acute myeloid leukemia—641 males and 554 females.
Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).
Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).
Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).
Chronic myeloid leukemia
There were 655 cases of chronic myeloid leukemia—408 males and 247 females.
Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).
Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).
Hodgkin lymphoma
There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.
The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).
Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).
And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).
Non-Hodkgin lymphoma
There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period—3064 males and 1421 females.
The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).
Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).
And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).
“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.
“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”
A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.
The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.
The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).
For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).
For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.
“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.
That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”
According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.
Survival data for patients with hematologic malignancies were as follows.
Acute lymphoblastic leukemia
There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.
Five-year survival was similar between males (43%) and females (41%).
Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).
Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).
Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).
Acute myeloid leukemia
There were 1195 cases of acute myeloid leukemia—641 males and 554 females.
Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).
Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).
Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).
Chronic myeloid leukemia
There were 655 cases of chronic myeloid leukemia—408 males and 247 females.
Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).
Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).
Hodgkin lymphoma
There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.
The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).
Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).
And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).
Non-Hodkgin lymphoma
There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period—3064 males and 1421 females.
The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).
Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).
And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).
“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.
“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”
A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.
The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.
The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).
For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).
For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.
“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.
That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”
According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.
Survival data for patients with hematologic malignancies were as follows.
Acute lymphoblastic leukemia
There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.
Five-year survival was similar between males (43%) and females (41%).
Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).
Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).
Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).
Acute myeloid leukemia
There were 1195 cases of acute myeloid leukemia—641 males and 554 females.
Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).
Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).
Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).
Chronic myeloid leukemia
There were 655 cases of chronic myeloid leukemia—408 males and 247 females.
Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).
Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).
Hodgkin lymphoma
There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.
The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).
Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).
And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).
Non-Hodkgin lymphoma
There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period—3064 males and 1421 females.
The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).
Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).
Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).
And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).
“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.
“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”
Marine animals aid development of cytotoxicity assay
Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.
The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.
The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.
Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.
“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”
“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”
Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.
The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.
Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.
To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.
The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.
Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.
The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.
“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.
In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.
Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.
“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.
Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.
The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.
The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.
Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.
“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”
“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”
Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.
The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.
Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.
To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.
The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.
Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.
The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.
“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.
In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.
Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.
“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.
Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.
The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.
The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.
Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.
“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”
“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”
Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.
The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.
Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.
To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.
The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.
Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.
The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.
“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.
In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.
Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.
“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.
Overcoming resistance to ibrutinib in CLL
New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).
It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.
But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.
Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.
The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.
These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.
With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.
Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.
The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.
The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.
“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.
“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”
Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.
The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.
Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”
The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.
“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.
New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).
It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.
But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.
Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.
The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.
These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.
With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.
Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.
The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.
The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.
“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.
“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”
Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.
The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.
Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”
The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.
“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.
New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).
It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.
But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.
Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.
The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.
These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.
With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.
Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.
The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.
The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.
“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.
“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”
Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.
The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.
Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”
The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.
“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.