User login
Team describes method of targeting LSCs in BC-CML
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.”
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.”
Acalabrutinib shows efficacy as monotherapy in untreated CLL
CHICAGO – Acalabrutinib, which has shown efficacy in relapsed chronic lymphocytic leukemia, has now shown efficacy as a monotherapy for patients with previously untreated CLL, based on results from an ongoing phase I-II study presented as a poster at the annual meeting of the American Society of Clinical Oncology.
In a 74-patient study, best overall response rate was 96%, and median time to response was 2 months. CLL has not progressed in any of the patients, and none have experienced Richter’s transformation, Dr. John C. Byrd, the D. Warren Brown Chair of Leukemia Research at The Ohio State University, Columbus, and his colleagues reported. Based on its favorable safety profile and durable response rates, a phase III trialof acalabrutinib therapy has been initiated (NCT02475681).
Oral acalabrutinib was given at doses of 100 mg twice daily to 37 patients or 200 mg daily to 37 other patients. About half of the patients had bulky lymph nodes of at least 5 cm and 38 of 67 patients had an unmutated IGHV gene. Median time on the study was 11 months.
All patients had rapid declines in lymphadenopathy. Both dose schedules were associated with clinical activity, with Bruton’s tyrosine kinase occupancy highest at 98% with twice-daily dosing and 93% with once-daily dosing. Treatment-related lymphocytosis occurred in 39 of 74 patients and resolved in 38 of the 39. In general, lymphocytosis peaked at a median of 1 week and resolved by a median of 7 weeks.
Acalabrutinib was well tolerated with 72 of 74 patients continuing on the drug. Most adverse events were grade 2 or less, and included headache (42%), diarrhea (35%), arthralgia (22%), contusion (18%), nausea (18%) and increased weight (18%). Grade 3-4 adverse events that occurred in at least two patients included syncope (two patients) and hypertension (two patients). There was one grade 3 upper GI bleed from a gastric ulcer and aspirin use, and one grade 5 case of pneumonia. No atrial fibrillation was reported.
Dr. Byrd receives research funding from Acerta Pharma, the maker of acalabrutinib, as well as from Genentech and Pharmacyclics.
On Twitter @maryjodales
CHICAGO – Acalabrutinib, which has shown efficacy in relapsed chronic lymphocytic leukemia, has now shown efficacy as a monotherapy for patients with previously untreated CLL, based on results from an ongoing phase I-II study presented as a poster at the annual meeting of the American Society of Clinical Oncology.
In a 74-patient study, best overall response rate was 96%, and median time to response was 2 months. CLL has not progressed in any of the patients, and none have experienced Richter’s transformation, Dr. John C. Byrd, the D. Warren Brown Chair of Leukemia Research at The Ohio State University, Columbus, and his colleagues reported. Based on its favorable safety profile and durable response rates, a phase III trialof acalabrutinib therapy has been initiated (NCT02475681).
Oral acalabrutinib was given at doses of 100 mg twice daily to 37 patients or 200 mg daily to 37 other patients. About half of the patients had bulky lymph nodes of at least 5 cm and 38 of 67 patients had an unmutated IGHV gene. Median time on the study was 11 months.
All patients had rapid declines in lymphadenopathy. Both dose schedules were associated with clinical activity, with Bruton’s tyrosine kinase occupancy highest at 98% with twice-daily dosing and 93% with once-daily dosing. Treatment-related lymphocytosis occurred in 39 of 74 patients and resolved in 38 of the 39. In general, lymphocytosis peaked at a median of 1 week and resolved by a median of 7 weeks.
Acalabrutinib was well tolerated with 72 of 74 patients continuing on the drug. Most adverse events were grade 2 or less, and included headache (42%), diarrhea (35%), arthralgia (22%), contusion (18%), nausea (18%) and increased weight (18%). Grade 3-4 adverse events that occurred in at least two patients included syncope (two patients) and hypertension (two patients). There was one grade 3 upper GI bleed from a gastric ulcer and aspirin use, and one grade 5 case of pneumonia. No atrial fibrillation was reported.
Dr. Byrd receives research funding from Acerta Pharma, the maker of acalabrutinib, as well as from Genentech and Pharmacyclics.
On Twitter @maryjodales
CHICAGO – Acalabrutinib, which has shown efficacy in relapsed chronic lymphocytic leukemia, has now shown efficacy as a monotherapy for patients with previously untreated CLL, based on results from an ongoing phase I-II study presented as a poster at the annual meeting of the American Society of Clinical Oncology.
In a 74-patient study, best overall response rate was 96%, and median time to response was 2 months. CLL has not progressed in any of the patients, and none have experienced Richter’s transformation, Dr. John C. Byrd, the D. Warren Brown Chair of Leukemia Research at The Ohio State University, Columbus, and his colleagues reported. Based on its favorable safety profile and durable response rates, a phase III trialof acalabrutinib therapy has been initiated (NCT02475681).
Oral acalabrutinib was given at doses of 100 mg twice daily to 37 patients or 200 mg daily to 37 other patients. About half of the patients had bulky lymph nodes of at least 5 cm and 38 of 67 patients had an unmutated IGHV gene. Median time on the study was 11 months.
All patients had rapid declines in lymphadenopathy. Both dose schedules were associated with clinical activity, with Bruton’s tyrosine kinase occupancy highest at 98% with twice-daily dosing and 93% with once-daily dosing. Treatment-related lymphocytosis occurred in 39 of 74 patients and resolved in 38 of the 39. In general, lymphocytosis peaked at a median of 1 week and resolved by a median of 7 weeks.
Acalabrutinib was well tolerated with 72 of 74 patients continuing on the drug. Most adverse events were grade 2 or less, and included headache (42%), diarrhea (35%), arthralgia (22%), contusion (18%), nausea (18%) and increased weight (18%). Grade 3-4 adverse events that occurred in at least two patients included syncope (two patients) and hypertension (two patients). There was one grade 3 upper GI bleed from a gastric ulcer and aspirin use, and one grade 5 case of pneumonia. No atrial fibrillation was reported.
Dr. Byrd receives research funding from Acerta Pharma, the maker of acalabrutinib, as well as from Genentech and Pharmacyclics.
On Twitter @maryjodales
FROM 2016 ASCO ANNUAL MEETING
Key clinical point: Acalabrutinib, which has shown efficacy in relapsed CLL, has now shown efficacy as a monotherapy for patients with previously untreated CLL.
Major finding: In a 74-patient study, best overall response rate was 96%, and median time to response was 2 months.
Data source: An ongoing phase I-II study.
Disclosures: Dr. Byrd receives research funding from Acerta Pharma, the maker of acalabrutinib, as well as from Genentech and Pharmacyclics.
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.
A new approach to treat AML?
Preclinical research suggests that activating the STING pathway may be a feasible approach for treating acute myeloid leukemia (AML).
The STING protein has been shown to play a crucial role in the immune system’s ability to “sense” cancer by recognizing and responding to DNA from tumor cells.
In past studies, researchers injected compounds that activate the STING pathway directly into solid tumors in mice, and this produced potent anti-tumor immune responses.
In a new study, researchers injected substances that mimic tumor-cell DNA into the bloodstream and found they could stimulate STING to provoke a life-extending immune response in mice with AML.
“Delivery of these substances into the blood led to massive immune responses,” said study author Justin Kline, MD, of the University of Chicago in Illinois.
“I’ve worked extensively with animal models of this disease, and have never seen responses like this.”
This research, published in Cell Reports, is the first demonstration that activating the STING pathway could be effective in hematologic malignancies.
STING (short for STimulator of INterferon Genes) plays a role in detecting threats, such as viral infections or cancer. STING is activated when DNA turns up in the wrong place, inside the cell but outside the nucleus.
When it encounters such misplaced DNA, STING induces the production of interferon-beta and other chemical signals that recruit certain components of the immune system to manage the threat, such as leukemia-specific killer T cells.
In this study, the researchers found that mice with established AML were rarely able to launch an effective immune response against the disease.
But when the team exposed the mice to DMXAA (5,6-dimethylxanthenone-4-acetic acid), a molecule that activates STING, the immune system responded aggressively, culminating in the activation of highly potent, cancer-cell killing T cells.
This response prolonged survival and, in some cases, cured the mice of their leukemia. About 60% of DMXAA-treated mice survived long-term. They were even able to protect themselves when “re-challenged” with AML cells.
Because of significant differences between mice and humans, DMXAA does not activate the human STING pathway, but researchers have found that several cyclic dinucleotides—signaling molecules produced by bacteria—have a comparable effect in stimulating the STING pathway.
This leads to an immune response that begins with the production of type I interferons and proceeds to later, more powerful stages, ultimately including leukemia-specific T cells.
“Our results provide strong rationale for the clinical translation of STING agonists as immune therapy for leukemia and possibly other hematologic
malignancies,” said study author Emily Curran, MD, of the University of Chicago.
However, Dr Kline noted that this approach is “not without risk.” He said it can induce “a lot of inflammation, fever, even shock.” Such a stimulated immune system can be “too effective,” especially when the therapy is given through the blood stream, rather than injected into a solid tumor.
“I think drug makers will want to focus on intra-tumoral injection studies before they are ready to bet on systemic infusion,” Dr Kline said. “But this is an important first step.”
Preclinical research suggests that activating the STING pathway may be a feasible approach for treating acute myeloid leukemia (AML).
The STING protein has been shown to play a crucial role in the immune system’s ability to “sense” cancer by recognizing and responding to DNA from tumor cells.
In past studies, researchers injected compounds that activate the STING pathway directly into solid tumors in mice, and this produced potent anti-tumor immune responses.
In a new study, researchers injected substances that mimic tumor-cell DNA into the bloodstream and found they could stimulate STING to provoke a life-extending immune response in mice with AML.
“Delivery of these substances into the blood led to massive immune responses,” said study author Justin Kline, MD, of the University of Chicago in Illinois.
“I’ve worked extensively with animal models of this disease, and have never seen responses like this.”
This research, published in Cell Reports, is the first demonstration that activating the STING pathway could be effective in hematologic malignancies.
STING (short for STimulator of INterferon Genes) plays a role in detecting threats, such as viral infections or cancer. STING is activated when DNA turns up in the wrong place, inside the cell but outside the nucleus.
When it encounters such misplaced DNA, STING induces the production of interferon-beta and other chemical signals that recruit certain components of the immune system to manage the threat, such as leukemia-specific killer T cells.
In this study, the researchers found that mice with established AML were rarely able to launch an effective immune response against the disease.
But when the team exposed the mice to DMXAA (5,6-dimethylxanthenone-4-acetic acid), a molecule that activates STING, the immune system responded aggressively, culminating in the activation of highly potent, cancer-cell killing T cells.
This response prolonged survival and, in some cases, cured the mice of their leukemia. About 60% of DMXAA-treated mice survived long-term. They were even able to protect themselves when “re-challenged” with AML cells.
Because of significant differences between mice and humans, DMXAA does not activate the human STING pathway, but researchers have found that several cyclic dinucleotides—signaling molecules produced by bacteria—have a comparable effect in stimulating the STING pathway.
This leads to an immune response that begins with the production of type I interferons and proceeds to later, more powerful stages, ultimately including leukemia-specific T cells.
“Our results provide strong rationale for the clinical translation of STING agonists as immune therapy for leukemia and possibly other hematologic
malignancies,” said study author Emily Curran, MD, of the University of Chicago.
However, Dr Kline noted that this approach is “not without risk.” He said it can induce “a lot of inflammation, fever, even shock.” Such a stimulated immune system can be “too effective,” especially when the therapy is given through the blood stream, rather than injected into a solid tumor.
“I think drug makers will want to focus on intra-tumoral injection studies before they are ready to bet on systemic infusion,” Dr Kline said. “But this is an important first step.”
Preclinical research suggests that activating the STING pathway may be a feasible approach for treating acute myeloid leukemia (AML).
The STING protein has been shown to play a crucial role in the immune system’s ability to “sense” cancer by recognizing and responding to DNA from tumor cells.
In past studies, researchers injected compounds that activate the STING pathway directly into solid tumors in mice, and this produced potent anti-tumor immune responses.
In a new study, researchers injected substances that mimic tumor-cell DNA into the bloodstream and found they could stimulate STING to provoke a life-extending immune response in mice with AML.
“Delivery of these substances into the blood led to massive immune responses,” said study author Justin Kline, MD, of the University of Chicago in Illinois.
“I’ve worked extensively with animal models of this disease, and have never seen responses like this.”
This research, published in Cell Reports, is the first demonstration that activating the STING pathway could be effective in hematologic malignancies.
STING (short for STimulator of INterferon Genes) plays a role in detecting threats, such as viral infections or cancer. STING is activated when DNA turns up in the wrong place, inside the cell but outside the nucleus.
When it encounters such misplaced DNA, STING induces the production of interferon-beta and other chemical signals that recruit certain components of the immune system to manage the threat, such as leukemia-specific killer T cells.
In this study, the researchers found that mice with established AML were rarely able to launch an effective immune response against the disease.
But when the team exposed the mice to DMXAA (5,6-dimethylxanthenone-4-acetic acid), a molecule that activates STING, the immune system responded aggressively, culminating in the activation of highly potent, cancer-cell killing T cells.
This response prolonged survival and, in some cases, cured the mice of their leukemia. About 60% of DMXAA-treated mice survived long-term. They were even able to protect themselves when “re-challenged” with AML cells.
Because of significant differences between mice and humans, DMXAA does not activate the human STING pathway, but researchers have found that several cyclic dinucleotides—signaling molecules produced by bacteria—have a comparable effect in stimulating the STING pathway.
This leads to an immune response that begins with the production of type I interferons and proceeds to later, more powerful stages, ultimately including leukemia-specific T cells.
“Our results provide strong rationale for the clinical translation of STING agonists as immune therapy for leukemia and possibly other hematologic
malignancies,” said study author Emily Curran, MD, of the University of Chicago.
However, Dr Kline noted that this approach is “not without risk.” He said it can induce “a lot of inflammation, fever, even shock.” Such a stimulated immune system can be “too effective,” especially when the therapy is given through the blood stream, rather than injected into a solid tumor.
“I think drug makers will want to focus on intra-tumoral injection studies before they are ready to bet on systemic infusion,” Dr Kline said. “But this is an important first step.”
Ibrutinib at below standard dose may achieve good survival in CLL
Ibrutinib given at doses lower than the standard dose of 420 mg/day was associated with comparable overall survival and progression-free survival as the standard dose in patients with chronic lymphocytic leukemia (CLL), based on the results of a multicenter, retrospective study submitted as a poster at the annual meeting of the American Society of Clinical Oncology.
The initial findings indicate patients who experience toxicity on the 420 mg/day dosage can still do well on a slightly lower dose of ibrutinib, reported Colleen Timlin, Pharm.D., of the Hospital of the University of Pennsylvania, Philadelphia, and her associates.
At a median follow-up of 13.5 months, the median progression-free survival was 37.4 months in the standard dose group and the median progression-free survival had not been reached in the reduced-dose group. The median overall survival had not been reached in either group. The hazard ratio in the reduced-dose group was 1.2 for progression-free survival and 0.6 for overall survival; neither difference was statistically significant. Best overall response rate was 85% in the standard-dose group and 84% in the reduced-dose group.
The study included 197 patients, 37 of whom were shifted to reduced doses of ibrutinib within 3 months of initiating therapy at the recommended 420 mg/day dosage. For reduced-dose patients, the median ibrutinib dose was 4.3 mg/kg per day. The most common reasons for reducing the ibrutinib dose were gastrointestinal toxicity, bleeding, rash, cardiotoxicity, and renal insufficiency, the researchers said.
Most of the patients treated with doses less than 420 mg/day still maintained a dose of greater than 2.5 mg/kg per day, which assured adequate Bruton’s tyrosine kinase occupancy. The 420 mg/day dosage noted in the labeling was established, based on achievement of greater than 90% Bruton’s tyrosine kinase occupancy. Fewer patients achieve greater than 90% occupancy at lower doses, but lower doses may not translate into inferior outcomes.
Weight-based dosing should be considered in future studies and pharmacoeconomic analyses. Comparative analyses of toxicity profiles stratified by ibrutinib dose are underway, according to Dr. Timlin and her colleagues.
Dr. Timlin had no relevant disclosures. Several of her colleagues had multiple financial disclosures.
On Twitter @maryjodales
Ibrutinib given at doses lower than the standard dose of 420 mg/day was associated with comparable overall survival and progression-free survival as the standard dose in patients with chronic lymphocytic leukemia (CLL), based on the results of a multicenter, retrospective study submitted as a poster at the annual meeting of the American Society of Clinical Oncology.
The initial findings indicate patients who experience toxicity on the 420 mg/day dosage can still do well on a slightly lower dose of ibrutinib, reported Colleen Timlin, Pharm.D., of the Hospital of the University of Pennsylvania, Philadelphia, and her associates.
At a median follow-up of 13.5 months, the median progression-free survival was 37.4 months in the standard dose group and the median progression-free survival had not been reached in the reduced-dose group. The median overall survival had not been reached in either group. The hazard ratio in the reduced-dose group was 1.2 for progression-free survival and 0.6 for overall survival; neither difference was statistically significant. Best overall response rate was 85% in the standard-dose group and 84% in the reduced-dose group.
The study included 197 patients, 37 of whom were shifted to reduced doses of ibrutinib within 3 months of initiating therapy at the recommended 420 mg/day dosage. For reduced-dose patients, the median ibrutinib dose was 4.3 mg/kg per day. The most common reasons for reducing the ibrutinib dose were gastrointestinal toxicity, bleeding, rash, cardiotoxicity, and renal insufficiency, the researchers said.
Most of the patients treated with doses less than 420 mg/day still maintained a dose of greater than 2.5 mg/kg per day, which assured adequate Bruton’s tyrosine kinase occupancy. The 420 mg/day dosage noted in the labeling was established, based on achievement of greater than 90% Bruton’s tyrosine kinase occupancy. Fewer patients achieve greater than 90% occupancy at lower doses, but lower doses may not translate into inferior outcomes.
Weight-based dosing should be considered in future studies and pharmacoeconomic analyses. Comparative analyses of toxicity profiles stratified by ibrutinib dose are underway, according to Dr. Timlin and her colleagues.
Dr. Timlin had no relevant disclosures. Several of her colleagues had multiple financial disclosures.
On Twitter @maryjodales
Ibrutinib given at doses lower than the standard dose of 420 mg/day was associated with comparable overall survival and progression-free survival as the standard dose in patients with chronic lymphocytic leukemia (CLL), based on the results of a multicenter, retrospective study submitted as a poster at the annual meeting of the American Society of Clinical Oncology.
The initial findings indicate patients who experience toxicity on the 420 mg/day dosage can still do well on a slightly lower dose of ibrutinib, reported Colleen Timlin, Pharm.D., of the Hospital of the University of Pennsylvania, Philadelphia, and her associates.
At a median follow-up of 13.5 months, the median progression-free survival was 37.4 months in the standard dose group and the median progression-free survival had not been reached in the reduced-dose group. The median overall survival had not been reached in either group. The hazard ratio in the reduced-dose group was 1.2 for progression-free survival and 0.6 for overall survival; neither difference was statistically significant. Best overall response rate was 85% in the standard-dose group and 84% in the reduced-dose group.
The study included 197 patients, 37 of whom were shifted to reduced doses of ibrutinib within 3 months of initiating therapy at the recommended 420 mg/day dosage. For reduced-dose patients, the median ibrutinib dose was 4.3 mg/kg per day. The most common reasons for reducing the ibrutinib dose were gastrointestinal toxicity, bleeding, rash, cardiotoxicity, and renal insufficiency, the researchers said.
Most of the patients treated with doses less than 420 mg/day still maintained a dose of greater than 2.5 mg/kg per day, which assured adequate Bruton’s tyrosine kinase occupancy. The 420 mg/day dosage noted in the labeling was established, based on achievement of greater than 90% Bruton’s tyrosine kinase occupancy. Fewer patients achieve greater than 90% occupancy at lower doses, but lower doses may not translate into inferior outcomes.
Weight-based dosing should be considered in future studies and pharmacoeconomic analyses. Comparative analyses of toxicity profiles stratified by ibrutinib dose are underway, according to Dr. Timlin and her colleagues.
Dr. Timlin had no relevant disclosures. Several of her colleagues had multiple financial disclosures.
On Twitter @maryjodales
Key clinical point: Ibrutinib given at doses lower than the standard dose of 420 mg/day may achieve comparable overall survival and progression-free survival.
Major finding: At a median follow-up of 13.5 months, the median progression-free survival was 37.4 months in the standard dose group, and the median progression-free survival had not been reached in the reduced-dose group.
Data source: A multicenter, retrospective study of 197 patients.
Disclosures: Dr. Timlin had no relevant disclosures. Several of her colleagues had multiple financial disclosures.
Study provides clues to AML survival after chemotherapy
Preclinical research suggests that some leukemia cells harvest energy resources from normal cells during chemotherapy, and this helps the leukemia cells survive and thrive after treatment.
Investigators found that acute myeloid leukemia (AML) cells are capable of stealing mitochondria from stromal cells, and these stolen mitochondria give an energy boost to surviving AML cells, which helps fuel the leukemia’s resurgence after chemotherapy.
“There are multiple mechanisms for resistance to chemotherapy, and it will be important to target them all in order to eliminate all leukemic cells,” said Jean-François Peyron, PhD, of the Centre Méditerranéen de Médecine Moléculaire (C3M) in Nice, France.
“Targeting this protective mitochondrial transfer could represent a new strategy to improve the efficacy of the current treatments for acute myeloid leukemia.”
Dr Peyron and his colleagues described their discovery of the mitochondrial transfer in Blood.
The team conducted their experiments using cell cultures and mouse models of AML. They found that nearly all AML cells died when exposed to chemotherapy drugs, but some survived. And these cells issued a “mayday” signal that “tricked” nearby non-cancerous cells into yielding their mitochondria to the AML cells, thus strengthening the leukemia cells.
“Mitochondria produce the energy that is vital for cell functions,” explained study author Emmanuel Griessinger, PhD, also of C3M.
“Through the uptake of mitochondria, chemotherapy-injured acute myeloid leukemia cells recover new energy to survive.”
The AML cells were found to increase their mitochondria mass by an average of 14%. This increase led to a 1.5-fold increase in energy production and significantly better survival rates. That is, the leukemia cells that had a high level of mitochondria were also more resistant to the chemotherapy.
The investigators observed the phenomenon in several types of leukemia cells, most notably leukemia-initiating cells. The team said this finding may explain why it can be difficult to treat AML and other cancers.
They also believe these findings offer new hope for developing better treatments for AML. If researchers can find a way to interfere with the transfer of mitochondria, that could reduce the risk of relapse.
The study may also shed light on other cancer types. Similar mechanisms may be at play in other hematologic malignancies and even solid tumors, according to the investigators.
For now, the team’s next step for this research is to identify the mechanism underlying the transfer of mitochondria in AML.
Preclinical research suggests that some leukemia cells harvest energy resources from normal cells during chemotherapy, and this helps the leukemia cells survive and thrive after treatment.
Investigators found that acute myeloid leukemia (AML) cells are capable of stealing mitochondria from stromal cells, and these stolen mitochondria give an energy boost to surviving AML cells, which helps fuel the leukemia’s resurgence after chemotherapy.
“There are multiple mechanisms for resistance to chemotherapy, and it will be important to target them all in order to eliminate all leukemic cells,” said Jean-François Peyron, PhD, of the Centre Méditerranéen de Médecine Moléculaire (C3M) in Nice, France.
“Targeting this protective mitochondrial transfer could represent a new strategy to improve the efficacy of the current treatments for acute myeloid leukemia.”
Dr Peyron and his colleagues described their discovery of the mitochondrial transfer in Blood.
The team conducted their experiments using cell cultures and mouse models of AML. They found that nearly all AML cells died when exposed to chemotherapy drugs, but some survived. And these cells issued a “mayday” signal that “tricked” nearby non-cancerous cells into yielding their mitochondria to the AML cells, thus strengthening the leukemia cells.
“Mitochondria produce the energy that is vital for cell functions,” explained study author Emmanuel Griessinger, PhD, also of C3M.
“Through the uptake of mitochondria, chemotherapy-injured acute myeloid leukemia cells recover new energy to survive.”
The AML cells were found to increase their mitochondria mass by an average of 14%. This increase led to a 1.5-fold increase in energy production and significantly better survival rates. That is, the leukemia cells that had a high level of mitochondria were also more resistant to the chemotherapy.
The investigators observed the phenomenon in several types of leukemia cells, most notably leukemia-initiating cells. The team said this finding may explain why it can be difficult to treat AML and other cancers.
They also believe these findings offer new hope for developing better treatments for AML. If researchers can find a way to interfere with the transfer of mitochondria, that could reduce the risk of relapse.
The study may also shed light on other cancer types. Similar mechanisms may be at play in other hematologic malignancies and even solid tumors, according to the investigators.
For now, the team’s next step for this research is to identify the mechanism underlying the transfer of mitochondria in AML.
Preclinical research suggests that some leukemia cells harvest energy resources from normal cells during chemotherapy, and this helps the leukemia cells survive and thrive after treatment.
Investigators found that acute myeloid leukemia (AML) cells are capable of stealing mitochondria from stromal cells, and these stolen mitochondria give an energy boost to surviving AML cells, which helps fuel the leukemia’s resurgence after chemotherapy.
“There are multiple mechanisms for resistance to chemotherapy, and it will be important to target them all in order to eliminate all leukemic cells,” said Jean-François Peyron, PhD, of the Centre Méditerranéen de Médecine Moléculaire (C3M) in Nice, France.
“Targeting this protective mitochondrial transfer could represent a new strategy to improve the efficacy of the current treatments for acute myeloid leukemia.”
Dr Peyron and his colleagues described their discovery of the mitochondrial transfer in Blood.
The team conducted their experiments using cell cultures and mouse models of AML. They found that nearly all AML cells died when exposed to chemotherapy drugs, but some survived. And these cells issued a “mayday” signal that “tricked” nearby non-cancerous cells into yielding their mitochondria to the AML cells, thus strengthening the leukemia cells.
“Mitochondria produce the energy that is vital for cell functions,” explained study author Emmanuel Griessinger, PhD, also of C3M.
“Through the uptake of mitochondria, chemotherapy-injured acute myeloid leukemia cells recover new energy to survive.”
The AML cells were found to increase their mitochondria mass by an average of 14%. This increase led to a 1.5-fold increase in energy production and significantly better survival rates. That is, the leukemia cells that had a high level of mitochondria were also more resistant to the chemotherapy.
The investigators observed the phenomenon in several types of leukemia cells, most notably leukemia-initiating cells. The team said this finding may explain why it can be difficult to treat AML and other cancers.
They also believe these findings offer new hope for developing better treatments for AML. If researchers can find a way to interfere with the transfer of mitochondria, that could reduce the risk of relapse.
The study may also shed light on other cancer types. Similar mechanisms may be at play in other hematologic malignancies and even solid tumors, according to the investigators.
For now, the team’s next step for this research is to identify the mechanism underlying the transfer of mitochondria in AML.
FDA reports shortage of doxorubicin for injection, initiates importation
A critical shortage of doxorubicin hydrochloride 50 mg powder for injection has been reported to the Food and Drug Administration.
Doxorubicin is approved to treat acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, gastric cancer, ovarian cancer, neuroblastoma, and other cancer types.
To increase availability, the pharmaceutical company Hospira (a Pfizer company) is coordinating with the FDA to import the drug from Ahmedabad, India, where it is manufactured by Zydus Hospira Oncology Private Ltd. at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements.
“It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved doxorubicin hydrochloride for injection, USP and the Hospira Limited’s doxorubicin hydrochloride 50 mg powder for injection,” Hospira reported in a letter to health care providers.
To place an order or to get questions answered, contact Hospira directly by calling customer care at 1-877-946-7747 (Mondays-Fridays, 7 a.m.-6 p.m. Central time).
For clinical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or email medcom@hospira.com.
According to the letter, adverse events or quality problems associated with use of this product should be reported by calling Hospira Global Complaint Management by phone, 1-800-441-4100; by sending an email to ProductComplaintsPP@hospira.com; or by submitting a report online to Medwatch.
On Twitter @jessnicolecraig
A critical shortage of doxorubicin hydrochloride 50 mg powder for injection has been reported to the Food and Drug Administration.
Doxorubicin is approved to treat acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, gastric cancer, ovarian cancer, neuroblastoma, and other cancer types.
To increase availability, the pharmaceutical company Hospira (a Pfizer company) is coordinating with the FDA to import the drug from Ahmedabad, India, where it is manufactured by Zydus Hospira Oncology Private Ltd. at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements.
“It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved doxorubicin hydrochloride for injection, USP and the Hospira Limited’s doxorubicin hydrochloride 50 mg powder for injection,” Hospira reported in a letter to health care providers.
To place an order or to get questions answered, contact Hospira directly by calling customer care at 1-877-946-7747 (Mondays-Fridays, 7 a.m.-6 p.m. Central time).
For clinical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or email medcom@hospira.com.
According to the letter, adverse events or quality problems associated with use of this product should be reported by calling Hospira Global Complaint Management by phone, 1-800-441-4100; by sending an email to ProductComplaintsPP@hospira.com; or by submitting a report online to Medwatch.
On Twitter @jessnicolecraig
A critical shortage of doxorubicin hydrochloride 50 mg powder for injection has been reported to the Food and Drug Administration.
Doxorubicin is approved to treat acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, gastric cancer, ovarian cancer, neuroblastoma, and other cancer types.
To increase availability, the pharmaceutical company Hospira (a Pfizer company) is coordinating with the FDA to import the drug from Ahmedabad, India, where it is manufactured by Zydus Hospira Oncology Private Ltd. at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements.
“It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved doxorubicin hydrochloride for injection, USP and the Hospira Limited’s doxorubicin hydrochloride 50 mg powder for injection,” Hospira reported in a letter to health care providers.
To place an order or to get questions answered, contact Hospira directly by calling customer care at 1-877-946-7747 (Mondays-Fridays, 7 a.m.-6 p.m. Central time).
For clinical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or email medcom@hospira.com.
According to the letter, adverse events or quality problems associated with use of this product should be reported by calling Hospira Global Complaint Management by phone, 1-800-441-4100; by sending an email to ProductComplaintsPP@hospira.com; or by submitting a report online to Medwatch.
On Twitter @jessnicolecraig
How CML cells respond to stress
Image by Difu Wu
Researchers have used a tiny force probe to compare how healthy hematopoietic cells and cancerous ones respond to stress.
They found that cells harvested from the bone marrow of 5 patients with chronic myeloid leukemia (CML) appeared much stiffer than comparable samples taken from 5 healthy volunteers.
In addition, the researchers were able to identify areas of localized brittle failure events in the CML cells.
“What makes this work so exciting to us is not simply seeing a difference between the stiffness of healthy and cancerous cells but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” said study author Françoise Argoul, PhD, of the French National Centre for Research (CNRS) in Lyon, France.
Dr Argoul and her colleagues described this work in Physical Biology.
The researchers believe the mechanical signatures obtained by squeezing or deforming cells could potentially assist physicians in determining the presence of CML and other hematologic malignancies.
The mechanical data might also provide clues as to how long the cells have been affected by the cancer.
“We would like to construct a hematopoietic cancer cell chart where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” Dr Argoul said.
Thinking about how the technique might be applied in a hospital setting, she added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures.
However, before the researchers can even progress to testing cells inside the body and preparing for clinical trials, they must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab.
Image by Difu Wu
Researchers have used a tiny force probe to compare how healthy hematopoietic cells and cancerous ones respond to stress.
They found that cells harvested from the bone marrow of 5 patients with chronic myeloid leukemia (CML) appeared much stiffer than comparable samples taken from 5 healthy volunteers.
In addition, the researchers were able to identify areas of localized brittle failure events in the CML cells.
“What makes this work so exciting to us is not simply seeing a difference between the stiffness of healthy and cancerous cells but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” said study author Françoise Argoul, PhD, of the French National Centre for Research (CNRS) in Lyon, France.
Dr Argoul and her colleagues described this work in Physical Biology.
The researchers believe the mechanical signatures obtained by squeezing or deforming cells could potentially assist physicians in determining the presence of CML and other hematologic malignancies.
The mechanical data might also provide clues as to how long the cells have been affected by the cancer.
“We would like to construct a hematopoietic cancer cell chart where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” Dr Argoul said.
Thinking about how the technique might be applied in a hospital setting, she added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures.
However, before the researchers can even progress to testing cells inside the body and preparing for clinical trials, they must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab.
Image by Difu Wu
Researchers have used a tiny force probe to compare how healthy hematopoietic cells and cancerous ones respond to stress.
They found that cells harvested from the bone marrow of 5 patients with chronic myeloid leukemia (CML) appeared much stiffer than comparable samples taken from 5 healthy volunteers.
In addition, the researchers were able to identify areas of localized brittle failure events in the CML cells.
“What makes this work so exciting to us is not simply seeing a difference between the stiffness of healthy and cancerous cells but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” said study author Françoise Argoul, PhD, of the French National Centre for Research (CNRS) in Lyon, France.
Dr Argoul and her colleagues described this work in Physical Biology.
The researchers believe the mechanical signatures obtained by squeezing or deforming cells could potentially assist physicians in determining the presence of CML and other hematologic malignancies.
The mechanical data might also provide clues as to how long the cells have been affected by the cancer.
“We would like to construct a hematopoietic cancer cell chart where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” Dr Argoul said.
Thinking about how the technique might be applied in a hospital setting, she added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures.
However, before the researchers can even progress to testing cells inside the body and preparing for clinical trials, they must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab.
Better ways to drive CAR T-cell therapy
© ASCO/Brian Powers
CHICAGO—Treatment dose and schedule, as well as a patient’s tumor burden, influence the outcome of therapy with chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASCO Annual Meeting.
One presentation suggested the dose and schedule of CTL019 can impact both complete response (CR) rates and the incidence of cytokine release syndrome (CRS).
Another presentation indicated that disease burden may determine the risk of toxicity and correlate with the efficacy of JCAR015.
CTL019
Noelle Frey, MD, of the University of Pennsylvania in Philadelphia, presented results observed with CTL019 in 30 adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated on 2 trials (NCT02030847 and NCT01029366) as abstract 7002.*
Dr Frey noted that CAR T-cell therapies, including CTL019, have led to “unprecedented remission rates of between 70% and 90%.” However, immune activation that leads to high response rates also confers significant treatment-related toxicity—namely, CRS.
She reported that, in the 2 trials of adult ALL patients, a high dose of CTL019 led to a 100% response rate and a 100% CRS rate. Splitting the dose over 3 days led to an 86% response rate and a 66% CRS rate. A single low dose reduced efficacy to 33% and CRS to 66%.
Three of 6 patients who received a single high dose developed CRS and died within weeks. All of these patients had infections or sepsis that likely led to their deaths, Dr Frey said. She suggested clinicians aggressively monitor infections and treat with antimicrobials prior to CAR T-cell therapy.
“The infusion dose and schedule of CTL019 correlate with toxicity and response,” she observed. “A fractionated dosing scheme allows for real-time intra-patient dose modification in response to toxicity and the maintenance of high response rates. Concurrent sepsis and CRS confers a poor outcome.”
Dr Frey said future studies will determine the optimal approach to minimize toxicity while maintaining high efficacy. A fractionated dosing scheme is only one way to mitigate CRS. Other attractive approaches include inverse dosing based on disease burden and varying the timing of anti-cytokine-directed therapy.
JCAR015
Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, reported data from a phase 1 clinical trial (NCT01044069) of JCAR015 in 51 adults with relapsed/refractory ALL as abstract 7003.*
Treatment with JCAR015 led to high CR rates and minimal residual disease (MRD)-negativity, regardless of the amount of disease at baseline. However, outcomes were superior among patients with minimal disease at baseline.
For patients with morphologic disease, 77% achieved a CR by 20 days after treatment, and 90% were MRD-negative.
For those with minimal disease, 90% achieved a CR by 25 days after treatment, and 78% were MRD-negative. These patients experienced significantly less CRS and neurotoxicity than patients with morphologic disease.
“High CR and MRD-negativity rates were observed regardless of pre-T-cell burden,” Dr Park noted. “We observed durable responses and survivals in a subset of patients with no subsequent allotransplant in both morphological and minimal disease cohorts.”
*Data in the abstracts differ from the presentations.
© ASCO/Brian Powers
CHICAGO—Treatment dose and schedule, as well as a patient’s tumor burden, influence the outcome of therapy with chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASCO Annual Meeting.
One presentation suggested the dose and schedule of CTL019 can impact both complete response (CR) rates and the incidence of cytokine release syndrome (CRS).
Another presentation indicated that disease burden may determine the risk of toxicity and correlate with the efficacy of JCAR015.
CTL019
Noelle Frey, MD, of the University of Pennsylvania in Philadelphia, presented results observed with CTL019 in 30 adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated on 2 trials (NCT02030847 and NCT01029366) as abstract 7002.*
Dr Frey noted that CAR T-cell therapies, including CTL019, have led to “unprecedented remission rates of between 70% and 90%.” However, immune activation that leads to high response rates also confers significant treatment-related toxicity—namely, CRS.
She reported that, in the 2 trials of adult ALL patients, a high dose of CTL019 led to a 100% response rate and a 100% CRS rate. Splitting the dose over 3 days led to an 86% response rate and a 66% CRS rate. A single low dose reduced efficacy to 33% and CRS to 66%.
Three of 6 patients who received a single high dose developed CRS and died within weeks. All of these patients had infections or sepsis that likely led to their deaths, Dr Frey said. She suggested clinicians aggressively monitor infections and treat with antimicrobials prior to CAR T-cell therapy.
“The infusion dose and schedule of CTL019 correlate with toxicity and response,” she observed. “A fractionated dosing scheme allows for real-time intra-patient dose modification in response to toxicity and the maintenance of high response rates. Concurrent sepsis and CRS confers a poor outcome.”
Dr Frey said future studies will determine the optimal approach to minimize toxicity while maintaining high efficacy. A fractionated dosing scheme is only one way to mitigate CRS. Other attractive approaches include inverse dosing based on disease burden and varying the timing of anti-cytokine-directed therapy.
JCAR015
Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, reported data from a phase 1 clinical trial (NCT01044069) of JCAR015 in 51 adults with relapsed/refractory ALL as abstract 7003.*
Treatment with JCAR015 led to high CR rates and minimal residual disease (MRD)-negativity, regardless of the amount of disease at baseline. However, outcomes were superior among patients with minimal disease at baseline.
For patients with morphologic disease, 77% achieved a CR by 20 days after treatment, and 90% were MRD-negative.
For those with minimal disease, 90% achieved a CR by 25 days after treatment, and 78% were MRD-negative. These patients experienced significantly less CRS and neurotoxicity than patients with morphologic disease.
“High CR and MRD-negativity rates were observed regardless of pre-T-cell burden,” Dr Park noted. “We observed durable responses and survivals in a subset of patients with no subsequent allotransplant in both morphological and minimal disease cohorts.”
*Data in the abstracts differ from the presentations.
© ASCO/Brian Powers
CHICAGO—Treatment dose and schedule, as well as a patient’s tumor burden, influence the outcome of therapy with chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASCO Annual Meeting.
One presentation suggested the dose and schedule of CTL019 can impact both complete response (CR) rates and the incidence of cytokine release syndrome (CRS).
Another presentation indicated that disease burden may determine the risk of toxicity and correlate with the efficacy of JCAR015.
CTL019
Noelle Frey, MD, of the University of Pennsylvania in Philadelphia, presented results observed with CTL019 in 30 adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated on 2 trials (NCT02030847 and NCT01029366) as abstract 7002.*
Dr Frey noted that CAR T-cell therapies, including CTL019, have led to “unprecedented remission rates of between 70% and 90%.” However, immune activation that leads to high response rates also confers significant treatment-related toxicity—namely, CRS.
She reported that, in the 2 trials of adult ALL patients, a high dose of CTL019 led to a 100% response rate and a 100% CRS rate. Splitting the dose over 3 days led to an 86% response rate and a 66% CRS rate. A single low dose reduced efficacy to 33% and CRS to 66%.
Three of 6 patients who received a single high dose developed CRS and died within weeks. All of these patients had infections or sepsis that likely led to their deaths, Dr Frey said. She suggested clinicians aggressively monitor infections and treat with antimicrobials prior to CAR T-cell therapy.
“The infusion dose and schedule of CTL019 correlate with toxicity and response,” she observed. “A fractionated dosing scheme allows for real-time intra-patient dose modification in response to toxicity and the maintenance of high response rates. Concurrent sepsis and CRS confers a poor outcome.”
Dr Frey said future studies will determine the optimal approach to minimize toxicity while maintaining high efficacy. A fractionated dosing scheme is only one way to mitigate CRS. Other attractive approaches include inverse dosing based on disease burden and varying the timing of anti-cytokine-directed therapy.
JCAR015
Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, reported data from a phase 1 clinical trial (NCT01044069) of JCAR015 in 51 adults with relapsed/refractory ALL as abstract 7003.*
Treatment with JCAR015 led to high CR rates and minimal residual disease (MRD)-negativity, regardless of the amount of disease at baseline. However, outcomes were superior among patients with minimal disease at baseline.
For patients with morphologic disease, 77% achieved a CR by 20 days after treatment, and 90% were MRD-negative.
For those with minimal disease, 90% achieved a CR by 25 days after treatment, and 78% were MRD-negative. These patients experienced significantly less CRS and neurotoxicity than patients with morphologic disease.
“High CR and MRD-negativity rates were observed regardless of pre-T-cell burden,” Dr Park noted. “We observed durable responses and survivals in a subset of patients with no subsequent allotransplant in both morphological and minimal disease cohorts.”
*Data in the abstracts differ from the presentations.
No kidding: Adults fare better with pediatric ALL regimen
COPENHAGEN – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.
In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.
“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).
The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.
In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.
The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol, consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.
Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.
All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.
The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.
After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.
There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.
Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).
Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.
“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.
“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.
The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.
COPENHAGEN – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.
In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.
“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).
The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.
In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.
The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol, consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.
Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.
All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.
The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.
After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.
There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.
Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).
Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.
“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.
“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.
The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.
COPENHAGEN – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.
In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.
“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).
The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.
In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.
The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol, consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.
Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.
All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.
The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.
After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.
There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.
Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).
Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.
“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.
“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.
The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.
AT THE EHA CONGRESS
Key clinical point: Younger adults with acute lymphoblastic leukemia have better outcomes when treated with more intensive chemotherapy regimens designed for children with ALL.
Major finding: No significant differences were found in event-free survival between children and adults, except for a slightly lower EFS among adults with intermediate risk.
Data source: A prospective study of 1,509 children and adults with ALL in seven Nordic and Baltic countries.
Disclosures: The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.