ALL

Photo by Rhoda Baer

Socioeconomic deprivation may decrease survival in adults with acute lymphoblastic leukemia (ALL), according to research published in BMC Cancer.

Researchers found that ALL patients living in more deprived areas of England had a 16% to 21% greater risk of dying than patients living in the least deprived areas.

The researchers also observed a 33% higher risk of mortality in patients who were treated at hospitals that manage few ALL patients.

“The findings are likely to have significant implications for the organization of NHS [National Health Service] services for the treatment of adults with this rare but serious condition,” said study author Ravi Maheswaran, MD, of the University of Sheffield in Sheffield, UK.

To conduct this study, Dr Maheswaran and Nick Morley, MBBS, of Royal Hallamshire Hospital in Sheffield, analyzed anonymized NHS data on hospital admissions.

The researchers identified 2921 adults (age 18 and older) who were diagnosed with ALL from 2001 to 2012 and assessed follow-up data on survival rates up to 2013.

There were 1870 deaths during follow-up, and the 5-year survival rate was 32%.

As expected, survival decreased with age but increased over time. The mortality hazard ratio (HR) was 1.38 for patients ages 30 to 39, 3.72 for patients ages 60 to 69, and 9.02 for patients age 80 and older.

The HR was 0.98 for patients diagnosed from 2005 to 2008 and 0.70 for patients diagnosed from 2009 to 2012, compared to 1.00 for patients diagnosed from 2001 to 2004.

Patients living in areas of socioeconomic deprivation had a greater risk of death, but it did not seem to matter whether the patients lived in rural or urban areas.

The mortality HR was 1.16 for patients living in the most deprived areas and 1.21 for patients in intermediate areas (with the least deprived areas as the reference, 1.00). The HR was 1.00 for both rural and urban areas.

The risk of death was higher for patients treated at hospitals with low volumes of adults with ALL. The mortality HR was 1.33 for low-volume hospitals, which were defined as hospitals with 15 or fewer ALL patients admitted over a 3-year time period for which data were available.

“These results, although concerning, are from a single study, and further work is needed to confirm our findings,” Dr Maheswaran said.

“If the association between high deprivation and poorer survival is confirmed, more investigation will be needed to understand why adults with this type of leukemia living in deprived areas have poorer survival and what can be done to address this inequality.”

“Confirmation that hospitals treating few patients with this rare condition have worse outcomes would mean that the NHS should seriously consider if treatment services for adults with acute lymphoblastic leukemia should mainly be provided by specialist centers in order to improve survival.”

Photo by Rhoda Baer

Socioeconomic deprivation may decrease survival in adults with acute lymphoblastic leukemia (ALL), according to research published in BMC Cancer.

Researchers found that ALL patients living in more deprived areas of England had a 16% to 21% greater risk of dying than patients living in the least deprived areas.

The researchers also observed a 33% higher risk of mortality in patients who were treated at hospitals that manage few ALL patients.

“The findings are likely to have significant implications for the organization of NHS [National Health Service] services for the treatment of adults with this rare but serious condition,” said study author Ravi Maheswaran, MD, of the University of Sheffield in Sheffield, UK.

To conduct this study, Dr Maheswaran and Nick Morley, MBBS, of Royal Hallamshire Hospital in Sheffield, analyzed anonymized NHS data on hospital admissions.

The researchers identified 2921 adults (age 18 and older) who were diagnosed with ALL from 2001 to 2012 and assessed follow-up data on survival rates up to 2013.

There were 1870 deaths during follow-up, and the 5-year survival rate was 32%.

As expected, survival decreased with age but increased over time. The mortality hazard ratio (HR) was 1.38 for patients ages 30 to 39, 3.72 for patients ages 60 to 69, and 9.02 for patients age 80 and older.

The HR was 0.98 for patients diagnosed from 2005 to 2008 and 0.70 for patients diagnosed from 2009 to 2012, compared to 1.00 for patients diagnosed from 2001 to 2004.

Patients living in areas of socioeconomic deprivation had a greater risk of death, but it did not seem to matter whether the patients lived in rural or urban areas.

The mortality HR was 1.16 for patients living in the most deprived areas and 1.21 for patients in intermediate areas (with the least deprived areas as the reference, 1.00). The HR was 1.00 for both rural and urban areas.

The risk of death was higher for patients treated at hospitals with low volumes of adults with ALL. The mortality HR was 1.33 for low-volume hospitals, which were defined as hospitals with 15 or fewer ALL patients admitted over a 3-year time period for which data were available.

“These results, although concerning, are from a single study, and further work is needed to confirm our findings,” Dr Maheswaran said.

“If the association between high deprivation and poorer survival is confirmed, more investigation will be needed to understand why adults with this type of leukemia living in deprived areas have poorer survival and what can be done to address this inequality.”

“Confirmation that hospitals treating few patients with this rare condition have worse outcomes would mean that the NHS should seriously consider if treatment services for adults with acute lymphoblastic leukemia should mainly be provided by specialist centers in order to improve survival.”

Photo by Rhoda Baer

Socioeconomic deprivation may decrease survival in adults with acute lymphoblastic leukemia (ALL), according to research published in BMC Cancer.

Researchers found that ALL patients living in more deprived areas of England had a 16% to 21% greater risk of dying than patients living in the least deprived areas.

The researchers also observed a 33% higher risk of mortality in patients who were treated at hospitals that manage few ALL patients.

“The findings are likely to have significant implications for the organization of NHS [National Health Service] services for the treatment of adults with this rare but serious condition,” said study author Ravi Maheswaran, MD, of the University of Sheffield in Sheffield, UK.

To conduct this study, Dr Maheswaran and Nick Morley, MBBS, of Royal Hallamshire Hospital in Sheffield, analyzed anonymized NHS data on hospital admissions.

The researchers identified 2921 adults (age 18 and older) who were diagnosed with ALL from 2001 to 2012 and assessed follow-up data on survival rates up to 2013.

There were 1870 deaths during follow-up, and the 5-year survival rate was 32%.

As expected, survival decreased with age but increased over time. The mortality hazard ratio (HR) was 1.38 for patients ages 30 to 39, 3.72 for patients ages 60 to 69, and 9.02 for patients age 80 and older.

The HR was 0.98 for patients diagnosed from 2005 to 2008 and 0.70 for patients diagnosed from 2009 to 2012, compared to 1.00 for patients diagnosed from 2001 to 2004.

Patients living in areas of socioeconomic deprivation had a greater risk of death, but it did not seem to matter whether the patients lived in rural or urban areas.

The mortality HR was 1.16 for patients living in the most deprived areas and 1.21 for patients in intermediate areas (with the least deprived areas as the reference, 1.00). The HR was 1.00 for both rural and urban areas.

The risk of death was higher for patients treated at hospitals with low volumes of adults with ALL. The mortality HR was 1.33 for low-volume hospitals, which were defined as hospitals with 15 or fewer ALL patients admitted over a 3-year time period for which data were available.

“These results, although concerning, are from a single study, and further work is needed to confirm our findings,” Dr Maheswaran said.

“If the association between high deprivation and poorer survival is confirmed, more investigation will be needed to understand why adults with this type of leukemia living in deprived areas have poorer survival and what can be done to address this inequality.”

“Confirmation that hospitals treating few patients with this rare condition have worse outcomes would mean that the NHS should seriously consider if treatment services for adults with acute lymphoblastic leukemia should mainly be provided by specialist centers in order to improve survival.”

Hospital of Philadelphia

Updated results from the phase 2 ELIANA study have shown that tisagenlecleucel can produce durable complete responses (CRs) in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).

Sixty percent of patients who received the chimeric antigen receptor (CAR) T-cell therapy achieved a CR, and 21% had a CR with incomplete hematologic recovery (CRi).

The median duration of CR/CRi was not reached at a median follow-up of 13.1 months.

The most common treatment-related adverse event (AE) was cytokine release syndrome (CRS), occurring in 77% of patients.

Researchers reported these results in NEJM. The study was sponsored by Novartis.

“This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed,” said study author Shannon L. Maude, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.

“Our data show not only can we can achieve longer-term durable remissions and longer-term survival for our patients but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job.”

The trial included 75 patients who received tisagenlecleucel. At enrollment, the patients’ median age was 11 (range, 3 to 23).

Patients had received a median of 3 prior therapies (range, 1 to 8), and they had a median marrow blast percentage of 74% (range, 5 to 99).

All patients received a single infusion of tisagenlecleucel. Most (n=72) received lymphodepleting chemotherapy prior to the CAR T cells.

Results

The median duration of follow-up was 13.1 months.

The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CRi within 3 months. The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

The researchers said tisagenlecleucel persisted in the blood for as long as 20 months.

The relapse-free survival rate among patients with a CR/CRi was 80% at 6 months and 59% at 12 months.

Seventeen patients who had achieved a CR relapsed before receiving subsequent treatment. Three patients went on to subsequent therapy before relapse but ultimately relapsed.

Relapse was also reported in 2 patients who had been classified as non-responders because they did not maintain a response for at least 28 days.

Eight patients underwent allogeneic hematopoietic stem cell transplant while in remission, and all 8 were alive when the manuscript for this study was submitted. Four patients had not relapsed, and the other 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the overall survival rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least 1 AE, and 95% had AEs thought to be related to tisagenlecleucel. Grade 3/4 AEs occurred in 88% of patients. In 73% of patients, these AEs were thought to be related to treatment.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

The median duration of CRS was 8 days (range, 1-36). Forty-seven patients were admitted to the intensive care unit to receive treatment for CRS, with a median stay of 7 days (range, 1-34).

“One of our more challenging questions—‘Can we manage the serious side effects of CAR T-cell therapy?’—was asked and answered in this global study,” said author Stephan A. Grupp, MD, PhD, of Children’s Hospital of Philadelphia.

“Some of our patients get very sick, but we showed that most toxic effects can be short-lived and reversible, with the potential for our patients to achieve durable complete remissions. That’s a pretty amazing turnaround for the high-risk child who, up until now, had little chance of surviving.”

Hospital of Philadelphia

Updated results from the phase 2 ELIANA study have shown that tisagenlecleucel can produce durable complete responses (CRs) in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).

Sixty percent of patients who received the chimeric antigen receptor (CAR) T-cell therapy achieved a CR, and 21% had a CR with incomplete hematologic recovery (CRi).

The median duration of CR/CRi was not reached at a median follow-up of 13.1 months.

The most common treatment-related adverse event (AE) was cytokine release syndrome (CRS), occurring in 77% of patients.

Researchers reported these results in NEJM. The study was sponsored by Novartis.

“This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed,” said study author Shannon L. Maude, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.

“Our data show not only can we can achieve longer-term durable remissions and longer-term survival for our patients but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job.”

The trial included 75 patients who received tisagenlecleucel. At enrollment, the patients’ median age was 11 (range, 3 to 23).

Patients had received a median of 3 prior therapies (range, 1 to 8), and they had a median marrow blast percentage of 74% (range, 5 to 99).

All patients received a single infusion of tisagenlecleucel. Most (n=72) received lymphodepleting chemotherapy prior to the CAR T cells.

Results

The median duration of follow-up was 13.1 months.

The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CRi within 3 months. The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

The researchers said tisagenlecleucel persisted in the blood for as long as 20 months.

The relapse-free survival rate among patients with a CR/CRi was 80% at 6 months and 59% at 12 months.

Seventeen patients who had achieved a CR relapsed before receiving subsequent treatment. Three patients went on to subsequent therapy before relapse but ultimately relapsed.

Relapse was also reported in 2 patients who had been classified as non-responders because they did not maintain a response for at least 28 days.

Eight patients underwent allogeneic hematopoietic stem cell transplant while in remission, and all 8 were alive when the manuscript for this study was submitted. Four patients had not relapsed, and the other 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the overall survival rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least 1 AE, and 95% had AEs thought to be related to tisagenlecleucel. Grade 3/4 AEs occurred in 88% of patients. In 73% of patients, these AEs were thought to be related to treatment.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

The median duration of CRS was 8 days (range, 1-36). Forty-seven patients were admitted to the intensive care unit to receive treatment for CRS, with a median stay of 7 days (range, 1-34).

“One of our more challenging questions—‘Can we manage the serious side effects of CAR T-cell therapy?’—was asked and answered in this global study,” said author Stephan A. Grupp, MD, PhD, of Children’s Hospital of Philadelphia.

“Some of our patients get very sick, but we showed that most toxic effects can be short-lived and reversible, with the potential for our patients to achieve durable complete remissions. That’s a pretty amazing turnaround for the high-risk child who, up until now, had little chance of surviving.”

Hospital of Philadelphia

Updated results from the phase 2 ELIANA study have shown that tisagenlecleucel can produce durable complete responses (CRs) in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).

Sixty percent of patients who received the chimeric antigen receptor (CAR) T-cell therapy achieved a CR, and 21% had a CR with incomplete hematologic recovery (CRi).

The median duration of CR/CRi was not reached at a median follow-up of 13.1 months.

The most common treatment-related adverse event (AE) was cytokine release syndrome (CRS), occurring in 77% of patients.

Researchers reported these results in NEJM. The study was sponsored by Novartis.

“This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed,” said study author Shannon L. Maude, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.

“Our data show not only can we can achieve longer-term durable remissions and longer-term survival for our patients but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job.”

The trial included 75 patients who received tisagenlecleucel. At enrollment, the patients’ median age was 11 (range, 3 to 23).

Patients had received a median of 3 prior therapies (range, 1 to 8), and they had a median marrow blast percentage of 74% (range, 5 to 99).

All patients received a single infusion of tisagenlecleucel. Most (n=72) received lymphodepleting chemotherapy prior to the CAR T cells.

Results

The median duration of follow-up was 13.1 months.

The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CRi within 3 months. The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

The researchers said tisagenlecleucel persisted in the blood for as long as 20 months.

The relapse-free survival rate among patients with a CR/CRi was 80% at 6 months and 59% at 12 months.

Seventeen patients who had achieved a CR relapsed before receiving subsequent treatment. Three patients went on to subsequent therapy before relapse but ultimately relapsed.

Relapse was also reported in 2 patients who had been classified as non-responders because they did not maintain a response for at least 28 days.

Eight patients underwent allogeneic hematopoietic stem cell transplant while in remission, and all 8 were alive when the manuscript for this study was submitted. Four patients had not relapsed, and the other 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the overall survival rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least 1 AE, and 95% had AEs thought to be related to tisagenlecleucel. Grade 3/4 AEs occurred in 88% of patients. In 73% of patients, these AEs were thought to be related to treatment.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

The median duration of CRS was 8 days (range, 1-36). Forty-seven patients were admitted to the intensive care unit to receive treatment for CRS, with a median stay of 7 days (range, 1-34).

“One of our more challenging questions—‘Can we manage the serious side effects of CAR T-cell therapy?’—was asked and answered in this global study,” said author Stephan A. Grupp, MD, PhD, of Children’s Hospital of Philadelphia.

“Some of our patients get very sick, but we showed that most toxic effects can be short-lived and reversible, with the potential for our patients to achieve durable complete remissions. That’s a pretty amazing turnaround for the high-risk child who, up until now, had little chance of surviving.”

Tisagenlecleucel was associated with durable remission and long-term persistence for younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to the results of a multicenter, multicontinent, phase 2 trial published in the New England Journal of Medicine.

Shannon L. Maude, MD, PhD, of the Children’s Hospital of Philadelphia and her coauthors reported that the anti-CD19 chimeric antigen receptor (CAR) therapy was highly toxic, but the effects were usually mitigated. Additionally, the investigators showed feasibility of a global supply chain for distribution of the therapy.

The investigators evaluated data from 75 patients with at least 5% lymphoblasts in their bone marrow at the time of screening. Patients were aged 3 years or older at the time of screening but were no older than 21 years of age at the time of diagnosis.

For 50 patients evaluated at the interim analysis, the primary endpoint of overall remission at 3 months was met, and the overall remission rate was 82% (P less than .001).

An updated analysis showed that 81% of 75 patients who had at least 3 months of follow-up experienced overall remission (95% confidence interval, 71-89). A total of 45 of those patients experienced complete remission, and 16 had complete remission with incomplete hematologic recovery.

Event-free survival was experienced by 73% of patients at 6 months and 50% of patients at 12 months. Overall survival was 90% at 6 months and 76% at 12 months, the investigators reported.

Before tisagenlecleucel infusion, 96% of patients received lymphodepleting chemotherapy. The administration of chemotherapy was not done at the discretion of the investigator if a patient had leukopenia.

The median duration of remission was not reached, and the persistence of tisagenlecleucel in the blood was observed for as long as 20 months.

“The remissions were durable, with a 6-month relapse-free survival rate of 80%,” the investigators wrote. “The durability of the clinical response was associated with persistence of tisagenlecleucel in peripheral blood and with persistent B-cell aplasia.”

The phase 1 study of tisagenlecleucel infusion therapy for younger patients with B-cell ALL showed the toxic nature of the therapy, so investigators were not surprised by the safety data they found. Nearly three-quarters of patients who were evaluated in the study experienced a grade 3 or 4 tisagenlecleucel-related adverse event. Cytokine release syndrome occurred in 77% of patients.

Previously reported data regarding anti-CD19 CAR T-cell therapy for ALL came from single-center studies where manufacturing occurred on site, but the current study employed a global, multicenter supply chain, according to the investigators.

“The toxicity and efficacy of tisagenlecleucel [in this study] were consistent with those in the single-center study, and the feasibility of a global supply chain was demonstrated,” they wrote. “Because this study used cryopreserved leukapheresis product, it did not require fresh product and an open manufacture slot for enrollment.”

This research was sponsored and designed by Novartis Pharmaceuticals. Dr. Maude reported having received personal fees from Novartis as well as grant funding from St. Baldrick’s Foundation.
 

hematologynews@frontlinemedcom.com

SOURCE: Maude SL, et al. N Engl J Med. 2018;378:439-48.

Tisagenlecleucel was associated with durable remission and long-term persistence for younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to the results of a multicenter, multicontinent, phase 2 trial published in the New England Journal of Medicine.

Shannon L. Maude, MD, PhD, of the Children’s Hospital of Philadelphia and her coauthors reported that the anti-CD19 chimeric antigen receptor (CAR) therapy was highly toxic, but the effects were usually mitigated. Additionally, the investigators showed feasibility of a global supply chain for distribution of the therapy.

The investigators evaluated data from 75 patients with at least 5% lymphoblasts in their bone marrow at the time of screening. Patients were aged 3 years or older at the time of screening but were no older than 21 years of age at the time of diagnosis.

For 50 patients evaluated at the interim analysis, the primary endpoint of overall remission at 3 months was met, and the overall remission rate was 82% (P less than .001).

An updated analysis showed that 81% of 75 patients who had at least 3 months of follow-up experienced overall remission (95% confidence interval, 71-89). A total of 45 of those patients experienced complete remission, and 16 had complete remission with incomplete hematologic recovery.

Event-free survival was experienced by 73% of patients at 6 months and 50% of patients at 12 months. Overall survival was 90% at 6 months and 76% at 12 months, the investigators reported.

Before tisagenlecleucel infusion, 96% of patients received lymphodepleting chemotherapy. The administration of chemotherapy was not done at the discretion of the investigator if a patient had leukopenia.

The median duration of remission was not reached, and the persistence of tisagenlecleucel in the blood was observed for as long as 20 months.

“The remissions were durable, with a 6-month relapse-free survival rate of 80%,” the investigators wrote. “The durability of the clinical response was associated with persistence of tisagenlecleucel in peripheral blood and with persistent B-cell aplasia.”

The phase 1 study of tisagenlecleucel infusion therapy for younger patients with B-cell ALL showed the toxic nature of the therapy, so investigators were not surprised by the safety data they found. Nearly three-quarters of patients who were evaluated in the study experienced a grade 3 or 4 tisagenlecleucel-related adverse event. Cytokine release syndrome occurred in 77% of patients.

Previously reported data regarding anti-CD19 CAR T-cell therapy for ALL came from single-center studies where manufacturing occurred on site, but the current study employed a global, multicenter supply chain, according to the investigators.

“The toxicity and efficacy of tisagenlecleucel [in this study] were consistent with those in the single-center study, and the feasibility of a global supply chain was demonstrated,” they wrote. “Because this study used cryopreserved leukapheresis product, it did not require fresh product and an open manufacture slot for enrollment.”

This research was sponsored and designed by Novartis Pharmaceuticals. Dr. Maude reported having received personal fees from Novartis as well as grant funding from St. Baldrick’s Foundation.
 

hematologynews@frontlinemedcom.com

SOURCE: Maude SL, et al. N Engl J Med. 2018;378:439-48.

Tisagenlecleucel was associated with durable remission and long-term persistence for younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to the results of a multicenter, multicontinent, phase 2 trial published in the New England Journal of Medicine.

Shannon L. Maude, MD, PhD, of the Children’s Hospital of Philadelphia and her coauthors reported that the anti-CD19 chimeric antigen receptor (CAR) therapy was highly toxic, but the effects were usually mitigated. Additionally, the investigators showed feasibility of a global supply chain for distribution of the therapy.

The investigators evaluated data from 75 patients with at least 5% lymphoblasts in their bone marrow at the time of screening. Patients were aged 3 years or older at the time of screening but were no older than 21 years of age at the time of diagnosis.

For 50 patients evaluated at the interim analysis, the primary endpoint of overall remission at 3 months was met, and the overall remission rate was 82% (P less than .001).

An updated analysis showed that 81% of 75 patients who had at least 3 months of follow-up experienced overall remission (95% confidence interval, 71-89). A total of 45 of those patients experienced complete remission, and 16 had complete remission with incomplete hematologic recovery.

Event-free survival was experienced by 73% of patients at 6 months and 50% of patients at 12 months. Overall survival was 90% at 6 months and 76% at 12 months, the investigators reported.

Before tisagenlecleucel infusion, 96% of patients received lymphodepleting chemotherapy. The administration of chemotherapy was not done at the discretion of the investigator if a patient had leukopenia.

The median duration of remission was not reached, and the persistence of tisagenlecleucel in the blood was observed for as long as 20 months.

“The remissions were durable, with a 6-month relapse-free survival rate of 80%,” the investigators wrote. “The durability of the clinical response was associated with persistence of tisagenlecleucel in peripheral blood and with persistent B-cell aplasia.”

The phase 1 study of tisagenlecleucel infusion therapy for younger patients with B-cell ALL showed the toxic nature of the therapy, so investigators were not surprised by the safety data they found. Nearly three-quarters of patients who were evaluated in the study experienced a grade 3 or 4 tisagenlecleucel-related adverse event. Cytokine release syndrome occurred in 77% of patients.

Previously reported data regarding anti-CD19 CAR T-cell therapy for ALL came from single-center studies where manufacturing occurred on site, but the current study employed a global, multicenter supply chain, according to the investigators.

“The toxicity and efficacy of tisagenlecleucel [in this study] were consistent with those in the single-center study, and the feasibility of a global supply chain was demonstrated,” they wrote. “Because this study used cryopreserved leukapheresis product, it did not require fresh product and an open manufacture slot for enrollment.”

This research was sponsored and designed by Novartis Pharmaceuticals. Dr. Maude reported having received personal fees from Novartis as well as grant funding from St. Baldrick’s Foundation.
 

hematologynews@frontlinemedcom.com

SOURCE: Maude SL, et al. N Engl J Med. 2018;378:439-48.

Among patients with B-cell acute lymphoblastic leukemia (ALL) who received an infusion of 19-28z CAR T cells, patients with low disease burden had better survival outcomes and fewer toxic effects than did patients with a high disease burden, according to long-term follow-up results of a phase 1 study.

Median overall survival for B-cell ALL patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02), and 12.9 months for the entire cohort, according to results published in the New England Journal of Medicine.

The 12.9-month overall survival for the full study cohort “compares favorably” to results from another recently reported clinical trial showing overall survival of 7.7 months for adult B-cell ALL patients treated with blinatumomab, an anti–CD19/CD3 bispecific T-cell engager, wrote Jae H. Park, MD, of the Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The CAR T-cell and blinatumomab results cannot be directly compared owing to the differences in study design, patient characteristics, and posttreatment consolidation, but “the observation of patients with durable remissions in these two studies highlights the potential of CD19-targeted immunotherapies,” Dr. Park and his colleagues wrote in their report.

The phase 1 trial by Dr. Park and his colleagues included 53 adults with relapsed B-cell ALL who received a single infusion of 19-28z CAR T-cell therapy manufactured at Memorial Sloan Kettering Cancer Center.

After the infusion, 41% of patients with high disease burden (at least 5% bone marrow blasts or extramedullary disease) experienced severe cytokine release syndrome, compared with 5% of those with low disease burden, according to the report.

Likewise, neurotoxic effects were seen in 59% of high disease burden B-ALL patients, compared with 14% of those with low disease burden, the investigators reported.

Low disease burden was associated with a higher rate of complete remission, but this finding did not reach statistical significance. However, low disease burden patients not only had improved overall survival, as noted, but also had a significantly longer event-free survival versus high disease burden patients (10.6 and 5.3 months, respectively; P = .01).

Robust expansion of CAR T cells in vivo was a good predictor of short-term response and toxic effects but did not correlate with longer-term efficacy, according to the researchers. Instead, the ratio of peak CAR T-cell expansion to tumor burden correlated significantly with event-free and overall survival.

That finding “raises the hypothesis that an effective ratio of CAR T cells to target CD19+ leukemia cells is more likely to occur in patients with a low disease burden than in those with a high disease burden, despite a smaller number of expanded T cells in patients with a low disease burden,” the investigators wrote.

The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.

SOURCE: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.

Among patients with B-cell acute lymphoblastic leukemia (ALL) who received an infusion of 19-28z CAR T cells, patients with low disease burden had better survival outcomes and fewer toxic effects than did patients with a high disease burden, according to long-term follow-up results of a phase 1 study.

Median overall survival for B-cell ALL patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02), and 12.9 months for the entire cohort, according to results published in the New England Journal of Medicine.

The 12.9-month overall survival for the full study cohort “compares favorably” to results from another recently reported clinical trial showing overall survival of 7.7 months for adult B-cell ALL patients treated with blinatumomab, an anti–CD19/CD3 bispecific T-cell engager, wrote Jae H. Park, MD, of the Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The CAR T-cell and blinatumomab results cannot be directly compared owing to the differences in study design, patient characteristics, and posttreatment consolidation, but “the observation of patients with durable remissions in these two studies highlights the potential of CD19-targeted immunotherapies,” Dr. Park and his colleagues wrote in their report.

The phase 1 trial by Dr. Park and his colleagues included 53 adults with relapsed B-cell ALL who received a single infusion of 19-28z CAR T-cell therapy manufactured at Memorial Sloan Kettering Cancer Center.

After the infusion, 41% of patients with high disease burden (at least 5% bone marrow blasts or extramedullary disease) experienced severe cytokine release syndrome, compared with 5% of those with low disease burden, according to the report.

Likewise, neurotoxic effects were seen in 59% of high disease burden B-ALL patients, compared with 14% of those with low disease burden, the investigators reported.

Low disease burden was associated with a higher rate of complete remission, but this finding did not reach statistical significance. However, low disease burden patients not only had improved overall survival, as noted, but also had a significantly longer event-free survival versus high disease burden patients (10.6 and 5.3 months, respectively; P = .01).

Robust expansion of CAR T cells in vivo was a good predictor of short-term response and toxic effects but did not correlate with longer-term efficacy, according to the researchers. Instead, the ratio of peak CAR T-cell expansion to tumor burden correlated significantly with event-free and overall survival.

That finding “raises the hypothesis that an effective ratio of CAR T cells to target CD19+ leukemia cells is more likely to occur in patients with a low disease burden than in those with a high disease burden, despite a smaller number of expanded T cells in patients with a low disease burden,” the investigators wrote.

The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.

SOURCE: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.

Among patients with B-cell acute lymphoblastic leukemia (ALL) who received an infusion of 19-28z CAR T cells, patients with low disease burden had better survival outcomes and fewer toxic effects than did patients with a high disease burden, according to long-term follow-up results of a phase 1 study.

Median overall survival for B-cell ALL patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02), and 12.9 months for the entire cohort, according to results published in the New England Journal of Medicine.

The 12.9-month overall survival for the full study cohort “compares favorably” to results from another recently reported clinical trial showing overall survival of 7.7 months for adult B-cell ALL patients treated with blinatumomab, an anti–CD19/CD3 bispecific T-cell engager, wrote Jae H. Park, MD, of the Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The CAR T-cell and blinatumomab results cannot be directly compared owing to the differences in study design, patient characteristics, and posttreatment consolidation, but “the observation of patients with durable remissions in these two studies highlights the potential of CD19-targeted immunotherapies,” Dr. Park and his colleagues wrote in their report.

The phase 1 trial by Dr. Park and his colleagues included 53 adults with relapsed B-cell ALL who received a single infusion of 19-28z CAR T-cell therapy manufactured at Memorial Sloan Kettering Cancer Center.

After the infusion, 41% of patients with high disease burden (at least 5% bone marrow blasts or extramedullary disease) experienced severe cytokine release syndrome, compared with 5% of those with low disease burden, according to the report.

Likewise, neurotoxic effects were seen in 59% of high disease burden B-ALL patients, compared with 14% of those with low disease burden, the investigators reported.

Low disease burden was associated with a higher rate of complete remission, but this finding did not reach statistical significance. However, low disease burden patients not only had improved overall survival, as noted, but also had a significantly longer event-free survival versus high disease burden patients (10.6 and 5.3 months, respectively; P = .01).

Robust expansion of CAR T cells in vivo was a good predictor of short-term response and toxic effects but did not correlate with longer-term efficacy, according to the researchers. Instead, the ratio of peak CAR T-cell expansion to tumor burden correlated significantly with event-free and overall survival.

That finding “raises the hypothesis that an effective ratio of CAR T cells to target CD19+ leukemia cells is more likely to occur in patients with a low disease burden than in those with a high disease burden, despite a smaller number of expanded T cells in patients with a low disease burden,” the investigators wrote.

The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.

SOURCE: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.

A contaminated hematopoietic stem cell (HSC) graft caused a clinically significant infection in a 15-year-old transplant recipient with B-cell acute lymphoblastic leukemia (B-ALL), according to a letter to the editor published in Infection Control & Hospital Epidemiology.

Strains of Staphylococcus aureus found in isolates from the HSC graft and the patient were confirmed to be identical using pulsed-field gel electrophoresis, the authors, led by Zachary I. Willis, MD, MPH, of the department of pediatrics at the University of North Carolina at Chapel Hill, said.

“While multiple reports have found that low-grade bacterial contamination of HSC products is rarely consequential, our patient’s experience demonstrated that clinically significant infections may occur,” Dr. Willis and his colleagues wrote in the case report.

When less virulent organisms are found in HSC grafts, close observation may be warranted, the investigators said; however, a more aggressive approach might be considered when more virulent organisms are found.

“In such a case, we suggest obtaining blood cultures and considering preemptive antibiotics as guided by the identity and susceptibility of the contaminating organism,” the investigators wrote.

Dr. Willis and his colleagues reported the case of a 15-year-old boy with hypodiploid B-ALL who achieved complete remission after treatment and then underwent a 10/10 HLA allele–matched unrelated donor hematopoietic cell transplant.

The patient developed a fever of 38.3º C with tachycardia but no other sepsis signs approximately 24 hours after the transplant. Soon afterward, the care team was informed that there was a single colony each of Micrococcus and S. aureus in the culture of the HSC product. Methicillin susceptibility was later confirmed. Antibiotic treatment was changed accordingly, and as of 117 days post transplant, the patient was “doing well with no evidence of further infectious complications,” the investigators said.

Bacterial contamination of HSC grafts is relatively common, with reported rates ranging from 1% to 45%. However, the clinical significance of the contamination has been unclear. Moreover, contamination is not an absolute contraindication to infusion, as options for the patient are limited after a myeloablative preparative regimen.

There are some previous case reports also identifying infections caused by contaminated grafts, but in those cases, the evidence linking the graft to the infection was based solely on finding identical species, while in the present report, the graft and patient isolates were confirmed to be identical using pulsed-field gel electrophoresis.

The investigators reported having no outside funding and no financial disclosures.

SOURCE: Willis Z et al, Infect Control Hosp Epidemiol. 2018 Jan 23. doi: 10.1017/ice.2017.285.

A contaminated hematopoietic stem cell (HSC) graft caused a clinically significant infection in a 15-year-old transplant recipient with B-cell acute lymphoblastic leukemia (B-ALL), according to a letter to the editor published in Infection Control & Hospital Epidemiology.

Strains of Staphylococcus aureus found in isolates from the HSC graft and the patient were confirmed to be identical using pulsed-field gel electrophoresis, the authors, led by Zachary I. Willis, MD, MPH, of the department of pediatrics at the University of North Carolina at Chapel Hill, said.

“While multiple reports have found that low-grade bacterial contamination of HSC products is rarely consequential, our patient’s experience demonstrated that clinically significant infections may occur,” Dr. Willis and his colleagues wrote in the case report.

When less virulent organisms are found in HSC grafts, close observation may be warranted, the investigators said; however, a more aggressive approach might be considered when more virulent organisms are found.

“In such a case, we suggest obtaining blood cultures and considering preemptive antibiotics as guided by the identity and susceptibility of the contaminating organism,” the investigators wrote.

Dr. Willis and his colleagues reported the case of a 15-year-old boy with hypodiploid B-ALL who achieved complete remission after treatment and then underwent a 10/10 HLA allele–matched unrelated donor hematopoietic cell transplant.

The patient developed a fever of 38.3º C with tachycardia but no other sepsis signs approximately 24 hours after the transplant. Soon afterward, the care team was informed that there was a single colony each of Micrococcus and S. aureus in the culture of the HSC product. Methicillin susceptibility was later confirmed. Antibiotic treatment was changed accordingly, and as of 117 days post transplant, the patient was “doing well with no evidence of further infectious complications,” the investigators said.

Bacterial contamination of HSC grafts is relatively common, with reported rates ranging from 1% to 45%. However, the clinical significance of the contamination has been unclear. Moreover, contamination is not an absolute contraindication to infusion, as options for the patient are limited after a myeloablative preparative regimen.

There are some previous case reports also identifying infections caused by contaminated grafts, but in those cases, the evidence linking the graft to the infection was based solely on finding identical species, while in the present report, the graft and patient isolates were confirmed to be identical using pulsed-field gel electrophoresis.

The investigators reported having no outside funding and no financial disclosures.

SOURCE: Willis Z et al, Infect Control Hosp Epidemiol. 2018 Jan 23. doi: 10.1017/ice.2017.285.

A contaminated hematopoietic stem cell (HSC) graft caused a clinically significant infection in a 15-year-old transplant recipient with B-cell acute lymphoblastic leukemia (B-ALL), according to a letter to the editor published in Infection Control & Hospital Epidemiology.

Strains of Staphylococcus aureus found in isolates from the HSC graft and the patient were confirmed to be identical using pulsed-field gel electrophoresis, the authors, led by Zachary I. Willis, MD, MPH, of the department of pediatrics at the University of North Carolina at Chapel Hill, said.

“While multiple reports have found that low-grade bacterial contamination of HSC products is rarely consequential, our patient’s experience demonstrated that clinically significant infections may occur,” Dr. Willis and his colleagues wrote in the case report.

When less virulent organisms are found in HSC grafts, close observation may be warranted, the investigators said; however, a more aggressive approach might be considered when more virulent organisms are found.

“In such a case, we suggest obtaining blood cultures and considering preemptive antibiotics as guided by the identity and susceptibility of the contaminating organism,” the investigators wrote.

Dr. Willis and his colleagues reported the case of a 15-year-old boy with hypodiploid B-ALL who achieved complete remission after treatment and then underwent a 10/10 HLA allele–matched unrelated donor hematopoietic cell transplant.

The patient developed a fever of 38.3º C with tachycardia but no other sepsis signs approximately 24 hours after the transplant. Soon afterward, the care team was informed that there was a single colony each of Micrococcus and S. aureus in the culture of the HSC product. Methicillin susceptibility was later confirmed. Antibiotic treatment was changed accordingly, and as of 117 days post transplant, the patient was “doing well with no evidence of further infectious complications,” the investigators said.

Bacterial contamination of HSC grafts is relatively common, with reported rates ranging from 1% to 45%. However, the clinical significance of the contamination has been unclear. Moreover, contamination is not an absolute contraindication to infusion, as options for the patient are limited after a myeloablative preparative regimen.

There are some previous case reports also identifying infections caused by contaminated grafts, but in those cases, the evidence linking the graft to the infection was based solely on finding identical species, while in the present report, the graft and patient isolates were confirmed to be identical using pulsed-field gel electrophoresis.

The investigators reported having no outside funding and no financial disclosures.

SOURCE: Willis Z et al, Infect Control Hosp Epidemiol. 2018 Jan 23. doi: 10.1017/ice.2017.285.

Micrograph showing ALL

A mutation that leads to relapse in patients with acute lymphoblastic leukemia (ALL) also causes a weakness that could be exploited to kill leukemia cells, according to research published in Nature.

Investigators found evidence to suggest that mutations in the NT5C2 gene make leukemic cells resistant to a common chemotherapy drug but vulnerable to a class of drugs called IMPDH inhibitors.

“Increased sensitivity to IMPDH inhibition shows proof of principle that the pathway for resistance provides a new therapeutic target,” said Adolfo Ferrando, MD, PhD, of Columbia University’s Herbert Irving Comprehensive Cancer Center in New York, New York.

Dr Ferrando’s lab had previously found that cancer cells from relapsed ALL patients frequently have mutations in NT5C2, which drives resistance to 6-mercaptopurine.

However, the investigators didn’t know how these mutations emerge as cancer recurs after remission.

In analyzing samples from ALL patients, the team found they could detect the NT5C2 mutation R367Q in cancer cells before patients were clinically diagnosed as relapsed. However, the mutation was not detectable in most cases at the time of diagnosis.

These findings suggest that cells with the R367Q mutation only multiply in response to treatment, and the mutation may help predict relapse.

“This seems to be a late mutation involved in disease progression,” Dr Ferrando said. “Our data support that it may not be present at diagnosis in many cases, and that, in cases where it may be present, it represents a very minor population.”

The investigators also found the R367Q mutation impaired leukemia cell growth and leukemia-initiating cell activity. This was “associated with excess export of purines to the extracellular space and depletion of the intracellular purine-nucleotide pool.”

These findings led the investigators to test mizoribine, an IMPDH inhibitor, in Nt5c2^+/R367Q mutant and Nt5c2^+/co-R367Q wild-type ALL lymphoblasts. The team found the mutant cells were significantly more sensitive to mizoribine.

In Nt5c2^+/R367Q leukemia-bearing mice, treatment with mizoribine produced a “marked” anti-leukemic response and significantly prolonged survival.

In immunodeficient mice transplanted with an NT5C2(R367Q) xenograft, mizoribine decreased tumor burden and tumor infiltration.

“IMPDH inhibitors could eventually emerge as relevant antileukemic drugs, but this would require additional preclinical work before clinical testing,” Dr Ferrando said.

Micrograph showing ALL

A mutation that leads to relapse in patients with acute lymphoblastic leukemia (ALL) also causes a weakness that could be exploited to kill leukemia cells, according to research published in Nature.

Investigators found evidence to suggest that mutations in the NT5C2 gene make leukemic cells resistant to a common chemotherapy drug but vulnerable to a class of drugs called IMPDH inhibitors.

“Increased sensitivity to IMPDH inhibition shows proof of principle that the pathway for resistance provides a new therapeutic target,” said Adolfo Ferrando, MD, PhD, of Columbia University’s Herbert Irving Comprehensive Cancer Center in New York, New York.

Dr Ferrando’s lab had previously found that cancer cells from relapsed ALL patients frequently have mutations in NT5C2, which drives resistance to 6-mercaptopurine.

However, the investigators didn’t know how these mutations emerge as cancer recurs after remission.

In analyzing samples from ALL patients, the team found they could detect the NT5C2 mutation R367Q in cancer cells before patients were clinically diagnosed as relapsed. However, the mutation was not detectable in most cases at the time of diagnosis.

These findings suggest that cells with the R367Q mutation only multiply in response to treatment, and the mutation may help predict relapse.

“This seems to be a late mutation involved in disease progression,” Dr Ferrando said. “Our data support that it may not be present at diagnosis in many cases, and that, in cases where it may be present, it represents a very minor population.”

The investigators also found the R367Q mutation impaired leukemia cell growth and leukemia-initiating cell activity. This was “associated with excess export of purines to the extracellular space and depletion of the intracellular purine-nucleotide pool.”

These findings led the investigators to test mizoribine, an IMPDH inhibitor, in Nt5c2^+/R367Q mutant and Nt5c2^+/co-R367Q wild-type ALL lymphoblasts. The team found the mutant cells were significantly more sensitive to mizoribine.

In Nt5c2^+/R367Q leukemia-bearing mice, treatment with mizoribine produced a “marked” anti-leukemic response and significantly prolonged survival.

In immunodeficient mice transplanted with an NT5C2(R367Q) xenograft, mizoribine decreased tumor burden and tumor infiltration.

“IMPDH inhibitors could eventually emerge as relevant antileukemic drugs, but this would require additional preclinical work before clinical testing,” Dr Ferrando said.

Micrograph showing ALL

A mutation that leads to relapse in patients with acute lymphoblastic leukemia (ALL) also causes a weakness that could be exploited to kill leukemia cells, according to research published in Nature.

Investigators found evidence to suggest that mutations in the NT5C2 gene make leukemic cells resistant to a common chemotherapy drug but vulnerable to a class of drugs called IMPDH inhibitors.

“Increased sensitivity to IMPDH inhibition shows proof of principle that the pathway for resistance provides a new therapeutic target,” said Adolfo Ferrando, MD, PhD, of Columbia University’s Herbert Irving Comprehensive Cancer Center in New York, New York.

Dr Ferrando’s lab had previously found that cancer cells from relapsed ALL patients frequently have mutations in NT5C2, which drives resistance to 6-mercaptopurine.

However, the investigators didn’t know how these mutations emerge as cancer recurs after remission.

In analyzing samples from ALL patients, the team found they could detect the NT5C2 mutation R367Q in cancer cells before patients were clinically diagnosed as relapsed. However, the mutation was not detectable in most cases at the time of diagnosis.

These findings suggest that cells with the R367Q mutation only multiply in response to treatment, and the mutation may help predict relapse.

“This seems to be a late mutation involved in disease progression,” Dr Ferrando said. “Our data support that it may not be present at diagnosis in many cases, and that, in cases where it may be present, it represents a very minor population.”

The investigators also found the R367Q mutation impaired leukemia cell growth and leukemia-initiating cell activity. This was “associated with excess export of purines to the extracellular space and depletion of the intracellular purine-nucleotide pool.”

These findings led the investigators to test mizoribine, an IMPDH inhibitor, in Nt5c2^+/R367Q mutant and Nt5c2^+/co-R367Q wild-type ALL lymphoblasts. The team found the mutant cells were significantly more sensitive to mizoribine.

In Nt5c2^+/R367Q leukemia-bearing mice, treatment with mizoribine produced a “marked” anti-leukemic response and significantly prolonged survival.

In immunodeficient mice transplanted with an NT5C2(R367Q) xenograft, mizoribine decreased tumor burden and tumor infiltration.

“IMPDH inhibitors could eventually emerge as relevant antileukemic drugs, but this would require additional preclinical work before clinical testing,” Dr Ferrando said.

Inotuzumab ozogamicin appeared active and safe when added to reduced-intensity chemotherapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukemia, according to the results of a single-arm phase 2 study.

After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.

Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.

They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.

Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.

Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.

“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.

Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.

They suggested that modifications to the regimen could further improve safety and that such modifications required further research.

For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.

The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.

SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.

Inotuzumab ozogamicin appeared active and safe when added to reduced-intensity chemotherapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukemia, according to the results of a single-arm phase 2 study.

After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.

Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.

They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.

Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.

Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.

“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.

Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.

They suggested that modifications to the regimen could further improve safety and that such modifications required further research.

For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.

The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.

SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.

Inotuzumab ozogamicin appeared active and safe when added to reduced-intensity chemotherapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukemia, according to the results of a single-arm phase 2 study.

After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.

Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.

They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.

Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.

Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.

“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.

Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.

They suggested that modifications to the regimen could further improve safety and that such modifications required further research.

For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.

The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.

SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.

Photo from Novartis

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.

Photo from Novartis

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.

Photo from Novartis

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.

Pathogenic loss-of-function germline variants in the TP53 gene predispose children to acute lymphoblastic leukemia (ALL), and, later, to solid tumors that may be related to cancer therapy, according to results from a genetic sequencing study.

Researchers at St. Jude Children’s Hospital in Memphis have identified 49 unique variants of the gene among 3,801 children with newly diagnosed B-cell ALL; 22 variants were deemed pathogenic. Children with these variants were at a “dramatically higher risk” of secondary cancers, which occurred in 25% within 5 years of ALL treatment, compared with 0.7% among children without the pathogenic genetic signal, according to Maoxiang Qian, PhD, and colleagues. The report was published in the Journal of Clinical Oncology.

The increased risk of secondary cancers is probably related to a common characteristic of the pathogenic variants: the ablation of the p53-mediated DNA damage response. This increases the risk of the genotoxic therapy given during ALL treatment, according to the researchers.

“In fact, of the five patients with TP53 pathogenic variants who also had second cancers, two received irradiation therapy, including total body irradiation, and both subsequently developed solid tumors,” the researchers wrote. “The exact lifelong risk of second cancer in these patients is difficult to ascertain as many patients might have succumbed to relapsed ALL before they had the chance to develop second cancers.”

The research team conducted targeted sequencing of TP53 coding regions in 3,801 children who were enrolled in two trials sponsored by the Children’s Oncology Group (AALL0232 and P9900). They compared the results to TP53 mutations seen in almost 61,000 children enrolled in the Exome Aggregation Consortium (ExAC) cohort.

The researchers identified nine exonic nonsilent TP53 variants in the ALL cohort, all of which had an allele frequency of less than 0.5%. Of the variants, 22 were deemed pathogenic: Twelve showed a complete loss of transcriptional activity, three showed a partial loss of p53 function, and seven showed loss of the critical core DNA-binding domain in p53. The rest of the variants were deemed of unknown significance (VUS).

Pathogenic variants occurred in 26 children in the ALL cohort – significantly more often than in the control cohort (0.7% vs. 0.1%; odds ratio, 5.2). The VUS risk was not significantly elevated compared to controls, however.

Children with the pathogenic variants were significantly older at ALL diagnosis (15.5 vs. 6.6 years) and had significantly lower leukocyte count. Of the 26 with a pathogenic variant, 17 (65.4%) showed hypodiploidy in ALL blasts.

Pathogenic variants negatively affected ALL treatment outcomes, quadrupling the risk of lower event-free survival and lower overall survival (hazard ratio, 4.2 and 3.9, respectively) in both ALL cohorts.

Of the children with pathogenic variants, 14 experienced a pathological clinical event, including five ALL relapses and five second cancers, each accounting for 36% of all events.

“This pattern of events was dramatically different from that in patients with wild-type TP53 or VUS, for whom ALL relapse accounted for 75% of all events, with only 4% as second cancers,” the researchers wrote. “In fact, within hypodiploid ALL patients who experienced an event, the frequency of second cancer was significantly higher in those with TP53 pathogenic variants than in those without [50% vs. 5%], which additionally suggests that germline TP53 variation, instead of hypodiploid ALL, was the underlying cause of second cancers in these patients.”

The study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. Dr. Qian reported having no financial disclosures. Other researchers reported funding from various pharmaceutical companies.

msullivan@frontlinemedcom.com

SOURCE: Qian et al. JCO 2018 Jan 4. doi: 10.1200/JCO.2017.75.5215

Pathogenic loss-of-function germline variants in the TP53 gene predispose children to acute lymphoblastic leukemia (ALL), and, later, to solid tumors that may be related to cancer therapy, according to results from a genetic sequencing study.

Researchers at St. Jude Children’s Hospital in Memphis have identified 49 unique variants of the gene among 3,801 children with newly diagnosed B-cell ALL; 22 variants were deemed pathogenic. Children with these variants were at a “dramatically higher risk” of secondary cancers, which occurred in 25% within 5 years of ALL treatment, compared with 0.7% among children without the pathogenic genetic signal, according to Maoxiang Qian, PhD, and colleagues. The report was published in the Journal of Clinical Oncology.

The increased risk of secondary cancers is probably related to a common characteristic of the pathogenic variants: the ablation of the p53-mediated DNA damage response. This increases the risk of the genotoxic therapy given during ALL treatment, according to the researchers.

“In fact, of the five patients with TP53 pathogenic variants who also had second cancers, two received irradiation therapy, including total body irradiation, and both subsequently developed solid tumors,” the researchers wrote. “The exact lifelong risk of second cancer in these patients is difficult to ascertain as many patients might have succumbed to relapsed ALL before they had the chance to develop second cancers.”

The research team conducted targeted sequencing of TP53 coding regions in 3,801 children who were enrolled in two trials sponsored by the Children’s Oncology Group (AALL0232 and P9900). They compared the results to TP53 mutations seen in almost 61,000 children enrolled in the Exome Aggregation Consortium (ExAC) cohort.

The researchers identified nine exonic nonsilent TP53 variants in the ALL cohort, all of which had an allele frequency of less than 0.5%. Of the variants, 22 were deemed pathogenic: Twelve showed a complete loss of transcriptional activity, three showed a partial loss of p53 function, and seven showed loss of the critical core DNA-binding domain in p53. The rest of the variants were deemed of unknown significance (VUS).

Pathogenic variants occurred in 26 children in the ALL cohort – significantly more often than in the control cohort (0.7% vs. 0.1%; odds ratio, 5.2). The VUS risk was not significantly elevated compared to controls, however.

Children with the pathogenic variants were significantly older at ALL diagnosis (15.5 vs. 6.6 years) and had significantly lower leukocyte count. Of the 26 with a pathogenic variant, 17 (65.4%) showed hypodiploidy in ALL blasts.

Pathogenic variants negatively affected ALL treatment outcomes, quadrupling the risk of lower event-free survival and lower overall survival (hazard ratio, 4.2 and 3.9, respectively) in both ALL cohorts.

Of the children with pathogenic variants, 14 experienced a pathological clinical event, including five ALL relapses and five second cancers, each accounting for 36% of all events.

“This pattern of events was dramatically different from that in patients with wild-type TP53 or VUS, for whom ALL relapse accounted for 75% of all events, with only 4% as second cancers,” the researchers wrote. “In fact, within hypodiploid ALL patients who experienced an event, the frequency of second cancer was significantly higher in those with TP53 pathogenic variants than in those without [50% vs. 5%], which additionally suggests that germline TP53 variation, instead of hypodiploid ALL, was the underlying cause of second cancers in these patients.”

The study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. Dr. Qian reported having no financial disclosures. Other researchers reported funding from various pharmaceutical companies.

msullivan@frontlinemedcom.com

SOURCE: Qian et al. JCO 2018 Jan 4. doi: 10.1200/JCO.2017.75.5215

Pathogenic loss-of-function germline variants in the TP53 gene predispose children to acute lymphoblastic leukemia (ALL), and, later, to solid tumors that may be related to cancer therapy, according to results from a genetic sequencing study.

Researchers at St. Jude Children’s Hospital in Memphis have identified 49 unique variants of the gene among 3,801 children with newly diagnosed B-cell ALL; 22 variants were deemed pathogenic. Children with these variants were at a “dramatically higher risk” of secondary cancers, which occurred in 25% within 5 years of ALL treatment, compared with 0.7% among children without the pathogenic genetic signal, according to Maoxiang Qian, PhD, and colleagues. The report was published in the Journal of Clinical Oncology.

The increased risk of secondary cancers is probably related to a common characteristic of the pathogenic variants: the ablation of the p53-mediated DNA damage response. This increases the risk of the genotoxic therapy given during ALL treatment, according to the researchers.

“In fact, of the five patients with TP53 pathogenic variants who also had second cancers, two received irradiation therapy, including total body irradiation, and both subsequently developed solid tumors,” the researchers wrote. “The exact lifelong risk of second cancer in these patients is difficult to ascertain as many patients might have succumbed to relapsed ALL before they had the chance to develop second cancers.”

The research team conducted targeted sequencing of TP53 coding regions in 3,801 children who were enrolled in two trials sponsored by the Children’s Oncology Group (AALL0232 and P9900). They compared the results to TP53 mutations seen in almost 61,000 children enrolled in the Exome Aggregation Consortium (ExAC) cohort.

The researchers identified nine exonic nonsilent TP53 variants in the ALL cohort, all of which had an allele frequency of less than 0.5%. Of the variants, 22 were deemed pathogenic: Twelve showed a complete loss of transcriptional activity, three showed a partial loss of p53 function, and seven showed loss of the critical core DNA-binding domain in p53. The rest of the variants were deemed of unknown significance (VUS).

Pathogenic variants occurred in 26 children in the ALL cohort – significantly more often than in the control cohort (0.7% vs. 0.1%; odds ratio, 5.2). The VUS risk was not significantly elevated compared to controls, however.

Children with the pathogenic variants were significantly older at ALL diagnosis (15.5 vs. 6.6 years) and had significantly lower leukocyte count. Of the 26 with a pathogenic variant, 17 (65.4%) showed hypodiploidy in ALL blasts.

Pathogenic variants negatively affected ALL treatment outcomes, quadrupling the risk of lower event-free survival and lower overall survival (hazard ratio, 4.2 and 3.9, respectively) in both ALL cohorts.

Of the children with pathogenic variants, 14 experienced a pathological clinical event, including five ALL relapses and five second cancers, each accounting for 36% of all events.

“This pattern of events was dramatically different from that in patients with wild-type TP53 or VUS, for whom ALL relapse accounted for 75% of all events, with only 4% as second cancers,” the researchers wrote. “In fact, within hypodiploid ALL patients who experienced an event, the frequency of second cancer was significantly higher in those with TP53 pathogenic variants than in those without [50% vs. 5%], which additionally suggests that germline TP53 variation, instead of hypodiploid ALL, was the underlying cause of second cancers in these patients.”

The study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities. Dr. Qian reported having no financial disclosures. Other researchers reported funding from various pharmaceutical companies.

msullivan@frontlinemedcom.com

SOURCE: Qian et al. JCO 2018 Jan 4. doi: 10.1200/JCO.2017.75.5215

Photo by Rhoda Baer

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.”

Photo by Rhoda Baer

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.”

Photo by Rhoda Baer

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.”