CML

Nilotinib is now approved for use by children aged 1 year and older with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in the chronic phase.

The Food and Drug Administration expanded the drug’s indication to include use as first- and second-line treatment in children.

Nilotinib (Tasigna) was already approved in adults with newly diagnosed Ph+ CML in the chronic phase and adults with chronic phase and accelerated phase Ph+ CML resistant or intolerant to prior therapy.

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Nilotinib is now approved for use by children aged 1 year and older with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in the chronic phase.

The Food and Drug Administration expanded the drug’s indication to include use as first- and second-line treatment in children.

Nilotinib (Tasigna) was already approved in adults with newly diagnosed Ph+ CML in the chronic phase and adults with chronic phase and accelerated phase Ph+ CML resistant or intolerant to prior therapy.

[email protected]

Nilotinib is now approved for use by children aged 1 year and older with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in the chronic phase.

The Food and Drug Administration expanded the drug’s indication to include use as first- and second-line treatment in children.

Nilotinib (Tasigna) was already approved in adults with newly diagnosed Ph+ CML in the chronic phase and adults with chronic phase and accelerated phase Ph+ CML resistant or intolerant to prior therapy.

[email protected]

Photo from Novartis

The US Food and Drug Administration (FDA) has expanded the approved indication for nilotinib (Tasigna®) to include the treatment of children.

The drug is now approved to treat patients age 1 and older who have newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

Nilotinib is also approved to treat pediatric patients age 1 and older who have chronic phase, Ph+ CML that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, as well as adults with Ph+ CML in chronic phase and accelerated phase that is resistant or intolerant to prior therapy including imatinib.

The new pediatric indications for nilotinib, granted under the FDA’s priority review designation, are based on results from 2 studies of the drug—a phase 1 and phase 2.

According to Novartis, the studies included 69 CML patients who ranged in age from 2 to 17. They had either newly diagnosed, chronic phase, Ph+ CML or chronic phase, Ph+ CML with resistance or intolerance to prior TKI therapy.

In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% at 12 cycles, with 15 patients achieving MMR.

In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR.

In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.

Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.

The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.

There were no deaths on treatment or after treatment discontinuation.

There was 1 patient with resistant/intolerant CML who progressed to advance phase/blast crisis after about 10 months on nilotinib.

Photo from Novartis

The US Food and Drug Administration (FDA) has expanded the approved indication for nilotinib (Tasigna®) to include the treatment of children.

The drug is now approved to treat patients age 1 and older who have newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

Nilotinib is also approved to treat pediatric patients age 1 and older who have chronic phase, Ph+ CML that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, as well as adults with Ph+ CML in chronic phase and accelerated phase that is resistant or intolerant to prior therapy including imatinib.

The new pediatric indications for nilotinib, granted under the FDA’s priority review designation, are based on results from 2 studies of the drug—a phase 1 and phase 2.

According to Novartis, the studies included 69 CML patients who ranged in age from 2 to 17. They had either newly diagnosed, chronic phase, Ph+ CML or chronic phase, Ph+ CML with resistance or intolerance to prior TKI therapy.

In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% at 12 cycles, with 15 patients achieving MMR.

In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR.

In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.

Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.

The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.

There were no deaths on treatment or after treatment discontinuation.

There was 1 patient with resistant/intolerant CML who progressed to advance phase/blast crisis after about 10 months on nilotinib.

Photo from Novartis

The US Food and Drug Administration (FDA) has expanded the approved indication for nilotinib (Tasigna®) to include the treatment of children.

The drug is now approved to treat patients age 1 and older who have newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.

Nilotinib is also approved to treat pediatric patients age 1 and older who have chronic phase, Ph+ CML that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, as well as adults with Ph+ CML in chronic phase and accelerated phase that is resistant or intolerant to prior therapy including imatinib.

The new pediatric indications for nilotinib, granted under the FDA’s priority review designation, are based on results from 2 studies of the drug—a phase 1 and phase 2.

According to Novartis, the studies included 69 CML patients who ranged in age from 2 to 17. They had either newly diagnosed, chronic phase, Ph+ CML or chronic phase, Ph+ CML with resistance or intolerance to prior TKI therapy.

In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% at 12 cycles, with 15 patients achieving MMR.

In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR.

In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.

Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.

The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.

There were no deaths on treatment or after treatment discontinuation.

There was 1 patient with resistant/intolerant CML who progressed to advance phase/blast crisis after about 10 months on nilotinib.

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Final results from the phase 2 PACE trial suggest dose reductions did not have an effect on the efficacy of ponatinib in patients with chronic phase (CP) chronic myeloid leukemia (CML).

Trial investigators began reducing ponatinib doses after the drug was linked to arterial occlusive events (AOEs).

Most patients who achieved a major molecular response (MMR) or major cytogenetic response (MCyR) on higher doses of ponatinib maintained those responses after dose reductions.

These results were published in Blood. The trial was sponsored by Ariad Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Earlier results from the PACE trial indicated that ponatinib increased a patient’s risk of vascular occlusive events (VOEs), including AOEs.

Therefore, in October 2013, a phase 3 trial of ponatinib was discontinued, and all other ponatinib trials were put on partial clinical hold. Trial enrollment was halted temporarily, and investigators began reducing ponatinib doses.

Then, the US Food and Drug Administration suspended sales and marketing of ponatinib, pending results of a safety evaluation.

However, in December 2013, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, the drug was back on the market.

Patients

The PACE trial included 449 patients with CML or acute lymphoblastic leukemia, but the results published in Blood focused only on patients with CP-CML. All of these patients were resistant or intolerant to dasatinib or nilotinib, or they had the BCR-ABL^T315I mutation.

There were 270 patients with CP-CML. They had a median age of 60 (range, 18-94), and 47% were female.

Ninety-three percent had received at least 2 prior approved tyrosine kinase inhibitors (TKIs), and 57% had received at least 3. The median duration of prior TKI treatment was 5.4 years (range, 0.4-13.3).

Eighty percent of patients were resistant to dasatinib or nilotinib, 14% were intolerant to either drug, and 19% were both resistant and intolerant. Twenty-four percent of patients had the T315I mutation.

Treatment

The starting dose of ponatinib was 45 mg once daily. Doses were reduced to 30 mg or 15 mg once daily to manage adverse events (AEs), or reductions were implemented proactively (starting on October 10, 2013) due to concerns about VOEs.

Unless a benefit-risk analysis justified use of a higher dose, the recommendation for CP-CML patients was a 15 mg daily dose for those with an MCyR and a 30 mg daily dose for those without an MCyR.

Patients received ponatinib until disease progression, intolerance, or the patient or investigator decided to stop treatment.

The median duration of treatment was 32.1 months (range, 0.1-73.0), and the median follow-up was 56.8 months (range, 0.1-73.1).

Efficacy

Of the 267 evaluable patients, 60% achieved an MCyR at any time, with 54% achieving a complete cytogenetic response. Forty-eight percent of patients were still in MCyR at the last response assessment, and 82% of patients who achieved an MCyR were estimated to remain in MCyR at 5 years.

There were 69 patients in MCyR as of October 10, 2013, when pre-emptive dose reduction began, who had their dose reduced. Ninety-six percent of these patients (n=66) maintained MCyR after dose reduction. Of the 34 patients in MCyR who did not have pre-emptive dose reductions, 94% (n=32) maintained MCyR.

Forty percent of patients attained a major molecular response (MMR) at any time during the study, with 30% achieving MR4 and 24% achieving MR4.5. Thirty percent of patients were in MMR at the last response assessment, and 59% of patients who achieved MMR were estimated to remain in MMR at 5 years.

There were 52 patients in MMR as of October 10, 2013, who had their dose reduced. Ninety percent (n=47) of these patients maintained MMR following dose reduction. Of the 19 patients in MMR who did not have pre-emptive dose reductions, 95% (n=18) maintained MMR.

“The PACE trial is among the longest and largest studies of patients with CP-CML who have received 2 or 3 prior TKIs, and the findings provide treating physicians with important updated information . . . ,” said study author Jorge Eduardo Cortes, MD, of MD Anderson Cancer Center in Houston, Texas.

“These final PACE results demonstrate that [ponatinib] provides lasting clinically meaningful responses, irrespective of dose reductions, in this population.”

At 5 years, the progression-free survival rate was 53%, and the overall survival rate was 73%.

AOEs

The incidence of AOEs was 31%, and the incidence of serious AOEs was 26%. This included cardiovascular AOEs (16%, 12% serious), cerebrovascular (13%, 10% serious), and peripheral vascular AOEs (14%, 11% serious). The exposure-adjusted incidence of AOEs was 14.1 per 100 patient-years.

Among patients without AOEs prior to October 2013 when pre-emptive dose reductions began, the incidence of AOEs was 19% in patients who had dose reductions and 18% in patients who did not.

The cumulative incidence of AOEs increased over time, but the exposure-adjusted incidence of new AOEs did not. It was 15.8 per 100 patient-years in year 1 and 4.9 per 100 patient-years in year 5.

The investigators said the lack of increase in exposure-adjusted AOE incidence could be due to the natural history or etiology of AOEs, dose reductions, or a change in the patient population (ie, an enrichment of patients who may have a lower risk of vascular events).

Therefore, it is unclear whether lower doses of ponatinib reduce the risk of AOEs in patients with risk factors. However, AOEs appear to be dose-related and modified by pre-existing cardiovascular disease and other risk factors.

Venous thromboembolism (VTE), on the other hand, does not seem to be dose-related. The investigators said the rate of VTE in this study was consistent with rates typically observed in cancer patients.

The incidence of VTE was 6%, and 5% of patients had serious VTEs. The exposure-adjusted incidence of VTEs was 2.1 per 100 patient-years.

Other AEs

The most common any-grade treatment-emergent AEs (≥40%) were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%).

The most common grade 3/4 treatment-emergent AEs (≥10%) were thrombocytopenia (35%), neutropenia (17%), hypertension (14%), increased lipase (13%), abdominal pain (10%), and anemia (10%).

Serious AEs (≥5%) included pancreatitis (7%), atrial fibrillation (6%), pneumonia (6%), and angina pectoris (5%).

There were 12 deaths (4%) that occurred on study or within 30 days of the end of study treatment. Two deaths were considered possibly or probably related to ponatinib, 1 due to pneumonia and 1 due to acute myocardial infarction.

Photo from Business Wire

Final results from the phase 2 PACE trial suggest dose reductions did not have an effect on the efficacy of ponatinib in patients with chronic phase (CP) chronic myeloid leukemia (CML).

Trial investigators began reducing ponatinib doses after the drug was linked to arterial occlusive events (AOEs).

Most patients who achieved a major molecular response (MMR) or major cytogenetic response (MCyR) on higher doses of ponatinib maintained those responses after dose reductions.

These results were published in Blood. The trial was sponsored by Ariad Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Earlier results from the PACE trial indicated that ponatinib increased a patient’s risk of vascular occlusive events (VOEs), including AOEs.

Therefore, in October 2013, a phase 3 trial of ponatinib was discontinued, and all other ponatinib trials were put on partial clinical hold. Trial enrollment was halted temporarily, and investigators began reducing ponatinib doses.

Then, the US Food and Drug Administration suspended sales and marketing of ponatinib, pending results of a safety evaluation.

However, in December 2013, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, the drug was back on the market.

Patients

The PACE trial included 449 patients with CML or acute lymphoblastic leukemia, but the results published in Blood focused only on patients with CP-CML. All of these patients were resistant or intolerant to dasatinib or nilotinib, or they had the BCR-ABL^T315I mutation.

There were 270 patients with CP-CML. They had a median age of 60 (range, 18-94), and 47% were female.

Ninety-three percent had received at least 2 prior approved tyrosine kinase inhibitors (TKIs), and 57% had received at least 3. The median duration of prior TKI treatment was 5.4 years (range, 0.4-13.3).

Eighty percent of patients were resistant to dasatinib or nilotinib, 14% were intolerant to either drug, and 19% were both resistant and intolerant. Twenty-four percent of patients had the T315I mutation.

Treatment

The starting dose of ponatinib was 45 mg once daily. Doses were reduced to 30 mg or 15 mg once daily to manage adverse events (AEs), or reductions were implemented proactively (starting on October 10, 2013) due to concerns about VOEs.

Unless a benefit-risk analysis justified use of a higher dose, the recommendation for CP-CML patients was a 15 mg daily dose for those with an MCyR and a 30 mg daily dose for those without an MCyR.

Patients received ponatinib until disease progression, intolerance, or the patient or investigator decided to stop treatment.

The median duration of treatment was 32.1 months (range, 0.1-73.0), and the median follow-up was 56.8 months (range, 0.1-73.1).

Efficacy

Of the 267 evaluable patients, 60% achieved an MCyR at any time, with 54% achieving a complete cytogenetic response. Forty-eight percent of patients were still in MCyR at the last response assessment, and 82% of patients who achieved an MCyR were estimated to remain in MCyR at 5 years.

There were 69 patients in MCyR as of October 10, 2013, when pre-emptive dose reduction began, who had their dose reduced. Ninety-six percent of these patients (n=66) maintained MCyR after dose reduction. Of the 34 patients in MCyR who did not have pre-emptive dose reductions, 94% (n=32) maintained MCyR.

Forty percent of patients attained a major molecular response (MMR) at any time during the study, with 30% achieving MR4 and 24% achieving MR4.5. Thirty percent of patients were in MMR at the last response assessment, and 59% of patients who achieved MMR were estimated to remain in MMR at 5 years.

There were 52 patients in MMR as of October 10, 2013, who had their dose reduced. Ninety percent (n=47) of these patients maintained MMR following dose reduction. Of the 19 patients in MMR who did not have pre-emptive dose reductions, 95% (n=18) maintained MMR.

“The PACE trial is among the longest and largest studies of patients with CP-CML who have received 2 or 3 prior TKIs, and the findings provide treating physicians with important updated information . . . ,” said study author Jorge Eduardo Cortes, MD, of MD Anderson Cancer Center in Houston, Texas.

“These final PACE results demonstrate that [ponatinib] provides lasting clinically meaningful responses, irrespective of dose reductions, in this population.”

At 5 years, the progression-free survival rate was 53%, and the overall survival rate was 73%.

AOEs

The incidence of AOEs was 31%, and the incidence of serious AOEs was 26%. This included cardiovascular AOEs (16%, 12% serious), cerebrovascular (13%, 10% serious), and peripheral vascular AOEs (14%, 11% serious). The exposure-adjusted incidence of AOEs was 14.1 per 100 patient-years.

Among patients without AOEs prior to October 2013 when pre-emptive dose reductions began, the incidence of AOEs was 19% in patients who had dose reductions and 18% in patients who did not.

The cumulative incidence of AOEs increased over time, but the exposure-adjusted incidence of new AOEs did not. It was 15.8 per 100 patient-years in year 1 and 4.9 per 100 patient-years in year 5.

The investigators said the lack of increase in exposure-adjusted AOE incidence could be due to the natural history or etiology of AOEs, dose reductions, or a change in the patient population (ie, an enrichment of patients who may have a lower risk of vascular events).

Therefore, it is unclear whether lower doses of ponatinib reduce the risk of AOEs in patients with risk factors. However, AOEs appear to be dose-related and modified by pre-existing cardiovascular disease and other risk factors.

Venous thromboembolism (VTE), on the other hand, does not seem to be dose-related. The investigators said the rate of VTE in this study was consistent with rates typically observed in cancer patients.

The incidence of VTE was 6%, and 5% of patients had serious VTEs. The exposure-adjusted incidence of VTEs was 2.1 per 100 patient-years.

Other AEs

The most common any-grade treatment-emergent AEs (≥40%) were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%).

The most common grade 3/4 treatment-emergent AEs (≥10%) were thrombocytopenia (35%), neutropenia (17%), hypertension (14%), increased lipase (13%), abdominal pain (10%), and anemia (10%).

Serious AEs (≥5%) included pancreatitis (7%), atrial fibrillation (6%), pneumonia (6%), and angina pectoris (5%).

There were 12 deaths (4%) that occurred on study or within 30 days of the end of study treatment. Two deaths were considered possibly or probably related to ponatinib, 1 due to pneumonia and 1 due to acute myocardial infarction.

Photo from Business Wire

Final results from the phase 2 PACE trial suggest dose reductions did not have an effect on the efficacy of ponatinib in patients with chronic phase (CP) chronic myeloid leukemia (CML).

Trial investigators began reducing ponatinib doses after the drug was linked to arterial occlusive events (AOEs).

Most patients who achieved a major molecular response (MMR) or major cytogenetic response (MCyR) on higher doses of ponatinib maintained those responses after dose reductions.

These results were published in Blood. The trial was sponsored by Ariad Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Earlier results from the PACE trial indicated that ponatinib increased a patient’s risk of vascular occlusive events (VOEs), including AOEs.

Therefore, in October 2013, a phase 3 trial of ponatinib was discontinued, and all other ponatinib trials were put on partial clinical hold. Trial enrollment was halted temporarily, and investigators began reducing ponatinib doses.

Then, the US Food and Drug Administration suspended sales and marketing of ponatinib, pending results of a safety evaluation.

However, in December 2013, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, the drug was back on the market.

Patients

The PACE trial included 449 patients with CML or acute lymphoblastic leukemia, but the results published in Blood focused only on patients with CP-CML. All of these patients were resistant or intolerant to dasatinib or nilotinib, or they had the BCR-ABL^T315I mutation.

There were 270 patients with CP-CML. They had a median age of 60 (range, 18-94), and 47% were female.

Ninety-three percent had received at least 2 prior approved tyrosine kinase inhibitors (TKIs), and 57% had received at least 3. The median duration of prior TKI treatment was 5.4 years (range, 0.4-13.3).

Eighty percent of patients were resistant to dasatinib or nilotinib, 14% were intolerant to either drug, and 19% were both resistant and intolerant. Twenty-four percent of patients had the T315I mutation.

Treatment

The starting dose of ponatinib was 45 mg once daily. Doses were reduced to 30 mg or 15 mg once daily to manage adverse events (AEs), or reductions were implemented proactively (starting on October 10, 2013) due to concerns about VOEs.

Unless a benefit-risk analysis justified use of a higher dose, the recommendation for CP-CML patients was a 15 mg daily dose for those with an MCyR and a 30 mg daily dose for those without an MCyR.

Patients received ponatinib until disease progression, intolerance, or the patient or investigator decided to stop treatment.

The median duration of treatment was 32.1 months (range, 0.1-73.0), and the median follow-up was 56.8 months (range, 0.1-73.1).

Efficacy

Of the 267 evaluable patients, 60% achieved an MCyR at any time, with 54% achieving a complete cytogenetic response. Forty-eight percent of patients were still in MCyR at the last response assessment, and 82% of patients who achieved an MCyR were estimated to remain in MCyR at 5 years.

There were 69 patients in MCyR as of October 10, 2013, when pre-emptive dose reduction began, who had their dose reduced. Ninety-six percent of these patients (n=66) maintained MCyR after dose reduction. Of the 34 patients in MCyR who did not have pre-emptive dose reductions, 94% (n=32) maintained MCyR.

Forty percent of patients attained a major molecular response (MMR) at any time during the study, with 30% achieving MR4 and 24% achieving MR4.5. Thirty percent of patients were in MMR at the last response assessment, and 59% of patients who achieved MMR were estimated to remain in MMR at 5 years.

There were 52 patients in MMR as of October 10, 2013, who had their dose reduced. Ninety percent (n=47) of these patients maintained MMR following dose reduction. Of the 19 patients in MMR who did not have pre-emptive dose reductions, 95% (n=18) maintained MMR.

“The PACE trial is among the longest and largest studies of patients with CP-CML who have received 2 or 3 prior TKIs, and the findings provide treating physicians with important updated information . . . ,” said study author Jorge Eduardo Cortes, MD, of MD Anderson Cancer Center in Houston, Texas.

“These final PACE results demonstrate that [ponatinib] provides lasting clinically meaningful responses, irrespective of dose reductions, in this population.”

At 5 years, the progression-free survival rate was 53%, and the overall survival rate was 73%.

AOEs

The incidence of AOEs was 31%, and the incidence of serious AOEs was 26%. This included cardiovascular AOEs (16%, 12% serious), cerebrovascular (13%, 10% serious), and peripheral vascular AOEs (14%, 11% serious). The exposure-adjusted incidence of AOEs was 14.1 per 100 patient-years.

Among patients without AOEs prior to October 2013 when pre-emptive dose reductions began, the incidence of AOEs was 19% in patients who had dose reductions and 18% in patients who did not.

The cumulative incidence of AOEs increased over time, but the exposure-adjusted incidence of new AOEs did not. It was 15.8 per 100 patient-years in year 1 and 4.9 per 100 patient-years in year 5.

The investigators said the lack of increase in exposure-adjusted AOE incidence could be due to the natural history or etiology of AOEs, dose reductions, or a change in the patient population (ie, an enrichment of patients who may have a lower risk of vascular events).

Therefore, it is unclear whether lower doses of ponatinib reduce the risk of AOEs in patients with risk factors. However, AOEs appear to be dose-related and modified by pre-existing cardiovascular disease and other risk factors.

Venous thromboembolism (VTE), on the other hand, does not seem to be dose-related. The investigators said the rate of VTE in this study was consistent with rates typically observed in cancer patients.

The incidence of VTE was 6%, and 5% of patients had serious VTEs. The exposure-adjusted incidence of VTEs was 2.1 per 100 patient-years.

Other AEs

The most common any-grade treatment-emergent AEs (≥40%) were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%).

The most common grade 3/4 treatment-emergent AEs (≥10%) were thrombocytopenia (35%), neutropenia (17%), hypertension (14%), increased lipase (13%), abdominal pain (10%), and anemia (10%).

Serious AEs (≥5%) included pancreatitis (7%), atrial fibrillation (6%), pneumonia (6%), and angina pectoris (5%).

There were 12 deaths (4%) that occurred on study or within 30 days of the end of study treatment. Two deaths were considered possibly or probably related to ponatinib, 1 due to pneumonia and 1 due to acute myocardial infarction.

Leukemia incidence varies considerably by geography and subtype, according to an analysis of World Health Organization cancer databases.

Incidence also is generally higher in males, with a global male to female ratio of 1.4. For men, the highest regional leukemia rate – estimated at 11.3 per 100,000 population for 2012 – was found in Australia and New Zealand, with northern America (the United States and Canada) next at 10.5 per 100,000. Australia/New Zealand and northern America had the highest rate for women at 7.2 per 100,000, followed by western Europe and northern Europe at 6.0 per 100,000, reported Adalberto Miranda-Filho, PhD, of the WHO’s International Agency for Research on Cancer in Lyon, France, and his associates.

The lowest regional rates for women were found in western Africa (1.2 per 100,000), middle Africa (1.8), and Micronesia/Polynesia (2.1). For men, leukemia incidence was lowest in western Africa (1.4 per 100,000), middle Africa (2.6), and south-central Asia (3.4), according to data from the WHO’s GLOBOCAN database. The report was published in The Lancet Haematology.

Estimates for leukemia subtypes in 2003-2007 – calculated for 54 countries, not regions – also showed a great deal of variation. For acute lymphoblastic leukemia, Ecuador had the highest rates for both males (2.8 per 100,000) and females (3.3), with high rates seen in Costa Rica, Columbia, and Cyprus. Rates in the United States were near the top: 2.1 for males and 1.6 for females. Rates were lowest for men in Jamaica (0.4) and Serbia (0.6) and for women in India (0.5) and Serbia and Cuba (0.6), Dr. Miranda-Filho and his associates said.

Incidence rates for acute myeloid leukemia were highest in Australia for men (2.8 per 100,000) and Austria for women (2.2), with the United States near the top for both men (2.6) and women (1.9). The lowest rates occurred in Cuba and Egypt for men (0.9 per 100,000) and Cuba for women (0.4), data from the WHO’s Cancer Incidence in Five Continents Volume X show.

Chronic lymphocytic leukemia incidence was highest for men in Canada (4.5 per 100,000), Ireland and Lithuania (4.4), and Slovakia (4.3). The incidence was highest for women in Lithuania (2.5), Canada (2.3), and Slovakia and Denmark (2.1). Incidence in the United States was 3.5 for men and 1.8 for women. At the other end of the scale, the lowest rates for both men and women were in Japan and Malaysia (0.1), the investigators’ analysis showed.

Chronic myeloid leukemia rates were the lowest of the subtypes, and Tunisia was the lowest for men at 0.4 per 100,000 and tied for lowest with Serbia, Slovenia, and Puerto Rico for women at 0.3. Incidence was highest for men in Australia at 1.8 per 100,000 and highest for women in Uruguay at 1.1. Rates in the United States were 1.3 for men and 0.8 for women, Dr. Miranda-Filho and his associates said.

“The higher incidence of acute lymphoblastic leukaemia in parts of South America, as well as of chronic lymphocytic leukaemia in populations across North America and Oceania, alongside a lower incidence in Asia, might be important markers for further epidemiological study, and a means to better understand the underlying factors to support future cancer prevention strategies,” the investigators wrote.

[email protected]

SOURCE: Miranda-Filho A et al. Lancet Haematol. 2018;5:e14-24.

Leukemia incidence varies considerably by geography and subtype, according to an analysis of World Health Organization cancer databases.

Incidence also is generally higher in males, with a global male to female ratio of 1.4. For men, the highest regional leukemia rate – estimated at 11.3 per 100,000 population for 2012 – was found in Australia and New Zealand, with northern America (the United States and Canada) next at 10.5 per 100,000. Australia/New Zealand and northern America had the highest rate for women at 7.2 per 100,000, followed by western Europe and northern Europe at 6.0 per 100,000, reported Adalberto Miranda-Filho, PhD, of the WHO’s International Agency for Research on Cancer in Lyon, France, and his associates.

The lowest regional rates for women were found in western Africa (1.2 per 100,000), middle Africa (1.8), and Micronesia/Polynesia (2.1). For men, leukemia incidence was lowest in western Africa (1.4 per 100,000), middle Africa (2.6), and south-central Asia (3.4), according to data from the WHO’s GLOBOCAN database. The report was published in The Lancet Haematology.

Estimates for leukemia subtypes in 2003-2007 – calculated for 54 countries, not regions – also showed a great deal of variation. For acute lymphoblastic leukemia, Ecuador had the highest rates for both males (2.8 per 100,000) and females (3.3), with high rates seen in Costa Rica, Columbia, and Cyprus. Rates in the United States were near the top: 2.1 for males and 1.6 for females. Rates were lowest for men in Jamaica (0.4) and Serbia (0.6) and for women in India (0.5) and Serbia and Cuba (0.6), Dr. Miranda-Filho and his associates said.

Incidence rates for acute myeloid leukemia were highest in Australia for men (2.8 per 100,000) and Austria for women (2.2), with the United States near the top for both men (2.6) and women (1.9). The lowest rates occurred in Cuba and Egypt for men (0.9 per 100,000) and Cuba for women (0.4), data from the WHO’s Cancer Incidence in Five Continents Volume X show.

Chronic lymphocytic leukemia incidence was highest for men in Canada (4.5 per 100,000), Ireland and Lithuania (4.4), and Slovakia (4.3). The incidence was highest for women in Lithuania (2.5), Canada (2.3), and Slovakia and Denmark (2.1). Incidence in the United States was 3.5 for men and 1.8 for women. At the other end of the scale, the lowest rates for both men and women were in Japan and Malaysia (0.1), the investigators’ analysis showed.

Chronic myeloid leukemia rates were the lowest of the subtypes, and Tunisia was the lowest for men at 0.4 per 100,000 and tied for lowest with Serbia, Slovenia, and Puerto Rico for women at 0.3. Incidence was highest for men in Australia at 1.8 per 100,000 and highest for women in Uruguay at 1.1. Rates in the United States were 1.3 for men and 0.8 for women, Dr. Miranda-Filho and his associates said.

“The higher incidence of acute lymphoblastic leukaemia in parts of South America, as well as of chronic lymphocytic leukaemia in populations across North America and Oceania, alongside a lower incidence in Asia, might be important markers for further epidemiological study, and a means to better understand the underlying factors to support future cancer prevention strategies,” the investigators wrote.

[email protected]

SOURCE: Miranda-Filho A et al. Lancet Haematol. 2018;5:e14-24.

Leukemia incidence varies considerably by geography and subtype, according to an analysis of World Health Organization cancer databases.

Incidence also is generally higher in males, with a global male to female ratio of 1.4. For men, the highest regional leukemia rate – estimated at 11.3 per 100,000 population for 2012 – was found in Australia and New Zealand, with northern America (the United States and Canada) next at 10.5 per 100,000. Australia/New Zealand and northern America had the highest rate for women at 7.2 per 100,000, followed by western Europe and northern Europe at 6.0 per 100,000, reported Adalberto Miranda-Filho, PhD, of the WHO’s International Agency for Research on Cancer in Lyon, France, and his associates.

The lowest regional rates for women were found in western Africa (1.2 per 100,000), middle Africa (1.8), and Micronesia/Polynesia (2.1). For men, leukemia incidence was lowest in western Africa (1.4 per 100,000), middle Africa (2.6), and south-central Asia (3.4), according to data from the WHO’s GLOBOCAN database. The report was published in The Lancet Haematology.

Estimates for leukemia subtypes in 2003-2007 – calculated for 54 countries, not regions – also showed a great deal of variation. For acute lymphoblastic leukemia, Ecuador had the highest rates for both males (2.8 per 100,000) and females (3.3), with high rates seen in Costa Rica, Columbia, and Cyprus. Rates in the United States were near the top: 2.1 for males and 1.6 for females. Rates were lowest for men in Jamaica (0.4) and Serbia (0.6) and for women in India (0.5) and Serbia and Cuba (0.6), Dr. Miranda-Filho and his associates said.

Incidence rates for acute myeloid leukemia were highest in Australia for men (2.8 per 100,000) and Austria for women (2.2), with the United States near the top for both men (2.6) and women (1.9). The lowest rates occurred in Cuba and Egypt for men (0.9 per 100,000) and Cuba for women (0.4), data from the WHO’s Cancer Incidence in Five Continents Volume X show.

Chronic lymphocytic leukemia incidence was highest for men in Canada (4.5 per 100,000), Ireland and Lithuania (4.4), and Slovakia (4.3). The incidence was highest for women in Lithuania (2.5), Canada (2.3), and Slovakia and Denmark (2.1). Incidence in the United States was 3.5 for men and 1.8 for women. At the other end of the scale, the lowest rates for both men and women were in Japan and Malaysia (0.1), the investigators’ analysis showed.

Chronic myeloid leukemia rates were the lowest of the subtypes, and Tunisia was the lowest for men at 0.4 per 100,000 and tied for lowest with Serbia, Slovenia, and Puerto Rico for women at 0.3. Incidence was highest for men in Australia at 1.8 per 100,000 and highest for women in Uruguay at 1.1. Rates in the United States were 1.3 for men and 0.8 for women, Dr. Miranda-Filho and his associates said.

“The higher incidence of acute lymphoblastic leukaemia in parts of South America, as well as of chronic lymphocytic leukaemia in populations across North America and Oceania, alongside a lower incidence in Asia, might be important markers for further epidemiological study, and a means to better understand the underlying factors to support future cancer prevention strategies,” the investigators wrote.

[email protected]

SOURCE: Miranda-Filho A et al. Lancet Haematol. 2018;5:e14-24.

Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR⁴ and MR^4.5, according to the researchers.

In an open-label phase 2 study, the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR^4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine.

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

[email protected]

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094.

Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR⁴ and MR^4.5, according to the researchers.

In an open-label phase 2 study, the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR^4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine.

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

[email protected]

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094.

Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR⁴ and MR^4.5, according to the researchers.

In an open-label phase 2 study, the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR^4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine.

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

[email protected]

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094.

Lab mouse

A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.

The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).

Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”

“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.

“Miristen could be the drug that sends the disease into permanent remission.”

For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.

The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.

The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.

The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.

The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.

“Our current study showed these findings may also apply to other types of leukemia.”

Lab mouse

A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.

The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).

Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”

“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.

“Miristen could be the drug that sends the disease into permanent remission.”

For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.

The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.

The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.

The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.

The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.

“Our current study showed these findings may also apply to other types of leukemia.”

Lab mouse

A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.

The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).

Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”

“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.

“Miristen could be the drug that sends the disease into permanent remission.”

For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.

The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.

The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.

The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.

The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.

“Our current study showed these findings may also apply to other types of leukemia.”

Image by Difu Wu

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of bosutinib (BOSULIF) to include treatment of patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib is currently approved in Europe to treat patients with Ph+ CML in chronic, accelerated, or blast phase who have received one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.

The CHMP’s opinion on bosutinib will be reviewed by the European Commission (EC). If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation for bosutinib is based on results from the BFORE trial, which were recently published in the Journal of Clinical Oncology.

The publication included data on 536 patients newly diagnosed with chronic phase CML. They were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The modified intent-to-treat population included Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

In the modified intent-to-treat population, the rate of major molecular response at 12 months was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

In the entire study population, 22.0% of patients receiving bosutinib and 26.8% of those receiving imatinib discontinued treatment—12.7% and 8.7%, respectively, due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Image by Difu Wu

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of bosutinib (BOSULIF) to include treatment of patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib is currently approved in Europe to treat patients with Ph+ CML in chronic, accelerated, or blast phase who have received one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.

The CHMP’s opinion on bosutinib will be reviewed by the European Commission (EC). If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation for bosutinib is based on results from the BFORE trial, which were recently published in the Journal of Clinical Oncology.

The publication included data on 536 patients newly diagnosed with chronic phase CML. They were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The modified intent-to-treat population included Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

In the modified intent-to-treat population, the rate of major molecular response at 12 months was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

In the entire study population, 22.0% of patients receiving bosutinib and 26.8% of those receiving imatinib discontinued treatment—12.7% and 8.7%, respectively, due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Image by Difu Wu

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved use of bosutinib (BOSULIF) to include treatment of patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib is currently approved in Europe to treat patients with Ph+ CML in chronic, accelerated, or blast phase who have received one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options.

The CHMP’s opinion on bosutinib will be reviewed by the European Commission (EC). If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation for bosutinib is based on results from the BFORE trial, which were recently published in the Journal of Clinical Oncology.

The publication included data on 536 patients newly diagnosed with chronic phase CML. They were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The modified intent-to-treat population included Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

In the modified intent-to-treat population, the rate of major molecular response at 12 months was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

In the entire study population, 22.0% of patients receiving bosutinib and 26.8% of those receiving imatinib discontinued treatment—12.7% and 8.7%, respectively, due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

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.”

Image by Joshua Stokes

Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.

The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.

The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.

Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.

“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”

“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”

Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.

The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.

Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.

To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.

The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.

Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.

The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.

“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.

In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.

Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.

“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.

Image by Joshua Stokes

Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.

The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.

The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.

Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.

“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”

“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”

Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.

The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.

Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.

To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.

The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.

Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.

The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.

“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.

In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.

Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.

“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.

Image by Joshua Stokes

Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.

The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.

The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.

Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.

“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”

“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”

Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.

The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.

Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.

To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.

The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.

Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.

The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.

“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.

In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.

Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.

“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.