Mary Jo Dales

Ibrutinib may prove useful for patients whose chronic lymphocytic leukemia (CLL) relapses after allogeneic stem cell transplantation, Dr. C. S. Link and colleagues reported.

Ibrutinib has shown efficacy in patients with high-risk CLL, but there are few data from patients who relapsed after allogeneic stem cell transplantation, wrote Dr. Link of the Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus and the DFG Research Center for Regenerative Therapies, both at the Technische Universität Dresden (Germany).

The researchers performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells in a study of five CLL patients treated with ibrutinib for relapse after allogeneic transplants. All patients had partial responses to ibrutinib and one had a minimal residual disease–negative remission.

At 1 year, none of the patients had relapsed; however, one patient died of pneumonia while on ibrutinib treatment. No other unexpected adverse events were observed, the researchers reported in the study, which was published online on Jan. 11.

No substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift were noted based on flow cytometry and analyses of T cell–mediated cytokine levels. No acute exacerbations of graft-versus-host disease occurred.

Click here to read the study (Bone Marrow Transplant. 2016 Jan 11. doi: 10.1038/bmt.2015.339).

[email protected]

On Twitter @maryjodales

Ibrutinib may prove useful for patients whose chronic lymphocytic leukemia (CLL) relapses after allogeneic stem cell transplantation, Dr. C. S. Link and colleagues reported.

Ibrutinib has shown efficacy in patients with high-risk CLL, but there are few data from patients who relapsed after allogeneic stem cell transplantation, wrote Dr. Link of the Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus and the DFG Research Center for Regenerative Therapies, both at the Technische Universität Dresden (Germany).

The researchers performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells in a study of five CLL patients treated with ibrutinib for relapse after allogeneic transplants. All patients had partial responses to ibrutinib and one had a minimal residual disease–negative remission.

At 1 year, none of the patients had relapsed; however, one patient died of pneumonia while on ibrutinib treatment. No other unexpected adverse events were observed, the researchers reported in the study, which was published online on Jan. 11.

No substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift were noted based on flow cytometry and analyses of T cell–mediated cytokine levels. No acute exacerbations of graft-versus-host disease occurred.

Click here to read the study (Bone Marrow Transplant. 2016 Jan 11. doi: 10.1038/bmt.2015.339).

[email protected]

On Twitter @maryjodales

Ibrutinib may prove useful for patients whose chronic lymphocytic leukemia (CLL) relapses after allogeneic stem cell transplantation, Dr. C. S. Link and colleagues reported.

Ibrutinib has shown efficacy in patients with high-risk CLL, but there are few data from patients who relapsed after allogeneic stem cell transplantation, wrote Dr. Link of the Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus and the DFG Research Center for Regenerative Therapies, both at the Technische Universität Dresden (Germany).

The researchers performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells in a study of five CLL patients treated with ibrutinib for relapse after allogeneic transplants. All patients had partial responses to ibrutinib and one had a minimal residual disease–negative remission.

At 1 year, none of the patients had relapsed; however, one patient died of pneumonia while on ibrutinib treatment. No other unexpected adverse events were observed, the researchers reported in the study, which was published online on Jan. 11.

No substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift were noted based on flow cytometry and analyses of T cell–mediated cytokine levels. No acute exacerbations of graft-versus-host disease occurred.

Click here to read the study (Bone Marrow Transplant. 2016 Jan 11. doi: 10.1038/bmt.2015.339).

[email protected]

On Twitter @maryjodales

Lesinurad (Zurampic) has been approved to treat hyperuricemia associated with gout, when used in combination with a xanthine oxidase inhibitor, the Food and Drug Administration announced on Dec. 22.

Lesinurad promotes uric acid excretion by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

“Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes,” said Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The drug’s safety and efficacy were evaluated in 1,537 participants in three randomized, placebo-controlled studies of its use in combination with a xanthine oxidase inhibitor. Participants treated for up to 12 months with lesinurad experienced reduced serum uric acid levels, compared with participants given placebo.

The most common adverse reactions in the clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad has a boxed warning that provides important safety information, including the risk for acute renal failure, which is more common when lesinurad is used without a xanthine oxidase inhibitor and with higher-than-approved doses.

The FDA also said in its statement that the agency is requiring a postmarketing study to further evaluate the renal and cardiovascular safety of lesinurad.

Zurampic is manufactured by AstraZeneca Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Lesinurad (Zurampic) has been approved to treat hyperuricemia associated with gout, when used in combination with a xanthine oxidase inhibitor, the Food and Drug Administration announced on Dec. 22.

Lesinurad promotes uric acid excretion by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

“Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes,” said Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The drug’s safety and efficacy were evaluated in 1,537 participants in three randomized, placebo-controlled studies of its use in combination with a xanthine oxidase inhibitor. Participants treated for up to 12 months with lesinurad experienced reduced serum uric acid levels, compared with participants given placebo.

The most common adverse reactions in the clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad has a boxed warning that provides important safety information, including the risk for acute renal failure, which is more common when lesinurad is used without a xanthine oxidase inhibitor and with higher-than-approved doses.

The FDA also said in its statement that the agency is requiring a postmarketing study to further evaluate the renal and cardiovascular safety of lesinurad.

Zurampic is manufactured by AstraZeneca Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Lesinurad (Zurampic) has been approved to treat hyperuricemia associated with gout, when used in combination with a xanthine oxidase inhibitor, the Food and Drug Administration announced on Dec. 22.

Lesinurad promotes uric acid excretion by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

“Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes,” said Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The drug’s safety and efficacy were evaluated in 1,537 participants in three randomized, placebo-controlled studies of its use in combination with a xanthine oxidase inhibitor. Participants treated for up to 12 months with lesinurad experienced reduced serum uric acid levels, compared with participants given placebo.

The most common adverse reactions in the clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad has a boxed warning that provides important safety information, including the risk for acute renal failure, which is more common when lesinurad is used without a xanthine oxidase inhibitor and with higher-than-approved doses.

The FDA also said in its statement that the agency is requiring a postmarketing study to further evaluate the renal and cardiovascular safety of lesinurad.

Zurampic is manufactured by AstraZeneca Pharmaceuticals.

[email protected]

On Twitter @maryjodales

In 2014, 47,055 people in the United States died from drug overdoses – more deaths than attributed to this cause in any previous year on record, according to data from the National Vital Statistics System.

Opioids, primarily prescription pain relievers and heroin, were the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths, Rose A. Rudd of the Centers for Disease Control and Prevention and her colleagues wrote (MMWR. 2015 Dec 18;64[Early release]:1-5).

The rate of opioid overdoses has tripled since 2000; the 15-year trend data implicate prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

From 2013 to 2014, synthetic opioids other than methadone (e.g., fentanyl and tramadol) drove the largest increase in the rate of drug overdose deaths. The rate nearly doubled from 1 per 100,000 persons to 1.8 per 100,000 persons. In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (for example, morphine, oxycodone, and hydrocodone) was 3.8 per 100,000. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

The five states with the highest rates of drug overdose deaths in 2014 were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7), and Ohio (24.6).

States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

The rates were noted in all adult age groups. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25-34 years, 35-44 years, 55-64 years, and 65 years and older. Based on ethnicity, increases were seen in non-Hispanic whites and non-Hispanic blacks. Based on residency, increases were most common in the Northeast, Midwest, and South.

The authors noted three limitations of the data: First, the substances tested for and circumstances under which toxicologic tests are performed vary by jurisdiction; in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved, and the percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Second, an increase from 2013 to 2014 in reporting of specific drugs involved in drug overdose deaths might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids. Finally, some heroin deaths might be misclassified or underreported because morphine and heroin are similarly metabolized.

Efforts to encourage safer prescribing of opioid pain relievers should be strengthened, according to the authors. CDC has developed a draft guideline for the prescribing of opioids for chronic pain to address this need. The guideline is available at www.cdc.gov/drugoverdose/prescribing/guideline.html.

[email protected]

On Twitter @maryjodales

In 2014, 47,055 people in the United States died from drug overdoses – more deaths than attributed to this cause in any previous year on record, according to data from the National Vital Statistics System.

Opioids, primarily prescription pain relievers and heroin, were the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths, Rose A. Rudd of the Centers for Disease Control and Prevention and her colleagues wrote (MMWR. 2015 Dec 18;64[Early release]:1-5).

The rate of opioid overdoses has tripled since 2000; the 15-year trend data implicate prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

From 2013 to 2014, synthetic opioids other than methadone (e.g., fentanyl and tramadol) drove the largest increase in the rate of drug overdose deaths. The rate nearly doubled from 1 per 100,000 persons to 1.8 per 100,000 persons. In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (for example, morphine, oxycodone, and hydrocodone) was 3.8 per 100,000. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

The five states with the highest rates of drug overdose deaths in 2014 were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7), and Ohio (24.6).

States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

The rates were noted in all adult age groups. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25-34 years, 35-44 years, 55-64 years, and 65 years and older. Based on ethnicity, increases were seen in non-Hispanic whites and non-Hispanic blacks. Based on residency, increases were most common in the Northeast, Midwest, and South.

The authors noted three limitations of the data: First, the substances tested for and circumstances under which toxicologic tests are performed vary by jurisdiction; in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved, and the percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Second, an increase from 2013 to 2014 in reporting of specific drugs involved in drug overdose deaths might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids. Finally, some heroin deaths might be misclassified or underreported because morphine and heroin are similarly metabolized.

Efforts to encourage safer prescribing of opioid pain relievers should be strengthened, according to the authors. CDC has developed a draft guideline for the prescribing of opioids for chronic pain to address this need. The guideline is available at www.cdc.gov/drugoverdose/prescribing/guideline.html.

[email protected]

On Twitter @maryjodales

In 2014, 47,055 people in the United States died from drug overdoses – more deaths than attributed to this cause in any previous year on record, according to data from the National Vital Statistics System.

Opioids, primarily prescription pain relievers and heroin, were the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths, Rose A. Rudd of the Centers for Disease Control and Prevention and her colleagues wrote (MMWR. 2015 Dec 18;64[Early release]:1-5).

The rate of opioid overdoses has tripled since 2000; the 15-year trend data implicate prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

From 2013 to 2014, synthetic opioids other than methadone (e.g., fentanyl and tramadol) drove the largest increase in the rate of drug overdose deaths. The rate nearly doubled from 1 per 100,000 persons to 1.8 per 100,000 persons. In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (for example, morphine, oxycodone, and hydrocodone) was 3.8 per 100,000. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

The five states with the highest rates of drug overdose deaths in 2014 were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7), and Ohio (24.6).

States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

The rates were noted in all adult age groups. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25-34 years, 35-44 years, 55-64 years, and 65 years and older. Based on ethnicity, increases were seen in non-Hispanic whites and non-Hispanic blacks. Based on residency, increases were most common in the Northeast, Midwest, and South.

The authors noted three limitations of the data: First, the substances tested for and circumstances under which toxicologic tests are performed vary by jurisdiction; in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved, and the percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Second, an increase from 2013 to 2014 in reporting of specific drugs involved in drug overdose deaths might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids. Finally, some heroin deaths might be misclassified or underreported because morphine and heroin are similarly metabolized.

Efforts to encourage safer prescribing of opioid pain relievers should be strengthened, according to the authors. CDC has developed a draft guideline for the prescribing of opioids for chronic pain to address this need. The guideline is available at www.cdc.gov/drugoverdose/prescribing/guideline.html.

[email protected]

On Twitter @maryjodales

Radotinib was associated with significantly higher complete cytogenetic responses and major molecular responses than imatinib was at a minimum 12 months of follow-up in a randomized, open-label, phase III clinical trialof patients with newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP).

Radotinib, an investigational BCR-ABL1 tyrosine kinase inhibitor developed by IL-YANG Pharmaceuticals, is approved in Korea for the treatment of CML-CP in patients who have failed prior TKIs.

Dr. Jae-Yong Kwak of Chonbuk National University Medical School and Hospital, Jeonju, South Korea, and his colleagues randomized 241 patients to either radotinib 300 mg twice daily (n = 79), radotinib 400 mg twice daily (n = 81), or imatinib 400 mg once daily (n = 81). All three study groups were balanced in regard to baseline age, gender, race, and Sokal risk score.

At a minimum follow-up of 12 months, the proportions of patients receiving a study drug were 86% (69/79) in the radotinib 300 mg twice-daily group, 72% (58/81) in the radotinib 400 mg twice-daily group, and 82% (66/81) in the imatinib 400 mg once-daily group.

The rates of major molecular response at 12 months were significantly higher in patients receiving radotinib 300 mg b.i.d. (52%, P = .0044) and radotinib 400 mg b.i.d. (46%, P = .0342), compared with imatinib (30%), Dr. Kwak reported at the annual meeting of the American Society of Hematology in Orlando.

Among responders, the median times to major molecular response were shorter on radotinib 300 mg b.i.d. (5.7 months) and radotinib 400 mg b.i.d. (5.6 months) than on imatinib (8.2 months). The MR4.5 rates by 12 months were also higher for both radotinib 300 mg b.i.d. (15%) and 400 mg b.i.d. (14%), compared with imatinib (9%). The complete cytogenetic response rates by 12 months were 91% for radotinib 300 mg b.i.d. (P = .0120), compared with imatinib (77%). None of the patients in the study had progressed to accelerated phase or blast crisis at 12 months.

Drug discontinuation due to adverse events (AEs) or laboratory abnormalities occurred in 9% of patients on radotinib 300 mg b.i.d., 20% on radotinib 400 mg b.i.d., and 6% on imatinib.

The major side effects included grade 3/4 thrombocytopenia in 16% of patients receiving radotinib 300 mg b.i.d., 14% on radotinib 400 mg b.i.d., and 20% receiving imatinib. Grade 3/4 neutropenia occurred in 19%, 24%, and 30% for radotinib 300 mg b.i.d., 400 mg b.i.d., and imatinib, respectively.

Overall, grade 3/4 nonlaboratory AEs were uncommon in all groups. The most common nonlaboratory AEs in the radotinib groups were skin rash (about 33% in both), nausea/vomiting (about 23% in both), headache (19% and 31%), and pruritus (19% and 30%). In the imatinib group, the most common adverse events were edema (35%), myalgia (28%), nausea/vomiting (27%), and skin rash (22%).

Dr. Kwak had no relevant disclosures. Some of his colleagues received research funding from IL-YANG Pharmaceutical Co. and Alexion Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Radotinib was associated with significantly higher complete cytogenetic responses and major molecular responses than imatinib was at a minimum 12 months of follow-up in a randomized, open-label, phase III clinical trialof patients with newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP).

Radotinib, an investigational BCR-ABL1 tyrosine kinase inhibitor developed by IL-YANG Pharmaceuticals, is approved in Korea for the treatment of CML-CP in patients who have failed prior TKIs.

Dr. Jae-Yong Kwak of Chonbuk National University Medical School and Hospital, Jeonju, South Korea, and his colleagues randomized 241 patients to either radotinib 300 mg twice daily (n = 79), radotinib 400 mg twice daily (n = 81), or imatinib 400 mg once daily (n = 81). All three study groups were balanced in regard to baseline age, gender, race, and Sokal risk score.

At a minimum follow-up of 12 months, the proportions of patients receiving a study drug were 86% (69/79) in the radotinib 300 mg twice-daily group, 72% (58/81) in the radotinib 400 mg twice-daily group, and 82% (66/81) in the imatinib 400 mg once-daily group.

The rates of major molecular response at 12 months were significantly higher in patients receiving radotinib 300 mg b.i.d. (52%, P = .0044) and radotinib 400 mg b.i.d. (46%, P = .0342), compared with imatinib (30%), Dr. Kwak reported at the annual meeting of the American Society of Hematology in Orlando.

Among responders, the median times to major molecular response were shorter on radotinib 300 mg b.i.d. (5.7 months) and radotinib 400 mg b.i.d. (5.6 months) than on imatinib (8.2 months). The MR4.5 rates by 12 months were also higher for both radotinib 300 mg b.i.d. (15%) and 400 mg b.i.d. (14%), compared with imatinib (9%). The complete cytogenetic response rates by 12 months were 91% for radotinib 300 mg b.i.d. (P = .0120), compared with imatinib (77%). None of the patients in the study had progressed to accelerated phase or blast crisis at 12 months.

Drug discontinuation due to adverse events (AEs) or laboratory abnormalities occurred in 9% of patients on radotinib 300 mg b.i.d., 20% on radotinib 400 mg b.i.d., and 6% on imatinib.

The major side effects included grade 3/4 thrombocytopenia in 16% of patients receiving radotinib 300 mg b.i.d., 14% on radotinib 400 mg b.i.d., and 20% receiving imatinib. Grade 3/4 neutropenia occurred in 19%, 24%, and 30% for radotinib 300 mg b.i.d., 400 mg b.i.d., and imatinib, respectively.

Overall, grade 3/4 nonlaboratory AEs were uncommon in all groups. The most common nonlaboratory AEs in the radotinib groups were skin rash (about 33% in both), nausea/vomiting (about 23% in both), headache (19% and 31%), and pruritus (19% and 30%). In the imatinib group, the most common adverse events were edema (35%), myalgia (28%), nausea/vomiting (27%), and skin rash (22%).

Dr. Kwak had no relevant disclosures. Some of his colleagues received research funding from IL-YANG Pharmaceutical Co. and Alexion Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Radotinib was associated with significantly higher complete cytogenetic responses and major molecular responses than imatinib was at a minimum 12 months of follow-up in a randomized, open-label, phase III clinical trialof patients with newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP).

Radotinib, an investigational BCR-ABL1 tyrosine kinase inhibitor developed by IL-YANG Pharmaceuticals, is approved in Korea for the treatment of CML-CP in patients who have failed prior TKIs.

Dr. Jae-Yong Kwak of Chonbuk National University Medical School and Hospital, Jeonju, South Korea, and his colleagues randomized 241 patients to either radotinib 300 mg twice daily (n = 79), radotinib 400 mg twice daily (n = 81), or imatinib 400 mg once daily (n = 81). All three study groups were balanced in regard to baseline age, gender, race, and Sokal risk score.

At a minimum follow-up of 12 months, the proportions of patients receiving a study drug were 86% (69/79) in the radotinib 300 mg twice-daily group, 72% (58/81) in the radotinib 400 mg twice-daily group, and 82% (66/81) in the imatinib 400 mg once-daily group.

The rates of major molecular response at 12 months were significantly higher in patients receiving radotinib 300 mg b.i.d. (52%, P = .0044) and radotinib 400 mg b.i.d. (46%, P = .0342), compared with imatinib (30%), Dr. Kwak reported at the annual meeting of the American Society of Hematology in Orlando.

Among responders, the median times to major molecular response were shorter on radotinib 300 mg b.i.d. (5.7 months) and radotinib 400 mg b.i.d. (5.6 months) than on imatinib (8.2 months). The MR4.5 rates by 12 months were also higher for both radotinib 300 mg b.i.d. (15%) and 400 mg b.i.d. (14%), compared with imatinib (9%). The complete cytogenetic response rates by 12 months were 91% for radotinib 300 mg b.i.d. (P = .0120), compared with imatinib (77%). None of the patients in the study had progressed to accelerated phase or blast crisis at 12 months.

Drug discontinuation due to adverse events (AEs) or laboratory abnormalities occurred in 9% of patients on radotinib 300 mg b.i.d., 20% on radotinib 400 mg b.i.d., and 6% on imatinib.

The major side effects included grade 3/4 thrombocytopenia in 16% of patients receiving radotinib 300 mg b.i.d., 14% on radotinib 400 mg b.i.d., and 20% receiving imatinib. Grade 3/4 neutropenia occurred in 19%, 24%, and 30% for radotinib 300 mg b.i.d., 400 mg b.i.d., and imatinib, respectively.

Overall, grade 3/4 nonlaboratory AEs were uncommon in all groups. The most common nonlaboratory AEs in the radotinib groups were skin rash (about 33% in both), nausea/vomiting (about 23% in both), headache (19% and 31%), and pruritus (19% and 30%). In the imatinib group, the most common adverse events were edema (35%), myalgia (28%), nausea/vomiting (27%), and skin rash (22%).

Dr. Kwak had no relevant disclosures. Some of his colleagues received research funding from IL-YANG Pharmaceutical Co. and Alexion Pharmaceuticals.

[email protected]

On Twitter @maryjodales

ORLANDO – Age did not affect molecular response or the incidence of adverse reactions to nilotinib among patients with chronic myeloid leukemia in chronic phase (CML-CP), based on results from a subanalysis of the ENEST1st study.

The analysis of the ENEST1st study, reported by Dr. Francis J. Giles, compared outcomes for 1,089 newly diagnosed CML-CP patients, 19% were aged 65 years or older and 81% were younger than age 65 years. All patients had typical transcripts and were treated for 3 months or less with nilotinib 300 mg twice daily in the open-label study.

For those 65 years and older, Sokal risk scores were low in 4.5%, intermediate in 61.2%, and high in 23.4%, with missing data for 10.9%. For younger patients, Sokal risk scores were low in 42.1%, intermediate in 32%, and high in 16.9%, with missing data for 9.

At 18 months, there was an overall 38.4% rate (95% CI, 35.5%-41.3%) of MR4 grade molecular response, which was defined as BCR-ABL level of 0.01% or less on the International Scale or undetectable BCR-ABL in cDNA with at least 10,000 ABL transcripts.

The MR4 rate at 18 months did not significantly vary by age. For patients under age 65, the cumulative incidence of MR4 by 18 months was 48.8% (95% CI, 45.4% - 52.1%); among patients aged 65 and older, the incidence of MR4 was 48.3% (95% CI, 41.4% - 55.2%). The MR4.5 rate by 18 months was 32.5% in younger patients and 28.4% in older patients, reported Dr. Giles of the Institute for Drug Development, Cancer Therapy and Research Center, at the University of Texas Health Science Center at San Antonio, and his colleagues.

Based on Sokal score, the MR4 rate by 18 months in younger patients was 53.6% (low), 45.2% (intermediate), and 35.4% (high), respectively. For older patients, the MR4 rate by 18 months based on Sokal score was 44.4% (low), 49.6% (intermediate), and 44.7% (high).

Six patients (0.6%) progressed to accelerated phase/blast crisis (AP/BC) on study; 13 patients (1.2%) died by 24 months. The most common adverse events were rash (21.4%), pruritus (16.5%), and headache (15.2%).

Novartis is the sponsor of the ENEST1st study. Dr. Giles consults for and receives honoraria and research funding from Novartis.

[email protected]

On Twitter @maryjodales

ORLANDO – Age did not affect molecular response or the incidence of adverse reactions to nilotinib among patients with chronic myeloid leukemia in chronic phase (CML-CP), based on results from a subanalysis of the ENEST1st study.

The analysis of the ENEST1st study, reported by Dr. Francis J. Giles, compared outcomes for 1,089 newly diagnosed CML-CP patients, 19% were aged 65 years or older and 81% were younger than age 65 years. All patients had typical transcripts and were treated for 3 months or less with nilotinib 300 mg twice daily in the open-label study.

For those 65 years and older, Sokal risk scores were low in 4.5%, intermediate in 61.2%, and high in 23.4%, with missing data for 10.9%. For younger patients, Sokal risk scores were low in 42.1%, intermediate in 32%, and high in 16.9%, with missing data for 9.

At 18 months, there was an overall 38.4% rate (95% CI, 35.5%-41.3%) of MR4 grade molecular response, which was defined as BCR-ABL level of 0.01% or less on the International Scale or undetectable BCR-ABL in cDNA with at least 10,000 ABL transcripts.

The MR4 rate at 18 months did not significantly vary by age. For patients under age 65, the cumulative incidence of MR4 by 18 months was 48.8% (95% CI, 45.4% - 52.1%); among patients aged 65 and older, the incidence of MR4 was 48.3% (95% CI, 41.4% - 55.2%). The MR4.5 rate by 18 months was 32.5% in younger patients and 28.4% in older patients, reported Dr. Giles of the Institute for Drug Development, Cancer Therapy and Research Center, at the University of Texas Health Science Center at San Antonio, and his colleagues.

Based on Sokal score, the MR4 rate by 18 months in younger patients was 53.6% (low), 45.2% (intermediate), and 35.4% (high), respectively. For older patients, the MR4 rate by 18 months based on Sokal score was 44.4% (low), 49.6% (intermediate), and 44.7% (high).

Six patients (0.6%) progressed to accelerated phase/blast crisis (AP/BC) on study; 13 patients (1.2%) died by 24 months. The most common adverse events were rash (21.4%), pruritus (16.5%), and headache (15.2%).

Novartis is the sponsor of the ENEST1st study. Dr. Giles consults for and receives honoraria and research funding from Novartis.

[email protected]

On Twitter @maryjodales

ORLANDO – Age did not affect molecular response or the incidence of adverse reactions to nilotinib among patients with chronic myeloid leukemia in chronic phase (CML-CP), based on results from a subanalysis of the ENEST1st study.

The analysis of the ENEST1st study, reported by Dr. Francis J. Giles, compared outcomes for 1,089 newly diagnosed CML-CP patients, 19% were aged 65 years or older and 81% were younger than age 65 years. All patients had typical transcripts and were treated for 3 months or less with nilotinib 300 mg twice daily in the open-label study.

For those 65 years and older, Sokal risk scores were low in 4.5%, intermediate in 61.2%, and high in 23.4%, with missing data for 10.9%. For younger patients, Sokal risk scores were low in 42.1%, intermediate in 32%, and high in 16.9%, with missing data for 9.

At 18 months, there was an overall 38.4% rate (95% CI, 35.5%-41.3%) of MR4 grade molecular response, which was defined as BCR-ABL level of 0.01% or less on the International Scale or undetectable BCR-ABL in cDNA with at least 10,000 ABL transcripts.

The MR4 rate at 18 months did not significantly vary by age. For patients under age 65, the cumulative incidence of MR4 by 18 months was 48.8% (95% CI, 45.4% - 52.1%); among patients aged 65 and older, the incidence of MR4 was 48.3% (95% CI, 41.4% - 55.2%). The MR4.5 rate by 18 months was 32.5% in younger patients and 28.4% in older patients, reported Dr. Giles of the Institute for Drug Development, Cancer Therapy and Research Center, at the University of Texas Health Science Center at San Antonio, and his colleagues.

Based on Sokal score, the MR4 rate by 18 months in younger patients was 53.6% (low), 45.2% (intermediate), and 35.4% (high), respectively. For older patients, the MR4 rate by 18 months based on Sokal score was 44.4% (low), 49.6% (intermediate), and 44.7% (high).

Six patients (0.6%) progressed to accelerated phase/blast crisis (AP/BC) on study; 13 patients (1.2%) died by 24 months. The most common adverse events were rash (21.4%), pruritus (16.5%), and headache (15.2%).

Novartis is the sponsor of the ENEST1st study. Dr. Giles consults for and receives honoraria and research funding from Novartis.

[email protected]

On Twitter @maryjodales

ORLANDO – Adding eltrombopag to standard immunosuppressive treatment for newly-diagnosed severe aplastic anemia boosted overall response rates from around 65% to over 90%, based on a late-breaker study presented by Dr. Danielle M. Townsley at the annual meeting of the American Society of Hematology.

Dr. Townsley said that starting the combination treatment immediately at diagnosis, rather than waiting to introduce eltrombopag at either 2 weeks or 3 months after initiating standard immunosuppressive therapy, was associated with better outcomes. As a result of the findings, a cohort extension of the trial will continue and is enrolling patients.

In our video interview, Dr. Townsley discusses the top-level results and says that it’s too early to introduce the protocol into practice outside a clinical trial. She urges hematologists to enroll their patients in the ongoing cohort study.

[email protected]

On Twitter @maryjodales

ORLANDO – Adding eltrombopag to standard immunosuppressive treatment for newly-diagnosed severe aplastic anemia boosted overall response rates from around 65% to over 90%, based on a late-breaker study presented by Dr. Danielle M. Townsley at the annual meeting of the American Society of Hematology.

Dr. Townsley said that starting the combination treatment immediately at diagnosis, rather than waiting to introduce eltrombopag at either 2 weeks or 3 months after initiating standard immunosuppressive therapy, was associated with better outcomes. As a result of the findings, a cohort extension of the trial will continue and is enrolling patients.

In our video interview, Dr. Townsley discusses the top-level results and says that it’s too early to introduce the protocol into practice outside a clinical trial. She urges hematologists to enroll their patients in the ongoing cohort study.

[email protected]

On Twitter @maryjodales

ORLANDO – Adding eltrombopag to standard immunosuppressive treatment for newly-diagnosed severe aplastic anemia boosted overall response rates from around 65% to over 90%, based on a late-breaker study presented by Dr. Danielle M. Townsley at the annual meeting of the American Society of Hematology.

Dr. Townsley said that starting the combination treatment immediately at diagnosis, rather than waiting to introduce eltrombopag at either 2 weeks or 3 months after initiating standard immunosuppressive therapy, was associated with better outcomes. As a result of the findings, a cohort extension of the trial will continue and is enrolling patients.

In our video interview, Dr. Townsley discusses the top-level results and says that it’s too early to introduce the protocol into practice outside a clinical trial. She urges hematologists to enroll their patients in the ongoing cohort study.

[email protected]

On Twitter @maryjodales

ORLANDO – Five “Choosing Wisely” initiatives selected from other specialties were featured at the annual meeting of the American Society of Hematology.

Dr. Lisa Hicks of St. Michael’s Hospital in Toronto led ASH’s Choosing Wisely list and moderated their presentation and the discussion of this year’s recommendations at the meeting. In a video interview, Dr. Hicks discussed the five recommendations and how hematologists can influence better patient care through cross-specialty collaborations. The complete Choosing Wisely list is available at www.hematology.org/choosingwisely

The 2015 Choosing Wisely recommendations, selected from recommendations made previously by other organizations, are:

• Don’t image for suspected pulmonary embolism (PE) without moderate or high pre-test probability of PE. (American College of Radiology)

• Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability. (Society of Hospital Medicine)

• Don’t routinely order thrombophilia testing on patients undergoing a routine infertility evaluation. (American Society of Reproductive Medicine)

• Don’t transfuse red blood cells for iron deficiency without hemodynamic instability. (American Association of Blood Banks)

• Avoid using PET or PET-CT scanning as part of routine follow-up care to monitor for a cancer recurrence in asymptomatic patients who have finished initial treatment to eliminate the cancer unless there is high-level evidence that such imaging will change the outcome. (American Society of Clinical Oncology)

Choosing Wisely is an initiative of the ABIM Foundation. Dr. Hicks had no relevant financial disclosures.

ORLANDO – Five “Choosing Wisely” initiatives selected from other specialties were featured at the annual meeting of the American Society of Hematology.

Dr. Lisa Hicks of St. Michael’s Hospital in Toronto led ASH’s Choosing Wisely list and moderated their presentation and the discussion of this year’s recommendations at the meeting. In a video interview, Dr. Hicks discussed the five recommendations and how hematologists can influence better patient care through cross-specialty collaborations. The complete Choosing Wisely list is available at www.hematology.org/choosingwisely

The 2015 Choosing Wisely recommendations, selected from recommendations made previously by other organizations, are:

• Don’t image for suspected pulmonary embolism (PE) without moderate or high pre-test probability of PE. (American College of Radiology)

• Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability. (Society of Hospital Medicine)

• Don’t routinely order thrombophilia testing on patients undergoing a routine infertility evaluation. (American Society of Reproductive Medicine)

• Don’t transfuse red blood cells for iron deficiency without hemodynamic instability. (American Association of Blood Banks)

• Avoid using PET or PET-CT scanning as part of routine follow-up care to monitor for a cancer recurrence in asymptomatic patients who have finished initial treatment to eliminate the cancer unless there is high-level evidence that such imaging will change the outcome. (American Society of Clinical Oncology)

Choosing Wisely is an initiative of the ABIM Foundation. Dr. Hicks had no relevant financial disclosures.

ORLANDO – Five “Choosing Wisely” initiatives selected from other specialties were featured at the annual meeting of the American Society of Hematology.

Dr. Lisa Hicks of St. Michael’s Hospital in Toronto led ASH’s Choosing Wisely list and moderated their presentation and the discussion of this year’s recommendations at the meeting. In a video interview, Dr. Hicks discussed the five recommendations and how hematologists can influence better patient care through cross-specialty collaborations. The complete Choosing Wisely list is available at www.hematology.org/choosingwisely

The 2015 Choosing Wisely recommendations, selected from recommendations made previously by other organizations, are:

• Don’t image for suspected pulmonary embolism (PE) without moderate or high pre-test probability of PE. (American College of Radiology)

• Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability. (Society of Hospital Medicine)

• Don’t routinely order thrombophilia testing on patients undergoing a routine infertility evaluation. (American Society of Reproductive Medicine)

• Don’t transfuse red blood cells for iron deficiency without hemodynamic instability. (American Association of Blood Banks)

• Avoid using PET or PET-CT scanning as part of routine follow-up care to monitor for a cancer recurrence in asymptomatic patients who have finished initial treatment to eliminate the cancer unless there is high-level evidence that such imaging will change the outcome. (American Society of Clinical Oncology)

Choosing Wisely is an initiative of the ABIM Foundation. Dr. Hicks had no relevant financial disclosures.

ORLANDO – The combination of the oral proteasome inhibitor ixazomib (Ninlaro, recently approved by the Food and Drug Administration) with lenalidomide and dexamethasone was associated with a 35% improvement in progression free survival in the Tourmaline trial.

In a video interview, Tourmaline investigator Dr. Shaji Kumar, professor of medicine at the Mayo Clinic, Rochester, Minn., discussed the top-line study results, the status of ongoing trials with ixazomib in other combination regimens, and the decision rationales that will need to be considered in selecting one of the newly approved multiple myeloma therapies.

Dr. Kumar has received funding from Takeda, the makers of ixazomib; he has also received funding from Celgene, Onyx, Janssen, and Sanofi.

[email protected]

ORLANDO – The combination of the oral proteasome inhibitor ixazomib (Ninlaro, recently approved by the Food and Drug Administration) with lenalidomide and dexamethasone was associated with a 35% improvement in progression free survival in the Tourmaline trial.

In a video interview, Tourmaline investigator Dr. Shaji Kumar, professor of medicine at the Mayo Clinic, Rochester, Minn., discussed the top-line study results, the status of ongoing trials with ixazomib in other combination regimens, and the decision rationales that will need to be considered in selecting one of the newly approved multiple myeloma therapies.

Dr. Kumar has received funding from Takeda, the makers of ixazomib; he has also received funding from Celgene, Onyx, Janssen, and Sanofi.

[email protected]

ORLANDO – The combination of the oral proteasome inhibitor ixazomib (Ninlaro, recently approved by the Food and Drug Administration) with lenalidomide and dexamethasone was associated with a 35% improvement in progression free survival in the Tourmaline trial.

In a video interview, Tourmaline investigator Dr. Shaji Kumar, professor of medicine at the Mayo Clinic, Rochester, Minn., discussed the top-line study results, the status of ongoing trials with ixazomib in other combination regimens, and the decision rationales that will need to be considered in selecting one of the newly approved multiple myeloma therapies.

Dr. Kumar has received funding from Takeda, the makers of ixazomib; he has also received funding from Celgene, Onyx, Janssen, and Sanofi.

[email protected]

ORLANDO – Children with chronic immune thrombocytopenia (ITP) have an increased frequency of damaging variants in genes associated with cellular immunity, notably IFNA17 and IFNLR1, based on the results of whole genome sequencing.

The links to IFNA17 and IFNLR1 genes, which are involved in T cell pathways, remain significant when patients are stratified according to disease severity, Dr. Jenny M. Despotovic reported at the annual meeting of the American Sociey of Hematology. The finding is further evidence for the role of T cell abnormalities in the pathophysiology of chronic ITP.

These may be important candidate genes involved in immune regulation and in sustained autoimmunity, which appears to be due to generalized immune dysregulation that includes altered T cell balance with a shift toward immune activation (increased Th1/Th2 ratio) as well as decreased number and impaired function of regulatory T cells, said Dr. Despotovic, of Texas Children’s Cancer and Hematology Centers, Baylor College of Medicine, Houston.

In their study, Dr. Despotovic and her colleagues performed whole exome sequencing on 262 samples with robust phenotype data from children with chronic ITP in the North American Chronic ITP Registry and the Platelet Disorders Center at the Weill-Cornell Medical Center. All but three patients were less than 20 years old at diagnosis; 83% had primary ITP, 10% had Evans syndrome, and 7% had other autoimmune disorders.

To identify candidate genes associated with ITP susceptibility, sequencing data were compared for 172 ITP cases of European American ancestry and 5,664 controls of European American ancestry with platelet levels over 150 x 10⁹/L in the Atherosclerosis Risk in Communities (ARIC) Study. In a separate analysis, phenotype data for ITP cases were reviewed and cases were stratified by disease severity according to the need for second line treatment.

A significant increase in the frequency of several damaging variants were identified in genes in the ITP cohort. The most significant associations were detected in the IFNA17 gene, which is involved in transforming growth factor beta secretion and could affect number and function of regulatory T cells.

IFNA17 rs9298814 was identified in 26% of cases in the ITP cohort compared to less than 0.01% of controls. In all, 43% of ITP patients had at a presumed deleterious variant of IFNA17.

IFNA17 gene variants remained significant in the most severely affected patients, specifically those requiring second line therapy, providing further evidence for this gene’s functional relevance in the pathogenesis and pathophysiology of ITP, Dr. Despotovic said.

Other genes with known impact on T cell number or function, including DGCR14, SMAD2 and CD83 also contained an increased frequency of variants in the European American ITP cohort. IFNLR1 and REL genes were also significantly associated with need for second line ITP therapy.

Analysis of this large cohort did not validate any of over 20 variants that have been previously published as candidates for ITP susceptibility or evolution to chronic ITP, she added.

[email protected]

On Twitter @maryjodales

ORLANDO – Children with chronic immune thrombocytopenia (ITP) have an increased frequency of damaging variants in genes associated with cellular immunity, notably IFNA17 and IFNLR1, based on the results of whole genome sequencing.

The links to IFNA17 and IFNLR1 genes, which are involved in T cell pathways, remain significant when patients are stratified according to disease severity, Dr. Jenny M. Despotovic reported at the annual meeting of the American Sociey of Hematology. The finding is further evidence for the role of T cell abnormalities in the pathophysiology of chronic ITP.

These may be important candidate genes involved in immune regulation and in sustained autoimmunity, which appears to be due to generalized immune dysregulation that includes altered T cell balance with a shift toward immune activation (increased Th1/Th2 ratio) as well as decreased number and impaired function of regulatory T cells, said Dr. Despotovic, of Texas Children’s Cancer and Hematology Centers, Baylor College of Medicine, Houston.

In their study, Dr. Despotovic and her colleagues performed whole exome sequencing on 262 samples with robust phenotype data from children with chronic ITP in the North American Chronic ITP Registry and the Platelet Disorders Center at the Weill-Cornell Medical Center. All but three patients were less than 20 years old at diagnosis; 83% had primary ITP, 10% had Evans syndrome, and 7% had other autoimmune disorders.

To identify candidate genes associated with ITP susceptibility, sequencing data were compared for 172 ITP cases of European American ancestry and 5,664 controls of European American ancestry with platelet levels over 150 x 10⁹/L in the Atherosclerosis Risk in Communities (ARIC) Study. In a separate analysis, phenotype data for ITP cases were reviewed and cases were stratified by disease severity according to the need for second line treatment.

A significant increase in the frequency of several damaging variants were identified in genes in the ITP cohort. The most significant associations were detected in the IFNA17 gene, which is involved in transforming growth factor beta secretion and could affect number and function of regulatory T cells.

IFNA17 rs9298814 was identified in 26% of cases in the ITP cohort compared to less than 0.01% of controls. In all, 43% of ITP patients had at a presumed deleterious variant of IFNA17.

IFNA17 gene variants remained significant in the most severely affected patients, specifically those requiring second line therapy, providing further evidence for this gene’s functional relevance in the pathogenesis and pathophysiology of ITP, Dr. Despotovic said.

Other genes with known impact on T cell number or function, including DGCR14, SMAD2 and CD83 also contained an increased frequency of variants in the European American ITP cohort. IFNLR1 and REL genes were also significantly associated with need for second line ITP therapy.

Analysis of this large cohort did not validate any of over 20 variants that have been previously published as candidates for ITP susceptibility or evolution to chronic ITP, she added.

[email protected]

On Twitter @maryjodales

ORLANDO – Children with chronic immune thrombocytopenia (ITP) have an increased frequency of damaging variants in genes associated with cellular immunity, notably IFNA17 and IFNLR1, based on the results of whole genome sequencing.

The links to IFNA17 and IFNLR1 genes, which are involved in T cell pathways, remain significant when patients are stratified according to disease severity, Dr. Jenny M. Despotovic reported at the annual meeting of the American Sociey of Hematology. The finding is further evidence for the role of T cell abnormalities in the pathophysiology of chronic ITP.

These may be important candidate genes involved in immune regulation and in sustained autoimmunity, which appears to be due to generalized immune dysregulation that includes altered T cell balance with a shift toward immune activation (increased Th1/Th2 ratio) as well as decreased number and impaired function of regulatory T cells, said Dr. Despotovic, of Texas Children’s Cancer and Hematology Centers, Baylor College of Medicine, Houston.

In their study, Dr. Despotovic and her colleagues performed whole exome sequencing on 262 samples with robust phenotype data from children with chronic ITP in the North American Chronic ITP Registry and the Platelet Disorders Center at the Weill-Cornell Medical Center. All but three patients were less than 20 years old at diagnosis; 83% had primary ITP, 10% had Evans syndrome, and 7% had other autoimmune disorders.

To identify candidate genes associated with ITP susceptibility, sequencing data were compared for 172 ITP cases of European American ancestry and 5,664 controls of European American ancestry with platelet levels over 150 x 10⁹/L in the Atherosclerosis Risk in Communities (ARIC) Study. In a separate analysis, phenotype data for ITP cases were reviewed and cases were stratified by disease severity according to the need for second line treatment.

A significant increase in the frequency of several damaging variants were identified in genes in the ITP cohort. The most significant associations were detected in the IFNA17 gene, which is involved in transforming growth factor beta secretion and could affect number and function of regulatory T cells.

IFNA17 rs9298814 was identified in 26% of cases in the ITP cohort compared to less than 0.01% of controls. In all, 43% of ITP patients had at a presumed deleterious variant of IFNA17.

IFNA17 gene variants remained significant in the most severely affected patients, specifically those requiring second line therapy, providing further evidence for this gene’s functional relevance in the pathogenesis and pathophysiology of ITP, Dr. Despotovic said.

Other genes with known impact on T cell number or function, including DGCR14, SMAD2 and CD83 also contained an increased frequency of variants in the European American ITP cohort. IFNLR1 and REL genes were also significantly associated with need for second line ITP therapy.

Analysis of this large cohort did not validate any of over 20 variants that have been previously published as candidates for ITP susceptibility or evolution to chronic ITP, she added.

[email protected]

On Twitter @maryjodales