Jennifer Smith

The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.

[email protected]

The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.

[email protected]

The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.

[email protected]

The Food and Drug Administration has granted accelerated approval to venetoclax for use in acute myeloid leukemia (AML).

The BCL-2 inhibitor is now approved for use in combination with azacitidine, decitabine, or low-dose cytarabine to treat newly diagnosed adults with AML who are aged 75 and older or who are ineligible for intensive chemotherapy.

The FDA grants accelerated approval based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Continued approval of venetoclax in AML may be contingent upon verification of clinical benefit in confirmatory trials.

The approval is based on data from two studies – the phase 1b M14-358 trial ( NCT02203773 ) and the phase 1/2 M14-387 trial ( NCT02287233 ).

In M14-358, newly diagnosed AML patients received venetoclax in combination with azacitidine (n=84) or decitabine (n=31). There were 67 patients in the azacitidine arm and 13 in the decitabine arm who were aged 75 or older or were ineligible for intensive induction chemotherapy.

Patients received venetoclax via a daily ramp-up to a final dose of 400 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.

They received azacitidine at 75 mg/m ² on days 1-7 of each 28-day cycle or decitabine at 20 mg/m ² on days 1-5 of each cycle. Patients continued treatment until disease progression or unacceptable toxicity.

The median follow-up was 7.9 months for the azacitidine arm and 11 months for the decitabine arm.

The complete response (CR) rate was 37% (25/67) in the azacitidine arm and 54% (7/13) in the decitabine arm. The rates of CR with partial hematologic recovery were 24% (16/67) and 7.7% (1/13), respectively. The most common adverse events (AEs) – occurring in at least 30% of patients in both arms – were nausea, diarrhea, constipation, neutropenia, thrombocytopenia, hemorrhage, peripheral edema, vomiting, fatigue, febrile neutropenia, rash, and anemia. The incidence of serious AEs was 75% overall. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome. The incidence of fatal AEs was 1.5% within 30 days of treatment initiation. The M14-387 trial included 82 AML patients who received venetoclax plus low-dose cytarabine. Patients were newly diagnosed with AML, but some had previous exposure to a hypomethylating agent for an antecedent hematologic disorder.

There were 61 patients who were aged 75 or older or were ineligible for intensive induction chemotherapy.

Patients received venetoclax via daily ramp-up to a final dose of 600 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.

Cytarabine was given at 20 mg/m ² on days 1-10 of each 28-day cycle. Patients continued to receive treatment until disease progression or unacceptable toxicity.

At a median follow-up of 6.5 months, the CR rate was 21% (13/61), and the rate of CR with partial hematologic recovery was 21% (13/61).

The most common AEs (occurring in at least 30% of patients) were nausea, thrombocytopenia, hemorrhage, febrile neutropenia, neutropenia, diarrhea, fatigue, constipation, and dyspnea. The incidence of serious AEs was 95%. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection. The incidence of fatal AEs was 4.9% within 30 days of treatment initiation.

Additional details from the M14-358 and M14-387 trials are available in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche.

[email protected]

The Food and Drug Administration has granted accelerated approval to venetoclax for use in acute myeloid leukemia (AML).

The BCL-2 inhibitor is now approved for use in combination with azacitidine, decitabine, or low-dose cytarabine to treat newly diagnosed adults with AML who are aged 75 and older or who are ineligible for intensive chemotherapy.

The FDA grants accelerated approval based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Continued approval of venetoclax in AML may be contingent upon verification of clinical benefit in confirmatory trials.

The approval is based on data from two studies – the phase 1b M14-358 trial ( NCT02203773 ) and the phase 1/2 M14-387 trial ( NCT02287233 ).

In M14-358, newly diagnosed AML patients received venetoclax in combination with azacitidine (n=84) or decitabine (n=31). There were 67 patients in the azacitidine arm and 13 in the decitabine arm who were aged 75 or older or were ineligible for intensive induction chemotherapy.

Patients received venetoclax via a daily ramp-up to a final dose of 400 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.

They received azacitidine at 75 mg/m ² on days 1-7 of each 28-day cycle or decitabine at 20 mg/m ² on days 1-5 of each cycle. Patients continued treatment until disease progression or unacceptable toxicity.

The median follow-up was 7.9 months for the azacitidine arm and 11 months for the decitabine arm.

The complete response (CR) rate was 37% (25/67) in the azacitidine arm and 54% (7/13) in the decitabine arm. The rates of CR with partial hematologic recovery were 24% (16/67) and 7.7% (1/13), respectively. The most common adverse events (AEs) – occurring in at least 30% of patients in both arms – were nausea, diarrhea, constipation, neutropenia, thrombocytopenia, hemorrhage, peripheral edema, vomiting, fatigue, febrile neutropenia, rash, and anemia. The incidence of serious AEs was 75% overall. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome. The incidence of fatal AEs was 1.5% within 30 days of treatment initiation. The M14-387 trial included 82 AML patients who received venetoclax plus low-dose cytarabine. Patients were newly diagnosed with AML, but some had previous exposure to a hypomethylating agent for an antecedent hematologic disorder.

There were 61 patients who were aged 75 or older or were ineligible for intensive induction chemotherapy.

Patients received venetoclax via daily ramp-up to a final dose of 600 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.

Cytarabine was given at 20 mg/m ² on days 1-10 of each 28-day cycle. Patients continued to receive treatment until disease progression or unacceptable toxicity.

At a median follow-up of 6.5 months, the CR rate was 21% (13/61), and the rate of CR with partial hematologic recovery was 21% (13/61).

The most common AEs (occurring in at least 30% of patients) were nausea, thrombocytopenia, hemorrhage, febrile neutropenia, neutropenia, diarrhea, fatigue, constipation, and dyspnea. The incidence of serious AEs was 95%. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection. The incidence of fatal AEs was 4.9% within 30 days of treatment initiation.

Additional details from the M14-358 and M14-387 trials are available in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche.

[email protected]

The Food and Drug Administration has granted accelerated approval to venetoclax for use in acute myeloid leukemia (AML).

The BCL-2 inhibitor is now approved for use in combination with azacitidine, decitabine, or low-dose cytarabine to treat newly diagnosed adults with AML who are aged 75 and older or who are ineligible for intensive chemotherapy.

The FDA grants accelerated approval based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. Continued approval of venetoclax in AML may be contingent upon verification of clinical benefit in confirmatory trials.

The approval is based on data from two studies – the phase 1b M14-358 trial ( NCT02203773 ) and the phase 1/2 M14-387 trial ( NCT02287233 ).

In M14-358, newly diagnosed AML patients received venetoclax in combination with azacitidine (n=84) or decitabine (n=31). There were 67 patients in the azacitidine arm and 13 in the decitabine arm who were aged 75 or older or were ineligible for intensive induction chemotherapy.

Patients received venetoclax via a daily ramp-up to a final dose of 400 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.

They received azacitidine at 75 mg/m ² on days 1-7 of each 28-day cycle or decitabine at 20 mg/m ² on days 1-5 of each cycle. Patients continued treatment until disease progression or unacceptable toxicity.

The median follow-up was 7.9 months for the azacitidine arm and 11 months for the decitabine arm.

The complete response (CR) rate was 37% (25/67) in the azacitidine arm and 54% (7/13) in the decitabine arm. The rates of CR with partial hematologic recovery were 24% (16/67) and 7.7% (1/13), respectively. The most common adverse events (AEs) – occurring in at least 30% of patients in both arms – were nausea, diarrhea, constipation, neutropenia, thrombocytopenia, hemorrhage, peripheral edema, vomiting, fatigue, febrile neutropenia, rash, and anemia. The incidence of serious AEs was 75% overall. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome. The incidence of fatal AEs was 1.5% within 30 days of treatment initiation. The M14-387 trial included 82 AML patients who received venetoclax plus low-dose cytarabine. Patients were newly diagnosed with AML, but some had previous exposure to a hypomethylating agent for an antecedent hematologic disorder.

There were 61 patients who were aged 75 or older or were ineligible for intensive induction chemotherapy.

Patients received venetoclax via daily ramp-up to a final dose of 600 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.

Cytarabine was given at 20 mg/m ² on days 1-10 of each 28-day cycle. Patients continued to receive treatment until disease progression or unacceptable toxicity.

At a median follow-up of 6.5 months, the CR rate was 21% (13/61), and the rate of CR with partial hematologic recovery was 21% (13/61).

The most common AEs (occurring in at least 30% of patients) were nausea, thrombocytopenia, hemorrhage, febrile neutropenia, neutropenia, diarrhea, fatigue, constipation, and dyspnea. The incidence of serious AEs was 95%. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection. The incidence of fatal AEs was 4.9% within 30 days of treatment initiation.

Additional details from the M14-358 and M14-387 trials are available in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche.

[email protected]

The Food and Drug Administration has approved emapalumab-lzsg (Gamifant) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

[email protected]

The Food and Drug Administration has approved emapalumab-lzsg (Gamifant) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

[email protected]

The Food and Drug Administration has approved emapalumab-lzsg (Gamifant) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

[email protected]

Research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.

Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score was able to identify all seven patients who developed thrombosis.

The researchers also found that patients’ TH2 scores changed quickly, within a matter of days, suggesting they should be reevaluated for thrombosis risk frequently.

Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ont., and her colleagues reported their findings in Blood.

To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The score consists of two thrombosis items and two bleeding items.

The thrombosis items are:

• High thrombotic risk, which includes patients with atrial fibrillation and a CHA₂DS₂-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome.
• Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.

The score’s bleeding items are:

• Platelet count less than 20 x 109/L.
• Major bleeding (grade 2 bleeding that does not involve the skin) at the time of visit.

Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests an increased risk of thrombosis, and a negative score suggests an increased risk of bleeding.

The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.

There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.

The median follow up was 9 months. During that time, there were 41 encounters between patients and clinicians. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.

Ten of the 13 patients had anticoagulation withheld during 22 encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.

Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.

Three of the 13 patients continued on anticoagulation during 10 encounters. The patients received additional ITP treatments at 6 of these encounters.

Major bleeding was present at 2 of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).

The TH2 score accurately predicted all seven thrombotic events. There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.

However, these patients had a positive or 0 score – suggesting an increased risk of thrombosis – when they were assessed again, after their platelet counts increased above 50 x 109/L.

The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.

The researchers said these findings suggest patients should be reevaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.

“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”

The researchers also noted that this study was limited by its retrospective, single-center design and the small number patients evaluated. The TH2 score should be validated in additional, larger studies, they advised.

One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.

[email protected]

SOURCE: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.

Research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.

Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score was able to identify all seven patients who developed thrombosis.

The researchers also found that patients’ TH2 scores changed quickly, within a matter of days, suggesting they should be reevaluated for thrombosis risk frequently.

Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ont., and her colleagues reported their findings in Blood.

To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The score consists of two thrombosis items and two bleeding items.

The thrombosis items are:

• High thrombotic risk, which includes patients with atrial fibrillation and a CHA₂DS₂-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome.
• Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.

The score’s bleeding items are:

• Platelet count less than 20 x 109/L.
• Major bleeding (grade 2 bleeding that does not involve the skin) at the time of visit.

Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests an increased risk of thrombosis, and a negative score suggests an increased risk of bleeding.

The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.

There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.

The median follow up was 9 months. During that time, there were 41 encounters between patients and clinicians. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.

Ten of the 13 patients had anticoagulation withheld during 22 encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.

Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.

Three of the 13 patients continued on anticoagulation during 10 encounters. The patients received additional ITP treatments at 6 of these encounters.

Major bleeding was present at 2 of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).

The TH2 score accurately predicted all seven thrombotic events. There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.

However, these patients had a positive or 0 score – suggesting an increased risk of thrombosis – when they were assessed again, after their platelet counts increased above 50 x 109/L.

The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.

The researchers said these findings suggest patients should be reevaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.

“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”

The researchers also noted that this study was limited by its retrospective, single-center design and the small number patients evaluated. The TH2 score should be validated in additional, larger studies, they advised.

One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.

[email protected]

SOURCE: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.

Research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.

Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score was able to identify all seven patients who developed thrombosis.

The researchers also found that patients’ TH2 scores changed quickly, within a matter of days, suggesting they should be reevaluated for thrombosis risk frequently.

Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ont., and her colleagues reported their findings in Blood.

To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The score consists of two thrombosis items and two bleeding items.

The thrombosis items are:

• High thrombotic risk, which includes patients with atrial fibrillation and a CHA₂DS₂-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome.
• Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.

The score’s bleeding items are:

• Platelet count less than 20 x 109/L.
• Major bleeding (grade 2 bleeding that does not involve the skin) at the time of visit.

Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests an increased risk of thrombosis, and a negative score suggests an increased risk of bleeding.

The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.

There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.

The median follow up was 9 months. During that time, there were 41 encounters between patients and clinicians. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.

Ten of the 13 patients had anticoagulation withheld during 22 encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.

Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.

Three of the 13 patients continued on anticoagulation during 10 encounters. The patients received additional ITP treatments at 6 of these encounters.

Major bleeding was present at 2 of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).

The TH2 score accurately predicted all seven thrombotic events. There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.

However, these patients had a positive or 0 score – suggesting an increased risk of thrombosis – when they were assessed again, after their platelet counts increased above 50 x 109/L.

The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.

The researchers said these findings suggest patients should be reevaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.

“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”

The researchers also noted that this study was limited by its retrospective, single-center design and the small number patients evaluated. The TH2 score should be validated in additional, larger studies, they advised.

One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.

[email protected]

SOURCE: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.

The Food and Drug Administration has approved use of eltrombopag (Promacta) for patients severe aplastic anemia (SAA), Novartis announced Nov. 16.

The agency’s move means that eltrombopag, a synthetic thrombopoietin-receptor agonist, is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults, and pediatric patients aged 2 and older with SAA. The drug received breakthrough therapy designation and priority review for this indication, the company said in a press release.

In addition, eltrombopag is FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, those with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and those with thrombocytopenia and with chronic hepatitis C infection.

The expanded approval is based on results of a phase 1-2 trial (NCT01623167), which were published last year (N Eng J Med. 2017 Apr 20;376[16]:1540-50). The trial included 153 previously untreated SAA patients aged 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag in the trial was 150 mg once daily for patients aged 12 and older (75 mg for East and Southeast Asians), 75 mg once daily for patients aged 6 to 11 (37.5 mg for East and Southeast Asians), and 2.5 mg/kg once daily for patients aged 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules. The recommended schedule from the third cohort (n = 92) was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%. The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were increases in ALT (29%), AST (17%), and blood bilirubin (17%). Also, rash (8%), and skin discoloration, including hyperpigmentation (5%), were cited as adverse events.

Updated results from the trial are available in the prescribing information for eltrombopag. In most countries outside of the United States, the drug is marketed as Revolade.

[email protected]

The Food and Drug Administration has approved use of eltrombopag (Promacta) for patients severe aplastic anemia (SAA), Novartis announced Nov. 16.

The agency’s move means that eltrombopag, a synthetic thrombopoietin-receptor agonist, is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults, and pediatric patients aged 2 and older with SAA. The drug received breakthrough therapy designation and priority review for this indication, the company said in a press release.

In addition, eltrombopag is FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, those with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and those with thrombocytopenia and with chronic hepatitis C infection.

The expanded approval is based on results of a phase 1-2 trial (NCT01623167), which were published last year (N Eng J Med. 2017 Apr 20;376[16]:1540-50). The trial included 153 previously untreated SAA patients aged 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag in the trial was 150 mg once daily for patients aged 12 and older (75 mg for East and Southeast Asians), 75 mg once daily for patients aged 6 to 11 (37.5 mg for East and Southeast Asians), and 2.5 mg/kg once daily for patients aged 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules. The recommended schedule from the third cohort (n = 92) was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%. The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were increases in ALT (29%), AST (17%), and blood bilirubin (17%). Also, rash (8%), and skin discoloration, including hyperpigmentation (5%), were cited as adverse events.

Updated results from the trial are available in the prescribing information for eltrombopag. In most countries outside of the United States, the drug is marketed as Revolade.

[email protected]

The Food and Drug Administration has approved use of eltrombopag (Promacta) for patients severe aplastic anemia (SAA), Novartis announced Nov. 16.

The agency’s move means that eltrombopag, a synthetic thrombopoietin-receptor agonist, is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults, and pediatric patients aged 2 and older with SAA. The drug received breakthrough therapy designation and priority review for this indication, the company said in a press release.

In addition, eltrombopag is FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, those with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and those with thrombocytopenia and with chronic hepatitis C infection.

The expanded approval is based on results of a phase 1-2 trial (NCT01623167), which were published last year (N Eng J Med. 2017 Apr 20;376[16]:1540-50). The trial included 153 previously untreated SAA patients aged 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag in the trial was 150 mg once daily for patients aged 12 and older (75 mg for East and Southeast Asians), 75 mg once daily for patients aged 6 to 11 (37.5 mg for East and Southeast Asians), and 2.5 mg/kg once daily for patients aged 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules. The recommended schedule from the third cohort (n = 92) was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%. The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were increases in ALT (29%), AST (17%), and blood bilirubin (17%). Also, rash (8%), and skin discoloration, including hyperpigmentation (5%), were cited as adverse events.

Updated results from the trial are available in the prescribing information for eltrombopag. In most countries outside of the United States, the drug is marketed as Revolade.

[email protected]

The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.

The overall response rate was 33%, and the median overall survival (OS) was 6.3 months. However, the researchers identified factors associated with improved response and survival that could be used to select patients for this treatment.

A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment related.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported these results in Cancer Discovery.

The trial included 70 patients with a median age of 70 years. More than half of the patients (56%) had de novo AML, and 44% had secondary AML. The median number of prior therapies was two; 64% of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).

For this trial, patients received azacitidine at 75 mg/m² on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was three. Patients had a median time on study of 3.5 months and reasons for discontinuation included primary refractory disease, relapse after initial response, proceeding to SCT, patient preference, and death.

The most common treatment-related, nonhematologic AEs were constipation, diarrhea, pneumonitis, nausea, and lung infection. The rate of immune-related AEs was 25% (n = 18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4); 14 responded to steroids and were safely rechallenged with nivolumab, according to the researchers.

Nine patients (13%) discontinued nivolumab (but continued with azacitidine) because of AEs. Two patients died of AEs that were considered possibly related to treatment. One death was caused by progressive pneumonia/pneumonitis, and one was caused by hemophagocytic lymphohistiocytosis.

The overall response rate was 33% (n = 23), with 4 patients achieving a complete response (CR) and 11 achieving a CR with incomplete count recovery (CRi). One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.

The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. Additionally, a higher frequency of pretherapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.

“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said in a statement.

At a median follow-up of 21.4 months, 81% of patients (n = 57) had died; 16 died on study treatment and 41 died after discontinuation. The median OS overall was 6.3 months, and the median event-free survival was 4.5 months.

The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in nonresponders (P less than .0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P less than .001).

The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.

Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver said.

This research was supported by Bristol-Myers Squibb, the University of Texas MD Anderson Cancer Center, and the Dick Clark Immunotherapy Research Fund. Individual researchers also reported financial relationships with Bristol-Myers Squibb.

[email protected]

SOURCE: Daver N et al. Cancer Discov. 2018 Nov 8. doi: 10.1158/2159-8290.CD-18-0774.

The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.

The overall response rate was 33%, and the median overall survival (OS) was 6.3 months. However, the researchers identified factors associated with improved response and survival that could be used to select patients for this treatment.

A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment related.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported these results in Cancer Discovery.

The trial included 70 patients with a median age of 70 years. More than half of the patients (56%) had de novo AML, and 44% had secondary AML. The median number of prior therapies was two; 64% of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).

For this trial, patients received azacitidine at 75 mg/m² on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was three. Patients had a median time on study of 3.5 months and reasons for discontinuation included primary refractory disease, relapse after initial response, proceeding to SCT, patient preference, and death.

The most common treatment-related, nonhematologic AEs were constipation, diarrhea, pneumonitis, nausea, and lung infection. The rate of immune-related AEs was 25% (n = 18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4); 14 responded to steroids and were safely rechallenged with nivolumab, according to the researchers.

Nine patients (13%) discontinued nivolumab (but continued with azacitidine) because of AEs. Two patients died of AEs that were considered possibly related to treatment. One death was caused by progressive pneumonia/pneumonitis, and one was caused by hemophagocytic lymphohistiocytosis.

The overall response rate was 33% (n = 23), with 4 patients achieving a complete response (CR) and 11 achieving a CR with incomplete count recovery (CRi). One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.

The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. Additionally, a higher frequency of pretherapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.

“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said in a statement.

At a median follow-up of 21.4 months, 81% of patients (n = 57) had died; 16 died on study treatment and 41 died after discontinuation. The median OS overall was 6.3 months, and the median event-free survival was 4.5 months.

The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in nonresponders (P less than .0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P less than .001).

The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.

Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver said.

This research was supported by Bristol-Myers Squibb, the University of Texas MD Anderson Cancer Center, and the Dick Clark Immunotherapy Research Fund. Individual researchers also reported financial relationships with Bristol-Myers Squibb.

[email protected]

SOURCE: Daver N et al. Cancer Discov. 2018 Nov 8. doi: 10.1158/2159-8290.CD-18-0774.

The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.

The overall response rate was 33%, and the median overall survival (OS) was 6.3 months. However, the researchers identified factors associated with improved response and survival that could be used to select patients for this treatment.

A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment related.

Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported these results in Cancer Discovery.

The trial included 70 patients with a median age of 70 years. More than half of the patients (56%) had de novo AML, and 44% had secondary AML. The median number of prior therapies was two; 64% of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).

For this trial, patients received azacitidine at 75 mg/m² on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was three. Patients had a median time on study of 3.5 months and reasons for discontinuation included primary refractory disease, relapse after initial response, proceeding to SCT, patient preference, and death.

The most common treatment-related, nonhematologic AEs were constipation, diarrhea, pneumonitis, nausea, and lung infection. The rate of immune-related AEs was 25% (n = 18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4); 14 responded to steroids and were safely rechallenged with nivolumab, according to the researchers.

Nine patients (13%) discontinued nivolumab (but continued with azacitidine) because of AEs. Two patients died of AEs that were considered possibly related to treatment. One death was caused by progressive pneumonia/pneumonitis, and one was caused by hemophagocytic lymphohistiocytosis.

The overall response rate was 33% (n = 23), with 4 patients achieving a complete response (CR) and 11 achieving a CR with incomplete count recovery (CRi). One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.

The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. Additionally, a higher frequency of pretherapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.

“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said in a statement.

At a median follow-up of 21.4 months, 81% of patients (n = 57) had died; 16 died on study treatment and 41 died after discontinuation. The median OS overall was 6.3 months, and the median event-free survival was 4.5 months.

The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in nonresponders (P less than .0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P less than .001).

The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.

Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver said.

This research was supported by Bristol-Myers Squibb, the University of Texas MD Anderson Cancer Center, and the Dick Clark Immunotherapy Research Fund. Individual researchers also reported financial relationships with Bristol-Myers Squibb.

[email protected]

SOURCE: Daver N et al. Cancer Discov. 2018 Nov 8. doi: 10.1158/2159-8290.CD-18-0774.

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

[email protected]

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

[email protected]

The Food and Drug Administration has granted marketing clearance for the immunohematology instrument NEO Iris.

NEO Iris is a fully automated blood bank instrument designed for the mid- to high-volume laboratory, according to Immucor, the company marketing the device. Immucor says NEO Iris provides the highest type and screen throughput on the market – up to 60 types and screens per hour.

NEO Iris performs ABO/Rh D typing, weak D testing, donor confirmation, cytomegalovirus screening, immunoglobulin G direct antiglobulin test and crossmatch, and antibody identification and screening.

The workflow management tool on Neo Iris has STAT priority and allows operators to run tests in any order at any time, according to Immucor.

The company says NEO Iris can hold up to 224 samples, and “modules can pipette, incubate, centrifuge, and read simultaneously.” NEO Iris integrates with Immucor’s data management software, ImmuLINK, to aggregate test results and produce reports with complete testing history.

[email protected]

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.

The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).


The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).

Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.

There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.

In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.

The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.

SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.

The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).


The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).

Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.

There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.

In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.

The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.

SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.

The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).


The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).

Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.

There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.

In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.

The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.

SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.

The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).

The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.

Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.

Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).

Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.

The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.

The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.

“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.

In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.

[email protected]

The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).

The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.

Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.

Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).

Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.

The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.

The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.

“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.

In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.

[email protected]

The Food and Drug Administration has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).

The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and who are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor (CAR) T-cell therapy.

Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.

Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (Abstract 1677).

Selinexor is an oral selective inhibitor of nuclear export compound being developed by Karyopharm Therapeutics.

The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.

The FDA’s fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs. Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.

“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm, said in a statement.

In October, the FDA accepted an NDA for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]