HT Staff

Red blood cells

Erytech Pharma said it plans to stop development of eryaspase for acute lymphoblastic leukemia (ALL).

This means withdrawal of the European marketing authorization application for eryaspase as a treatment for relapsed and refractory ALL.

However, Erytech will continue development of eryaspase as a treatment for certain solid tumor malignancies.

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.

Erytech noted that eryaspase has produced favorable efficacy and safety results in ALL.

However, based on recent feedback from regulatory agencies in Europe and the US, the company believes significant additional investment would be required to seek regulatory approval of eryaspase for the treatment of ALL. Erytech also believes there would be a limited market opportunity for eryaspase in ALL.

Therefore, the company decided to cease further clinical development efforts in ALL. The resources that will become available as a result of this decision will be allocated to the development of eryaspase in solid tumors.

In 2017, Erytech announced results from a phase 2b clinical trial of eryaspase plus chemotherapy in patients with second-line metastatic pancreatic cancer. The company expects to begin enrollment in a phase 3 trial of this patient population in the third quarter of 2018.

In addition, Erytech is preparing for a pair of phase 2 proof-of-concept trials of eryaspase. One is in first-line pancreatic cancer, and the other is in metastatic triple-negative breast cancer. The company is also evaluating development options in additional solid tumor indications with high unmet medical need.

To ensure an adequate supply of eryaspase, Erytech is constructing a large-scale manufacturing facility in Princeton, New Jersey, and is expanding its manufacturing capacity in Lyon, France. The company expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Red blood cells

Erytech Pharma said it plans to stop development of eryaspase for acute lymphoblastic leukemia (ALL).

This means withdrawal of the European marketing authorization application for eryaspase as a treatment for relapsed and refractory ALL.

However, Erytech will continue development of eryaspase as a treatment for certain solid tumor malignancies.

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.

Erytech noted that eryaspase has produced favorable efficacy and safety results in ALL.

However, based on recent feedback from regulatory agencies in Europe and the US, the company believes significant additional investment would be required to seek regulatory approval of eryaspase for the treatment of ALL. Erytech also believes there would be a limited market opportunity for eryaspase in ALL.

Therefore, the company decided to cease further clinical development efforts in ALL. The resources that will become available as a result of this decision will be allocated to the development of eryaspase in solid tumors.

In 2017, Erytech announced results from a phase 2b clinical trial of eryaspase plus chemotherapy in patients with second-line metastatic pancreatic cancer. The company expects to begin enrollment in a phase 3 trial of this patient population in the third quarter of 2018.

In addition, Erytech is preparing for a pair of phase 2 proof-of-concept trials of eryaspase. One is in first-line pancreatic cancer, and the other is in metastatic triple-negative breast cancer. The company is also evaluating development options in additional solid tumor indications with high unmet medical need.

To ensure an adequate supply of eryaspase, Erytech is constructing a large-scale manufacturing facility in Princeton, New Jersey, and is expanding its manufacturing capacity in Lyon, France. The company expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Red blood cells

Erytech Pharma said it plans to stop development of eryaspase for acute lymphoblastic leukemia (ALL).

This means withdrawal of the European marketing authorization application for eryaspase as a treatment for relapsed and refractory ALL.

However, Erytech will continue development of eryaspase as a treatment for certain solid tumor malignancies.

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.

Erytech noted that eryaspase has produced favorable efficacy and safety results in ALL.

However, based on recent feedback from regulatory agencies in Europe and the US, the company believes significant additional investment would be required to seek regulatory approval of eryaspase for the treatment of ALL. Erytech also believes there would be a limited market opportunity for eryaspase in ALL.

Therefore, the company decided to cease further clinical development efforts in ALL. The resources that will become available as a result of this decision will be allocated to the development of eryaspase in solid tumors.

In 2017, Erytech announced results from a phase 2b clinical trial of eryaspase plus chemotherapy in patients with second-line metastatic pancreatic cancer. The company expects to begin enrollment in a phase 3 trial of this patient population in the third quarter of 2018.

In addition, Erytech is preparing for a pair of phase 2 proof-of-concept trials of eryaspase. One is in first-line pancreatic cancer, and the other is in metastatic triple-negative breast cancer. The company is also evaluating development options in additional solid tumor indications with high unmet medical need.

To ensure an adequate supply of eryaspase, Erytech is constructing a large-scale manufacturing facility in Princeton, New Jersey, and is expanding its manufacturing capacity in Lyon, France. The company expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Photo from EHA

STOCKHOLM—An ongoing phase 2 study suggests voxelotor (GBT440) can benefit adolescents with sickle cell disease (SCD).

In the HOPE-KIDS 1 study, voxelotor produced sustained improvements in hemoglobin levels and a reduction in clinical measures of hemolysis in a cohort of adolescents with SCD, most of whom were also receiving hydroxyurea (HU).

The most common adverse events (AEs) related to voxelotor were nausea, vomiting, headache, and rash.

These results were presented in a poster (abstract PF709) at the 23rd Congress of the European Hematology Association (EHA).

HOPE-KIDS 1 is sponsored by Global Blood Therapeutics, Inc.

In this study, researchers are evaluating voxelotor in SCD patients ages 6 to 17. In part A, researchers evaluated a 600 mg daily dose of voxelotor. In part B, they are testing voxelotor at daily doses of 900 mg and 1500 mg in patients ages 12 to 17.

At EHA, the researchers presented data on 25 patients who received voxelotor at 900 mg/day for 24 weeks in part B. Eighty-eight percent of the patients (n=22) were also taking HU.

The patients’ median age was 14 (range, 12-17), and 56% were male. Ninety-six percent (n=24) had the HbSS genotype.

Forty-eight percent of patients had 1 to 4 vaso-occlusive crises (VOCs) in the past year, 8% had more than 4 VOCs, and 44% had 0 VOCs.

At baseline, the median hemoglobin was 8.9 g/dL, the median fetal hemoglobin was 10.8 g/dL, and the median time-averaged mean of maximum velocity was 110 cm/s.

All 25 patients were dosed with voxelotor, and 22 completed 24 weeks of dosing. One patient withdrew consent, 1 was lost to follow-up, and 1 patient discontinued due to noncompliance.

Of the 22 patients who completed 24 weeks of voxelotor treatment, all but 3 were receiving concurrent HU.

Results

Voxelotor-related AEs occurring in at least 2 patients included nausea (12%, n=3), vomiting (8%, n=2), headache (8%, n=2), and rash (8%, n=2).

There was 1 case of grade 3 urticaria, which resolved and did not recur with continued dosing. There were no discontinuations of voxelotor due to AEs.

Patients experienced increased hemoglobin levels and improved clinical measures of hemolysis at 24 weeks, as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin.

In all, 43% of patients (9/21) achieved a hemoglobin response (>1 g/dL) at 24 weeks. The median hemoglobin change from baseline was 0.7 g/dL, the median reduction in reticulocytes was 22.9%, and the median reduction in unconjugated bilirubin was 38.6%.

Sixty-two percent of patients (13/21) had a reduction in daily symptoms at 24 weeks, as assessed by total symptom scores (TSS). There was a 39% median reduction in TSS from baseline.

Fifty-five percent of patients (11/20) had a numerical decrease in transcranial doppler (TCD) flow at 24 weeks. Among hemoglobin responders (>1 g/dL), 88% (7/8) had a numerical decrease in TCD at 24 weeks.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our phase 3 HOPE study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults. We continue to expect to announce top-line clinical data from part A of the HOPE study by the end of this quarter.”

Photo from EHA

STOCKHOLM—An ongoing phase 2 study suggests voxelotor (GBT440) can benefit adolescents with sickle cell disease (SCD).

In the HOPE-KIDS 1 study, voxelotor produced sustained improvements in hemoglobin levels and a reduction in clinical measures of hemolysis in a cohort of adolescents with SCD, most of whom were also receiving hydroxyurea (HU).

The most common adverse events (AEs) related to voxelotor were nausea, vomiting, headache, and rash.

These results were presented in a poster (abstract PF709) at the 23rd Congress of the European Hematology Association (EHA).

HOPE-KIDS 1 is sponsored by Global Blood Therapeutics, Inc.

In this study, researchers are evaluating voxelotor in SCD patients ages 6 to 17. In part A, researchers evaluated a 600 mg daily dose of voxelotor. In part B, they are testing voxelotor at daily doses of 900 mg and 1500 mg in patients ages 12 to 17.

At EHA, the researchers presented data on 25 patients who received voxelotor at 900 mg/day for 24 weeks in part B. Eighty-eight percent of the patients (n=22) were also taking HU.

The patients’ median age was 14 (range, 12-17), and 56% were male. Ninety-six percent (n=24) had the HbSS genotype.

Forty-eight percent of patients had 1 to 4 vaso-occlusive crises (VOCs) in the past year, 8% had more than 4 VOCs, and 44% had 0 VOCs.

At baseline, the median hemoglobin was 8.9 g/dL, the median fetal hemoglobin was 10.8 g/dL, and the median time-averaged mean of maximum velocity was 110 cm/s.

All 25 patients were dosed with voxelotor, and 22 completed 24 weeks of dosing. One patient withdrew consent, 1 was lost to follow-up, and 1 patient discontinued due to noncompliance.

Of the 22 patients who completed 24 weeks of voxelotor treatment, all but 3 were receiving concurrent HU.

Results

Voxelotor-related AEs occurring in at least 2 patients included nausea (12%, n=3), vomiting (8%, n=2), headache (8%, n=2), and rash (8%, n=2).

There was 1 case of grade 3 urticaria, which resolved and did not recur with continued dosing. There were no discontinuations of voxelotor due to AEs.

Patients experienced increased hemoglobin levels and improved clinical measures of hemolysis at 24 weeks, as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin.

In all, 43% of patients (9/21) achieved a hemoglobin response (>1 g/dL) at 24 weeks. The median hemoglobin change from baseline was 0.7 g/dL, the median reduction in reticulocytes was 22.9%, and the median reduction in unconjugated bilirubin was 38.6%.

Sixty-two percent of patients (13/21) had a reduction in daily symptoms at 24 weeks, as assessed by total symptom scores (TSS). There was a 39% median reduction in TSS from baseline.

Fifty-five percent of patients (11/20) had a numerical decrease in transcranial doppler (TCD) flow at 24 weeks. Among hemoglobin responders (>1 g/dL), 88% (7/8) had a numerical decrease in TCD at 24 weeks.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our phase 3 HOPE study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults. We continue to expect to announce top-line clinical data from part A of the HOPE study by the end of this quarter.”

Photo from EHA

STOCKHOLM—An ongoing phase 2 study suggests voxelotor (GBT440) can benefit adolescents with sickle cell disease (SCD).

In the HOPE-KIDS 1 study, voxelotor produced sustained improvements in hemoglobin levels and a reduction in clinical measures of hemolysis in a cohort of adolescents with SCD, most of whom were also receiving hydroxyurea (HU).

The most common adverse events (AEs) related to voxelotor were nausea, vomiting, headache, and rash.

These results were presented in a poster (abstract PF709) at the 23rd Congress of the European Hematology Association (EHA).

HOPE-KIDS 1 is sponsored by Global Blood Therapeutics, Inc.

In this study, researchers are evaluating voxelotor in SCD patients ages 6 to 17. In part A, researchers evaluated a 600 mg daily dose of voxelotor. In part B, they are testing voxelotor at daily doses of 900 mg and 1500 mg in patients ages 12 to 17.

At EHA, the researchers presented data on 25 patients who received voxelotor at 900 mg/day for 24 weeks in part B. Eighty-eight percent of the patients (n=22) were also taking HU.

The patients’ median age was 14 (range, 12-17), and 56% were male. Ninety-six percent (n=24) had the HbSS genotype.

Forty-eight percent of patients had 1 to 4 vaso-occlusive crises (VOCs) in the past year, 8% had more than 4 VOCs, and 44% had 0 VOCs.

At baseline, the median hemoglobin was 8.9 g/dL, the median fetal hemoglobin was 10.8 g/dL, and the median time-averaged mean of maximum velocity was 110 cm/s.

All 25 patients were dosed with voxelotor, and 22 completed 24 weeks of dosing. One patient withdrew consent, 1 was lost to follow-up, and 1 patient discontinued due to noncompliance.

Of the 22 patients who completed 24 weeks of voxelotor treatment, all but 3 were receiving concurrent HU.

Results

Voxelotor-related AEs occurring in at least 2 patients included nausea (12%, n=3), vomiting (8%, n=2), headache (8%, n=2), and rash (8%, n=2).

There was 1 case of grade 3 urticaria, which resolved and did not recur with continued dosing. There were no discontinuations of voxelotor due to AEs.

Patients experienced increased hemoglobin levels and improved clinical measures of hemolysis at 24 weeks, as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin.

In all, 43% of patients (9/21) achieved a hemoglobin response (>1 g/dL) at 24 weeks. The median hemoglobin change from baseline was 0.7 g/dL, the median reduction in reticulocytes was 22.9%, and the median reduction in unconjugated bilirubin was 38.6%.

Sixty-two percent of patients (13/21) had a reduction in daily symptoms at 24 weeks, as assessed by total symptom scores (TSS). There was a 39% median reduction in TSS from baseline.

Fifty-five percent of patients (11/20) had a numerical decrease in transcranial doppler (TCD) flow at 24 weeks. Among hemoglobin responders (>1 g/dL), 88% (7/8) had a numerical decrease in TCD at 24 weeks.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our phase 3 HOPE study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults. We continue to expect to announce top-line clinical data from part A of the HOPE study by the end of this quarter.”

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®) to be used in combination with rituximab in patients with Waldenström’s macroglobulinemia (WM).

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Ibrutinib is already FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, previously treated chronic graft-versus-host disease, and WM.

If the new sNDA is approved, the use of ibrutinib in WM will extend beyond its current approved use as a single agent.

Phase 3 trial

The sNDA for ibrutinib and rituximab in WM is supported by data from the phase 3 iNNOVATE study. Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 8003) and were simultaneously published in NEJM.

iNNOVATE is a placebo-controlled, double-blind, phase 3 study that enrolled 150 patients with relapsed/refractory and treatment-naïve WM.

All patients received rituximab at 375 mg/m² with weekly infusions at weeks 1 to 4 and 17 to 20. They also received either ibrutinib (420 mg) or placebo once daily continuously until criteria for permanent discontinuation were met.

Overall response rates were significantly higher in the ibrutinib arm than the placebo arm—92% and 47%, respectively (P<0.0001). Complete response rates were 3% and 1%, respectively.

The median time to next treatment was not reached for the ibrutinib arm and was 18 months for the placebo arm (hazard ratio=0.096; P<0.0001). Of the patients randomized to ibrutinib plus rituximab, 75% continued on treatment at last follow-up.

The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio=0.20; P<0.0001).

The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.

Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm.

Serious AEs occurred in 43% and 33% of patients, respectively. There were no fatal AEs in the ibrutinib arm and 3 in the rituximab arm.

Grade 3 or higher AEs that occurred more frequently in the ibrutinib arm than the placebo arm included atrial fibrillation (12% vs 1%) and hypertension (13% vs 4%).

AEs that occurred less frequently in the ibrutinib arm than the placebo arm included grade 3 or higher infusion reactions (1% vs 16%) and any-grade IgM flare (8% vs 47%).

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®) to be used in combination with rituximab in patients with Waldenström’s macroglobulinemia (WM).

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Ibrutinib is already FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, previously treated chronic graft-versus-host disease, and WM.

If the new sNDA is approved, the use of ibrutinib in WM will extend beyond its current approved use as a single agent.

Phase 3 trial

The sNDA for ibrutinib and rituximab in WM is supported by data from the phase 3 iNNOVATE study. Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 8003) and were simultaneously published in NEJM.

iNNOVATE is a placebo-controlled, double-blind, phase 3 study that enrolled 150 patients with relapsed/refractory and treatment-naïve WM.

All patients received rituximab at 375 mg/m² with weekly infusions at weeks 1 to 4 and 17 to 20. They also received either ibrutinib (420 mg) or placebo once daily continuously until criteria for permanent discontinuation were met.

Overall response rates were significantly higher in the ibrutinib arm than the placebo arm—92% and 47%, respectively (P<0.0001). Complete response rates were 3% and 1%, respectively.

The median time to next treatment was not reached for the ibrutinib arm and was 18 months for the placebo arm (hazard ratio=0.096; P<0.0001). Of the patients randomized to ibrutinib plus rituximab, 75% continued on treatment at last follow-up.

The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio=0.20; P<0.0001).

The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.

Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm.

Serious AEs occurred in 43% and 33% of patients, respectively. There were no fatal AEs in the ibrutinib arm and 3 in the rituximab arm.

Grade 3 or higher AEs that occurred more frequently in the ibrutinib arm than the placebo arm included atrial fibrillation (12% vs 1%) and hypertension (13% vs 4%).

AEs that occurred less frequently in the ibrutinib arm than the placebo arm included grade 3 or higher infusion reactions (1% vs 16%) and any-grade IgM flare (8% vs 47%).

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®) to be used in combination with rituximab in patients with Waldenström’s macroglobulinemia (WM).

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Ibrutinib is already FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, previously treated chronic graft-versus-host disease, and WM.

If the new sNDA is approved, the use of ibrutinib in WM will extend beyond its current approved use as a single agent.

Phase 3 trial

The sNDA for ibrutinib and rituximab in WM is supported by data from the phase 3 iNNOVATE study. Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 8003) and were simultaneously published in NEJM.

iNNOVATE is a placebo-controlled, double-blind, phase 3 study that enrolled 150 patients with relapsed/refractory and treatment-naïve WM.

All patients received rituximab at 375 mg/m² with weekly infusions at weeks 1 to 4 and 17 to 20. They also received either ibrutinib (420 mg) or placebo once daily continuously until criteria for permanent discontinuation were met.

Overall response rates were significantly higher in the ibrutinib arm than the placebo arm—92% and 47%, respectively (P<0.0001). Complete response rates were 3% and 1%, respectively.

The median time to next treatment was not reached for the ibrutinib arm and was 18 months for the placebo arm (hazard ratio=0.096; P<0.0001). Of the patients randomized to ibrutinib plus rituximab, 75% continued on treatment at last follow-up.

The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio=0.20; P<0.0001).

The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.

Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm.

Serious AEs occurred in 43% and 33% of patients, respectively. There were no fatal AEs in the ibrutinib arm and 3 in the rituximab arm.

Grade 3 or higher AEs that occurred more frequently in the ibrutinib arm than the placebo arm included atrial fibrillation (12% vs 1%) and hypertension (13% vs 4%).

AEs that occurred less frequently in the ibrutinib arm than the placebo arm included grade 3 or higher infusion reactions (1% vs 16%) and any-grade IgM flare (8% vs 47%).

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Photo from EHA

STOCKHOLM—The KIT/PDGFRA inhibitor avapritinib has produced durable responses in patients with systemic mastocytosis (SM).

In the phase 1 EXPLORER trial, avapritinib produced an overall response rate of 83%.

Responses have lasted up to 22 months, and 79% of responders remained on avapritinib as of the data cutoff.

The most common treatment-related adverse events (AEs) were periorbital edema, anemia, nausea, and fatigue.

These data were presented in a poster (abstract PF612) at the 23rd Congress of the European Hematology Association (EHA).

The trial was sponsored by Blueprint Medicines Corporation.

As of the data cutoff (April 30, 2018), 52 patients had been treated with avapritinib in the dose-escalation and expansion portions of the EXPLORER trial.

This included 25 patients with aggressive SM (ASM), 15 with advanced SM and an associated hematologic neoplasm (SM-AHN), 5 with mast cell leukemia (MCL), 5 pending central pathology diagnosis, and 2 with smoldering SM.

Thirty-five patients (67%) were previously treated, including 10 (19%) who previously received midostaurin. The patients’ median age was 63 (range, 34-83), and 52% were male.

Treatment

Thirty-two patients were treated in the dose-escalation portion of the study and received avapritinib at doses ranging from 30 mg to 400 mg daily. The 35 patients in the expansion portion received avapritinib at 300 mg daily.

Among all 52 enrolled patients, 42 remained on treatment as of the data cutoff date. Four patients discontinued treatment with avapritinib due to AEs. Three of these were treatment-related, and 1 was unrelated.

Three patients discontinued treatment due to clinical progression as determined by the investigator. None of the patients had documented disease progression by IWG-MRT-ECNM criteria.

Two patients discontinued due to investigator decision, and 1 withdrew consent.

Safety

All 52 patients were evaluable for safety.

Treatment-related AEs included periorbital edema (62%), anemia (33%), nausea (33%), fatigue (31%), peripheral edema (27%), diarrhea (25%), hair color changes (23%), thrombocytopenia (19%), cognitive effects (19%), vomiting (19%), and dizziness (12%).

Grade 3 or higher AEs, regardless of drug relationship, included thrombocytopenia (17%), anemia (15%), fatigue (6%), vomiting (6%), periorbital edema (4%), nausea (4%), diarrhea (2%), hair color changes (2%), and cognitive effects (2%).

Efficacy

As of the data cutoff, 23 patients were evaluable for response by IWG-MRT-ECNM criteria. This included 8 patients with ASM, 10 with SM-AHN, and 5 with MCL.

The overall response rate was 83% (n=19). All responses observed in the dose-escalation portion of the trial have been confirmed, and all responses in the dose-expansion portion of the trial are pending confirmation.

Four patients (17%) had a confirmed complete response with a full (n=1) or partial (n=3) recovery of peripheral blood counts. All of these responses occurred in patients with ASM.

Twelve patients (52%) had a partial response (7 confirmed, 5 pending confirmation). This included 6 patients with SM-AHN, 4 with MCL, and 2 with ASM.

Three patients (13%) had clinical improvement (2 confirmed, 1 pending confirmation), and 4 had stable disease. None of the patients progressed.

The duration of response ranged from 8 months to 22 months, and 79% of responders (15/19) remained on treatment at the data cutoff.

“As a clinician treating patients with this devastating and sometimes fatal rare disease, I’m excited to see that most patients with advanced systemic mastocytosis respond to treatment with avapritinib, and these responses deepen over time and are durable,” said study investigator Michael W. Deininger, MD, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.

“These data further support avapritinib’s unique approach of selectively targeting D816V mutant KIT, the disease driver in most patients with systemic mastocytosis. If these results are confirmed in the planned phase 2 trial, avapritinib has the potential to become a new standard of care for patients with advanced forms of the disease.”

Photo from EHA

STOCKHOLM—The KIT/PDGFRA inhibitor avapritinib has produced durable responses in patients with systemic mastocytosis (SM).

In the phase 1 EXPLORER trial, avapritinib produced an overall response rate of 83%.

Responses have lasted up to 22 months, and 79% of responders remained on avapritinib as of the data cutoff.

The most common treatment-related adverse events (AEs) were periorbital edema, anemia, nausea, and fatigue.

These data were presented in a poster (abstract PF612) at the 23rd Congress of the European Hematology Association (EHA).

The trial was sponsored by Blueprint Medicines Corporation.

As of the data cutoff (April 30, 2018), 52 patients had been treated with avapritinib in the dose-escalation and expansion portions of the EXPLORER trial.

This included 25 patients with aggressive SM (ASM), 15 with advanced SM and an associated hematologic neoplasm (SM-AHN), 5 with mast cell leukemia (MCL), 5 pending central pathology diagnosis, and 2 with smoldering SM.

Thirty-five patients (67%) were previously treated, including 10 (19%) who previously received midostaurin. The patients’ median age was 63 (range, 34-83), and 52% were male.

Treatment

Thirty-two patients were treated in the dose-escalation portion of the study and received avapritinib at doses ranging from 30 mg to 400 mg daily. The 35 patients in the expansion portion received avapritinib at 300 mg daily.

Among all 52 enrolled patients, 42 remained on treatment as of the data cutoff date. Four patients discontinued treatment with avapritinib due to AEs. Three of these were treatment-related, and 1 was unrelated.

Three patients discontinued treatment due to clinical progression as determined by the investigator. None of the patients had documented disease progression by IWG-MRT-ECNM criteria.

Two patients discontinued due to investigator decision, and 1 withdrew consent.

Safety

All 52 patients were evaluable for safety.

Treatment-related AEs included periorbital edema (62%), anemia (33%), nausea (33%), fatigue (31%), peripheral edema (27%), diarrhea (25%), hair color changes (23%), thrombocytopenia (19%), cognitive effects (19%), vomiting (19%), and dizziness (12%).

Grade 3 or higher AEs, regardless of drug relationship, included thrombocytopenia (17%), anemia (15%), fatigue (6%), vomiting (6%), periorbital edema (4%), nausea (4%), diarrhea (2%), hair color changes (2%), and cognitive effects (2%).

Efficacy

As of the data cutoff, 23 patients were evaluable for response by IWG-MRT-ECNM criteria. This included 8 patients with ASM, 10 with SM-AHN, and 5 with MCL.

The overall response rate was 83% (n=19). All responses observed in the dose-escalation portion of the trial have been confirmed, and all responses in the dose-expansion portion of the trial are pending confirmation.

Four patients (17%) had a confirmed complete response with a full (n=1) or partial (n=3) recovery of peripheral blood counts. All of these responses occurred in patients with ASM.

Twelve patients (52%) had a partial response (7 confirmed, 5 pending confirmation). This included 6 patients with SM-AHN, 4 with MCL, and 2 with ASM.

Three patients (13%) had clinical improvement (2 confirmed, 1 pending confirmation), and 4 had stable disease. None of the patients progressed.

The duration of response ranged from 8 months to 22 months, and 79% of responders (15/19) remained on treatment at the data cutoff.

“As a clinician treating patients with this devastating and sometimes fatal rare disease, I’m excited to see that most patients with advanced systemic mastocytosis respond to treatment with avapritinib, and these responses deepen over time and are durable,” said study investigator Michael W. Deininger, MD, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.

“These data further support avapritinib’s unique approach of selectively targeting D816V mutant KIT, the disease driver in most patients with systemic mastocytosis. If these results are confirmed in the planned phase 2 trial, avapritinib has the potential to become a new standard of care for patients with advanced forms of the disease.”

Photo from EHA

STOCKHOLM—The KIT/PDGFRA inhibitor avapritinib has produced durable responses in patients with systemic mastocytosis (SM).

In the phase 1 EXPLORER trial, avapritinib produced an overall response rate of 83%.

Responses have lasted up to 22 months, and 79% of responders remained on avapritinib as of the data cutoff.

The most common treatment-related adverse events (AEs) were periorbital edema, anemia, nausea, and fatigue.

These data were presented in a poster (abstract PF612) at the 23rd Congress of the European Hematology Association (EHA).

The trial was sponsored by Blueprint Medicines Corporation.

As of the data cutoff (April 30, 2018), 52 patients had been treated with avapritinib in the dose-escalation and expansion portions of the EXPLORER trial.

This included 25 patients with aggressive SM (ASM), 15 with advanced SM and an associated hematologic neoplasm (SM-AHN), 5 with mast cell leukemia (MCL), 5 pending central pathology diagnosis, and 2 with smoldering SM.

Thirty-five patients (67%) were previously treated, including 10 (19%) who previously received midostaurin. The patients’ median age was 63 (range, 34-83), and 52% were male.

Treatment

Thirty-two patients were treated in the dose-escalation portion of the study and received avapritinib at doses ranging from 30 mg to 400 mg daily. The 35 patients in the expansion portion received avapritinib at 300 mg daily.

Among all 52 enrolled patients, 42 remained on treatment as of the data cutoff date. Four patients discontinued treatment with avapritinib due to AEs. Three of these were treatment-related, and 1 was unrelated.

Three patients discontinued treatment due to clinical progression as determined by the investigator. None of the patients had documented disease progression by IWG-MRT-ECNM criteria.

Two patients discontinued due to investigator decision, and 1 withdrew consent.

Safety

All 52 patients were evaluable for safety.

Treatment-related AEs included periorbital edema (62%), anemia (33%), nausea (33%), fatigue (31%), peripheral edema (27%), diarrhea (25%), hair color changes (23%), thrombocytopenia (19%), cognitive effects (19%), vomiting (19%), and dizziness (12%).

Grade 3 or higher AEs, regardless of drug relationship, included thrombocytopenia (17%), anemia (15%), fatigue (6%), vomiting (6%), periorbital edema (4%), nausea (4%), diarrhea (2%), hair color changes (2%), and cognitive effects (2%).

Efficacy

As of the data cutoff, 23 patients were evaluable for response by IWG-MRT-ECNM criteria. This included 8 patients with ASM, 10 with SM-AHN, and 5 with MCL.

The overall response rate was 83% (n=19). All responses observed in the dose-escalation portion of the trial have been confirmed, and all responses in the dose-expansion portion of the trial are pending confirmation.

Four patients (17%) had a confirmed complete response with a full (n=1) or partial (n=3) recovery of peripheral blood counts. All of these responses occurred in patients with ASM.

Twelve patients (52%) had a partial response (7 confirmed, 5 pending confirmation). This included 6 patients with SM-AHN, 4 with MCL, and 2 with ASM.

Three patients (13%) had clinical improvement (2 confirmed, 1 pending confirmation), and 4 had stable disease. None of the patients progressed.

The duration of response ranged from 8 months to 22 months, and 79% of responders (15/19) remained on treatment at the data cutoff.

“As a clinician treating patients with this devastating and sometimes fatal rare disease, I’m excited to see that most patients with advanced systemic mastocytosis respond to treatment with avapritinib, and these responses deepen over time and are durable,” said study investigator Michael W. Deininger, MD, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.

“These data further support avapritinib’s unique approach of selectively targeting D816V mutant KIT, the disease driver in most patients with systemic mastocytosis. If these results are confirmed in the planned phase 2 trial, avapritinib has the potential to become a new standard of care for patients with advanced forms of the disease.”

Photo from EHA

STOCKHOLM—A new survey has revealed patients’ perceptions of immune thrombocytopenia (ITP) and how the condition impacts their quality of life (QOL).

Patients reported delays in diagnosis, lack of support, severe fatigue, and impacts on both emotional well-being and their ability to work.

Interim results of this survey, the ITP World Impact Survey (I-WISh), were presented in a poster (abstract PF654) at the 23rd Congress of the European Hematology Association (EHA).

I-WISh is a cross-sectional survey of ITP patients developed by global ITP experts, patient groups, and Novartis.

Interim results of the survey included patients from 12 countries (Canada, China, Colombia, France, Germany, Italy, India, Japan, Spain, Turkey, UK, and US) who completed an online questionnaire beginning in January 2018.

As of May 14, 2018, 1400 adults (age 18 and older) had completed the survey. Sixty-five percent were female, and they had a mean age of 47.1 years. The patients’ mean length of time with ITP was 110 months.

Most patients (63%) reported a high score for their current health state (5 to 7 on the Likert scale), but 15% reported a low score (1-3).

Most patients were working full-time (45%) or part-time (16%) at the time of the survey. Nineteen percent were retired, 6% were homemakers, 4% were students, and 10% were not seeking employment, on long-term sick leave or disability, or “other.”

Diagnosis

Twenty-two percent of all patients (307/1400) felt they had a delay in their ITP diagnosis caused by waiting for additional tests (49%, 150/307) or referral to a specialist (37%, 114/307).

Three-quarters of patients with a perceived delay (229/307) were anxious throughout diagnosis.

And 66% of all patients (927/1400) wanted more support during their diagnosis.

Symptoms

Patients reported fatigue as one of the most severe symptoms at diagnosis (75%, 627/839) and at survey completion (66%, 480/722).

The other “most severe” symptoms at diagnosis were heavy menstrual bleeding (85%, 353/416) and anxiety surrounding unstable platelet count (78%, 382/487). The other “most severe” symptoms at survey completion were thrombosis (73%, 24/33) and anxiety surrounding unstable platelet count (66%, 284/431).

“Severe fatigue, in particular, was reported by many patients as the most difficult-to-manage symptom of ITP,” said study investigator Nichola Cooper, MD, of Hammersmith Hospital, Imperial College London, in the UK.

“This is an important message for healthcare providers treating patients with this rare disease. ITP is about more than bruising and risk of bleeding.”

QOL

Forty-four percent of respondents (611/1398) said ITP impacted their energy levels more than half the time, and 36% (501/1398) said ITP had a negative impact on their normal capacity to exercise more than half the time.

Half of all patients (697/1400) said ITP had a high impact on their emotional well-being.

Eighty-three percent (1157/1400) said they felt a stable and safe platelet count was important, 64% (900/1400) worried that their condition will get worse, and 63% (888/1400) were concerned that their platelet count changes for no apparent reason.

Thirty-seven percent of all patients (511/1400) had reduced their work hours because of ITP, 37% (522/1400) seriously considered reducing their hours, and 21% (294/1400) considered terminating their employment.

Thirty-five percent of patients (491/1400) said obtaining healthy blood counts was their most important treatment goal. Twenty-one percent (299/1400) said increasing their energy levels was most important, and 15% (203/1400) said reducing spontaneous bleeds/bruising was most important.

Photo from EHA

STOCKHOLM—A new survey has revealed patients’ perceptions of immune thrombocytopenia (ITP) and how the condition impacts their quality of life (QOL).

Patients reported delays in diagnosis, lack of support, severe fatigue, and impacts on both emotional well-being and their ability to work.

Interim results of this survey, the ITP World Impact Survey (I-WISh), were presented in a poster (abstract PF654) at the 23rd Congress of the European Hematology Association (EHA).

I-WISh is a cross-sectional survey of ITP patients developed by global ITP experts, patient groups, and Novartis.

Interim results of the survey included patients from 12 countries (Canada, China, Colombia, France, Germany, Italy, India, Japan, Spain, Turkey, UK, and US) who completed an online questionnaire beginning in January 2018.

As of May 14, 2018, 1400 adults (age 18 and older) had completed the survey. Sixty-five percent were female, and they had a mean age of 47.1 years. The patients’ mean length of time with ITP was 110 months.

Most patients (63%) reported a high score for their current health state (5 to 7 on the Likert scale), but 15% reported a low score (1-3).

Most patients were working full-time (45%) or part-time (16%) at the time of the survey. Nineteen percent were retired, 6% were homemakers, 4% were students, and 10% were not seeking employment, on long-term sick leave or disability, or “other.”

Diagnosis

Twenty-two percent of all patients (307/1400) felt they had a delay in their ITP diagnosis caused by waiting for additional tests (49%, 150/307) or referral to a specialist (37%, 114/307).

Three-quarters of patients with a perceived delay (229/307) were anxious throughout diagnosis.

And 66% of all patients (927/1400) wanted more support during their diagnosis.

Symptoms

Patients reported fatigue as one of the most severe symptoms at diagnosis (75%, 627/839) and at survey completion (66%, 480/722).

The other “most severe” symptoms at diagnosis were heavy menstrual bleeding (85%, 353/416) and anxiety surrounding unstable platelet count (78%, 382/487). The other “most severe” symptoms at survey completion were thrombosis (73%, 24/33) and anxiety surrounding unstable platelet count (66%, 284/431).

“Severe fatigue, in particular, was reported by many patients as the most difficult-to-manage symptom of ITP,” said study investigator Nichola Cooper, MD, of Hammersmith Hospital, Imperial College London, in the UK.

“This is an important message for healthcare providers treating patients with this rare disease. ITP is about more than bruising and risk of bleeding.”

QOL

Forty-four percent of respondents (611/1398) said ITP impacted their energy levels more than half the time, and 36% (501/1398) said ITP had a negative impact on their normal capacity to exercise more than half the time.

Half of all patients (697/1400) said ITP had a high impact on their emotional well-being.

Eighty-three percent (1157/1400) said they felt a stable and safe platelet count was important, 64% (900/1400) worried that their condition will get worse, and 63% (888/1400) were concerned that their platelet count changes for no apparent reason.

Thirty-seven percent of all patients (511/1400) had reduced their work hours because of ITP, 37% (522/1400) seriously considered reducing their hours, and 21% (294/1400) considered terminating their employment.

Thirty-five percent of patients (491/1400) said obtaining healthy blood counts was their most important treatment goal. Twenty-one percent (299/1400) said increasing their energy levels was most important, and 15% (203/1400) said reducing spontaneous bleeds/bruising was most important.

Photo from EHA

STOCKHOLM—A new survey has revealed patients’ perceptions of immune thrombocytopenia (ITP) and how the condition impacts their quality of life (QOL).

Patients reported delays in diagnosis, lack of support, severe fatigue, and impacts on both emotional well-being and their ability to work.

Interim results of this survey, the ITP World Impact Survey (I-WISh), were presented in a poster (abstract PF654) at the 23rd Congress of the European Hematology Association (EHA).

I-WISh is a cross-sectional survey of ITP patients developed by global ITP experts, patient groups, and Novartis.

Interim results of the survey included patients from 12 countries (Canada, China, Colombia, France, Germany, Italy, India, Japan, Spain, Turkey, UK, and US) who completed an online questionnaire beginning in January 2018.

As of May 14, 2018, 1400 adults (age 18 and older) had completed the survey. Sixty-five percent were female, and they had a mean age of 47.1 years. The patients’ mean length of time with ITP was 110 months.

Most patients (63%) reported a high score for their current health state (5 to 7 on the Likert scale), but 15% reported a low score (1-3).

Most patients were working full-time (45%) or part-time (16%) at the time of the survey. Nineteen percent were retired, 6% were homemakers, 4% were students, and 10% were not seeking employment, on long-term sick leave or disability, or “other.”

Diagnosis

Twenty-two percent of all patients (307/1400) felt they had a delay in their ITP diagnosis caused by waiting for additional tests (49%, 150/307) or referral to a specialist (37%, 114/307).

Three-quarters of patients with a perceived delay (229/307) were anxious throughout diagnosis.

And 66% of all patients (927/1400) wanted more support during their diagnosis.

Symptoms

Patients reported fatigue as one of the most severe symptoms at diagnosis (75%, 627/839) and at survey completion (66%, 480/722).

The other “most severe” symptoms at diagnosis were heavy menstrual bleeding (85%, 353/416) and anxiety surrounding unstable platelet count (78%, 382/487). The other “most severe” symptoms at survey completion were thrombosis (73%, 24/33) and anxiety surrounding unstable platelet count (66%, 284/431).

“Severe fatigue, in particular, was reported by many patients as the most difficult-to-manage symptom of ITP,” said study investigator Nichola Cooper, MD, of Hammersmith Hospital, Imperial College London, in the UK.

“This is an important message for healthcare providers treating patients with this rare disease. ITP is about more than bruising and risk of bleeding.”

QOL

Forty-four percent of respondents (611/1398) said ITP impacted their energy levels more than half the time, and 36% (501/1398) said ITP had a negative impact on their normal capacity to exercise more than half the time.

Half of all patients (697/1400) said ITP had a high impact on their emotional well-being.

Eighty-three percent (1157/1400) said they felt a stable and safe platelet count was important, 64% (900/1400) worried that their condition will get worse, and 63% (888/1400) were concerned that their platelet count changes for no apparent reason.

Thirty-seven percent of all patients (511/1400) had reduced their work hours because of ITP, 37% (522/1400) seriously considered reducing their hours, and 21% (294/1400) considered terminating their employment.

Thirty-five percent of patients (491/1400) said obtaining healthy blood counts was their most important treatment goal. Twenty-one percent (299/1400) said increasing their energy levels was most important, and 15% (203/1400) said reducing spontaneous bleeds/bruising was most important.

Photo by Daniel Gay

The US Food and Drug Administration (FDA) has approved 2 Grifols blood screening assays—Procleix Ultrio Elite and Procleix WNV.

Procleix WNV is a qualitative in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Procleix Ultrio Elite is a blood screening assay that delivers simultaneous results for human immunodeficiency virus type 1, hepatitis C virus, and hepatitis B virus. It also detects human immunodeficiency virus type 2.

Procleix Ultrio Elite can be used to test pools of plasma composed of up to 96 individual donations from donors of source plasma.

Grifols will begin commercializing the Procleix Ultrio Elite and Procleix WNV assays in the US later this year.

“These FDA approvals demonstrate our ongoing commitment to expand Grifols comprehensive nucleic acid testing (NAT) solutions portfolio to help labs administer NAT,” said Carsten Schroeder, president of Grifols’s Diagnostic Division.

Procleix Ultrio Elite and Procleix WNV will run on the fully automated NAT blood screening platform Procleix Panther system. The device is an integrated NAT system that fully automates all necessary steps to perform Procleix assays, from sample processing through amplification, detection, and data reduction.

“The addition of the Procleix Panther system with these assays will allow blood centers to efficiently screen for infectious diseases on one simple, automated platform while adapting to changes in donation volume and regulatory requirements,” Schroeder said.

Photo by Daniel Gay

The US Food and Drug Administration (FDA) has approved 2 Grifols blood screening assays—Procleix Ultrio Elite and Procleix WNV.

Procleix WNV is a qualitative in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Procleix Ultrio Elite is a blood screening assay that delivers simultaneous results for human immunodeficiency virus type 1, hepatitis C virus, and hepatitis B virus. It also detects human immunodeficiency virus type 2.

Procleix Ultrio Elite can be used to test pools of plasma composed of up to 96 individual donations from donors of source plasma.

Grifols will begin commercializing the Procleix Ultrio Elite and Procleix WNV assays in the US later this year.

“These FDA approvals demonstrate our ongoing commitment to expand Grifols comprehensive nucleic acid testing (NAT) solutions portfolio to help labs administer NAT,” said Carsten Schroeder, president of Grifols’s Diagnostic Division.

Procleix Ultrio Elite and Procleix WNV will run on the fully automated NAT blood screening platform Procleix Panther system. The device is an integrated NAT system that fully automates all necessary steps to perform Procleix assays, from sample processing through amplification, detection, and data reduction.

“The addition of the Procleix Panther system with these assays will allow blood centers to efficiently screen for infectious diseases on one simple, automated platform while adapting to changes in donation volume and regulatory requirements,” Schroeder said.

Photo by Daniel Gay

The US Food and Drug Administration (FDA) has approved 2 Grifols blood screening assays—Procleix Ultrio Elite and Procleix WNV.

Procleix WNV is a qualitative in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Procleix Ultrio Elite is a blood screening assay that delivers simultaneous results for human immunodeficiency virus type 1, hepatitis C virus, and hepatitis B virus. It also detects human immunodeficiency virus type 2.

Procleix Ultrio Elite can be used to test pools of plasma composed of up to 96 individual donations from donors of source plasma.

Grifols will begin commercializing the Procleix Ultrio Elite and Procleix WNV assays in the US later this year.

“These FDA approvals demonstrate our ongoing commitment to expand Grifols comprehensive nucleic acid testing (NAT) solutions portfolio to help labs administer NAT,” said Carsten Schroeder, president of Grifols’s Diagnostic Division.

Procleix Ultrio Elite and Procleix WNV will run on the fully automated NAT blood screening platform Procleix Panther system. The device is an integrated NAT system that fully automates all necessary steps to perform Procleix assays, from sample processing through amplification, detection, and data reduction.

“The addition of the Procleix Panther system with these assays will allow blood centers to efficiently screen for infectious diseases on one simple, automated platform while adapting to changes in donation volume and regulatory requirements,” Schroeder said.

Photo courtesy of Amgen

The European Commission (EC) has granted a full marketing authorization for blinatumomab (BLINCYTO®) as a treatment for adults with Philadelphia chromosome-negative (Ph-), relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The EC granted blinatumomab conditional authorization for this indication in 2015. Now, the drug has full authorization based on overall survival (OS) data from the phase 3 TOWER study.

This authorization is valid in all European Union and European Economic Area-European Free Trade Association states (Norway, Iceland, and Liechtenstein).

Blinatumomab is a bispecific CD19-directed CD3 T cell engager (BiTE®) immunotherapy construct. It binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of effector T cells.

The TOWER study was a phase 3, randomized trial in which researchers compared blinatumomab to standard of care (SOC) chemotherapy in 405 adults with Ph-, relapsed/refractory B-cell precursor ALL.

Patients were randomized in a 2:1 ratio to receive blinatumomab (n=271) or investigator’s choice of SOC chemotherapy (n=134).

On the recommendation of an independent data monitoring committee, Amgen ended the study early for evidence of superior efficacy in the blinatumomab arm.

The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm (hazard ratio=0.71; P=0.012).

For patients treated in first salvage, the median OS was 11.1 months in the blinatumomab arm and 5.3 months in the SOC arm (hazard ratio=0.6).

Safety results in the blinatumomab arm were comparable to those seen in previous phase 2 studies.

These results were published in NEJM in March 2017.

Photo courtesy of Amgen

The European Commission (EC) has granted a full marketing authorization for blinatumomab (BLINCYTO®) as a treatment for adults with Philadelphia chromosome-negative (Ph-), relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The EC granted blinatumomab conditional authorization for this indication in 2015. Now, the drug has full authorization based on overall survival (OS) data from the phase 3 TOWER study.

This authorization is valid in all European Union and European Economic Area-European Free Trade Association states (Norway, Iceland, and Liechtenstein).

Blinatumomab is a bispecific CD19-directed CD3 T cell engager (BiTE®) immunotherapy construct. It binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of effector T cells.

The TOWER study was a phase 3, randomized trial in which researchers compared blinatumomab to standard of care (SOC) chemotherapy in 405 adults with Ph-, relapsed/refractory B-cell precursor ALL.

Patients were randomized in a 2:1 ratio to receive blinatumomab (n=271) or investigator’s choice of SOC chemotherapy (n=134).

On the recommendation of an independent data monitoring committee, Amgen ended the study early for evidence of superior efficacy in the blinatumomab arm.

The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm (hazard ratio=0.71; P=0.012).

For patients treated in first salvage, the median OS was 11.1 months in the blinatumomab arm and 5.3 months in the SOC arm (hazard ratio=0.6).

Safety results in the blinatumomab arm were comparable to those seen in previous phase 2 studies.

These results were published in NEJM in March 2017.

Photo courtesy of Amgen

The European Commission (EC) has granted a full marketing authorization for blinatumomab (BLINCYTO®) as a treatment for adults with Philadelphia chromosome-negative (Ph-), relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The EC granted blinatumomab conditional authorization for this indication in 2015. Now, the drug has full authorization based on overall survival (OS) data from the phase 3 TOWER study.

This authorization is valid in all European Union and European Economic Area-European Free Trade Association states (Norway, Iceland, and Liechtenstein).

Blinatumomab is a bispecific CD19-directed CD3 T cell engager (BiTE®) immunotherapy construct. It binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of effector T cells.

The TOWER study was a phase 3, randomized trial in which researchers compared blinatumomab to standard of care (SOC) chemotherapy in 405 adults with Ph-, relapsed/refractory B-cell precursor ALL.

Patients were randomized in a 2:1 ratio to receive blinatumomab (n=271) or investigator’s choice of SOC chemotherapy (n=134).

On the recommendation of an independent data monitoring committee, Amgen ended the study early for evidence of superior efficacy in the blinatumomab arm.

The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm (hazard ratio=0.71; P=0.012).

For patients treated in first salvage, the median OS was 11.1 months in the blinatumomab arm and 5.3 months in the SOC arm (hazard ratio=0.6).

Safety results in the blinatumomab arm were comparable to those seen in previous phase 2 studies.

These results were published in NEJM in March 2017.

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

follicular lymphoma

Autologous and allogeneic hematopoietic stem cell transplantation (HCT) both offer excellent long-term survival in follicular lymphoma (FL) patients who experience early treatment failure, an analysis of a large transplant registry suggests.

Five-year survival rates exceeded 70% for patients who received autologous or matched sibling donor (MSD) transplants, according to the analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The database included 440 patients who underwent a procedure between 2002 and 2014.

“Until better risk-stratification tools are available for FL, auto-HCT and MSD allo-HCT should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” Sonali M. Smith, MD, of the University of Chicago, and co-investigators wrote in the journal Cancer.

Early treatment failure in FL is associated with worse overall survival. In the National LymphoCare Study (NLCS), patients who received upfront R-CHOP therapy and progressed within 24 months had a 5-year overall survival of 50%, versus 90% for patients without early progression.

By contrast, survival figures in the present study are “provocatively higher” than those in the NLCS, in which only 8 out of 110 patients underwent HCT, Dr Smith and co-authors said.

Dr Smith’s study showed that with a median follow-up of 69 to 73 months, adjusted probability of 5-year overall survival was 70% for autologous and 73% for MSD HCT, versus 49% for matched unrelated donor HCT (P=0.0008).

Ryan C. Lynch, MD, and Ajay K. Gopal, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said that the finding “convincingly demonstrates” the benefit of transplant in the setting of early treatment failure.

“Select patients (particularly younger patients) with chemoresponsive disease who understand the risk-benefit ratio in comparison with currently approved and experimental therapies still remain good candidates for autologous HCT,” Drs Lynch and Gopal said in an editorial.

“For older patients or patients with comorbidities, we would continue to recommend clinical trials or treatment with an approved PI3K inhibitor,” they added.

The study by Dr Smith and colleagues is not the first to show a benefit of HCT in this clinical scenario. In a recent NLCS/CIBMTR analysis of FL patients, 5-year overall survival was 73% for those undergoing autologous HCT done within a year of early treatment failure, versus 60% for those who did not (P=0.05).

The two studies “collectively suggest that transplantation should be considered in this high-risk group of patients with early relapse,” Dr Smith and co-authors wrote. 

follicular lymphoma

Autologous and allogeneic hematopoietic stem cell transplantation (HCT) both offer excellent long-term survival in follicular lymphoma (FL) patients who experience early treatment failure, an analysis of a large transplant registry suggests.

Five-year survival rates exceeded 70% for patients who received autologous or matched sibling donor (MSD) transplants, according to the analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The database included 440 patients who underwent a procedure between 2002 and 2014.

“Until better risk-stratification tools are available for FL, auto-HCT and MSD allo-HCT should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” Sonali M. Smith, MD, of the University of Chicago, and co-investigators wrote in the journal Cancer.

Early treatment failure in FL is associated with worse overall survival. In the National LymphoCare Study (NLCS), patients who received upfront R-CHOP therapy and progressed within 24 months had a 5-year overall survival of 50%, versus 90% for patients without early progression.

By contrast, survival figures in the present study are “provocatively higher” than those in the NLCS, in which only 8 out of 110 patients underwent HCT, Dr Smith and co-authors said.

Dr Smith’s study showed that with a median follow-up of 69 to 73 months, adjusted probability of 5-year overall survival was 70% for autologous and 73% for MSD HCT, versus 49% for matched unrelated donor HCT (P=0.0008).

Ryan C. Lynch, MD, and Ajay K. Gopal, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said that the finding “convincingly demonstrates” the benefit of transplant in the setting of early treatment failure.

“Select patients (particularly younger patients) with chemoresponsive disease who understand the risk-benefit ratio in comparison with currently approved and experimental therapies still remain good candidates for autologous HCT,” Drs Lynch and Gopal said in an editorial.

“For older patients or patients with comorbidities, we would continue to recommend clinical trials or treatment with an approved PI3K inhibitor,” they added.

The study by Dr Smith and colleagues is not the first to show a benefit of HCT in this clinical scenario. In a recent NLCS/CIBMTR analysis of FL patients, 5-year overall survival was 73% for those undergoing autologous HCT done within a year of early treatment failure, versus 60% for those who did not (P=0.05).

The two studies “collectively suggest that transplantation should be considered in this high-risk group of patients with early relapse,” Dr Smith and co-authors wrote. 

follicular lymphoma

Autologous and allogeneic hematopoietic stem cell transplantation (HCT) both offer excellent long-term survival in follicular lymphoma (FL) patients who experience early treatment failure, an analysis of a large transplant registry suggests.

Five-year survival rates exceeded 70% for patients who received autologous or matched sibling donor (MSD) transplants, according to the analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The database included 440 patients who underwent a procedure between 2002 and 2014.

“Until better risk-stratification tools are available for FL, auto-HCT and MSD allo-HCT should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” Sonali M. Smith, MD, of the University of Chicago, and co-investigators wrote in the journal Cancer.

Early treatment failure in FL is associated with worse overall survival. In the National LymphoCare Study (NLCS), patients who received upfront R-CHOP therapy and progressed within 24 months had a 5-year overall survival of 50%, versus 90% for patients without early progression.

By contrast, survival figures in the present study are “provocatively higher” than those in the NLCS, in which only 8 out of 110 patients underwent HCT, Dr Smith and co-authors said.

Dr Smith’s study showed that with a median follow-up of 69 to 73 months, adjusted probability of 5-year overall survival was 70% for autologous and 73% for MSD HCT, versus 49% for matched unrelated donor HCT (P=0.0008).

Ryan C. Lynch, MD, and Ajay K. Gopal, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said that the finding “convincingly demonstrates” the benefit of transplant in the setting of early treatment failure.

“Select patients (particularly younger patients) with chemoresponsive disease who understand the risk-benefit ratio in comparison with currently approved and experimental therapies still remain good candidates for autologous HCT,” Drs Lynch and Gopal said in an editorial.

“For older patients or patients with comorbidities, we would continue to recommend clinical trials or treatment with an approved PI3K inhibitor,” they added.

The study by Dr Smith and colleagues is not the first to show a benefit of HCT in this clinical scenario. In a recent NLCS/CIBMTR analysis of FL patients, 5-year overall survival was 73% for those undergoing autologous HCT done within a year of early treatment failure, versus 60% for those who did not (P=0.05).

The two studies “collectively suggest that transplantation should be considered in this high-risk group of patients with early relapse,” Dr Smith and co-authors wrote.