MONTREAL – Enhanced and prolonged rhythm monitoring for atrial fibrillation in patients with a recent acute ischemic stroke did not find more arrhythmias, it just found them faster, in a randomized study with 398 German patients.

Mitchel L. Zoler/MDedge News

“Prolonged and enhanced monitoring identified atrial fibrillation cases that otherwise were detected years later,” Rolf Wachter, MD, said at the World Stroke Congress. Enhanced and prolonged monitoring (EPM) “should be considered for all stroke patients, regardless of the suspected stroke etiology, if detection of atrial fibrillation is of clinical relevance,” said Dr. Wachter, a cardiologist and professor at the University Clinic in Leipzig, Germany.

Based on 3-year follow-up of patients enrolled in the FIND-AF study, which randomized patients within 7 days of an acute ischemic stroke to either EPM for atrial fibrillation (AF) or standard work-up and follow-up, Dr. Wachter calculated that every six such patients who underwent EMP for AF yielded one added patient who could receive anticoagulant prophylaxis for 1 year, an effect that should result in fewer incident strokes and deaths. The data he reported showed after 3 years a “favorable trend” toward fewer strokes and deaths among patients who underwent EPM.

FIND-AF RANDOMISED (A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients) ran at four German centers during May 2013–August 2014. It enrolled 398 patients aged 60 years or older within 7 days of an acute ischemic stroke who were in sinus rhythm and had no AF history. Enrolled patients could have any type of suspected stroke etiology, but the study excluded patients with severe stenosis in their ipsilateral carotid or intracranial arteries. The study randomized patients to received EPM or a standard work-up. The “enhanced” part of EPM meant review of Holter monitor recordings by a single, dedicated core laboratory. The “prolonged” part meant routinely screening patients for an atrial arrhythmia using a Holter monitor worn for 10 consecutive days on three occasions: at entry into the study, 3 months later, and 6 months later.

The study’s primary endpoint was the number of patients diagnosed with AF after 6 months, which was 27 of 200 patients (13.5%) in the EPM arm and 9 of 198 patients (4.5%) in the control arm, a statistically significant difference, Dr. Wachter and his associates reported in Lancet Neurology (2017 Apr 1;16[4]:282-90).

The additional 30 months of follow-up included in the new report by Dr. Wachter resulted in identification of 3 more patients with AF in the EPM group and 13 more patients in the control arm, which brought the total number of patients with AF identified over 3 years to 30 in the EPM group (15%), and 22 in the control group (11%), a difference that was not statistically significant. In other words, both approaches found roughly the same percentage of patients with AF, but the EPM method found them quicker.

During the extended 36-month follow-up, 12 patients in the EPM group had an ischemic stroke and 9 patients died, with a combined stroke and death rate of about 8%. In the control group, 19 patients had a second ischemic stroke and 13 died, with a combined rate of about 15%. A statistical test of the difference between the combined stroke and death rates in these two groups produced a P value of .08.

FIND-AF was funded by Boehringer Ingelheim. Dr. Wachter has been a speaker on behalf of and has received research funding from Boehringer Ingelheim, and he has also been a speaker on behalf of Bayer, BMS/Pfizer, and Daiichi Sankyo.

[email protected]

SOURCE: Wachter R et al. World Stroke Congress, Abstract.

MONTREAL – Enhanced and prolonged rhythm monitoring for atrial fibrillation in patients with a recent acute ischemic stroke did not find more arrhythmias, it just found them faster, in a randomized study with 398 German patients.

Mitchel L. Zoler/MDedge News

“Prolonged and enhanced monitoring identified atrial fibrillation cases that otherwise were detected years later,” Rolf Wachter, MD, said at the World Stroke Congress. Enhanced and prolonged monitoring (EPM) “should be considered for all stroke patients, regardless of the suspected stroke etiology, if detection of atrial fibrillation is of clinical relevance,” said Dr. Wachter, a cardiologist and professor at the University Clinic in Leipzig, Germany.

Based on 3-year follow-up of patients enrolled in the FIND-AF study, which randomized patients within 7 days of an acute ischemic stroke to either EPM for atrial fibrillation (AF) or standard work-up and follow-up, Dr. Wachter calculated that every six such patients who underwent EMP for AF yielded one added patient who could receive anticoagulant prophylaxis for 1 year, an effect that should result in fewer incident strokes and deaths. The data he reported showed after 3 years a “favorable trend” toward fewer strokes and deaths among patients who underwent EPM.

FIND-AF RANDOMISED (A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients) ran at four German centers during May 2013–August 2014. It enrolled 398 patients aged 60 years or older within 7 days of an acute ischemic stroke who were in sinus rhythm and had no AF history. Enrolled patients could have any type of suspected stroke etiology, but the study excluded patients with severe stenosis in their ipsilateral carotid or intracranial arteries. The study randomized patients to received EPM or a standard work-up. The “enhanced” part of EPM meant review of Holter monitor recordings by a single, dedicated core laboratory. The “prolonged” part meant routinely screening patients for an atrial arrhythmia using a Holter monitor worn for 10 consecutive days on three occasions: at entry into the study, 3 months later, and 6 months later.

The study’s primary endpoint was the number of patients diagnosed with AF after 6 months, which was 27 of 200 patients (13.5%) in the EPM arm and 9 of 198 patients (4.5%) in the control arm, a statistically significant difference, Dr. Wachter and his associates reported in Lancet Neurology (2017 Apr 1;16[4]:282-90).

The additional 30 months of follow-up included in the new report by Dr. Wachter resulted in identification of 3 more patients with AF in the EPM group and 13 more patients in the control arm, which brought the total number of patients with AF identified over 3 years to 30 in the EPM group (15%), and 22 in the control group (11%), a difference that was not statistically significant. In other words, both approaches found roughly the same percentage of patients with AF, but the EPM method found them quicker.

During the extended 36-month follow-up, 12 patients in the EPM group had an ischemic stroke and 9 patients died, with a combined stroke and death rate of about 8%. In the control group, 19 patients had a second ischemic stroke and 13 died, with a combined rate of about 15%. A statistical test of the difference between the combined stroke and death rates in these two groups produced a P value of .08.

FIND-AF was funded by Boehringer Ingelheim. Dr. Wachter has been a speaker on behalf of and has received research funding from Boehringer Ingelheim, and he has also been a speaker on behalf of Bayer, BMS/Pfizer, and Daiichi Sankyo.

[email protected]

SOURCE: Wachter R et al. World Stroke Congress, Abstract.

MONTREAL – Enhanced and prolonged rhythm monitoring for atrial fibrillation in patients with a recent acute ischemic stroke did not find more arrhythmias, it just found them faster, in a randomized study with 398 German patients.

Mitchel L. Zoler/MDedge News

“Prolonged and enhanced monitoring identified atrial fibrillation cases that otherwise were detected years later,” Rolf Wachter, MD, said at the World Stroke Congress. Enhanced and prolonged monitoring (EPM) “should be considered for all stroke patients, regardless of the suspected stroke etiology, if detection of atrial fibrillation is of clinical relevance,” said Dr. Wachter, a cardiologist and professor at the University Clinic in Leipzig, Germany.

Based on 3-year follow-up of patients enrolled in the FIND-AF study, which randomized patients within 7 days of an acute ischemic stroke to either EPM for atrial fibrillation (AF) or standard work-up and follow-up, Dr. Wachter calculated that every six such patients who underwent EMP for AF yielded one added patient who could receive anticoagulant prophylaxis for 1 year, an effect that should result in fewer incident strokes and deaths. The data he reported showed after 3 years a “favorable trend” toward fewer strokes and deaths among patients who underwent EPM.

FIND-AF RANDOMISED (A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients) ran at four German centers during May 2013–August 2014. It enrolled 398 patients aged 60 years or older within 7 days of an acute ischemic stroke who were in sinus rhythm and had no AF history. Enrolled patients could have any type of suspected stroke etiology, but the study excluded patients with severe stenosis in their ipsilateral carotid or intracranial arteries. The study randomized patients to received EPM or a standard work-up. The “enhanced” part of EPM meant review of Holter monitor recordings by a single, dedicated core laboratory. The “prolonged” part meant routinely screening patients for an atrial arrhythmia using a Holter monitor worn for 10 consecutive days on three occasions: at entry into the study, 3 months later, and 6 months later.

The study’s primary endpoint was the number of patients diagnosed with AF after 6 months, which was 27 of 200 patients (13.5%) in the EPM arm and 9 of 198 patients (4.5%) in the control arm, a statistically significant difference, Dr. Wachter and his associates reported in Lancet Neurology (2017 Apr 1;16[4]:282-90).

The additional 30 months of follow-up included in the new report by Dr. Wachter resulted in identification of 3 more patients with AF in the EPM group and 13 more patients in the control arm, which brought the total number of patients with AF identified over 3 years to 30 in the EPM group (15%), and 22 in the control group (11%), a difference that was not statistically significant. In other words, both approaches found roughly the same percentage of patients with AF, but the EPM method found them quicker.

During the extended 36-month follow-up, 12 patients in the EPM group had an ischemic stroke and 9 patients died, with a combined stroke and death rate of about 8%. In the control group, 19 patients had a second ischemic stroke and 13 died, with a combined rate of about 15%. A statistical test of the difference between the combined stroke and death rates in these two groups produced a P value of .08.

FIND-AF was funded by Boehringer Ingelheim. Dr. Wachter has been a speaker on behalf of and has received research funding from Boehringer Ingelheim, and he has also been a speaker on behalf of Bayer, BMS/Pfizer, and Daiichi Sankyo.

[email protected]

SOURCE: Wachter R et al. World Stroke Congress, Abstract.

The Food and Drug Administration has approved romiplostim (Nplate) for pediatric patients aged 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The FDA based the approval on two trials in pediatric patients 1 year and older with ITP for at least 6 months duration.

In the first trial, 62 patients were randomized 2:1 to receive romiplostim or placebo; differences in durable platelet response, overall platelet response, and duration of response were all statistically significant, with P values less than .05.

Durable platelet response (at least 6 weekly platelet counts greater than or equal to 50 × 10⁹/L during weeks 18 through 25 of treatment) was achieved in 22 patients (52%) who received romiplostim and 2 (10%) who received placebo. Overall platelet response was achieved in 30 (71%) and 4 (20%) patients, respectively. Patients who received romiplostim had platelet counts greater than or equal to 50 x 10⁹/L for a median of 12 weeks, compared with 1 week in patients who received placebo, the FDA said in a statement.

In the second randomized trial, 22 patients were randomized 3:1 to receive romiplostim or placebo; 15 patients in the romiplostim arm achieved a platelet count greater than or equal to 50 x 10⁹/L for 2 consecutive weeks and an increase in platelet count of greater than or equal to 20 × 10⁹/L above baseline for 2 consecutive weeks during the treatment period (88%; 95% confidence interval, 64%-99%), compared with 0 patients in the placebo arm.

The most common adverse reactions observed in children receiving romiplostim include contusion, upper respiratory tract infection, and oropharyngeal pain.

The recommended initial romiplostim dose for pediatric patients is 1 mcg/kg based on actual body weight and administered as a weekly subcutaneous injection. Dose should be adjusted in increments of 1 mcg/kg until the patient achieves a platelet count greater than or equal to 50 x 10⁹/L. Body weight should be reassessed every 12 weeks, according to the FDA announcement.

[email protected]

The Food and Drug Administration has approved romiplostim (Nplate) for pediatric patients aged 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The FDA based the approval on two trials in pediatric patients 1 year and older with ITP for at least 6 months duration.

In the first trial, 62 patients were randomized 2:1 to receive romiplostim or placebo; differences in durable platelet response, overall platelet response, and duration of response were all statistically significant, with P values less than .05.

Durable platelet response (at least 6 weekly platelet counts greater than or equal to 50 × 10⁹/L during weeks 18 through 25 of treatment) was achieved in 22 patients (52%) who received romiplostim and 2 (10%) who received placebo. Overall platelet response was achieved in 30 (71%) and 4 (20%) patients, respectively. Patients who received romiplostim had platelet counts greater than or equal to 50 x 10⁹/L for a median of 12 weeks, compared with 1 week in patients who received placebo, the FDA said in a statement.

In the second randomized trial, 22 patients were randomized 3:1 to receive romiplostim or placebo; 15 patients in the romiplostim arm achieved a platelet count greater than or equal to 50 x 10⁹/L for 2 consecutive weeks and an increase in platelet count of greater than or equal to 20 × 10⁹/L above baseline for 2 consecutive weeks during the treatment period (88%; 95% confidence interval, 64%-99%), compared with 0 patients in the placebo arm.

The most common adverse reactions observed in children receiving romiplostim include contusion, upper respiratory tract infection, and oropharyngeal pain.

The recommended initial romiplostim dose for pediatric patients is 1 mcg/kg based on actual body weight and administered as a weekly subcutaneous injection. Dose should be adjusted in increments of 1 mcg/kg until the patient achieves a platelet count greater than or equal to 50 x 10⁹/L. Body weight should be reassessed every 12 weeks, according to the FDA announcement.

[email protected]

The Food and Drug Administration has approved romiplostim (Nplate) for pediatric patients aged 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The FDA based the approval on two trials in pediatric patients 1 year and older with ITP for at least 6 months duration.

In the first trial, 62 patients were randomized 2:1 to receive romiplostim or placebo; differences in durable platelet response, overall platelet response, and duration of response were all statistically significant, with P values less than .05.

Durable platelet response (at least 6 weekly platelet counts greater than or equal to 50 × 10⁹/L during weeks 18 through 25 of treatment) was achieved in 22 patients (52%) who received romiplostim and 2 (10%) who received placebo. Overall platelet response was achieved in 30 (71%) and 4 (20%) patients, respectively. Patients who received romiplostim had platelet counts greater than or equal to 50 x 10⁹/L for a median of 12 weeks, compared with 1 week in patients who received placebo, the FDA said in a statement.

In the second randomized trial, 22 patients were randomized 3:1 to receive romiplostim or placebo; 15 patients in the romiplostim arm achieved a platelet count greater than or equal to 50 x 10⁹/L for 2 consecutive weeks and an increase in platelet count of greater than or equal to 20 × 10⁹/L above baseline for 2 consecutive weeks during the treatment period (88%; 95% confidence interval, 64%-99%), compared with 0 patients in the placebo arm.

The most common adverse reactions observed in children receiving romiplostim include contusion, upper respiratory tract infection, and oropharyngeal pain.

The recommended initial romiplostim dose for pediatric patients is 1 mcg/kg based on actual body weight and administered as a weekly subcutaneous injection. Dose should be adjusted in increments of 1 mcg/kg until the patient achieves a platelet count greater than or equal to 50 x 10⁹/L. Body weight should be reassessed every 12 weeks, according to the FDA announcement.

[email protected]

A group of internists is suing the American Board of Internal Medicine over its maintenance of certification. Also today, drug test results should not dictate treatment, duodenoscopes contain more bacteria than expected, and weight-loss medications may have a role following bariatric surgery.

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A group of internists is suing the American Board of Internal Medicine over its maintenance of certification. Also today, drug test results should not dictate treatment, duodenoscopes contain more bacteria than expected, and weight-loss medications may have a role following bariatric surgery.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A group of internists is suing the American Board of Internal Medicine over its maintenance of certification. Also today, drug test results should not dictate treatment, duodenoscopes contain more bacteria than expected, and weight-loss medications may have a role following bariatric surgery.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Photo courtesy of ASH

SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

And this was particularly the case at the middle dose level of 1 x 10⁶ cells/kg.

William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).

Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.

“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”

ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.

Dr. Wierda presented the phase 1 data available at the cutoff of August 16.

Study design

Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.

Conditioning chemotherapy included fludarabine at 25 mg/m² on days -4, -3, and -2 and cyclophosphamide at 900 mg/m² on day -2.

Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.

The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.

The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 10⁶ CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).

If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 10⁶ dose level or explore lower doses of the product (1 x 10⁶ cells/kg and 0.5 x 10⁶ cells/kg).

Investigators defined DLTs as:

• KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
• Grade 3 nonhematologic toxicities lasting more than 7 days
• Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
• Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.

Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.

Patients

As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.

So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 10⁶/kg), 22 received the middle dose (1 x 10⁶/kg), and 16 received the lowest dose (0.5 x 10⁶/kg).

The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.

Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.

The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.

“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.

The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.

Safety

All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.

Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.

Two patients died of KTE-X19-related AEs. One patient in the 2 x 10⁶ dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 10⁶ dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.

Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 10⁶ dose cohort and 19% in the 0.5 x 10⁶ dose cohort.

Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 10⁶ dose cohort and 50% in the 2 x 10⁶ dose cohort.

Due to the incidence of grade 3 and greater NEs observed in the 1 x 10⁶ dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.

Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.

“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.

In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.

The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.

Efficacy

The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).

Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10^-4 sensitivity at 3 months of follow-up.

All patients in the 1 x 10⁶ dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.

The median duration of response was 12.9 months in the 1 x 10⁶ cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.

ZUMA-3 was sponsored by Kite, a Gilead Company.

Dr. Wierda disclosed research funding from AbbVie and Genentech. 

* Data in the abstract differ from the presentation.

Photo courtesy of ASH

SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

And this was particularly the case at the middle dose level of 1 x 10⁶ cells/kg.

William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).

Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.

“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”

ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.

Dr. Wierda presented the phase 1 data available at the cutoff of August 16.

Study design

Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.

Conditioning chemotherapy included fludarabine at 25 mg/m² on days -4, -3, and -2 and cyclophosphamide at 900 mg/m² on day -2.

Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.

The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.

The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 10⁶ CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).

If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 10⁶ dose level or explore lower doses of the product (1 x 10⁶ cells/kg and 0.5 x 10⁶ cells/kg).

Investigators defined DLTs as:

• KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
• Grade 3 nonhematologic toxicities lasting more than 7 days
• Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
• Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.

Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.

Patients

As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.

So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 10⁶/kg), 22 received the middle dose (1 x 10⁶/kg), and 16 received the lowest dose (0.5 x 10⁶/kg).

The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.

Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.

The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.

“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.

The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.

Safety

All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.

Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.

Two patients died of KTE-X19-related AEs. One patient in the 2 x 10⁶ dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 10⁶ dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.

Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 10⁶ dose cohort and 19% in the 0.5 x 10⁶ dose cohort.

Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 10⁶ dose cohort and 50% in the 2 x 10⁶ dose cohort.

Due to the incidence of grade 3 and greater NEs observed in the 1 x 10⁶ dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.

Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.

“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.

In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.

The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.

Efficacy

The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).

Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10^-4 sensitivity at 3 months of follow-up.

All patients in the 1 x 10⁶ dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.

The median duration of response was 12.9 months in the 1 x 10⁶ cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.

ZUMA-3 was sponsored by Kite, a Gilead Company.

Dr. Wierda disclosed research funding from AbbVie and Genentech. 

* Data in the abstract differ from the presentation.

Photo courtesy of ASH

SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

And this was particularly the case at the middle dose level of 1 x 10⁶ cells/kg.

William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).

Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.

“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”

ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.

Dr. Wierda presented the phase 1 data available at the cutoff of August 16.

Study design

Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.

Conditioning chemotherapy included fludarabine at 25 mg/m² on days -4, -3, and -2 and cyclophosphamide at 900 mg/m² on day -2.

Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.

The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.

The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 10⁶ CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).

If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 10⁶ dose level or explore lower doses of the product (1 x 10⁶ cells/kg and 0.5 x 10⁶ cells/kg).

Investigators defined DLTs as:

• KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
• Grade 3 nonhematologic toxicities lasting more than 7 days
• Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
• Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.

Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.

Patients

As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.

So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 10⁶/kg), 22 received the middle dose (1 x 10⁶/kg), and 16 received the lowest dose (0.5 x 10⁶/kg).

The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.

Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.

The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.

“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.

The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.

Safety

All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.

Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.

Two patients died of KTE-X19-related AEs. One patient in the 2 x 10⁶ dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 10⁶ dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.

Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 10⁶ dose cohort and 19% in the 0.5 x 10⁶ dose cohort.

Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 10⁶ dose cohort and 50% in the 2 x 10⁶ dose cohort.

Due to the incidence of grade 3 and greater NEs observed in the 1 x 10⁶ dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.

Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.

“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.

In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.

The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.

Efficacy

The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).

Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10^-4 sensitivity at 3 months of follow-up.

All patients in the 1 x 10⁶ dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.

The median duration of response was 12.9 months in the 1 x 10⁶ cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.

ZUMA-3 was sponsored by Kite, a Gilead Company.

Dr. Wierda disclosed research funding from AbbVie and Genentech. 

* Data in the abstract differ from the presentation.

Dear Readers,

As 2018 draws to a close, Clinician Reviews is looking ahead to its 29th year of publication. In 1991, when our publication was founded, it was a unique idea to present information to both NPs and PAs together—a recognition of common educational needs and a unified focus on delivering the best possible patient care. For the past six years, as Editor, I have been privileged to ensure the fulfillment of CR’s editorial purpose—keeping NPs and PAs up to date on all aspects of clinical practice—while navigating changes both internal and external.

When CR started, personal computers existed but were not yet in widespread use (the office had one, to be shared). Manuscripts, peer reviews, even radiographs—all were submitted on paper, via the US Postal Service. How far the world has come in the ensuing decades. Now, we can stay connected to anyone, anywhere, via devices that fit in our pockets.

And so I’m excited to share with you one of the changes we’re making: In 2019, Clinician Reviews will be published 100% digitally! Why? Yes, printing and postage costs have increased to the point of unsustainability (and all that paper is not very environmentally friendly). But most importantly, online publication allows us to provide you with more of what you need for your practice—at any time of day or night, on any device you choose. And this gives us more scope to be creative in presenting information in engaging ways.

To ensure that we are moving in the right direction in making ClinicianReviews.com a more robust and useful resource, we surveyed NPs and PAs like you about our site, our competitors’ sites, and potential new offerings. Your answers were very enlightening, providing us guidance on

Building new functionality to make the site more user friendly

✓ Automatic notification when new content is posted

✓ Video player with a list of recently posted videos

Providing new content, including

✓ Clinical crossword puzzle

✓ Malpractice Chronicle by David Lang (both of which make their debut in this print issue)

Continue to: Offering you must-have content

Offering you must-have content

✓ Enhanced disease-specific content

✓ CE/CME with transcript tracking

✓ Peer-reviewed, evidence-based articles

✓ NP/PA- and MD-specific content

✓ Real-time news and conference reports

To ensure you stay informed about new offerings—and can continue to find the content you’ve enjoyed for years—we invite you to register on our website. You can do so by scanning the QR code below, and as a thank you, you’ll be able to download a free pocket guide, “PURLs in Primary Care.” And don’t forget to bookmark ClinicianReviews.com so that you can easily access our continually updated content.

We’re excited to take this step forward—and as always, we appreciate your support. We’re here to continue to serve the NP and PA professions, so please don’t hesitate to share your feedback and suggestions with us.

Best regards,

Karen J. Clemments

Dear Readers,

As 2018 draws to a close, Clinician Reviews is looking ahead to its 29th year of publication. In 1991, when our publication was founded, it was a unique idea to present information to both NPs and PAs together—a recognition of common educational needs and a unified focus on delivering the best possible patient care. For the past six years, as Editor, I have been privileged to ensure the fulfillment of CR’s editorial purpose—keeping NPs and PAs up to date on all aspects of clinical practice—while navigating changes both internal and external.

When CR started, personal computers existed but were not yet in widespread use (the office had one, to be shared). Manuscripts, peer reviews, even radiographs—all were submitted on paper, via the US Postal Service. How far the world has come in the ensuing decades. Now, we can stay connected to anyone, anywhere, via devices that fit in our pockets.

And so I’m excited to share with you one of the changes we’re making: In 2019, Clinician Reviews will be published 100% digitally! Why? Yes, printing and postage costs have increased to the point of unsustainability (and all that paper is not very environmentally friendly). But most importantly, online publication allows us to provide you with more of what you need for your practice—at any time of day or night, on any device you choose. And this gives us more scope to be creative in presenting information in engaging ways.

To ensure that we are moving in the right direction in making ClinicianReviews.com a more robust and useful resource, we surveyed NPs and PAs like you about our site, our competitors’ sites, and potential new offerings. Your answers were very enlightening, providing us guidance on

Building new functionality to make the site more user friendly

✓ Automatic notification when new content is posted

✓ Video player with a list of recently posted videos

Providing new content, including

✓ Clinical crossword puzzle

✓ Malpractice Chronicle by David Lang (both of which make their debut in this print issue)

Continue to: Offering you must-have content

Offering you must-have content

✓ Enhanced disease-specific content

✓ CE/CME with transcript tracking

✓ Peer-reviewed, evidence-based articles

✓ NP/PA- and MD-specific content

✓ Real-time news and conference reports

To ensure you stay informed about new offerings—and can continue to find the content you’ve enjoyed for years—we invite you to register on our website. You can do so by scanning the QR code below, and as a thank you, you’ll be able to download a free pocket guide, “PURLs in Primary Care.” And don’t forget to bookmark ClinicianReviews.com so that you can easily access our continually updated content.

We’re excited to take this step forward—and as always, we appreciate your support. We’re here to continue to serve the NP and PA professions, so please don’t hesitate to share your feedback and suggestions with us.

Best regards,

Karen J. Clemments

Dear Readers,

As 2018 draws to a close, Clinician Reviews is looking ahead to its 29th year of publication. In 1991, when our publication was founded, it was a unique idea to present information to both NPs and PAs together—a recognition of common educational needs and a unified focus on delivering the best possible patient care. For the past six years, as Editor, I have been privileged to ensure the fulfillment of CR’s editorial purpose—keeping NPs and PAs up to date on all aspects of clinical practice—while navigating changes both internal and external.

When CR started, personal computers existed but were not yet in widespread use (the office had one, to be shared). Manuscripts, peer reviews, even radiographs—all were submitted on paper, via the US Postal Service. How far the world has come in the ensuing decades. Now, we can stay connected to anyone, anywhere, via devices that fit in our pockets.

And so I’m excited to share with you one of the changes we’re making: In 2019, Clinician Reviews will be published 100% digitally! Why? Yes, printing and postage costs have increased to the point of unsustainability (and all that paper is not very environmentally friendly). But most importantly, online publication allows us to provide you with more of what you need for your practice—at any time of day or night, on any device you choose. And this gives us more scope to be creative in presenting information in engaging ways.

To ensure that we are moving in the right direction in making ClinicianReviews.com a more robust and useful resource, we surveyed NPs and PAs like you about our site, our competitors’ sites, and potential new offerings. Your answers were very enlightening, providing us guidance on

Building new functionality to make the site more user friendly

✓ Automatic notification when new content is posted

✓ Video player with a list of recently posted videos

Providing new content, including

✓ Clinical crossword puzzle

✓ Malpractice Chronicle by David Lang (both of which make their debut in this print issue)

Continue to: Offering you must-have content

Offering you must-have content

✓ Enhanced disease-specific content

✓ CE/CME with transcript tracking

✓ Peer-reviewed, evidence-based articles

✓ NP/PA- and MD-specific content

✓ Real-time news and conference reports

To ensure you stay informed about new offerings—and can continue to find the content you’ve enjoyed for years—we invite you to register on our website. You can do so by scanning the QR code below, and as a thank you, you’ll be able to download a free pocket guide, “PURLs in Primary Care.” And don’t forget to bookmark ClinicianReviews.com so that you can easily access our continually updated content.

We’re excited to take this step forward—and as always, we appreciate your support. We’re here to continue to serve the NP and PA professions, so please don’t hesitate to share your feedback and suggestions with us.

Best regards,

Karen J. Clemments

This year’s Vascular Annual Meeting will have a new and elegant air about it, with the introduction of a Gala to benefit the SVS Foundation. It is replacing the traditional President’s Reception, at the request of SVS President Michel S. Makaroun. Tickets are $250 each, of which $150 is a tax-deductible contribution to the SVS Foundation’s general fund, the Greatest Need Fund. The Gala will be held Friday, June 14, at the Gaylord National Resort & Convention Center, the site for VAM. The event will include a silent auction, cocktails, dinner and entertainment. Many details are still in the planning stages and a link to purchase tickets will be available in January. Keep checking the SVS site for future details.

This year’s Vascular Annual Meeting will have a new and elegant air about it, with the introduction of a Gala to benefit the SVS Foundation. It is replacing the traditional President’s Reception, at the request of SVS President Michel S. Makaroun. Tickets are $250 each, of which $150 is a tax-deductible contribution to the SVS Foundation’s general fund, the Greatest Need Fund. The Gala will be held Friday, June 14, at the Gaylord National Resort & Convention Center, the site for VAM. The event will include a silent auction, cocktails, dinner and entertainment. Many details are still in the planning stages and a link to purchase tickets will be available in January. Keep checking the SVS site for future details.

This year’s Vascular Annual Meeting will have a new and elegant air about it, with the introduction of a Gala to benefit the SVS Foundation. It is replacing the traditional President’s Reception, at the request of SVS President Michel S. Makaroun. Tickets are $250 each, of which $150 is a tax-deductible contribution to the SVS Foundation’s general fund, the Greatest Need Fund. The Gala will be held Friday, June 14, at the Gaylord National Resort & Convention Center, the site for VAM. The event will include a silent auction, cocktails, dinner and entertainment. Many details are still in the planning stages and a link to purchase tickets will be available in January. Keep checking the SVS site for future details.

SVSConnect, your online community, is now open! This online space gives members a place for discussion, collaboration and a chance to expand their professional networks. This initial launch starts with a single forum for all members to get signed up and post discussions on everything from case complications and surgical procedures, to research projects, wellness topics and more. Users also have an opportunity to leave general questions for SVS. Login to engage and help shape this community, and your Society, for the future.

SVSConnect, your online community, is now open! This online space gives members a place for discussion, collaboration and a chance to expand their professional networks. This initial launch starts with a single forum for all members to get signed up and post discussions on everything from case complications and surgical procedures, to research projects, wellness topics and more. Users also have an opportunity to leave general questions for SVS. Login to engage and help shape this community, and your Society, for the future.

SVSConnect, your online community, is now open! This online space gives members a place for discussion, collaboration and a chance to expand their professional networks. This initial launch starts with a single forum for all members to get signed up and post discussions on everything from case complications and surgical procedures, to research projects, wellness topics and more. Users also have an opportunity to leave general questions for SVS. Login to engage and help shape this community, and your Society, for the future.

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks.