HT Staff

Photo courtesy of Celgene

The US Food and Drug Administration (FDA) has approved a new indication for lenalidomide (Revlimid).

The drug is now approved for use as maintenance therapy after autologous hematopoietic stem cell transplant (auto-HSCT) in patients with multiple myeloma (MM).

The expanded indication makes lenalidomide the first treatment to receive FDA approval for maintenance following auto-HSCT.

The drug was previously FDA-approved for use in combination with dexamethasone to treat patients with MM.

Lenalidomide is also FDA-approved to treat patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes associated with deletion 5q, with or without additional cytogenetic abnormalities.

And lenalidomide is FDA-approved to treat patients with mantle cell lymphoma who have relapsed or progressed after 2 prior therapies, one of which included bortezomib.

Lenalidomide is a product of Celgene.

Studies: Lenalidomide maintenance

The latest approval for lenalidomide was based on results of 2 cooperative group-led studies, CALGB 10010410 and IFM 2005-0211.

Results from both studies were published in NEJM in May 2012 (CALGB 100104, IFM 2005-02). The updated data reported here are included in the prescribing information for lenalidomide.

CALGB 100104 was a phase 3, double-blind study of 460 patients with newly diagnosed MM undergoing auto-HSCT. The patients received continuous daily treatment with lenalidomide or placebo until relapse.

IFM 2005-02 was a phase 3, double-blind study of 614 patients newly diagnosed with MM. The patients were randomized to receive a 2-month consolidation regimen after auto-HSCT, which consisted of lenalidomide monotherapy followed by continuous daily treatment with lenalidomide or placebo until relapse.

Survival

In both studies, the primary efficacy endpoint was progression-free survival (PFS). The PFS data for both studies were updated to reflect results as of March 2015.

In the CALGB study, the median PFS was 5.7 years in the lenalidomide arm and 1.9 years in the placebo arm (hazard ratio [HR]=0.38 [95% CI: 0.28-0.50]).

In the IFM study, the median PFS was 3.9 years in the lenalidomide arm and 2 years in the placebo arm (HR=0.53 [95% CI: 0.44-0.64]).

These studies were not powered for an overall survival (OS) endpoint. However, OS was recorded, and the OS data for both studies were updated to reflect results as of February 2016.

The median OS in the CALGB study was 9.3 years in the lenalidomide arm and 7 years in the placebo arm (HR=0.59 [95% CI: 0.44-0.78]).

In the IFM study, the median OS was 8.8 years in the lenalidomide arm and 7.3 years in the placebo arm (HR=0.90 [95% CI: 0.72-1.13]).

Adverse events

The most frequently reported adverse events in ≥20% of patients in the lenalidomide arm across both  studies (CALGB and IFM, respectively) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%).

The most frequently reported grade 3/4 events (more than 20% in the lenalidomide arm) were neutropenia, thrombocytopenia, and leukopenia.

Hematologic second primary malignancies (SPM) occurred in 7.5% of patients receiving lenalidomide maintenance and 3.3% of controls.

The incidence of hematologic plus solid tumor SPM (excluding squamous cell carcinoma and basal cell carcinoma) was 14.9% in the lenalidomide group and 8.8% in the control group, with a median follow-up of 91.5 months.

Non-melanoma skin cancer SPM, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving lenalidomide maintenance and 2.6% of controls.

Photo courtesy of Celgene

The US Food and Drug Administration (FDA) has approved a new indication for lenalidomide (Revlimid).

The drug is now approved for use as maintenance therapy after autologous hematopoietic stem cell transplant (auto-HSCT) in patients with multiple myeloma (MM).

The expanded indication makes lenalidomide the first treatment to receive FDA approval for maintenance following auto-HSCT.

The drug was previously FDA-approved for use in combination with dexamethasone to treat patients with MM.

Lenalidomide is also FDA-approved to treat patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes associated with deletion 5q, with or without additional cytogenetic abnormalities.

And lenalidomide is FDA-approved to treat patients with mantle cell lymphoma who have relapsed or progressed after 2 prior therapies, one of which included bortezomib.

Lenalidomide is a product of Celgene.

Studies: Lenalidomide maintenance

The latest approval for lenalidomide was based on results of 2 cooperative group-led studies, CALGB 10010410 and IFM 2005-0211.

Results from both studies were published in NEJM in May 2012 (CALGB 100104, IFM 2005-02). The updated data reported here are included in the prescribing information for lenalidomide.

CALGB 100104 was a phase 3, double-blind study of 460 patients with newly diagnosed MM undergoing auto-HSCT. The patients received continuous daily treatment with lenalidomide or placebo until relapse.

IFM 2005-02 was a phase 3, double-blind study of 614 patients newly diagnosed with MM. The patients were randomized to receive a 2-month consolidation regimen after auto-HSCT, which consisted of lenalidomide monotherapy followed by continuous daily treatment with lenalidomide or placebo until relapse.

Survival

In both studies, the primary efficacy endpoint was progression-free survival (PFS). The PFS data for both studies were updated to reflect results as of March 2015.

In the CALGB study, the median PFS was 5.7 years in the lenalidomide arm and 1.9 years in the placebo arm (hazard ratio [HR]=0.38 [95% CI: 0.28-0.50]).

In the IFM study, the median PFS was 3.9 years in the lenalidomide arm and 2 years in the placebo arm (HR=0.53 [95% CI: 0.44-0.64]).

These studies were not powered for an overall survival (OS) endpoint. However, OS was recorded, and the OS data for both studies were updated to reflect results as of February 2016.

The median OS in the CALGB study was 9.3 years in the lenalidomide arm and 7 years in the placebo arm (HR=0.59 [95% CI: 0.44-0.78]).

In the IFM study, the median OS was 8.8 years in the lenalidomide arm and 7.3 years in the placebo arm (HR=0.90 [95% CI: 0.72-1.13]).

Adverse events

The most frequently reported adverse events in ≥20% of patients in the lenalidomide arm across both  studies (CALGB and IFM, respectively) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%).

The most frequently reported grade 3/4 events (more than 20% in the lenalidomide arm) were neutropenia, thrombocytopenia, and leukopenia.

Hematologic second primary malignancies (SPM) occurred in 7.5% of patients receiving lenalidomide maintenance and 3.3% of controls.

The incidence of hematologic plus solid tumor SPM (excluding squamous cell carcinoma and basal cell carcinoma) was 14.9% in the lenalidomide group and 8.8% in the control group, with a median follow-up of 91.5 months.

Non-melanoma skin cancer SPM, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving lenalidomide maintenance and 2.6% of controls.

Photo courtesy of Celgene

The US Food and Drug Administration (FDA) has approved a new indication for lenalidomide (Revlimid).

The drug is now approved for use as maintenance therapy after autologous hematopoietic stem cell transplant (auto-HSCT) in patients with multiple myeloma (MM).

The expanded indication makes lenalidomide the first treatment to receive FDA approval for maintenance following auto-HSCT.

The drug was previously FDA-approved for use in combination with dexamethasone to treat patients with MM.

Lenalidomide is also FDA-approved to treat patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes associated with deletion 5q, with or without additional cytogenetic abnormalities.

And lenalidomide is FDA-approved to treat patients with mantle cell lymphoma who have relapsed or progressed after 2 prior therapies, one of which included bortezomib.

Lenalidomide is a product of Celgene.

Studies: Lenalidomide maintenance

The latest approval for lenalidomide was based on results of 2 cooperative group-led studies, CALGB 10010410 and IFM 2005-0211.

Results from both studies were published in NEJM in May 2012 (CALGB 100104, IFM 2005-02). The updated data reported here are included in the prescribing information for lenalidomide.

CALGB 100104 was a phase 3, double-blind study of 460 patients with newly diagnosed MM undergoing auto-HSCT. The patients received continuous daily treatment with lenalidomide or placebo until relapse.

IFM 2005-02 was a phase 3, double-blind study of 614 patients newly diagnosed with MM. The patients were randomized to receive a 2-month consolidation regimen after auto-HSCT, which consisted of lenalidomide monotherapy followed by continuous daily treatment with lenalidomide or placebo until relapse.

Survival

In both studies, the primary efficacy endpoint was progression-free survival (PFS). The PFS data for both studies were updated to reflect results as of March 2015.

In the CALGB study, the median PFS was 5.7 years in the lenalidomide arm and 1.9 years in the placebo arm (hazard ratio [HR]=0.38 [95% CI: 0.28-0.50]).

In the IFM study, the median PFS was 3.9 years in the lenalidomide arm and 2 years in the placebo arm (HR=0.53 [95% CI: 0.44-0.64]).

These studies were not powered for an overall survival (OS) endpoint. However, OS was recorded, and the OS data for both studies were updated to reflect results as of February 2016.

The median OS in the CALGB study was 9.3 years in the lenalidomide arm and 7 years in the placebo arm (HR=0.59 [95% CI: 0.44-0.78]).

In the IFM study, the median OS was 8.8 years in the lenalidomide arm and 7.3 years in the placebo arm (HR=0.90 [95% CI: 0.72-1.13]).

Adverse events

The most frequently reported adverse events in ≥20% of patients in the lenalidomide arm across both  studies (CALGB and IFM, respectively) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%).

The most frequently reported grade 3/4 events (more than 20% in the lenalidomide arm) were neutropenia, thrombocytopenia, and leukopenia.

Hematologic second primary malignancies (SPM) occurred in 7.5% of patients receiving lenalidomide maintenance and 3.3% of controls.

The incidence of hematologic plus solid tumor SPM (excluding squamous cell carcinoma and basal cell carcinoma) was 14.9% in the lenalidomide group and 8.8% in the control group, with a median follow-up of 91.5 months.

Non-melanoma skin cancer SPM, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving lenalidomide maintenance and 2.6% of controls.

Photo by Bill Branson

ORLANDO, FL—Results of a phase 3 trial suggest an inactivated varicella zoster virus (VZV) vaccine known as V212 can reduce the risk of herpes zoster (HZ) in patients who have undergone autologous hematopoietic stem cell transplant (HSCT).

V212 reduced the hazard rate of HZ by an estimated 64% compared to placebo.

The vaccine also reduced the incidence of moderate-to-severe HZ pain and other HZ-related complications, such as hospitalization.

The overall incidence of adverse events (AEs) and the incidence of serious AEs were similar among vaccinated patients and those who received placebo.

Drew J. Winston, MD, of the University of California Los Angeles Medical Center, presented these results as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 6). The trial was sponsored by Merck, the company developing V212.

Treatment

This randomized, double-blind trial enrolled 1230 patients age 18 and older who were undergoing HSCT for any indication and had a history of varicella infection and/or were seropositive for VZV antibody.

The patients were randomized to receive:

• A 4-dose regimen of V212 (n=560) from a consistency lot (a lot having a targeted potency as required by regulators in order to demonstrate that the vaccine can be manufactured consistently)
• A 4-dose regimen of V212 (n=106) from a high-antigen lot (a lot having a higher antigen potency added to assess the safety profile of V212)
• Placebo (n=564).

Randomization was stratified by age (< 50 years vs ≥ 50 years) and by intended duration of post-transplant antiviral prophylaxis (≤3 months vs >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90 days after HSCT.

Patient characteristics

The median patient age was 57 (range, 19-76) for the consistency lot group, 56 (range, 21-75) for the high-antigen lot group, and 56 (range, 19-79) for the placebo group.

Underlying diseases were non-Hodgkin lymphoma (42%, 40%, and 44%, respectively), Hodgkin lymphoma (10%, 9%, and 9%, respectively), multiple myeloma (44%, 47% and 41%, respectively), acute leukemia (2%, 1%, and 2%, respectively), and “other” diseases (2%, 3% and 4%, respectively).

Roughly 30% of patients in each group received anti-viral agents for 3 months or less after HSCT. Twenty percent to 25% received antiviral therapy for more than 3 months to 6 months.

Thirty-seven percent to 40% received antiviral agents for more than 6 months. And 7% to 12% of patients did not receive any antiviral therapy.

HZ incidence

The average follow-up time for HZ surveillance was approximately 2.3 years (median: 2.6 years) post-vaccination.

Confirmed HZ occurred in 42 of the 538 patients who received V212 from a consistency lot and 113 of the 535 patients who received placebo. (Patients receiving V212 from a high-antigen lot were only included in the safety analysis.)

The estimated efficacy of V212 was 63.8% after adjustment for patient age and the duration of antiviral prophylaxis. Vaccine efficacy against HZ was defined as the relative reduction of hazard rate of HZ in vaccine recipients compared with placebo recipients.

The vaccine met the pre-specified criterion for success, as the lower bound of the 95% confidence interval (CI) was greater than 25%. The 95% CI was 48.4% to 74.6% (P<0.0001).

“The study demonstrates that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr Winston said.

Pain, PHN, and other complications

V212 also reduced the incidence of moderate-to-severe HZ pain—according to the Zoster Brief Pain Inventory (ZBPI) score—by an estimated 69.5% (95% CI, 0.490-0.818).

Nineteen patients in the V212 consistency lot group had moderate-to-severe pain, as did 61 placebo-treated patients.

V212 conferred an estimated 83.7% (95% CI, 0.446-0.952) reduction in the incidence of post-herpetic neuralgia (PHN). Three patients in the V212 consistency lot group and 18 patients in the placebo group had PHN.

PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0-10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following HSCT.

Patients who received V212 also saw an estimated 73.5% (95% CI, 0.498-0.860) reduction in “other” HZ complications. Twelve patients in the V212 consistency group and 44 in the placebo group had such complications.

“Other” complications included hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, and the administration of intravenous acyclovir therapy for the treatment of HZ post-HSCT.

Safety

All patients who received at least 1 dose of the vaccine or placebo and had follow-up data were included in the safety analysis. Patients were followed for AEs up to 28 days after the fourth vaccination dose.

AEs occurred in 97% of patients who received the vaccine (consistency and high-antigen groups assessed together) and 96.9% of placebo-treated patients. Vaccine-related AEs occurred in 32.6% and 12.6%, respectively.

“Of course, in this population of autologous stem cell transplant patients, adverse events of any type were very common in almost all patients,” Dr Winston said. “However, vaccine-related adverse events were greater in the vaccine recipients compared to the placebo patients, but this was primarily due to an increased incidence of injection-site adverse events in the vaccine recipients.”

Injection-site reactions occurred in 191 vaccinated patients and 36 placebo-treated patients.

The most common systemic AEs—in vaccinated and placebo-treated patients, respectively—were diarrhea (60.1% and 61.9%), nausea (56.5% and 57.8%), pyrexia (49.8% and 46.9%), mucosal inflammation (39.7% and 41.7%), thrombocytopenia (36.4% and 38.4%), febrile neutropenia (33.9% and 28.3%), vomiting (32.6% and 36.6%), anemia (26.6% and 24.4%), neutropenia (25.1% and 23.5%), decreased appetite (23.1% and 23.8%), fatigue (21.8% and 20.7%), hypokalemia (21.3% and 19.9%), and constipation (16.1% and 18.4%).

The incidence of serious AEs was 32.9% in vaccinated patients and 32.7% in the placebo group. The incidence of serious vaccine-related AEs was 0.8% and 0.9%, respectively.

The most common serious AEs—in vaccinated and placebo-treated patients, respectively—were infection (12.3% and 11.9%), relapsed malignancy (7.8% for both), febrile neutropenia (5.3% and 4.9%), pyrexia (3.2% and 4.0%), gastrointestinal disorders (3.2% and 3.6%), respiratory failure (2.7% and 2.2%), cardiac disorders (1.7% and 1.6%), and mucositis (1.2% and 0.9%).

Death occurred in 6.2% of vaccinated patients and 6.3% of placebo-treated patients. Three percent and 3.1%, respectively, discontinued the study due to AEs.

Photo by Bill Branson

ORLANDO, FL—Results of a phase 3 trial suggest an inactivated varicella zoster virus (VZV) vaccine known as V212 can reduce the risk of herpes zoster (HZ) in patients who have undergone autologous hematopoietic stem cell transplant (HSCT).

V212 reduced the hazard rate of HZ by an estimated 64% compared to placebo.

The vaccine also reduced the incidence of moderate-to-severe HZ pain and other HZ-related complications, such as hospitalization.

The overall incidence of adverse events (AEs) and the incidence of serious AEs were similar among vaccinated patients and those who received placebo.

Drew J. Winston, MD, of the University of California Los Angeles Medical Center, presented these results as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 6). The trial was sponsored by Merck, the company developing V212.

Treatment

This randomized, double-blind trial enrolled 1230 patients age 18 and older who were undergoing HSCT for any indication and had a history of varicella infection and/or were seropositive for VZV antibody.

The patients were randomized to receive:

• A 4-dose regimen of V212 (n=560) from a consistency lot (a lot having a targeted potency as required by regulators in order to demonstrate that the vaccine can be manufactured consistently)
• A 4-dose regimen of V212 (n=106) from a high-antigen lot (a lot having a higher antigen potency added to assess the safety profile of V212)
• Placebo (n=564).

Randomization was stratified by age (< 50 years vs ≥ 50 years) and by intended duration of post-transplant antiviral prophylaxis (≤3 months vs >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90 days after HSCT.

Patient characteristics

The median patient age was 57 (range, 19-76) for the consistency lot group, 56 (range, 21-75) for the high-antigen lot group, and 56 (range, 19-79) for the placebo group.

Underlying diseases were non-Hodgkin lymphoma (42%, 40%, and 44%, respectively), Hodgkin lymphoma (10%, 9%, and 9%, respectively), multiple myeloma (44%, 47% and 41%, respectively), acute leukemia (2%, 1%, and 2%, respectively), and “other” diseases (2%, 3% and 4%, respectively).

Roughly 30% of patients in each group received anti-viral agents for 3 months or less after HSCT. Twenty percent to 25% received antiviral therapy for more than 3 months to 6 months.

Thirty-seven percent to 40% received antiviral agents for more than 6 months. And 7% to 12% of patients did not receive any antiviral therapy.

HZ incidence

The average follow-up time for HZ surveillance was approximately 2.3 years (median: 2.6 years) post-vaccination.

Confirmed HZ occurred in 42 of the 538 patients who received V212 from a consistency lot and 113 of the 535 patients who received placebo. (Patients receiving V212 from a high-antigen lot were only included in the safety analysis.)

The estimated efficacy of V212 was 63.8% after adjustment for patient age and the duration of antiviral prophylaxis. Vaccine efficacy against HZ was defined as the relative reduction of hazard rate of HZ in vaccine recipients compared with placebo recipients.

The vaccine met the pre-specified criterion for success, as the lower bound of the 95% confidence interval (CI) was greater than 25%. The 95% CI was 48.4% to 74.6% (P<0.0001).

“The study demonstrates that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr Winston said.

Pain, PHN, and other complications

V212 also reduced the incidence of moderate-to-severe HZ pain—according to the Zoster Brief Pain Inventory (ZBPI) score—by an estimated 69.5% (95% CI, 0.490-0.818).

Nineteen patients in the V212 consistency lot group had moderate-to-severe pain, as did 61 placebo-treated patients.

V212 conferred an estimated 83.7% (95% CI, 0.446-0.952) reduction in the incidence of post-herpetic neuralgia (PHN). Three patients in the V212 consistency lot group and 18 patients in the placebo group had PHN.

PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0-10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following HSCT.

Patients who received V212 also saw an estimated 73.5% (95% CI, 0.498-0.860) reduction in “other” HZ complications. Twelve patients in the V212 consistency group and 44 in the placebo group had such complications.

“Other” complications included hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, and the administration of intravenous acyclovir therapy for the treatment of HZ post-HSCT.

Safety

All patients who received at least 1 dose of the vaccine or placebo and had follow-up data were included in the safety analysis. Patients were followed for AEs up to 28 days after the fourth vaccination dose.

AEs occurred in 97% of patients who received the vaccine (consistency and high-antigen groups assessed together) and 96.9% of placebo-treated patients. Vaccine-related AEs occurred in 32.6% and 12.6%, respectively.

“Of course, in this population of autologous stem cell transplant patients, adverse events of any type were very common in almost all patients,” Dr Winston said. “However, vaccine-related adverse events were greater in the vaccine recipients compared to the placebo patients, but this was primarily due to an increased incidence of injection-site adverse events in the vaccine recipients.”

Injection-site reactions occurred in 191 vaccinated patients and 36 placebo-treated patients.

The most common systemic AEs—in vaccinated and placebo-treated patients, respectively—were diarrhea (60.1% and 61.9%), nausea (56.5% and 57.8%), pyrexia (49.8% and 46.9%), mucosal inflammation (39.7% and 41.7%), thrombocytopenia (36.4% and 38.4%), febrile neutropenia (33.9% and 28.3%), vomiting (32.6% and 36.6%), anemia (26.6% and 24.4%), neutropenia (25.1% and 23.5%), decreased appetite (23.1% and 23.8%), fatigue (21.8% and 20.7%), hypokalemia (21.3% and 19.9%), and constipation (16.1% and 18.4%).

The incidence of serious AEs was 32.9% in vaccinated patients and 32.7% in the placebo group. The incidence of serious vaccine-related AEs was 0.8% and 0.9%, respectively.

The most common serious AEs—in vaccinated and placebo-treated patients, respectively—were infection (12.3% and 11.9%), relapsed malignancy (7.8% for both), febrile neutropenia (5.3% and 4.9%), pyrexia (3.2% and 4.0%), gastrointestinal disorders (3.2% and 3.6%), respiratory failure (2.7% and 2.2%), cardiac disorders (1.7% and 1.6%), and mucositis (1.2% and 0.9%).

Death occurred in 6.2% of vaccinated patients and 6.3% of placebo-treated patients. Three percent and 3.1%, respectively, discontinued the study due to AEs.

Photo by Bill Branson

ORLANDO, FL—Results of a phase 3 trial suggest an inactivated varicella zoster virus (VZV) vaccine known as V212 can reduce the risk of herpes zoster (HZ) in patients who have undergone autologous hematopoietic stem cell transplant (HSCT).

V212 reduced the hazard rate of HZ by an estimated 64% compared to placebo.

The vaccine also reduced the incidence of moderate-to-severe HZ pain and other HZ-related complications, such as hospitalization.

The overall incidence of adverse events (AEs) and the incidence of serious AEs were similar among vaccinated patients and those who received placebo.

Drew J. Winston, MD, of the University of California Los Angeles Medical Center, presented these results as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 6). The trial was sponsored by Merck, the company developing V212.

Treatment

This randomized, double-blind trial enrolled 1230 patients age 18 and older who were undergoing HSCT for any indication and had a history of varicella infection and/or were seropositive for VZV antibody.

The patients were randomized to receive:

• A 4-dose regimen of V212 (n=560) from a consistency lot (a lot having a targeted potency as required by regulators in order to demonstrate that the vaccine can be manufactured consistently)
• A 4-dose regimen of V212 (n=106) from a high-antigen lot (a lot having a higher antigen potency added to assess the safety profile of V212)
• Placebo (n=564).

Randomization was stratified by age (< 50 years vs ≥ 50 years) and by intended duration of post-transplant antiviral prophylaxis (≤3 months vs >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90 days after HSCT.

Patient characteristics

The median patient age was 57 (range, 19-76) for the consistency lot group, 56 (range, 21-75) for the high-antigen lot group, and 56 (range, 19-79) for the placebo group.

Underlying diseases were non-Hodgkin lymphoma (42%, 40%, and 44%, respectively), Hodgkin lymphoma (10%, 9%, and 9%, respectively), multiple myeloma (44%, 47% and 41%, respectively), acute leukemia (2%, 1%, and 2%, respectively), and “other” diseases (2%, 3% and 4%, respectively).

Roughly 30% of patients in each group received anti-viral agents for 3 months or less after HSCT. Twenty percent to 25% received antiviral therapy for more than 3 months to 6 months.

Thirty-seven percent to 40% received antiviral agents for more than 6 months. And 7% to 12% of patients did not receive any antiviral therapy.

HZ incidence

The average follow-up time for HZ surveillance was approximately 2.3 years (median: 2.6 years) post-vaccination.

Confirmed HZ occurred in 42 of the 538 patients who received V212 from a consistency lot and 113 of the 535 patients who received placebo. (Patients receiving V212 from a high-antigen lot were only included in the safety analysis.)

The estimated efficacy of V212 was 63.8% after adjustment for patient age and the duration of antiviral prophylaxis. Vaccine efficacy against HZ was defined as the relative reduction of hazard rate of HZ in vaccine recipients compared with placebo recipients.

The vaccine met the pre-specified criterion for success, as the lower bound of the 95% confidence interval (CI) was greater than 25%. The 95% CI was 48.4% to 74.6% (P<0.0001).

“The study demonstrates that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr Winston said.

Pain, PHN, and other complications

V212 also reduced the incidence of moderate-to-severe HZ pain—according to the Zoster Brief Pain Inventory (ZBPI) score—by an estimated 69.5% (95% CI, 0.490-0.818).

Nineteen patients in the V212 consistency lot group had moderate-to-severe pain, as did 61 placebo-treated patients.

V212 conferred an estimated 83.7% (95% CI, 0.446-0.952) reduction in the incidence of post-herpetic neuralgia (PHN). Three patients in the V212 consistency lot group and 18 patients in the placebo group had PHN.

PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0-10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following HSCT.

Patients who received V212 also saw an estimated 73.5% (95% CI, 0.498-0.860) reduction in “other” HZ complications. Twelve patients in the V212 consistency group and 44 in the placebo group had such complications.

“Other” complications included hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, and the administration of intravenous acyclovir therapy for the treatment of HZ post-HSCT.

Safety

All patients who received at least 1 dose of the vaccine or placebo and had follow-up data were included in the safety analysis. Patients were followed for AEs up to 28 days after the fourth vaccination dose.

AEs occurred in 97% of patients who received the vaccine (consistency and high-antigen groups assessed together) and 96.9% of placebo-treated patients. Vaccine-related AEs occurred in 32.6% and 12.6%, respectively.

“Of course, in this population of autologous stem cell transplant patients, adverse events of any type were very common in almost all patients,” Dr Winston said. “However, vaccine-related adverse events were greater in the vaccine recipients compared to the placebo patients, but this was primarily due to an increased incidence of injection-site adverse events in the vaccine recipients.”

Injection-site reactions occurred in 191 vaccinated patients and 36 placebo-treated patients.

The most common systemic AEs—in vaccinated and placebo-treated patients, respectively—were diarrhea (60.1% and 61.9%), nausea (56.5% and 57.8%), pyrexia (49.8% and 46.9%), mucosal inflammation (39.7% and 41.7%), thrombocytopenia (36.4% and 38.4%), febrile neutropenia (33.9% and 28.3%), vomiting (32.6% and 36.6%), anemia (26.6% and 24.4%), neutropenia (25.1% and 23.5%), decreased appetite (23.1% and 23.8%), fatigue (21.8% and 20.7%), hypokalemia (21.3% and 19.9%), and constipation (16.1% and 18.4%).

The incidence of serious AEs was 32.9% in vaccinated patients and 32.7% in the placebo group. The incidence of serious vaccine-related AEs was 0.8% and 0.9%, respectively.

The most common serious AEs—in vaccinated and placebo-treated patients, respectively—were infection (12.3% and 11.9%), relapsed malignancy (7.8% for both), febrile neutropenia (5.3% and 4.9%), pyrexia (3.2% and 4.0%), gastrointestinal disorders (3.2% and 3.6%), respiratory failure (2.7% and 2.2%), cardiac disorders (1.7% and 1.6%), and mucositis (1.2% and 0.9%).

Death occurred in 6.2% of vaccinated patients and 6.3% of placebo-treated patients. Three percent and 3.1%, respectively, discontinued the study due to AEs.

Kristyna Wentz-Graff

A newly discovered issue with the Ba/F3 transformation assay could “jeopardize attempts to characterize the signaling mechanisms and drug sensitivities of leukemic oncogenes,” researchers reported in Oncotarget.

The researchers said the assay “remains an invaluable tool” for validating activating mutations in primary leukemias.

However, the assay is prone to a previously unreported flaw, where Ba/F3 cells can acquire additional mutations.

This issue was discovered by Kevin Watanabe-Smith, PhD, of Oregon Health & Science University in Portland.

He identified the problem while studying a growth-activating mutation in a patient with T-cell leukemia. (The results of that research were published in Leukemia in April 2016).

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there,” Dr Watanabe-Smith said. “And I was getting different mutations every time.”

“After we saw this in several cases, we knew it was worth further study,” added Cristina Tognon, PhD, of Oregon Health & Science University.

So the researchers decided to study Ba/F3 cell lines with and without 4 mutations (found in 3 cytokine receptors) that have “known transformative capacity,” including:

• CSF2RB R461C, a germline mutation found in a patient with T-cell acute lymphoblastic leukemia (ALL)
• CSF3R T618I, a mutation found in chronic neutrophilic leukemia (CNL) and atypical chronic myelogenous leukemia (aCML)
• CSF3R W791X, also found in CNL and aCML
• IL7R 243InsPPCL, which was found in a patient with B-cell ALL.

The researchers said they observed acquired mutations in 1 of 3 CSF2RB wild-type cell lines that transformed and all 4 CSF3R wild-type cell lines, which all transformed.

Furthermore, most CSF2RB R461C lines (4/5) and CSF3R W791X lines (3/4) had additional acquired mutations. However, the CSF3R T618I lines and the IL7R 243InsPPCL lines did not contain acquired mutations.

The researchers said acquired mutations were observed only in weakly transforming oncogenes, which were defined as mutations with a weaker ability to transform cells (less than 1 in every 200 cells) or a slower time to outgrowth (5 days or longer to reach a 5-fold increase over the initial cell number).

The team also said their findings indicate that the majority of the acquired mutations likely exist before IL-3 withdrawal but only expand to levels detectable by Sanger sequencing in the absence of IL-3.

“The potential impact [of these acquired mutations] is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Dr Watanabe-Smith said.

To overcome this problem, Dr Watanabe-Smith and his colleagues recommended taking an additional step when using the Ba/F3 assay—sequencing outgrown cell lines. They also said additional research is needed to devise methods that reduce the incidence of acquired mutations in such assays. 

Kristyna Wentz-Graff

A newly discovered issue with the Ba/F3 transformation assay could “jeopardize attempts to characterize the signaling mechanisms and drug sensitivities of leukemic oncogenes,” researchers reported in Oncotarget.

The researchers said the assay “remains an invaluable tool” for validating activating mutations in primary leukemias.

However, the assay is prone to a previously unreported flaw, where Ba/F3 cells can acquire additional mutations.

This issue was discovered by Kevin Watanabe-Smith, PhD, of Oregon Health & Science University in Portland.

He identified the problem while studying a growth-activating mutation in a patient with T-cell leukemia. (The results of that research were published in Leukemia in April 2016).

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there,” Dr Watanabe-Smith said. “And I was getting different mutations every time.”

“After we saw this in several cases, we knew it was worth further study,” added Cristina Tognon, PhD, of Oregon Health & Science University.

So the researchers decided to study Ba/F3 cell lines with and without 4 mutations (found in 3 cytokine receptors) that have “known transformative capacity,” including:

• CSF2RB R461C, a germline mutation found in a patient with T-cell acute lymphoblastic leukemia (ALL)
• CSF3R T618I, a mutation found in chronic neutrophilic leukemia (CNL) and atypical chronic myelogenous leukemia (aCML)
• CSF3R W791X, also found in CNL and aCML
• IL7R 243InsPPCL, which was found in a patient with B-cell ALL.

The researchers said they observed acquired mutations in 1 of 3 CSF2RB wild-type cell lines that transformed and all 4 CSF3R wild-type cell lines, which all transformed.

Furthermore, most CSF2RB R461C lines (4/5) and CSF3R W791X lines (3/4) had additional acquired mutations. However, the CSF3R T618I lines and the IL7R 243InsPPCL lines did not contain acquired mutations.

The researchers said acquired mutations were observed only in weakly transforming oncogenes, which were defined as mutations with a weaker ability to transform cells (less than 1 in every 200 cells) or a slower time to outgrowth (5 days or longer to reach a 5-fold increase over the initial cell number).

The team also said their findings indicate that the majority of the acquired mutations likely exist before IL-3 withdrawal but only expand to levels detectable by Sanger sequencing in the absence of IL-3.

“The potential impact [of these acquired mutations] is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Dr Watanabe-Smith said.

To overcome this problem, Dr Watanabe-Smith and his colleagues recommended taking an additional step when using the Ba/F3 assay—sequencing outgrown cell lines. They also said additional research is needed to devise methods that reduce the incidence of acquired mutations in such assays. 

Kristyna Wentz-Graff

A newly discovered issue with the Ba/F3 transformation assay could “jeopardize attempts to characterize the signaling mechanisms and drug sensitivities of leukemic oncogenes,” researchers reported in Oncotarget.

The researchers said the assay “remains an invaluable tool” for validating activating mutations in primary leukemias.

However, the assay is prone to a previously unreported flaw, where Ba/F3 cells can acquire additional mutations.

This issue was discovered by Kevin Watanabe-Smith, PhD, of Oregon Health & Science University in Portland.

He identified the problem while studying a growth-activating mutation in a patient with T-cell leukemia. (The results of that research were published in Leukemia in April 2016).

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there,” Dr Watanabe-Smith said. “And I was getting different mutations every time.”

“After we saw this in several cases, we knew it was worth further study,” added Cristina Tognon, PhD, of Oregon Health & Science University.

So the researchers decided to study Ba/F3 cell lines with and without 4 mutations (found in 3 cytokine receptors) that have “known transformative capacity,” including:

• CSF2RB R461C, a germline mutation found in a patient with T-cell acute lymphoblastic leukemia (ALL)
• CSF3R T618I, a mutation found in chronic neutrophilic leukemia (CNL) and atypical chronic myelogenous leukemia (aCML)
• CSF3R W791X, also found in CNL and aCML
• IL7R 243InsPPCL, which was found in a patient with B-cell ALL.

The researchers said they observed acquired mutations in 1 of 3 CSF2RB wild-type cell lines that transformed and all 4 CSF3R wild-type cell lines, which all transformed.

Furthermore, most CSF2RB R461C lines (4/5) and CSF3R W791X lines (3/4) had additional acquired mutations. However, the CSF3R T618I lines and the IL7R 243InsPPCL lines did not contain acquired mutations.

The researchers said acquired mutations were observed only in weakly transforming oncogenes, which were defined as mutations with a weaker ability to transform cells (less than 1 in every 200 cells) or a slower time to outgrowth (5 days or longer to reach a 5-fold increase over the initial cell number).

The team also said their findings indicate that the majority of the acquired mutations likely exist before IL-3 withdrawal but only expand to levels detectable by Sanger sequencing in the absence of IL-3.

“The potential impact [of these acquired mutations] is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Dr Watanabe-Smith said.

To overcome this problem, Dr Watanabe-Smith and his colleagues recommended taking an additional step when using the Ba/F3 assay—sequencing outgrown cell lines. They also said additional research is needed to devise methods that reduce the incidence of acquired mutations in such assays. 

Image from CDC/Mae Melvin

An investigational malaria vaccine can protect healthy adults from infection with a malaria strain different from that contained in the vaccine, according to a phase 1 study published in PNAS.

The vaccine, known as the PfSPZ Vaccine, contains weakened Plasmodium falciparum sporozoites that are able to generate a protective immune response against live malaria infection.

Prior research showed that the PfSPZ Vaccine can provide long-term protection against a single malaria strain matched to the vaccine.

The new study has shown that the PfSPZ Vaccine can protect against a different strain of P falciparum as well.

“An effective malaria vaccine will need to protect people living in endemic areas against multiple strains of the mosquito-borne disease,” said Anthony S. Fauci, MD, of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

“These new findings showing cross-protection with the PfSPZ Vaccine suggest that it may be able to accomplish this goal.”

The PfSPZ Vaccine was developed by Sanaria Inc. The company designed, manufactured, and provided PfSPZ Vaccine and the heterologous challenge mosquitoes for this trial. The NIAID supported the development of the vaccine through several grants.

Study details

The study enrolled 31 healthy, malaria-naive adults ages 19 to 45.

Fifteen subjects were scheduled to receive 3 doses of the PfSPZ Vaccine—9.0 × 10⁵ PfSPZ administered intravenously 3 times at 8-week intervals. The remaining subjects served as controls.

Nineteen weeks after receiving the final dose of the test vaccine, vaccinated subjects and controls were exposed to bites from mosquitoes infected with the same strain of P falciparum parasites (NF54) that were used to manufacture PfSPZ Vaccine.

Nine of the 14 subjects (64%) who received PfSPZ Vaccine demonstrated no evidence of malaria parasites. All 6 of the non-vaccinated subjects who were challenged at the same time had malaria parasites in their blood.

Of the 9 subjects who showed no evidence of malaria, 6 subjects were again exposed to mosquito bites, this time from mosquitoes infected with a different strain of P falciparum (Pf7G8), 33 weeks after the final immunization.

In this group, 5 of the 6 subjects (83%) were protected against malaria infection. None of the 6 control subjects who were challenged were protected.

“Achieving durable protection against a malaria strain different from the vaccine strain, over 8 months after vaccination, is an indication of this vaccine’s potential,” said Robert A. Seder, MD, of NIAID.

“If we can build on these findings with the PfSPZ Vaccine and induce higher efficacy, we may be on our way to a vaccine that could effectively protect people against a variety of malaria parasites where the disease is prevalent.”

The researchers found the PfSPZ Vaccine activated T cells and induced antibody responses in all vaccine recipients. Vaccine-specific T-cell responses were comparable when measured against both malaria challenge strains, providing some insight into how the vaccine was mediating protection.

Ongoing research should determine whether protective efficacy can be improved by changes to the PfSPZ Vaccine dose and number of immunizations.

A phase 2 trial testing 3 different dosages in a 3-dose vaccine regimen is now underway in 5-to 12-month-old infants in Western Kenya to assess safety and efficacy of the vaccine against natural infection.

Image from CDC/Mae Melvin

An investigational malaria vaccine can protect healthy adults from infection with a malaria strain different from that contained in the vaccine, according to a phase 1 study published in PNAS.

The vaccine, known as the PfSPZ Vaccine, contains weakened Plasmodium falciparum sporozoites that are able to generate a protective immune response against live malaria infection.

Prior research showed that the PfSPZ Vaccine can provide long-term protection against a single malaria strain matched to the vaccine.

The new study has shown that the PfSPZ Vaccine can protect against a different strain of P falciparum as well.

“An effective malaria vaccine will need to protect people living in endemic areas against multiple strains of the mosquito-borne disease,” said Anthony S. Fauci, MD, of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

“These new findings showing cross-protection with the PfSPZ Vaccine suggest that it may be able to accomplish this goal.”

The PfSPZ Vaccine was developed by Sanaria Inc. The company designed, manufactured, and provided PfSPZ Vaccine and the heterologous challenge mosquitoes for this trial. The NIAID supported the development of the vaccine through several grants.

Study details

The study enrolled 31 healthy, malaria-naive adults ages 19 to 45.

Fifteen subjects were scheduled to receive 3 doses of the PfSPZ Vaccine—9.0 × 10⁵ PfSPZ administered intravenously 3 times at 8-week intervals. The remaining subjects served as controls.

Nineteen weeks after receiving the final dose of the test vaccine, vaccinated subjects and controls were exposed to bites from mosquitoes infected with the same strain of P falciparum parasites (NF54) that were used to manufacture PfSPZ Vaccine.

Nine of the 14 subjects (64%) who received PfSPZ Vaccine demonstrated no evidence of malaria parasites. All 6 of the non-vaccinated subjects who were challenged at the same time had malaria parasites in their blood.

Of the 9 subjects who showed no evidence of malaria, 6 subjects were again exposed to mosquito bites, this time from mosquitoes infected with a different strain of P falciparum (Pf7G8), 33 weeks after the final immunization.

In this group, 5 of the 6 subjects (83%) were protected against malaria infection. None of the 6 control subjects who were challenged were protected.

“Achieving durable protection against a malaria strain different from the vaccine strain, over 8 months after vaccination, is an indication of this vaccine’s potential,” said Robert A. Seder, MD, of NIAID.

“If we can build on these findings with the PfSPZ Vaccine and induce higher efficacy, we may be on our way to a vaccine that could effectively protect people against a variety of malaria parasites where the disease is prevalent.”

The researchers found the PfSPZ Vaccine activated T cells and induced antibody responses in all vaccine recipients. Vaccine-specific T-cell responses were comparable when measured against both malaria challenge strains, providing some insight into how the vaccine was mediating protection.

Ongoing research should determine whether protective efficacy can be improved by changes to the PfSPZ Vaccine dose and number of immunizations.

A phase 2 trial testing 3 different dosages in a 3-dose vaccine regimen is now underway in 5-to 12-month-old infants in Western Kenya to assess safety and efficacy of the vaccine against natural infection.

Image from CDC/Mae Melvin

An investigational malaria vaccine can protect healthy adults from infection with a malaria strain different from that contained in the vaccine, according to a phase 1 study published in PNAS.

The vaccine, known as the PfSPZ Vaccine, contains weakened Plasmodium falciparum sporozoites that are able to generate a protective immune response against live malaria infection.

Prior research showed that the PfSPZ Vaccine can provide long-term protection against a single malaria strain matched to the vaccine.

The new study has shown that the PfSPZ Vaccine can protect against a different strain of P falciparum as well.

“An effective malaria vaccine will need to protect people living in endemic areas against multiple strains of the mosquito-borne disease,” said Anthony S. Fauci, MD, of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

“These new findings showing cross-protection with the PfSPZ Vaccine suggest that it may be able to accomplish this goal.”

The PfSPZ Vaccine was developed by Sanaria Inc. The company designed, manufactured, and provided PfSPZ Vaccine and the heterologous challenge mosquitoes for this trial. The NIAID supported the development of the vaccine through several grants.

Study details

The study enrolled 31 healthy, malaria-naive adults ages 19 to 45.

Fifteen subjects were scheduled to receive 3 doses of the PfSPZ Vaccine—9.0 × 10⁵ PfSPZ administered intravenously 3 times at 8-week intervals. The remaining subjects served as controls.

Nineteen weeks after receiving the final dose of the test vaccine, vaccinated subjects and controls were exposed to bites from mosquitoes infected with the same strain of P falciparum parasites (NF54) that were used to manufacture PfSPZ Vaccine.

Nine of the 14 subjects (64%) who received PfSPZ Vaccine demonstrated no evidence of malaria parasites. All 6 of the non-vaccinated subjects who were challenged at the same time had malaria parasites in their blood.

Of the 9 subjects who showed no evidence of malaria, 6 subjects were again exposed to mosquito bites, this time from mosquitoes infected with a different strain of P falciparum (Pf7G8), 33 weeks after the final immunization.

In this group, 5 of the 6 subjects (83%) were protected against malaria infection. None of the 6 control subjects who were challenged were protected.

“Achieving durable protection against a malaria strain different from the vaccine strain, over 8 months after vaccination, is an indication of this vaccine’s potential,” said Robert A. Seder, MD, of NIAID.

“If we can build on these findings with the PfSPZ Vaccine and induce higher efficacy, we may be on our way to a vaccine that could effectively protect people against a variety of malaria parasites where the disease is prevalent.”

The researchers found the PfSPZ Vaccine activated T cells and induced antibody responses in all vaccine recipients. Vaccine-specific T-cell responses were comparable when measured against both malaria challenge strains, providing some insight into how the vaccine was mediating protection.

Ongoing research should determine whether protective efficacy can be improved by changes to the PfSPZ Vaccine dose and number of immunizations.

A phase 2 trial testing 3 different dosages in a 3-dose vaccine regimen is now underway in 5-to 12-month-old infants in Western Kenya to assess safety and efficacy of the vaccine against natural infection.

Seventh Sense Biosystems

The US Food and Drug Administration (FDA) has granted 510(k) clearance for a push-button blood collection device called TAP.

It provides “virtually painless, simple, and fast” blood collection, according to Seventh Sense Biosystems, Inc., the company marketing the device.

The FDA clearance allows healthcare workers to use TAP only for the collection of capillary blood for hemoglobin A1c testing.

However, Seventh Sense Biosystems said it is working with the FDA to expand the use of TAP to add additional tests, as well as at-home blood collection.

How TAP works

The TAP device is placed on a patient’s upper arm, and blood collection starts with the press of a button. The process typically takes 2 to 3 minutes.

When TAP is placed on the arm, the base of the device generates a seal with the skin to create a vacuum. When the user presses the button, TAP deploys microneedles that puncture the skin above the dermis.

The vacuum draws capillary blood out of the micropunctures and through microfluidic channels into a collection chamber prefilled with lithium heparin.

TAP collects up to 100 μL of blood. To transfer the blood to an analyzer, a precision pipette is placed in an access port at the bottom of the device.

Seventh Sense Biosystems said it will launch TAP over the coming months. For up-to-date information, visit www.7sbio.com. 

Seventh Sense Biosystems

The US Food and Drug Administration (FDA) has granted 510(k) clearance for a push-button blood collection device called TAP.

It provides “virtually painless, simple, and fast” blood collection, according to Seventh Sense Biosystems, Inc., the company marketing the device.

The FDA clearance allows healthcare workers to use TAP only for the collection of capillary blood for hemoglobin A1c testing.

However, Seventh Sense Biosystems said it is working with the FDA to expand the use of TAP to add additional tests, as well as at-home blood collection.

How TAP works

The TAP device is placed on a patient’s upper arm, and blood collection starts with the press of a button. The process typically takes 2 to 3 minutes.

When TAP is placed on the arm, the base of the device generates a seal with the skin to create a vacuum. When the user presses the button, TAP deploys microneedles that puncture the skin above the dermis.

The vacuum draws capillary blood out of the micropunctures and through microfluidic channels into a collection chamber prefilled with lithium heparin.

TAP collects up to 100 μL of blood. To transfer the blood to an analyzer, a precision pipette is placed in an access port at the bottom of the device.

Seventh Sense Biosystems said it will launch TAP over the coming months. For up-to-date information, visit www.7sbio.com. 

Seventh Sense Biosystems

The US Food and Drug Administration (FDA) has granted 510(k) clearance for a push-button blood collection device called TAP.

It provides “virtually painless, simple, and fast” blood collection, according to Seventh Sense Biosystems, Inc., the company marketing the device.

The FDA clearance allows healthcare workers to use TAP only for the collection of capillary blood for hemoglobin A1c testing.

However, Seventh Sense Biosystems said it is working with the FDA to expand the use of TAP to add additional tests, as well as at-home blood collection.

How TAP works

The TAP device is placed on a patient’s upper arm, and blood collection starts with the press of a button. The process typically takes 2 to 3 minutes.

When TAP is placed on the arm, the base of the device generates a seal with the skin to create a vacuum. When the user presses the button, TAP deploys microneedles that puncture the skin above the dermis.

The vacuum draws capillary blood out of the micropunctures and through microfluidic channels into a collection chamber prefilled with lithium heparin.

TAP collects up to 100 μL of blood. To transfer the blood to an analyzer, a precision pipette is placed in an access port at the bottom of the device.

Seventh Sense Biosystems said it will launch TAP over the coming months. For up-to-date information, visit www.7sbio.com. 

Photo by Rhoda Baer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiemetic agent rolapitant (Varuby) as a treatment for adults with cancer.

The drug is intended to be used in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.

The CHMP’s recommendation regarding rolapitant has been forwarded to the European Commission, which is expected to make a decision about the drug within 2 months.

If the commission authorizes marketing of rolapitant, the drug will be available as 90 mg film-coated tablets.

The applicant for rolapitant is Tesaro UK Limited.

Rolapitant clinical trials

Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).

The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.

Highly emetogenic chemotherapy

The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were published in The Lancet Oncology in August 2015.

Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.

In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).

In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).

The most common adverse events (in the rolapitant and control groups, respectively) were neutropenia (9% and 8%), hiccups (5% and 4%), and abdominal pain (3% and 2%).

Moderately emetogenic chemotherapy

Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy. Results from this trial were also published in The Lancet Oncology in August 2015.

This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).

The most common adverse events (in the rolapitant and control groups, respectively) were decreased appetite (9% and 7%), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).

Photo by Rhoda Baer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiemetic agent rolapitant (Varuby) as a treatment for adults with cancer.

The drug is intended to be used in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.

The CHMP’s recommendation regarding rolapitant has been forwarded to the European Commission, which is expected to make a decision about the drug within 2 months.

If the commission authorizes marketing of rolapitant, the drug will be available as 90 mg film-coated tablets.

The applicant for rolapitant is Tesaro UK Limited.

Rolapitant clinical trials

Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).

The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.

Highly emetogenic chemotherapy

The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were published in The Lancet Oncology in August 2015.

Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.

In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).

In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).

The most common adverse events (in the rolapitant and control groups, respectively) were neutropenia (9% and 8%), hiccups (5% and 4%), and abdominal pain (3% and 2%).

Moderately emetogenic chemotherapy

Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy. Results from this trial were also published in The Lancet Oncology in August 2015.

This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).

The most common adverse events (in the rolapitant and control groups, respectively) were decreased appetite (9% and 7%), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).

Photo by Rhoda Baer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiemetic agent rolapitant (Varuby) as a treatment for adults with cancer.

The drug is intended to be used in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.

The CHMP’s recommendation regarding rolapitant has been forwarded to the European Commission, which is expected to make a decision about the drug within 2 months.

If the commission authorizes marketing of rolapitant, the drug will be available as 90 mg film-coated tablets.

The applicant for rolapitant is Tesaro UK Limited.

Rolapitant clinical trials

Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).

The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.

Highly emetogenic chemotherapy

The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were published in The Lancet Oncology in August 2015.

Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.

In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).

In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).

The most common adverse events (in the rolapitant and control groups, respectively) were neutropenia (9% and 8%), hiccups (5% and 4%), and abdominal pain (3% and 2%).

Moderately emetogenic chemotherapy

Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy. Results from this trial were also published in The Lancet Oncology in August 2015.

This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).

The most common adverse events (in the rolapitant and control groups, respectively) were decreased appetite (9% and 7%), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Roteas receive marketing authorization for the same indications as Lixiana.

Both Roteas and Lixiana are oral factor Xa inhibitors that contain the active ingredient edoxaban.

The CHMP has recommended approving Roteas for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

In addition, the CHMP has recommended approving Roteas for the prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation (NVAF) who have 1 or more risk factors, such as congestive heart failure, hypertension, age of 75 or older, diabetes mellitus, prior stroke, or transient ischemic attack.

The European Commission approved Lixiana for these indications in June 2015.

If the European Commission decides to approve Roteas as well, the product will be available as film-coated tablets (15 mg, 30 mg, and 60 mg).

The European Commission is expected to make a decision about Roteas within 67 days from the CHMP’s adoption of its opinion (which occurred on February 23).

The application for Roteas was an informed consent application. In this type of application, reference is made to an authorized medicine if the marketing authorization holder of the reference medicine has given consent to the use of their dossier in the application procedure.

The applicant for Roteas is Daiichi Sankyo Europe GmbH, the company that also developed Lixiana.

Lixiana was approved based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.

Hokusai-VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic DVT/PE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).

ENGAGE-AF TIMI 48

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Roteas receive marketing authorization for the same indications as Lixiana.

Both Roteas and Lixiana are oral factor Xa inhibitors that contain the active ingredient edoxaban.

The CHMP has recommended approving Roteas for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

In addition, the CHMP has recommended approving Roteas for the prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation (NVAF) who have 1 or more risk factors, such as congestive heart failure, hypertension, age of 75 or older, diabetes mellitus, prior stroke, or transient ischemic attack.

The European Commission approved Lixiana for these indications in June 2015.

If the European Commission decides to approve Roteas as well, the product will be available as film-coated tablets (15 mg, 30 mg, and 60 mg).

The European Commission is expected to make a decision about Roteas within 67 days from the CHMP’s adoption of its opinion (which occurred on February 23).

The application for Roteas was an informed consent application. In this type of application, reference is made to an authorized medicine if the marketing authorization holder of the reference medicine has given consent to the use of their dossier in the application procedure.

The applicant for Roteas is Daiichi Sankyo Europe GmbH, the company that also developed Lixiana.

Lixiana was approved based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.

Hokusai-VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic DVT/PE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).

ENGAGE-AF TIMI 48

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Roteas receive marketing authorization for the same indications as Lixiana.

Both Roteas and Lixiana are oral factor Xa inhibitors that contain the active ingredient edoxaban.

The CHMP has recommended approving Roteas for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

In addition, the CHMP has recommended approving Roteas for the prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation (NVAF) who have 1 or more risk factors, such as congestive heart failure, hypertension, age of 75 or older, diabetes mellitus, prior stroke, or transient ischemic attack.

The European Commission approved Lixiana for these indications in June 2015.

If the European Commission decides to approve Roteas as well, the product will be available as film-coated tablets (15 mg, 30 mg, and 60 mg).

The European Commission is expected to make a decision about Roteas within 67 days from the CHMP’s adoption of its opinion (which occurred on February 23).

The application for Roteas was an informed consent application. In this type of application, reference is made to an authorized medicine if the marketing authorization holder of the reference medicine has given consent to the use of their dossier in the application procedure.

The applicant for Roteas is Daiichi Sankyo Europe GmbH, the company that also developed Lixiana.

Lixiana was approved based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.

Hokusai-VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic DVT/PE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).

ENGAGE-AF TIMI 48

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Daratumumab (Darzalex) Photo courtesy of Janssen

The CHMP recommended approving daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone as treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation has been forwarded to the European Commission, which is expected to make its decision on daratumumab within 2 months.

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

Phase 3 trials

The CHMP’s recommendation regarding daratumumab was based on data from the phase 3 POLLUX and CASTOR trials.

In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.

Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.

However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.

Results from this trial were published in NEJM in October 2016.

In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.

Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.

Results from this trial were published in NEJM in August 2016.

Daratumumab (Darzalex) Photo courtesy of Janssen

The CHMP recommended approving daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone as treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation has been forwarded to the European Commission, which is expected to make its decision on daratumumab within 2 months.

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

Phase 3 trials

The CHMP’s recommendation regarding daratumumab was based on data from the phase 3 POLLUX and CASTOR trials.

In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.

Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.

However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.

Results from this trial were published in NEJM in October 2016.

In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.

Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.

Results from this trial were published in NEJM in August 2016.

Daratumumab (Darzalex) Photo courtesy of Janssen

The CHMP recommended approving daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone as treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation has been forwarded to the European Commission, which is expected to make its decision on daratumumab within 2 months.

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

Phase 3 trials

The CHMP’s recommendation regarding daratumumab was based on data from the phase 3 POLLUX and CASTOR trials.

In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.

Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.

However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.

Results from this trial were published in NEJM in October 2016.

In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.

Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.

Results from this trial were published in NEJM in August 2016.

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Children’s Research Hospital

Researchers have identified the first known case of artemisinin-resistant malaria originating in Africa, according to a letter published in NEJM.

Resistant Plasmodium falciparum parasites were detected in a Chinese man who had travelled from Equatorial Guinea to China.

The finding means Africa has joined Southeast Asia in hosting parasites that are partially resistant to the first-line antimalaria drug, artemisinin.

Researchers were able to confirm that the parasites in the current case carried a new mutation in the Kelch13 (K13) gene, the main driver for artemisinin resistance in Asia.

Then, the team set out to determine whether the parasite originated from Africa or Southeast Asia.

“We used whole-genome sequencing and bioinformatics tools we had previously developed—like detectives trying to link the culprit parasite to the crime scene,” explained Arnab Pain, PhD, of King Abdullah University of Science and Technology in Thuwal, Saudi Arabia.

Sequencing and analysis of P falciparum DNA unveiled its origin by disclosing the single nucleotide polymorphisms that vary according to the geographical source of the strain.

The researchers used the nuclear DNA, as well as the one present in 2 organelles of the parasite—the mitochondrium and the apicoplast.

Both methods independently validated the origin of the parasite as West African, confirming the first case of artemisinin resistance mediated by a K13 gene mutation on the African continent.

“The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT [artemisinin-based combination therapy] is the only effective and widely used antimalarial treatment at the moment,” Dr Pain said. “Therefore, it is very important to regularly monitor artemisinin resistance worldwide.”

Children’s Research Hospital

Researchers have identified the first known case of artemisinin-resistant malaria originating in Africa, according to a letter published in NEJM.

Resistant Plasmodium falciparum parasites were detected in a Chinese man who had travelled from Equatorial Guinea to China.

The finding means Africa has joined Southeast Asia in hosting parasites that are partially resistant to the first-line antimalaria drug, artemisinin.

Researchers were able to confirm that the parasites in the current case carried a new mutation in the Kelch13 (K13) gene, the main driver for artemisinin resistance in Asia.

Then, the team set out to determine whether the parasite originated from Africa or Southeast Asia.

“We used whole-genome sequencing and bioinformatics tools we had previously developed—like detectives trying to link the culprit parasite to the crime scene,” explained Arnab Pain, PhD, of King Abdullah University of Science and Technology in Thuwal, Saudi Arabia.

Sequencing and analysis of P falciparum DNA unveiled its origin by disclosing the single nucleotide polymorphisms that vary according to the geographical source of the strain.

The researchers used the nuclear DNA, as well as the one present in 2 organelles of the parasite—the mitochondrium and the apicoplast.

Both methods independently validated the origin of the parasite as West African, confirming the first case of artemisinin resistance mediated by a K13 gene mutation on the African continent.

“The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT [artemisinin-based combination therapy] is the only effective and widely used antimalarial treatment at the moment,” Dr Pain said. “Therefore, it is very important to regularly monitor artemisinin resistance worldwide.”

Children’s Research Hospital

Researchers have identified the first known case of artemisinin-resistant malaria originating in Africa, according to a letter published in NEJM.

Resistant Plasmodium falciparum parasites were detected in a Chinese man who had travelled from Equatorial Guinea to China.

The finding means Africa has joined Southeast Asia in hosting parasites that are partially resistant to the first-line antimalaria drug, artemisinin.

Researchers were able to confirm that the parasites in the current case carried a new mutation in the Kelch13 (K13) gene, the main driver for artemisinin resistance in Asia.

Then, the team set out to determine whether the parasite originated from Africa or Southeast Asia.

“We used whole-genome sequencing and bioinformatics tools we had previously developed—like detectives trying to link the culprit parasite to the crime scene,” explained Arnab Pain, PhD, of King Abdullah University of Science and Technology in Thuwal, Saudi Arabia.

Sequencing and analysis of P falciparum DNA unveiled its origin by disclosing the single nucleotide polymorphisms that vary according to the geographical source of the strain.

The researchers used the nuclear DNA, as well as the one present in 2 organelles of the parasite—the mitochondrium and the apicoplast.

Both methods independently validated the origin of the parasite as West African, confirming the first case of artemisinin resistance mediated by a K13 gene mutation on the African continent.

“The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT [artemisinin-based combination therapy] is the only effective and widely used antimalarial treatment at the moment,” Dr Pain said. “Therefore, it is very important to regularly monitor artemisinin resistance worldwide.”