Hematology Times

Photo by Bill Branson

ORLANDO—Results of a pilot study suggest a web-based, reward-driven intervention can motivate adolescent cancer survivors to stay physically active.

Time spent performing moderate-to-vigorous physical activity (MVPA) increased by an average of 5 minutes a week for subjects who were randomized to the intervention.

For control subjects, MVPA decreased by an average of 24 minutes a week.

These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 102).

“Compared to the general population, childhood cancer survivors have an increased risk for obesity and metabolic syndrome, conditions that can lead to heart disease, stroke, and diabetes, so it is really important that they are physically active,” said study investigator Carrie R. Howell, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“By intervening in this young age group, we hope to help kids develop healthy exercise habits for life.”

Dr Howell and her colleagues studied cancer survivors, ages 11 to 15, who were no longer receiving cancer treatment and were physically active less than 60 minutes a day.

The subjects were randomized to the intervention or to a control group. Controls received a wearable activity monitor and an educational handout with information about the importance of physical activity and examples of activities.

The intervention group received the handout and activity monitor but also had access to an interactive website. On at least a weekly basis, subjects would connect their monitor to a computer and log their activity through the website. Upon achieving certain thresholds of activity, they received rewards, such as T-shirts and gift cards by mail.

At the beginning and end of the study, participants visited St. Jude for an assessment of their physical fitness (strength, flexibility, and endurance) and neurocognitive measures (attention and memory), as well as health-related quality of life (assessed using the Pediatric Quality of Life Inventory questionnaire).

Results

Seventy-eight cancer survivors completed the 24-week study, 53 of them in the intervention group and 25 in the control group.

MVPA increased by an average of 4.7 minutes per week in the intervention group and decreased by an average of 24.3 minutes per week in the control group.

“In this age group, it is common to see a decrease in physical activity over time, even among healthy kids,” Dr Howell said. “Therefore, we are encouraged that our intervention was successful at maintaining physical activity levels, but a longer program may be needed to create lasting exercise habits.”

In addition to increases in MVPA, the intervention group had the following improvements in fitness:

• Increase in hand grip strength from an average of 19.9 kg to 21.0 kg
• Increase in number of push-ups from an average of 15 to 18
• Increase in number of sit-ups from an average of 11 to 14.

Furthermore, subjects in the intervention group saw their verbal fluency z-score increase by an average of 0.13 points and their general cognition z-score increase by an average of 0.23 points.

Their quality of life scores increased as well. Both overall quality of life and physical-function-related quality of life scores increased from an average of 74.2 to 78.0.

Control subjects had no significant changes in fitness, neurocognitive measures, or quality of life.

This study was supported by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and HopeLab.

Based on the results of this study, the investigators have designed a larger trial (ALTE1631) to test a web-based physical activity intervention. They hope to enroll 384 survivors of childhood acute lymphoblastic leukemia at institutions across the US. The intervention will last a year, with follow-up at 18 months.

Further down the line, the investigators plan to explore the relationship between physical activity and cognition.

Photo by Bill Branson

ORLANDO—Results of a pilot study suggest a web-based, reward-driven intervention can motivate adolescent cancer survivors to stay physically active.

Time spent performing moderate-to-vigorous physical activity (MVPA) increased by an average of 5 minutes a week for subjects who were randomized to the intervention.

For control subjects, MVPA decreased by an average of 24 minutes a week.

These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 102).

“Compared to the general population, childhood cancer survivors have an increased risk for obesity and metabolic syndrome, conditions that can lead to heart disease, stroke, and diabetes, so it is really important that they are physically active,” said study investigator Carrie R. Howell, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“By intervening in this young age group, we hope to help kids develop healthy exercise habits for life.”

Dr Howell and her colleagues studied cancer survivors, ages 11 to 15, who were no longer receiving cancer treatment and were physically active less than 60 minutes a day.

The subjects were randomized to the intervention or to a control group. Controls received a wearable activity monitor and an educational handout with information about the importance of physical activity and examples of activities.

The intervention group received the handout and activity monitor but also had access to an interactive website. On at least a weekly basis, subjects would connect their monitor to a computer and log their activity through the website. Upon achieving certain thresholds of activity, they received rewards, such as T-shirts and gift cards by mail.

At the beginning and end of the study, participants visited St. Jude for an assessment of their physical fitness (strength, flexibility, and endurance) and neurocognitive measures (attention and memory), as well as health-related quality of life (assessed using the Pediatric Quality of Life Inventory questionnaire).

Results

Seventy-eight cancer survivors completed the 24-week study, 53 of them in the intervention group and 25 in the control group.

MVPA increased by an average of 4.7 minutes per week in the intervention group and decreased by an average of 24.3 minutes per week in the control group.

“In this age group, it is common to see a decrease in physical activity over time, even among healthy kids,” Dr Howell said. “Therefore, we are encouraged that our intervention was successful at maintaining physical activity levels, but a longer program may be needed to create lasting exercise habits.”

In addition to increases in MVPA, the intervention group had the following improvements in fitness:

• Increase in hand grip strength from an average of 19.9 kg to 21.0 kg
• Increase in number of push-ups from an average of 15 to 18
• Increase in number of sit-ups from an average of 11 to 14.

Furthermore, subjects in the intervention group saw their verbal fluency z-score increase by an average of 0.13 points and their general cognition z-score increase by an average of 0.23 points.

Their quality of life scores increased as well. Both overall quality of life and physical-function-related quality of life scores increased from an average of 74.2 to 78.0.

Control subjects had no significant changes in fitness, neurocognitive measures, or quality of life.

This study was supported by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and HopeLab.

Based on the results of this study, the investigators have designed a larger trial (ALTE1631) to test a web-based physical activity intervention. They hope to enroll 384 survivors of childhood acute lymphoblastic leukemia at institutions across the US. The intervention will last a year, with follow-up at 18 months.

Further down the line, the investigators plan to explore the relationship between physical activity and cognition.

Photo by Bill Branson

ORLANDO—Results of a pilot study suggest a web-based, reward-driven intervention can motivate adolescent cancer survivors to stay physically active.

Time spent performing moderate-to-vigorous physical activity (MVPA) increased by an average of 5 minutes a week for subjects who were randomized to the intervention.

For control subjects, MVPA decreased by an average of 24 minutes a week.

These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 102).

“Compared to the general population, childhood cancer survivors have an increased risk for obesity and metabolic syndrome, conditions that can lead to heart disease, stroke, and diabetes, so it is really important that they are physically active,” said study investigator Carrie R. Howell, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“By intervening in this young age group, we hope to help kids develop healthy exercise habits for life.”

Dr Howell and her colleagues studied cancer survivors, ages 11 to 15, who were no longer receiving cancer treatment and were physically active less than 60 minutes a day.

The subjects were randomized to the intervention or to a control group. Controls received a wearable activity monitor and an educational handout with information about the importance of physical activity and examples of activities.

The intervention group received the handout and activity monitor but also had access to an interactive website. On at least a weekly basis, subjects would connect their monitor to a computer and log their activity through the website. Upon achieving certain thresholds of activity, they received rewards, such as T-shirts and gift cards by mail.

At the beginning and end of the study, participants visited St. Jude for an assessment of their physical fitness (strength, flexibility, and endurance) and neurocognitive measures (attention and memory), as well as health-related quality of life (assessed using the Pediatric Quality of Life Inventory questionnaire).

Results

Seventy-eight cancer survivors completed the 24-week study, 53 of them in the intervention group and 25 in the control group.

MVPA increased by an average of 4.7 minutes per week in the intervention group and decreased by an average of 24.3 minutes per week in the control group.

“In this age group, it is common to see a decrease in physical activity over time, even among healthy kids,” Dr Howell said. “Therefore, we are encouraged that our intervention was successful at maintaining physical activity levels, but a longer program may be needed to create lasting exercise habits.”

In addition to increases in MVPA, the intervention group had the following improvements in fitness:

• Increase in hand grip strength from an average of 19.9 kg to 21.0 kg
• Increase in number of push-ups from an average of 15 to 18
• Increase in number of sit-ups from an average of 11 to 14.

Furthermore, subjects in the intervention group saw their verbal fluency z-score increase by an average of 0.13 points and their general cognition z-score increase by an average of 0.23 points.

Their quality of life scores increased as well. Both overall quality of life and physical-function-related quality of life scores increased from an average of 74.2 to 78.0.

Control subjects had no significant changes in fitness, neurocognitive measures, or quality of life.

This study was supported by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and HopeLab.

Based on the results of this study, the investigators have designed a larger trial (ALTE1631) to test a web-based physical activity intervention. They hope to enroll 384 survivors of childhood acute lymphoblastic leukemia at institutions across the US. The intervention will last a year, with follow-up at 18 months.

Further down the line, the investigators plan to explore the relationship between physical activity and cognition.

Photo by Rhoda Baer

ORLANDO—A new study suggests many US cancer centers do not have therapeutic aids for patients who experience sexual dysfunction after cancer treatment.

Of 25 cancer centers polled, 80% said they had no sexual aids available on site for men, and 64% said they had no such aids for women.

Sharon Bober, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues presented this research at the 2018 Cancer Survivorship Symposium (abstract 134*).

“[P]roviding sexual aids is one step toward treating sexual health like any other aspect of survivorship care,” Dr Bober said.

“It should be no different than providing wigs and head coverings to women who have lost their hair due to chemotherapy. It’s important to give patients the message that regaining sexual health is a perfectly valid and life-affirming aspect of regaining overall quality of life.”

Dr Bober and her colleagues conducted this study to determine the availability of sexual aids at 25 National Cancer Institute-designated cancer centers.

The researchers called these centers posing as a spouse, adult child, or sibling of a patient. The team made separate calls to ask about sexual aids for women and those for men.

Women’s sexual aids

Twenty-four percent of cancer centers (n=6) said they had sexual aids for women, 64% (n=16) did not, and 12% of centers were unreachable (n=3).

The most common aids were personal lubrication, vaginal moisturizer, and vaginal dilators—all of which were available at 5 centers.

Three centers had vibrators, 2 had books/pamphlets, 2 had pelvic floor exercisers, and 2 had product lists.

Men’s sexual aids

Twelve percent of cancer centers (n=3) said they had sexual aids for men, 80% (n=20) did not, and 8% (n=2) were unreachable.

Two centers said they had personal lubrication available for men, 2 had penile support rings, 1 had vacuum erection devices, and 1 had books/pamphlets.

Next steps

Now, Dr Bober and her colleagues hope to query the other 44 National Cancer Institute-designated cancer centers to see what products they are selling and perhaps conduct patient surveys to find out what types of resources are most useful for cancer survivors.

“What we really need to do is go to the centers that are successfully providing sexual health products and find out how they promote and provide resources to their patients,” Dr Bober said.

“We can’t keep the conversation at the 10,000-foot level. We need to talk concretely about how to partner with providers to make sexual health resources, including sexual health aids, available so cancer survivors can get the help that they need.”

*Information presented differs from the abstract.

Photo by Rhoda Baer

ORLANDO—A new study suggests many US cancer centers do not have therapeutic aids for patients who experience sexual dysfunction after cancer treatment.

Of 25 cancer centers polled, 80% said they had no sexual aids available on site for men, and 64% said they had no such aids for women.

Sharon Bober, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues presented this research at the 2018 Cancer Survivorship Symposium (abstract 134*).

“[P]roviding sexual aids is one step toward treating sexual health like any other aspect of survivorship care,” Dr Bober said.

“It should be no different than providing wigs and head coverings to women who have lost their hair due to chemotherapy. It’s important to give patients the message that regaining sexual health is a perfectly valid and life-affirming aspect of regaining overall quality of life.”

Dr Bober and her colleagues conducted this study to determine the availability of sexual aids at 25 National Cancer Institute-designated cancer centers.

The researchers called these centers posing as a spouse, adult child, or sibling of a patient. The team made separate calls to ask about sexual aids for women and those for men.

Women’s sexual aids

Twenty-four percent of cancer centers (n=6) said they had sexual aids for women, 64% (n=16) did not, and 12% of centers were unreachable (n=3).

The most common aids were personal lubrication, vaginal moisturizer, and vaginal dilators—all of which were available at 5 centers.

Three centers had vibrators, 2 had books/pamphlets, 2 had pelvic floor exercisers, and 2 had product lists.

Men’s sexual aids

Twelve percent of cancer centers (n=3) said they had sexual aids for men, 80% (n=20) did not, and 8% (n=2) were unreachable.

Two centers said they had personal lubrication available for men, 2 had penile support rings, 1 had vacuum erection devices, and 1 had books/pamphlets.

Next steps

Now, Dr Bober and her colleagues hope to query the other 44 National Cancer Institute-designated cancer centers to see what products they are selling and perhaps conduct patient surveys to find out what types of resources are most useful for cancer survivors.

“What we really need to do is go to the centers that are successfully providing sexual health products and find out how they promote and provide resources to their patients,” Dr Bober said.

“We can’t keep the conversation at the 10,000-foot level. We need to talk concretely about how to partner with providers to make sexual health resources, including sexual health aids, available so cancer survivors can get the help that they need.”

*Information presented differs from the abstract.

Photo by Rhoda Baer

ORLANDO—A new study suggests many US cancer centers do not have therapeutic aids for patients who experience sexual dysfunction after cancer treatment.

Of 25 cancer centers polled, 80% said they had no sexual aids available on site for men, and 64% said they had no such aids for women.

Sharon Bober, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues presented this research at the 2018 Cancer Survivorship Symposium (abstract 134*).

“[P]roviding sexual aids is one step toward treating sexual health like any other aspect of survivorship care,” Dr Bober said.

“It should be no different than providing wigs and head coverings to women who have lost their hair due to chemotherapy. It’s important to give patients the message that regaining sexual health is a perfectly valid and life-affirming aspect of regaining overall quality of life.”

Dr Bober and her colleagues conducted this study to determine the availability of sexual aids at 25 National Cancer Institute-designated cancer centers.

The researchers called these centers posing as a spouse, adult child, or sibling of a patient. The team made separate calls to ask about sexual aids for women and those for men.

Women’s sexual aids

Twenty-four percent of cancer centers (n=6) said they had sexual aids for women, 64% (n=16) did not, and 12% of centers were unreachable (n=3).

The most common aids were personal lubrication, vaginal moisturizer, and vaginal dilators—all of which were available at 5 centers.

Three centers had vibrators, 2 had books/pamphlets, 2 had pelvic floor exercisers, and 2 had product lists.

Men’s sexual aids

Twelve percent of cancer centers (n=3) said they had sexual aids for men, 80% (n=20) did not, and 8% (n=2) were unreachable.

Two centers said they had personal lubrication available for men, 2 had penile support rings, 1 had vacuum erection devices, and 1 had books/pamphlets.

Next steps

Now, Dr Bober and her colleagues hope to query the other 44 National Cancer Institute-designated cancer centers to see what products they are selling and perhaps conduct patient surveys to find out what types of resources are most useful for cancer survivors.

“What we really need to do is go to the centers that are successfully providing sexual health products and find out how they promote and provide resources to their patients,” Dr Bober said.

“We can’t keep the conversation at the 10,000-foot level. We need to talk concretely about how to partner with providers to make sexual health resources, including sexual health aids, available so cancer survivors can get the help that they need.”

*Information presented differs from the abstract.

AML cells

The US Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for ivosidenib, a targeted inhibitor of mutant IDH1.

With this NDA, Agios Pharmaceuticals, Inc., is seeking approval for ivosidenib (formerly AG-120) to treat patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation.

The FDA expects to make a decision on the NDA by August 21, 2018.

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

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

Phase 1 data

The priority review for the ivosidenib NDA is based on results from AG120-C-001, a phase 1 trial of patients with advanced hematologic malignancies and an IDH1 mutation. Data from this study were presented at the 2017 ASH Annual Meeting (abstract 725).

This ongoing trial includes a dose-escalation phase and 4 expansion arms. Ivosidenib doses ranged from 200 mg to 1200 mg in the dose-escalation phase. Patients in the dose-expansion arms received a 500 mg daily dose of the drug.

Arm 1 includes IDH1-mutant-positive AML patients who relapsed after bone marrow transplant, were in second or later relapse, were refractory to initial induction or re-induction treatment, or who relapsed within a year of initial treatment, excluding patients with favorable-risk status.

Arms 2, 3 and 4 were not included in the primary efficacy analysis.

The primary analysis set consists of 125 relapsed/refractory AML patients—92 from arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for arm 1 and received ivosidenib at 500 mg once daily.

The median age of these patients was 67 (range, 18-87), and the median number of prior regimens they received was 2 (range, 1-6).

The primary endpoint for these patients is the rate of complete response (CR) and CR with partial hematologic recovery (CRh), which was 30.4%. The CR rate was 21.6% (27/125), and the CRh rate was 8.8% (11/125).

The overall response rate was 41.6% (52/125). The median duration of response was 6.5 months for all patients, 9.3 months for those who achieved a CR, and 8.2 months for those who had a CR/CRh.

At the time of the data cut-off, the median overall survival was 8.8 months. The median overall survival was not reached for patients who achieved a CR/CRh, was 9.3 months for non-CR/CRh responders, and was 3.9 months for non-responders.

There were a few adverse events of interest. Eight percent of patients reported grade 3 or higher leukocytosis, which was managed with hydroxyurea, and none of the cases were fatal.

Eight percent of patients reported grade 3 QT prolongation. Ivosidenib was reduced in 1 patient and held in 5 patients (for any grade of QT prolongation). There were no grade 4 or 5 cases of QT prolongation.

Finally, 9.6% of patients reported IDH-differentiation syndrome, which was managed with corticosteroids and diuretics. None of the cases were grade 4 or 5.

Companion diagnostic

Abbott has submitted a premarket approval application to the FDA for an IDH1 assay to be used on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.

In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for the development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay is intended to serve as a companion diagnostic for ivosidenib.

AML cells

The US Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for ivosidenib, a targeted inhibitor of mutant IDH1.

With this NDA, Agios Pharmaceuticals, Inc., is seeking approval for ivosidenib (formerly AG-120) to treat patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation.

The FDA expects to make a decision on the NDA by August 21, 2018.

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

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

Phase 1 data

The priority review for the ivosidenib NDA is based on results from AG120-C-001, a phase 1 trial of patients with advanced hematologic malignancies and an IDH1 mutation. Data from this study were presented at the 2017 ASH Annual Meeting (abstract 725).

This ongoing trial includes a dose-escalation phase and 4 expansion arms. Ivosidenib doses ranged from 200 mg to 1200 mg in the dose-escalation phase. Patients in the dose-expansion arms received a 500 mg daily dose of the drug.

Arm 1 includes IDH1-mutant-positive AML patients who relapsed after bone marrow transplant, were in second or later relapse, were refractory to initial induction or re-induction treatment, or who relapsed within a year of initial treatment, excluding patients with favorable-risk status.

Arms 2, 3 and 4 were not included in the primary efficacy analysis.

The primary analysis set consists of 125 relapsed/refractory AML patients—92 from arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for arm 1 and received ivosidenib at 500 mg once daily.

The median age of these patients was 67 (range, 18-87), and the median number of prior regimens they received was 2 (range, 1-6).

The primary endpoint for these patients is the rate of complete response (CR) and CR with partial hematologic recovery (CRh), which was 30.4%. The CR rate was 21.6% (27/125), and the CRh rate was 8.8% (11/125).

The overall response rate was 41.6% (52/125). The median duration of response was 6.5 months for all patients, 9.3 months for those who achieved a CR, and 8.2 months for those who had a CR/CRh.

At the time of the data cut-off, the median overall survival was 8.8 months. The median overall survival was not reached for patients who achieved a CR/CRh, was 9.3 months for non-CR/CRh responders, and was 3.9 months for non-responders.

There were a few adverse events of interest. Eight percent of patients reported grade 3 or higher leukocytosis, which was managed with hydroxyurea, and none of the cases were fatal.

Eight percent of patients reported grade 3 QT prolongation. Ivosidenib was reduced in 1 patient and held in 5 patients (for any grade of QT prolongation). There were no grade 4 or 5 cases of QT prolongation.

Finally, 9.6% of patients reported IDH-differentiation syndrome, which was managed with corticosteroids and diuretics. None of the cases were grade 4 or 5.

Companion diagnostic

Abbott has submitted a premarket approval application to the FDA for an IDH1 assay to be used on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.

In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for the development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay is intended to serve as a companion diagnostic for ivosidenib.

AML cells

The US Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for ivosidenib, a targeted inhibitor of mutant IDH1.

With this NDA, Agios Pharmaceuticals, Inc., is seeking approval for ivosidenib (formerly AG-120) to treat patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation.

The FDA expects to make a decision on the NDA by August 21, 2018.

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

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

Phase 1 data

The priority review for the ivosidenib NDA is based on results from AG120-C-001, a phase 1 trial of patients with advanced hematologic malignancies and an IDH1 mutation. Data from this study were presented at the 2017 ASH Annual Meeting (abstract 725).

This ongoing trial includes a dose-escalation phase and 4 expansion arms. Ivosidenib doses ranged from 200 mg to 1200 mg in the dose-escalation phase. Patients in the dose-expansion arms received a 500 mg daily dose of the drug.

Arm 1 includes IDH1-mutant-positive AML patients who relapsed after bone marrow transplant, were in second or later relapse, were refractory to initial induction or re-induction treatment, or who relapsed within a year of initial treatment, excluding patients with favorable-risk status.

Arms 2, 3 and 4 were not included in the primary efficacy analysis.

The primary analysis set consists of 125 relapsed/refractory AML patients—92 from arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for arm 1 and received ivosidenib at 500 mg once daily.

The median age of these patients was 67 (range, 18-87), and the median number of prior regimens they received was 2 (range, 1-6).

The primary endpoint for these patients is the rate of complete response (CR) and CR with partial hematologic recovery (CRh), which was 30.4%. The CR rate was 21.6% (27/125), and the CRh rate was 8.8% (11/125).

The overall response rate was 41.6% (52/125). The median duration of response was 6.5 months for all patients, 9.3 months for those who achieved a CR, and 8.2 months for those who had a CR/CRh.

At the time of the data cut-off, the median overall survival was 8.8 months. The median overall survival was not reached for patients who achieved a CR/CRh, was 9.3 months for non-CR/CRh responders, and was 3.9 months for non-responders.

There were a few adverse events of interest. Eight percent of patients reported grade 3 or higher leukocytosis, which was managed with hydroxyurea, and none of the cases were fatal.

Eight percent of patients reported grade 3 QT prolongation. Ivosidenib was reduced in 1 patient and held in 5 patients (for any grade of QT prolongation). There were no grade 4 or 5 cases of QT prolongation.

Finally, 9.6% of patients reported IDH-differentiation syndrome, which was managed with corticosteroids and diuretics. None of the cases were grade 4 or 5.

Companion diagnostic

Abbott has submitted a premarket approval application to the FDA for an IDH1 assay to be used on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.

In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for the development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay is intended to serve as a companion diagnostic for ivosidenib.

Image by Joshua Stokes

Results of a phase 1/2 trial suggest treatment with haploidentical natural killer (NK) cells can be effective against relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

NK-cell therapy elicited responses in 6 of the 16 patients studied and provided a bridge to transplant for 5 patients.

Three responders were still alive at more than 3 years of follow-up.

There were 4 grade 3 adverse events (AEs) and 2 grade 5 AEs considered possibly or probably related to NK-cell therapy.

Investigators reported these results in Clinical Cancer Research.

The trial enrolled 16 patients. Eight had MDS/AML, 3 had de novo AML, and 5 had high-risk MDS, including refractory anemia with excess blasts (RAEB) type 1 progressing toward type 2, RAEB-2, and chronic myelomonocytic leukemia type 2.

The patients’ median age was 64 (range, 40-70), and they had received a median of 3 prior therapies (range, 1-6). Six patients had received an allogeneic hematopoietic stem cell transplant (HSCT).

For this study, all patients received fludarabine, cyclophosphamide, and total lymphoid irradiation prior to receiving haploidentical NK cells.

The median follow-up was 8 months for all patients and 28 months for responders.

Efficacy

Six patients responded to treatment. One patient with de novo AML had a complete response (CR). Two high-risk MDS patients had a marrow CR (mCR), as did 2 MDS/AML patients. One MDS/AML patient had a partial response (PR).

Two patients had stable disease (SD)—1 with MDS and 1 with MDS/AML. One patient with de novo AML had a morphologic leukemia-free state after NK-cell therapy.

Five patients proceeded to HSCT—3 in mCR, 1 in PR, and 1 with SD.

Three patients were still alive at last follow-up—1 with MDS who achieved an mCR and went on to HSCT, 1 with MDS/AML who achieved an mCR and went on to HSCT, and 1 with MDS/AML who achieved an mCR and went on to receive chemotherapy and donor lymphocyte infusion.

One survivor has more than 5 years of follow-up (the MDS patient), and the other 2 have more than 3 years of follow-up.

“Our study shows that patients with MDS, AML, and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” said study author Hans-Gustaf Ljunggren, MD, PhD, of Karolinska Institutet in Stockholm, Sweden.

Safety

The most common AEs of any grade considered possibly or probably related to NK-cell therapy were chills (n=13) and nausea (n=4).

Two patients had cytokine release syndrome (CRS) likely associated with hemophagocytic lymphohistiocytosis (HLH).

Each of the following potentially related AEs were reported once: headache, vomiting, encephalitis infection, sinus tachycardia, bone pain, pain in extremity, and maculopapular rash.

There were 4 grade 3 AEs—CRS/HLH (n=1), chills (n=1), and nausea (n=2)—but no grade 4 AEs.

There were 2 grade 5 AEs—CRS/HLH and encephalitis infection. These occurred in a single patient who died with HLH, human herpes virus-6 encephalitis, and AML relapse.

Two investigators involved in this study serve on the scientific advisory board of Fate Therapeutics. Dr Ljunggren serves on the scientific advisory board of CellProtect, Nordic Pharmaceuticals, and HOPE Bio-Sciences. He is also on the board of directors of Vycellix and is a collaborator with Fate Therapeutics.

Image by Joshua Stokes

Results of a phase 1/2 trial suggest treatment with haploidentical natural killer (NK) cells can be effective against relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

NK-cell therapy elicited responses in 6 of the 16 patients studied and provided a bridge to transplant for 5 patients.

Three responders were still alive at more than 3 years of follow-up.

There were 4 grade 3 adverse events (AEs) and 2 grade 5 AEs considered possibly or probably related to NK-cell therapy.

Investigators reported these results in Clinical Cancer Research.

The trial enrolled 16 patients. Eight had MDS/AML, 3 had de novo AML, and 5 had high-risk MDS, including refractory anemia with excess blasts (RAEB) type 1 progressing toward type 2, RAEB-2, and chronic myelomonocytic leukemia type 2.

The patients’ median age was 64 (range, 40-70), and they had received a median of 3 prior therapies (range, 1-6). Six patients had received an allogeneic hematopoietic stem cell transplant (HSCT).

For this study, all patients received fludarabine, cyclophosphamide, and total lymphoid irradiation prior to receiving haploidentical NK cells.

The median follow-up was 8 months for all patients and 28 months for responders.

Efficacy

Six patients responded to treatment. One patient with de novo AML had a complete response (CR). Two high-risk MDS patients had a marrow CR (mCR), as did 2 MDS/AML patients. One MDS/AML patient had a partial response (PR).

Two patients had stable disease (SD)—1 with MDS and 1 with MDS/AML. One patient with de novo AML had a morphologic leukemia-free state after NK-cell therapy.

Five patients proceeded to HSCT—3 in mCR, 1 in PR, and 1 with SD.

Three patients were still alive at last follow-up—1 with MDS who achieved an mCR and went on to HSCT, 1 with MDS/AML who achieved an mCR and went on to HSCT, and 1 with MDS/AML who achieved an mCR and went on to receive chemotherapy and donor lymphocyte infusion.

One survivor has more than 5 years of follow-up (the MDS patient), and the other 2 have more than 3 years of follow-up.

“Our study shows that patients with MDS, AML, and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” said study author Hans-Gustaf Ljunggren, MD, PhD, of Karolinska Institutet in Stockholm, Sweden.

Safety

The most common AEs of any grade considered possibly or probably related to NK-cell therapy were chills (n=13) and nausea (n=4).

Two patients had cytokine release syndrome (CRS) likely associated with hemophagocytic lymphohistiocytosis (HLH).

Each of the following potentially related AEs were reported once: headache, vomiting, encephalitis infection, sinus tachycardia, bone pain, pain in extremity, and maculopapular rash.

There were 4 grade 3 AEs—CRS/HLH (n=1), chills (n=1), and nausea (n=2)—but no grade 4 AEs.

There were 2 grade 5 AEs—CRS/HLH and encephalitis infection. These occurred in a single patient who died with HLH, human herpes virus-6 encephalitis, and AML relapse.

Two investigators involved in this study serve on the scientific advisory board of Fate Therapeutics. Dr Ljunggren serves on the scientific advisory board of CellProtect, Nordic Pharmaceuticals, and HOPE Bio-Sciences. He is also on the board of directors of Vycellix and is a collaborator with Fate Therapeutics.

Image by Joshua Stokes

Results of a phase 1/2 trial suggest treatment with haploidentical natural killer (NK) cells can be effective against relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

NK-cell therapy elicited responses in 6 of the 16 patients studied and provided a bridge to transplant for 5 patients.

Three responders were still alive at more than 3 years of follow-up.

There were 4 grade 3 adverse events (AEs) and 2 grade 5 AEs considered possibly or probably related to NK-cell therapy.

Investigators reported these results in Clinical Cancer Research.

The trial enrolled 16 patients. Eight had MDS/AML, 3 had de novo AML, and 5 had high-risk MDS, including refractory anemia with excess blasts (RAEB) type 1 progressing toward type 2, RAEB-2, and chronic myelomonocytic leukemia type 2.

The patients’ median age was 64 (range, 40-70), and they had received a median of 3 prior therapies (range, 1-6). Six patients had received an allogeneic hematopoietic stem cell transplant (HSCT).

For this study, all patients received fludarabine, cyclophosphamide, and total lymphoid irradiation prior to receiving haploidentical NK cells.

The median follow-up was 8 months for all patients and 28 months for responders.

Efficacy

Six patients responded to treatment. One patient with de novo AML had a complete response (CR). Two high-risk MDS patients had a marrow CR (mCR), as did 2 MDS/AML patients. One MDS/AML patient had a partial response (PR).

Two patients had stable disease (SD)—1 with MDS and 1 with MDS/AML. One patient with de novo AML had a morphologic leukemia-free state after NK-cell therapy.

Five patients proceeded to HSCT—3 in mCR, 1 in PR, and 1 with SD.

Three patients were still alive at last follow-up—1 with MDS who achieved an mCR and went on to HSCT, 1 with MDS/AML who achieved an mCR and went on to HSCT, and 1 with MDS/AML who achieved an mCR and went on to receive chemotherapy and donor lymphocyte infusion.

One survivor has more than 5 years of follow-up (the MDS patient), and the other 2 have more than 3 years of follow-up.

“Our study shows that patients with MDS, AML, and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” said study author Hans-Gustaf Ljunggren, MD, PhD, of Karolinska Institutet in Stockholm, Sweden.

Safety

The most common AEs of any grade considered possibly or probably related to NK-cell therapy were chills (n=13) and nausea (n=4).

Two patients had cytokine release syndrome (CRS) likely associated with hemophagocytic lymphohistiocytosis (HLH).

Each of the following potentially related AEs were reported once: headache, vomiting, encephalitis infection, sinus tachycardia, bone pain, pain in extremity, and maculopapular rash.

There were 4 grade 3 AEs—CRS/HLH (n=1), chills (n=1), and nausea (n=2)—but no grade 4 AEs.

There were 2 grade 5 AEs—CRS/HLH and encephalitis infection. These occurred in a single patient who died with HLH, human herpes virus-6 encephalitis, and AML relapse.

Two investigators involved in this study serve on the scientific advisory board of Fate Therapeutics. Dr Ljunggren serves on the scientific advisory board of CellProtect, Nordic Pharmaceuticals, and HOPE Bio-Sciences. He is also on the board of directors of Vycellix and is a collaborator with Fate Therapeutics.

Photo by Rob Felt

Researchers have engineered a miniature model system for studying hemostasis.

They believe the device could serve as a drug discovery platform and potential diagnostic tool.

The team has already used the device to assess the effects of an antiplatelet agent and analyze blood from hemophilia A patients.

The researchers described this work in Nature Communications.

The team noted that hemostasis encompasses the interactions of platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces.

“Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,” said study author Wilbur Lam, MD, PhD, of Georgia Institute of Technology and Emory University in Atlanta, Georgia.

With this in mind, Dr Lam and his colleagues developed their device.

They believe it is the first system to reproduce all aspects of blood vessel injury seen in the microvasculature—blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. However, it does not reproduce aspects of larger blood vessels.

The researchers’ device has 3 layers. The top “vascular” layer consists of human endothelial cells cultured in a microchannel. The middle valve layer consists of a polydimethylsiloxane membrane, and the bottom is a “valve actuator” layer.

To assess hemostatic response, the researchers create a “wound” in this system. They exert both positive and negative pressure to create an opening about 130 micrometers across. Donated human blood can flow through this opening for testing.

The researchers said they used this system to demonstrate the importance of von Willebrand factor and endothelial phosphatidylserine in hemostasis.

The team used the device to test the antiplatelet agent eptifibatide as well. They found the drug leads to decreased clot contraction and a lower density of platelets within the hemostatic plug.

Finally, the researchers analyzed blood from hemophilia A patients and found that it “confers unstable hemostatic plug formation and altered fibrin architecture.”

Photo by Rob Felt

Researchers have engineered a miniature model system for studying hemostasis.

They believe the device could serve as a drug discovery platform and potential diagnostic tool.

The team has already used the device to assess the effects of an antiplatelet agent and analyze blood from hemophilia A patients.

The researchers described this work in Nature Communications.

The team noted that hemostasis encompasses the interactions of platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces.

“Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,” said study author Wilbur Lam, MD, PhD, of Georgia Institute of Technology and Emory University in Atlanta, Georgia.

With this in mind, Dr Lam and his colleagues developed their device.

They believe it is the first system to reproduce all aspects of blood vessel injury seen in the microvasculature—blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. However, it does not reproduce aspects of larger blood vessels.

The researchers’ device has 3 layers. The top “vascular” layer consists of human endothelial cells cultured in a microchannel. The middle valve layer consists of a polydimethylsiloxane membrane, and the bottom is a “valve actuator” layer.

To assess hemostatic response, the researchers create a “wound” in this system. They exert both positive and negative pressure to create an opening about 130 micrometers across. Donated human blood can flow through this opening for testing.

The researchers said they used this system to demonstrate the importance of von Willebrand factor and endothelial phosphatidylserine in hemostasis.

The team used the device to test the antiplatelet agent eptifibatide as well. They found the drug leads to decreased clot contraction and a lower density of platelets within the hemostatic plug.

Finally, the researchers analyzed blood from hemophilia A patients and found that it “confers unstable hemostatic plug formation and altered fibrin architecture.”

Photo by Rob Felt

Researchers have engineered a miniature model system for studying hemostasis.

They believe the device could serve as a drug discovery platform and potential diagnostic tool.

The team has already used the device to assess the effects of an antiplatelet agent and analyze blood from hemophilia A patients.

The researchers described this work in Nature Communications.

The team noted that hemostasis encompasses the interactions of platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces.

“Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,” said study author Wilbur Lam, MD, PhD, of Georgia Institute of Technology and Emory University in Atlanta, Georgia.

With this in mind, Dr Lam and his colleagues developed their device.

They believe it is the first system to reproduce all aspects of blood vessel injury seen in the microvasculature—blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. However, it does not reproduce aspects of larger blood vessels.

The researchers’ device has 3 layers. The top “vascular” layer consists of human endothelial cells cultured in a microchannel. The middle valve layer consists of a polydimethylsiloxane membrane, and the bottom is a “valve actuator” layer.

To assess hemostatic response, the researchers create a “wound” in this system. They exert both positive and negative pressure to create an opening about 130 micrometers across. Donated human blood can flow through this opening for testing.

The researchers said they used this system to demonstrate the importance of von Willebrand factor and endothelial phosphatidylserine in hemostasis.

The team used the device to test the antiplatelet agent eptifibatide as well. They found the drug leads to decreased clot contraction and a lower density of platelets within the hemostatic plug.

Finally, the researchers analyzed blood from hemophilia A patients and found that it “confers unstable hemostatic plug formation and altered fibrin architecture.”

showing MM

The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).

PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.

PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).

Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.

In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.

Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.

This research was presented at the 2017 ASH Annual Meeting (abstract 1797).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

showing MM

The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).

PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.

PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).

Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.

In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.

Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.

This research was presented at the 2017 ASH Annual Meeting (abstract 1797).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

showing MM

The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).

PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.

PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).

Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.

In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.

Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.

This research was presented at the 2017 ASH Annual Meeting (abstract 1797).

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo from Business Wire

Two cancer organizations have released guidelines for managing the side effects of immune checkpoint inhibitors.

The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) developed these guidelines because patients who receive immune checkpoint inhibitors experience unique side effects that can be severe, irreversible, and life-threatening.

Given that checkpoint inhibitors have entered the clinic fairly recently, clinicians may need guidance in recognizing and treating these side effects.

“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles,” said ASCO Chief Executive Officer Clifford A. Hudis, MD.

“These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care.”

To the develop their guidelines, ASCO and NCCN convened multidisciplinary panels with representation from hematology, oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, emergency medicine, and nursing, as well as patient advocacy experts.

The clinical recommendations are based on a systematic review of the literature and an informal consensus process. The recommendations pertain only to checkpoint inhibitors currently approved in the US—pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, and durvalumab.

Key recommendations from the guidelines include:

• In general, checkpoint inhibitors can be continued with close monitoring if patients experience grade 1 toxicities, with the exception of some neurologic, cardiac, and hematologic toxicities.
• For grade 2 toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
• For grade 3 toxicities, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after grade 3 toxicity, if it is restarted at all.
• In general, grade 4 toxicities necessitate stopping checkpoint inhibitor therapy permanently.

Consult the guidelines for specific recommendations.

ASCO’s guidelines, “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline,” have been published in the Journal of Clinical Oncology.

NCCN’s guidelines, “Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities),” are available on the NCCN website.

Photo from Business Wire

Two cancer organizations have released guidelines for managing the side effects of immune checkpoint inhibitors.

The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) developed these guidelines because patients who receive immune checkpoint inhibitors experience unique side effects that can be severe, irreversible, and life-threatening.

Given that checkpoint inhibitors have entered the clinic fairly recently, clinicians may need guidance in recognizing and treating these side effects.

“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles,” said ASCO Chief Executive Officer Clifford A. Hudis, MD.

“These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care.”

To the develop their guidelines, ASCO and NCCN convened multidisciplinary panels with representation from hematology, oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, emergency medicine, and nursing, as well as patient advocacy experts.

The clinical recommendations are based on a systematic review of the literature and an informal consensus process. The recommendations pertain only to checkpoint inhibitors currently approved in the US—pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, and durvalumab.

Key recommendations from the guidelines include:

• In general, checkpoint inhibitors can be continued with close monitoring if patients experience grade 1 toxicities, with the exception of some neurologic, cardiac, and hematologic toxicities.
• For grade 2 toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
• For grade 3 toxicities, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after grade 3 toxicity, if it is restarted at all.
• In general, grade 4 toxicities necessitate stopping checkpoint inhibitor therapy permanently.

Consult the guidelines for specific recommendations.

ASCO’s guidelines, “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline,” have been published in the Journal of Clinical Oncology.

NCCN’s guidelines, “Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities),” are available on the NCCN website.

Photo from Business Wire

Two cancer organizations have released guidelines for managing the side effects of immune checkpoint inhibitors.

The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) developed these guidelines because patients who receive immune checkpoint inhibitors experience unique side effects that can be severe, irreversible, and life-threatening.

Given that checkpoint inhibitors have entered the clinic fairly recently, clinicians may need guidance in recognizing and treating these side effects.

“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles,” said ASCO Chief Executive Officer Clifford A. Hudis, MD.

“These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care.”

To the develop their guidelines, ASCO and NCCN convened multidisciplinary panels with representation from hematology, oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, emergency medicine, and nursing, as well as patient advocacy experts.

The clinical recommendations are based on a systematic review of the literature and an informal consensus process. The recommendations pertain only to checkpoint inhibitors currently approved in the US—pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, and durvalumab.

Key recommendations from the guidelines include:

• In general, checkpoint inhibitors can be continued with close monitoring if patients experience grade 1 toxicities, with the exception of some neurologic, cardiac, and hematologic toxicities.
• For grade 2 toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
• For grade 3 toxicities, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after grade 3 toxicity, if it is restarted at all.
• In general, grade 4 toxicities necessitate stopping checkpoint inhibitor therapy permanently.

Consult the guidelines for specific recommendations.

ASCO’s guidelines, “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline,” have been published in the Journal of Clinical Oncology.

NCCN’s guidelines, “Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities),” are available on the NCCN website.

Biogen Idec

Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.

Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.

Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.

In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.

No adverse events were reported in this study.

Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.

The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.

The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.

First-timer results

Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.

Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.

The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.

Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.

The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.

All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.

Rescue results

Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).

Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.

Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.

There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.

Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.

In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.

“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.

“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”

Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).

Biogen Idec

Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.

Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.

Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.

In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.

No adverse events were reported in this study.

Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.

The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.

The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.

First-timer results

Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.

Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.

The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.

Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.

The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.

All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.

Rescue results

Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).

Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.

Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.

There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.

Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.

In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.

“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.

“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”

Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).

Biogen Idec

Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.

Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.

Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.

In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.

No adverse events were reported in this study.

Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.

The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.

The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.

First-timer results

Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.

Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.

The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.

Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.

The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.

All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.

Rescue results

Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).

Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.

Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.

There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.

Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.

In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.

“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.

“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”

Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).

Children’s Research Hospital

Many young children with sickle cell anemia (SCA) may not be taking the recommended antibiotics to prevent invasive pneumococcal disease (IPD), according to research published in Pediatrics.

Results of a previous study indicated that daily treatment with penicillin could reduce the risk of IPD by 84% in young children with SCA.

In the current study, only 18% of young SCA patients received daily penicillin or an equivalent antibiotic as IPD prophylaxis.

“Most children with sickle cell anemia are not getting the antibiotics they should be to adequately protect against potentially deadly infections,” said study author Sarah Reeves, PhD, of the University of Michigan Medical School in Ann Arbor.

“Long-standing recommendations say children with sickle cell anemia should take antibiotics daily for their first 5 years of life. It can be life-saving.”

For this study, Dr Reeves and her colleagues analyzed data on 2821 SCA patients, ages 3 months to 5 years, living in Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas.

The patients were continuously enrolled in the Medicaid program for at least 1 calendar year between 2005 and 2012. The researchers evaluated the receipt of antibiotics through the insurance claims for filled prescriptions.

The team found that, overall, 18% of patients received at least 300 days of antibiotics.

Sixteen percent of patients received at least 300 days of penicillin; 16% received at least 300 days of penicillin or erythromycin; 18% received at least 300 days of penicillin, erythromycin, or amoxicillin; and 22% received at least 300 days of any antibiotic to prevent Streptococcus pneumoniae.

On average, patients received 162 days of penicillin; 164 days of penicillin or erythromycin; 178 days of penicillin, erythromycin, or amoxicillin; and 193 days of any antibiotic to prevent S pneumoniae.

Multivariable analysis suggested that medical visits and a patient’s state of residence were associated with receiving at least 300 days of antibiotics.

The researchers said that each additional SCA-related outpatient visit and well-child visit was associated with incrementally increased odds of receiving at least 300 days of antibiotics. The odds ratio (OR) was 1.01 for SCA-related outpatient visits and 1.08 for well-child visits (P<0.05 for both).

Patients in Florida (OR=0.51, P<0.05), Louisiana (OR=0.57, P<0.05), Michigan (OR=0.60, P<0.05), and South Carolina (OR=0.62, P<0.05) had lower odds of receiving at least 300 days of antibiotics than patients in Illinois (OR=1.00) or Texas (OR=1.01).

The researchers did not investigate why children were not receiving recommended antibiotics, but Dr Reeves identified possible barriers to compliance. She noted that caregiver challenges include picking up prescriptions every 2 weeks from a pharmacy as well as remembering to administer an antibiotic to a young, healthy-appearing child twice a day.

“The types of challenges involved in making sure children get the recommended dose of antibiotics is exacerbated by the substantial burden of care already experienced by families to help control the symptoms of this disease,” Dr Reeves said.

She added that future studies should more deeply explore barriers preventing families from getting antibiotics and potential interventions to improve the rate of children receiving recommended prescriptions.

“Interventions to improve the receipt of antibiotics among children with sickle cell anemia should include enhanced collaboration between healthcare providers, pharmacists, and families,” Dr Reeves said.

“Doctors need to repeatedly discuss the importance of taking antibiotics with families of children with sickle cell anemia. Social factors that may impact receiving filled prescriptions should also be considered, such as the availability of transportation and time to travel to pharmacies to pick up the prescriptions.”

Children’s Research Hospital

Many young children with sickle cell anemia (SCA) may not be taking the recommended antibiotics to prevent invasive pneumococcal disease (IPD), according to research published in Pediatrics.

Results of a previous study indicated that daily treatment with penicillin could reduce the risk of IPD by 84% in young children with SCA.

In the current study, only 18% of young SCA patients received daily penicillin or an equivalent antibiotic as IPD prophylaxis.

“Most children with sickle cell anemia are not getting the antibiotics they should be to adequately protect against potentially deadly infections,” said study author Sarah Reeves, PhD, of the University of Michigan Medical School in Ann Arbor.

“Long-standing recommendations say children with sickle cell anemia should take antibiotics daily for their first 5 years of life. It can be life-saving.”

For this study, Dr Reeves and her colleagues analyzed data on 2821 SCA patients, ages 3 months to 5 years, living in Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas.

The patients were continuously enrolled in the Medicaid program for at least 1 calendar year between 2005 and 2012. The researchers evaluated the receipt of antibiotics through the insurance claims for filled prescriptions.

The team found that, overall, 18% of patients received at least 300 days of antibiotics.

Sixteen percent of patients received at least 300 days of penicillin; 16% received at least 300 days of penicillin or erythromycin; 18% received at least 300 days of penicillin, erythromycin, or amoxicillin; and 22% received at least 300 days of any antibiotic to prevent Streptococcus pneumoniae.

On average, patients received 162 days of penicillin; 164 days of penicillin or erythromycin; 178 days of penicillin, erythromycin, or amoxicillin; and 193 days of any antibiotic to prevent S pneumoniae.

Multivariable analysis suggested that medical visits and a patient’s state of residence were associated with receiving at least 300 days of antibiotics.

The researchers said that each additional SCA-related outpatient visit and well-child visit was associated with incrementally increased odds of receiving at least 300 days of antibiotics. The odds ratio (OR) was 1.01 for SCA-related outpatient visits and 1.08 for well-child visits (P<0.05 for both).

Patients in Florida (OR=0.51, P<0.05), Louisiana (OR=0.57, P<0.05), Michigan (OR=0.60, P<0.05), and South Carolina (OR=0.62, P<0.05) had lower odds of receiving at least 300 days of antibiotics than patients in Illinois (OR=1.00) or Texas (OR=1.01).

The researchers did not investigate why children were not receiving recommended antibiotics, but Dr Reeves identified possible barriers to compliance. She noted that caregiver challenges include picking up prescriptions every 2 weeks from a pharmacy as well as remembering to administer an antibiotic to a young, healthy-appearing child twice a day.

“The types of challenges involved in making sure children get the recommended dose of antibiotics is exacerbated by the substantial burden of care already experienced by families to help control the symptoms of this disease,” Dr Reeves said.

She added that future studies should more deeply explore barriers preventing families from getting antibiotics and potential interventions to improve the rate of children receiving recommended prescriptions.

“Interventions to improve the receipt of antibiotics among children with sickle cell anemia should include enhanced collaboration between healthcare providers, pharmacists, and families,” Dr Reeves said.

“Doctors need to repeatedly discuss the importance of taking antibiotics with families of children with sickle cell anemia. Social factors that may impact receiving filled prescriptions should also be considered, such as the availability of transportation and time to travel to pharmacies to pick up the prescriptions.”

Children’s Research Hospital

Many young children with sickle cell anemia (SCA) may not be taking the recommended antibiotics to prevent invasive pneumococcal disease (IPD), according to research published in Pediatrics.

Results of a previous study indicated that daily treatment with penicillin could reduce the risk of IPD by 84% in young children with SCA.

In the current study, only 18% of young SCA patients received daily penicillin or an equivalent antibiotic as IPD prophylaxis.

“Most children with sickle cell anemia are not getting the antibiotics they should be to adequately protect against potentially deadly infections,” said study author Sarah Reeves, PhD, of the University of Michigan Medical School in Ann Arbor.

“Long-standing recommendations say children with sickle cell anemia should take antibiotics daily for their first 5 years of life. It can be life-saving.”

For this study, Dr Reeves and her colleagues analyzed data on 2821 SCA patients, ages 3 months to 5 years, living in Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas.

The patients were continuously enrolled in the Medicaid program for at least 1 calendar year between 2005 and 2012. The researchers evaluated the receipt of antibiotics through the insurance claims for filled prescriptions.

The team found that, overall, 18% of patients received at least 300 days of antibiotics.

Sixteen percent of patients received at least 300 days of penicillin; 16% received at least 300 days of penicillin or erythromycin; 18% received at least 300 days of penicillin, erythromycin, or amoxicillin; and 22% received at least 300 days of any antibiotic to prevent Streptococcus pneumoniae.

On average, patients received 162 days of penicillin; 164 days of penicillin or erythromycin; 178 days of penicillin, erythromycin, or amoxicillin; and 193 days of any antibiotic to prevent S pneumoniae.

Multivariable analysis suggested that medical visits and a patient’s state of residence were associated with receiving at least 300 days of antibiotics.

The researchers said that each additional SCA-related outpatient visit and well-child visit was associated with incrementally increased odds of receiving at least 300 days of antibiotics. The odds ratio (OR) was 1.01 for SCA-related outpatient visits and 1.08 for well-child visits (P<0.05 for both).

Patients in Florida (OR=0.51, P<0.05), Louisiana (OR=0.57, P<0.05), Michigan (OR=0.60, P<0.05), and South Carolina (OR=0.62, P<0.05) had lower odds of receiving at least 300 days of antibiotics than patients in Illinois (OR=1.00) or Texas (OR=1.01).

The researchers did not investigate why children were not receiving recommended antibiotics, but Dr Reeves identified possible barriers to compliance. She noted that caregiver challenges include picking up prescriptions every 2 weeks from a pharmacy as well as remembering to administer an antibiotic to a young, healthy-appearing child twice a day.

“The types of challenges involved in making sure children get the recommended dose of antibiotics is exacerbated by the substantial burden of care already experienced by families to help control the symptoms of this disease,” Dr Reeves said.

She added that future studies should more deeply explore barriers preventing families from getting antibiotics and potential interventions to improve the rate of children receiving recommended prescriptions.

“Interventions to improve the receipt of antibiotics among children with sickle cell anemia should include enhanced collaboration between healthcare providers, pharmacists, and families,” Dr Reeves said.

“Doctors need to repeatedly discuss the importance of taking antibiotics with families of children with sickle cell anemia. Social factors that may impact receiving filled prescriptions should also be considered, such as the availability of transportation and time to travel to pharmacies to pick up the prescriptions.”