Leukemia, Myelodysplasia, Transplantation

SAN FRANCISCO – Pursue a deep remission that allows a patient to stay treatment free for some period of time, or go for long-term disease control that might not allow for a drug holiday?

It’s a key decision facing physicians in the frontline setting of chronic lymphocytic leukemia, William Wierda, MD, PhD, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

SAN FRANCISCO – Pursue a deep remission that allows a patient to stay treatment free for some period of time, or go for long-term disease control that might not allow for a drug holiday?

It’s a key decision facing physicians in the frontline setting of chronic lymphocytic leukemia, William Wierda, MD, PhD, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

SAN FRANCISCO – Pursue a deep remission that allows a patient to stay treatment free for some period of time, or go for long-term disease control that might not allow for a drug holiday?

It’s a key decision facing physicians in the frontline setting of chronic lymphocytic leukemia, William Wierda, MD, PhD, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Photo by Aaron Logan

Targeting two pathways simultaneously—one critical for oncogenesis and one essential for cell survival—may be an effective strategy for treating acute myeloid leukemia (AML), according to researchers.

The team studied mouse models of FLT3-ITD AML and found an inhibitor targeting the FLT3 pathway was largely effective against the disease.

However, targeting the BCL-2 pathway as well proved even more effective, completely eliminating AML in most cases.

Fumihiko Ishikawa, MD, PhD, of RIKEN Center for Integrative Medical Sciences in Yokohama, Kanagawa, Japan, and his colleagues described this work in Science Translational Medicine.

The researchers noted that mutations observed in AML patients have also been observed in elderly people without AML. So the team set out to determine which mutations actually contribute to the disease.

The researchers obtained bone marrow or blood samples from patients with FLT3-ITD AML and transplanted different cellular populations from each individual into mice. The team then examined how the cells behaved.

They were surprised to find that cells with similar surface marker profiles behaved differently. Therefore, the team used single-cell genomic sequencing to correlate mutational profiles with malignant potential.

The researchers said their results suggest that FLT3-ITD is “a critical trigger for leukemia initiation,” and it cooperates with accumulated mutations in DNMT3A, TET2, NPM1, and/or WT1.

The team went on to treat the FLT3-ITD AML mice with RK-20449, a FLT3/HCK inhibitor, and they observed “significant responses.”

In fact, RK-20449 eradicated leukemia originating from 5 different patients. The recipient mice experienced complete elimination of AML cells, in spite of the fact that they also carried mutations not directly targeted by RK-20449.

However, the researchers also noted the presence of RK-20449-resistant AML cells in some mice. The team therefore theorized that co-inhibition of an antiapoptotic signal—BCL-2—might remedy this.

So they treated resistant mice with the BCL-2 inhibitor venetoclax as well as RK-20449. The combination produced responses in all mice treated and completely eliminated AML cells in 9 of 12 cases.

“This shows that determining which of the mutations in a diverse landscape are critical in leukemia onset and which of the pathways are critical for therapeutic resistance in leukemia, and simultaneously targeting those pathways, is an encouraging way to treat difficult cancers such as AML,” Dr Ishikawa said.

Photo by Aaron Logan

Targeting two pathways simultaneously—one critical for oncogenesis and one essential for cell survival—may be an effective strategy for treating acute myeloid leukemia (AML), according to researchers.

The team studied mouse models of FLT3-ITD AML and found an inhibitor targeting the FLT3 pathway was largely effective against the disease.

However, targeting the BCL-2 pathway as well proved even more effective, completely eliminating AML in most cases.

Fumihiko Ishikawa, MD, PhD, of RIKEN Center for Integrative Medical Sciences in Yokohama, Kanagawa, Japan, and his colleagues described this work in Science Translational Medicine.

The researchers noted that mutations observed in AML patients have also been observed in elderly people without AML. So the team set out to determine which mutations actually contribute to the disease.

The researchers obtained bone marrow or blood samples from patients with FLT3-ITD AML and transplanted different cellular populations from each individual into mice. The team then examined how the cells behaved.

They were surprised to find that cells with similar surface marker profiles behaved differently. Therefore, the team used single-cell genomic sequencing to correlate mutational profiles with malignant potential.

The researchers said their results suggest that FLT3-ITD is “a critical trigger for leukemia initiation,” and it cooperates with accumulated mutations in DNMT3A, TET2, NPM1, and/or WT1.

The team went on to treat the FLT3-ITD AML mice with RK-20449, a FLT3/HCK inhibitor, and they observed “significant responses.”

In fact, RK-20449 eradicated leukemia originating from 5 different patients. The recipient mice experienced complete elimination of AML cells, in spite of the fact that they also carried mutations not directly targeted by RK-20449.

However, the researchers also noted the presence of RK-20449-resistant AML cells in some mice. The team therefore theorized that co-inhibition of an antiapoptotic signal—BCL-2—might remedy this.

So they treated resistant mice with the BCL-2 inhibitor venetoclax as well as RK-20449. The combination produced responses in all mice treated and completely eliminated AML cells in 9 of 12 cases.

“This shows that determining which of the mutations in a diverse landscape are critical in leukemia onset and which of the pathways are critical for therapeutic resistance in leukemia, and simultaneously targeting those pathways, is an encouraging way to treat difficult cancers such as AML,” Dr Ishikawa said.

Photo by Aaron Logan

Targeting two pathways simultaneously—one critical for oncogenesis and one essential for cell survival—may be an effective strategy for treating acute myeloid leukemia (AML), according to researchers.

The team studied mouse models of FLT3-ITD AML and found an inhibitor targeting the FLT3 pathway was largely effective against the disease.

However, targeting the BCL-2 pathway as well proved even more effective, completely eliminating AML in most cases.

Fumihiko Ishikawa, MD, PhD, of RIKEN Center for Integrative Medical Sciences in Yokohama, Kanagawa, Japan, and his colleagues described this work in Science Translational Medicine.

The researchers noted that mutations observed in AML patients have also been observed in elderly people without AML. So the team set out to determine which mutations actually contribute to the disease.

The researchers obtained bone marrow or blood samples from patients with FLT3-ITD AML and transplanted different cellular populations from each individual into mice. The team then examined how the cells behaved.

They were surprised to find that cells with similar surface marker profiles behaved differently. Therefore, the team used single-cell genomic sequencing to correlate mutational profiles with malignant potential.

The researchers said their results suggest that FLT3-ITD is “a critical trigger for leukemia initiation,” and it cooperates with accumulated mutations in DNMT3A, TET2, NPM1, and/or WT1.

The team went on to treat the FLT3-ITD AML mice with RK-20449, a FLT3/HCK inhibitor, and they observed “significant responses.”

In fact, RK-20449 eradicated leukemia originating from 5 different patients. The recipient mice experienced complete elimination of AML cells, in spite of the fact that they also carried mutations not directly targeted by RK-20449.

However, the researchers also noted the presence of RK-20449-resistant AML cells in some mice. The team therefore theorized that co-inhibition of an antiapoptotic signal—BCL-2—might remedy this.

So they treated resistant mice with the BCL-2 inhibitor venetoclax as well as RK-20449. The combination produced responses in all mice treated and completely eliminated AML cells in 9 of 12 cases.

“This shows that determining which of the mutations in a diverse landscape are critical in leukemia onset and which of the pathways are critical for therapeutic resistance in leukemia, and simultaneously targeting those pathways, is an encouraging way to treat difficult cancers such as AML,” Dr Ishikawa said.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

multiple myeloma

Preclinical research has revealed a potential method of overcoming resistance to proteasome inhibitors.

By studying a rare genetic disease known as NGLY1 deficiency, researchers have gained new understanding of resistance to proteasome inhibitors.

The team found that treatment with a NGLY1 inhibitor can enhance the activity of the proteasome inhibitor carfilzomib against multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL).

Carolyn Bertozzi, PhD, of Stanford University in California, and her colleagues reported these findings in ACS Central Science.

Previous studies have suggested that proteasome inhibitor resistance could be linked to a protein called Nrf1. When proteasome inhibitors swing into action, Nrf1 is spurred into overdrive to restore cancer cells’ normal activities and keep them alive.

Researchers theorized that, if they could block Nrf1, they might be able to overcome proteasome inhibitor resistance.

Through studying NGLY1 deficiency, Dr Bertozzi and her colleagues may have hit upon an approach to do just that.

The researchers were investigating how lacking NGLY1 causes a host of debilitating symptoms, and they found that NGLY1 is responsible for activating Nrf1.

Further testing revealed that inhibiting NGLY1 eliminated interference from Nrf1 and enhanced the cytotoxicity of carfilzomib in MM and T-ALL cell lines.

The researchers treated the MM cell lines U266 and H929 with the NGLY1 inhibitor, known as WRR139, and carfilzomib and observed a significant decrease in cell survival when compared to treatment with carfilzomib alone. The team observed the same results when testing the T-ALL Jurkat cell line.

The addition of WRR139 resulted in a 2.6-fold reduction in carfilzomib’s LD50 for U266, a 2.0-fold reduction for H929, and a 1.5-fold reduction for Jurkat cells.

The researchers said these findings hold promise for the development of combination therapies for hematologic malignancies.

multiple myeloma

Preclinical research has revealed a potential method of overcoming resistance to proteasome inhibitors.

By studying a rare genetic disease known as NGLY1 deficiency, researchers have gained new understanding of resistance to proteasome inhibitors.

The team found that treatment with a NGLY1 inhibitor can enhance the activity of the proteasome inhibitor carfilzomib against multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL).

Carolyn Bertozzi, PhD, of Stanford University in California, and her colleagues reported these findings in ACS Central Science.

Previous studies have suggested that proteasome inhibitor resistance could be linked to a protein called Nrf1. When proteasome inhibitors swing into action, Nrf1 is spurred into overdrive to restore cancer cells’ normal activities and keep them alive.

Researchers theorized that, if they could block Nrf1, they might be able to overcome proteasome inhibitor resistance.

Through studying NGLY1 deficiency, Dr Bertozzi and her colleagues may have hit upon an approach to do just that.

The researchers were investigating how lacking NGLY1 causes a host of debilitating symptoms, and they found that NGLY1 is responsible for activating Nrf1.

Further testing revealed that inhibiting NGLY1 eliminated interference from Nrf1 and enhanced the cytotoxicity of carfilzomib in MM and T-ALL cell lines.

The researchers treated the MM cell lines U266 and H929 with the NGLY1 inhibitor, known as WRR139, and carfilzomib and observed a significant decrease in cell survival when compared to treatment with carfilzomib alone. The team observed the same results when testing the T-ALL Jurkat cell line.

The addition of WRR139 resulted in a 2.6-fold reduction in carfilzomib’s LD50 for U266, a 2.0-fold reduction for H929, and a 1.5-fold reduction for Jurkat cells.

The researchers said these findings hold promise for the development of combination therapies for hematologic malignancies.

multiple myeloma

Preclinical research has revealed a potential method of overcoming resistance to proteasome inhibitors.

By studying a rare genetic disease known as NGLY1 deficiency, researchers have gained new understanding of resistance to proteasome inhibitors.

The team found that treatment with a NGLY1 inhibitor can enhance the activity of the proteasome inhibitor carfilzomib against multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL).

Carolyn Bertozzi, PhD, of Stanford University in California, and her colleagues reported these findings in ACS Central Science.

Previous studies have suggested that proteasome inhibitor resistance could be linked to a protein called Nrf1. When proteasome inhibitors swing into action, Nrf1 is spurred into overdrive to restore cancer cells’ normal activities and keep them alive.

Researchers theorized that, if they could block Nrf1, they might be able to overcome proteasome inhibitor resistance.

Through studying NGLY1 deficiency, Dr Bertozzi and her colleagues may have hit upon an approach to do just that.

The researchers were investigating how lacking NGLY1 causes a host of debilitating symptoms, and they found that NGLY1 is responsible for activating Nrf1.

Further testing revealed that inhibiting NGLY1 eliminated interference from Nrf1 and enhanced the cytotoxicity of carfilzomib in MM and T-ALL cell lines.

The researchers treated the MM cell lines U266 and H929 with the NGLY1 inhibitor, known as WRR139, and carfilzomib and observed a significant decrease in cell survival when compared to treatment with carfilzomib alone. The team observed the same results when testing the T-ALL Jurkat cell line.

The addition of WRR139 resulted in a 2.6-fold reduction in carfilzomib’s LD50 for U266, a 2.0-fold reduction for H929, and a 1.5-fold reduction for Jurkat cells.

The researchers said these findings hold promise for the development of combination therapies for hematologic malignancies.

SAN FRANCISCO – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.

“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.

SAN FRANCISCO – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.

“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.

SAN FRANCISCO – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.

“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.

Image from PLOS ONE

Results of a phase 3 trial suggest rabbit anti-T lymphocyte globulin (ATLG) can reduce graft-versus-host disease (GVHD) but also decrease survival in patients who have received a hematopoietic stem cell transplant (HSCT) from a matched, unrelated donor.

In this randomized trial, ATLG significantly decreased the incidence of moderate-to-severe chronic GVHD and acute grade 2-4 GVHD, when compared to placebo.

However, patients who received ATLG also had significantly lower progression-free survival (PFS) and overall survival (OS) than placebo-treated patients.

On the other hand, the data also suggest that patients who receive conditioning regimens that do not lower absolute lymphocyte counts (ALCs) substantially may not experience a significant decrease in survival with ATLG.

These results were published in the Journal of Clinical Oncology. The study was sponsored by Neovii Pharmaceuticals AG, which is developing ATLG as Grafalon®.

The study was a prospective, randomized, double-blind trial conducted in North America and Australia (NCT01295710). It enrolled 254 patients, ages 18 to 65, who had acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndromes. All patients were undergoing myeloablative, HLA-matched, unrelated HSCT.

Patients were randomized in a 1:1 fashion to receive ATLG (given at 20 mg/kg/day, n=126) or placebo (250 ml of normal saline, n=128) on days -3, -2, and -1 prior to HSCT.

In addition, all patients received antihistamine and methylprednisolone (at 2 mg/kg on day -3 and 1 mg/kg on days -2 and -1).

Patients also received GVHD prophylaxis in the form of tacrolimus (with a target serum trough level of 5 to 15 ng/mL) and methotrexate (15 mg/m² on day 1, then 10 mg/m² on days 3, 6, and 11). If patients did not develop clinical GVHD, tacrolimus was tapered starting on day 50 or later over a minimum of 26 weeks and ultimately discontinued.

Patients received 1 of 3 conditioning regimens, which were declared prior to randomization and included:

• Cyclophosphamide at 120 mg/kg intravenously (IV) and fractionated total body irradiation (TBI, ≥12 Gy)
• Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and cyclophosphamide at 120 mg/kg IV
• Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and fludarabine at 120 mg/m2 IV.

Overall results

Compared to placebo-treated patients, those who received ATLG had a significant reduction in grade 2-4 acute GVHD—23% and 40%, respectively (P=0.004)—and moderate-to-severe chronic GVHD—12% and 33%, respectively (P<0.001).

However, there was no significant difference between the ATLG and placebo arms with regard to moderate-severe chronic GVHD-free survival. The 2-year estimate was 48% and 44%, respectively (P=0.47).

In addition, PFS and OS were significantly lower in patients who received ATLG. The estimated 2-year PFS was 47% in the ATLG arm and 65% in the placebo arm (P=0.04). The estimated 2-year OS was 59% and 74%, respectively (P=0.034).

In a multivariable analysis, ATLG remained significantly associated with inferior PFS (hazard ratio [HR]=1.55, P=0.026) and OS (hazard ratio=1.74, P=0.01).

Role of conditioning, ALC

The researchers found evidence to suggest that conditioning regimen and ALC played a role in patient outcomes.

For patients who received cyclophosphamide and TBI, 2-year moderate-severe chronic GVHD-free survival was 61% in the placebo arm and 38% in the ATLG arm (P=0.080). Two-year OS was 88% and 48%, respectively (P=0.006). And 2-year PFS was 75% and 29%, respectively (P=0.007).

For patients who received busulfan and cyclophosphamide, 2-year moderate-severe chronic GVHD-free survival was 47% in the placebo arm and 53% in the ATLG arm (P=0.650). Two-year OS was 77% and 71%, respectively (P=0.350). And 2-year PFS was 73% and 60%, respectively (P=0.460).

For patients who received busulfan and fludarabine, 2-year moderate-severe chronic GVHD-free survival was 33% in the placebo arm and 49% in the ATLG arm (P=0.047). Two-year OS was 66% and 53%, respectively (P=0.520). And 2-year PFS was 58% and 48%, respectively (P=0.540).

The researchers noted that the choice of conditioning regimen had a “profound effect” on ALC at day -3 (the time of ATLG/placebo initiation). More than 70% of patients who received TBI had an ALC <0.1 x 10⁹/L, compared to less than 35% of patients who received busulfan-based conditioning.

ALC, in turn, had an impact on PFS and OS. In patients with an ALC ≥ 0.1 x 10⁹/L on day -3, ATLG did not compromise PFS or OS, but PFS and OS were negatively affected in patients with an ALC < 0.1.

ATLG recipients with an ALC < 0.1 had significantly worse OS (HR=4.13, P<0.001) and PFS (HR=3.19, P<0.001) than patients with an ALC ≥ 0.1.

Image from PLOS ONE

Results of a phase 3 trial suggest rabbit anti-T lymphocyte globulin (ATLG) can reduce graft-versus-host disease (GVHD) but also decrease survival in patients who have received a hematopoietic stem cell transplant (HSCT) from a matched, unrelated donor.

In this randomized trial, ATLG significantly decreased the incidence of moderate-to-severe chronic GVHD and acute grade 2-4 GVHD, when compared to placebo.

However, patients who received ATLG also had significantly lower progression-free survival (PFS) and overall survival (OS) than placebo-treated patients.

On the other hand, the data also suggest that patients who receive conditioning regimens that do not lower absolute lymphocyte counts (ALCs) substantially may not experience a significant decrease in survival with ATLG.

These results were published in the Journal of Clinical Oncology. The study was sponsored by Neovii Pharmaceuticals AG, which is developing ATLG as Grafalon®.

The study was a prospective, randomized, double-blind trial conducted in North America and Australia (NCT01295710). It enrolled 254 patients, ages 18 to 65, who had acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndromes. All patients were undergoing myeloablative, HLA-matched, unrelated HSCT.

Patients were randomized in a 1:1 fashion to receive ATLG (given at 20 mg/kg/day, n=126) or placebo (250 ml of normal saline, n=128) on days -3, -2, and -1 prior to HSCT.

In addition, all patients received antihistamine and methylprednisolone (at 2 mg/kg on day -3 and 1 mg/kg on days -2 and -1).

Patients also received GVHD prophylaxis in the form of tacrolimus (with a target serum trough level of 5 to 15 ng/mL) and methotrexate (15 mg/m² on day 1, then 10 mg/m² on days 3, 6, and 11). If patients did not develop clinical GVHD, tacrolimus was tapered starting on day 50 or later over a minimum of 26 weeks and ultimately discontinued.

Patients received 1 of 3 conditioning regimens, which were declared prior to randomization and included:

• Cyclophosphamide at 120 mg/kg intravenously (IV) and fractionated total body irradiation (TBI, ≥12 Gy)
• Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and cyclophosphamide at 120 mg/kg IV
• Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and fludarabine at 120 mg/m2 IV.

Overall results

Compared to placebo-treated patients, those who received ATLG had a significant reduction in grade 2-4 acute GVHD—23% and 40%, respectively (P=0.004)—and moderate-to-severe chronic GVHD—12% and 33%, respectively (P<0.001).

However, there was no significant difference between the ATLG and placebo arms with regard to moderate-severe chronic GVHD-free survival. The 2-year estimate was 48% and 44%, respectively (P=0.47).

In addition, PFS and OS were significantly lower in patients who received ATLG. The estimated 2-year PFS was 47% in the ATLG arm and 65% in the placebo arm (P=0.04). The estimated 2-year OS was 59% and 74%, respectively (P=0.034).

In a multivariable analysis, ATLG remained significantly associated with inferior PFS (hazard ratio [HR]=1.55, P=0.026) and OS (hazard ratio=1.74, P=0.01).

Role of conditioning, ALC

The researchers found evidence to suggest that conditioning regimen and ALC played a role in patient outcomes.

For patients who received cyclophosphamide and TBI, 2-year moderate-severe chronic GVHD-free survival was 61% in the placebo arm and 38% in the ATLG arm (P=0.080). Two-year OS was 88% and 48%, respectively (P=0.006). And 2-year PFS was 75% and 29%, respectively (P=0.007).

For patients who received busulfan and cyclophosphamide, 2-year moderate-severe chronic GVHD-free survival was 47% in the placebo arm and 53% in the ATLG arm (P=0.650). Two-year OS was 77% and 71%, respectively (P=0.350). And 2-year PFS was 73% and 60%, respectively (P=0.460).

For patients who received busulfan and fludarabine, 2-year moderate-severe chronic GVHD-free survival was 33% in the placebo arm and 49% in the ATLG arm (P=0.047). Two-year OS was 66% and 53%, respectively (P=0.520). And 2-year PFS was 58% and 48%, respectively (P=0.540).

The researchers noted that the choice of conditioning regimen had a “profound effect” on ALC at day -3 (the time of ATLG/placebo initiation). More than 70% of patients who received TBI had an ALC <0.1 x 10⁹/L, compared to less than 35% of patients who received busulfan-based conditioning.

ALC, in turn, had an impact on PFS and OS. In patients with an ALC ≥ 0.1 x 10⁹/L on day -3, ATLG did not compromise PFS or OS, but PFS and OS were negatively affected in patients with an ALC < 0.1.

ATLG recipients with an ALC < 0.1 had significantly worse OS (HR=4.13, P<0.001) and PFS (HR=3.19, P<0.001) than patients with an ALC ≥ 0.1.

Image from PLOS ONE

Results of a phase 3 trial suggest rabbit anti-T lymphocyte globulin (ATLG) can reduce graft-versus-host disease (GVHD) but also decrease survival in patients who have received a hematopoietic stem cell transplant (HSCT) from a matched, unrelated donor.

In this randomized trial, ATLG significantly decreased the incidence of moderate-to-severe chronic GVHD and acute grade 2-4 GVHD, when compared to placebo.

However, patients who received ATLG also had significantly lower progression-free survival (PFS) and overall survival (OS) than placebo-treated patients.

On the other hand, the data also suggest that patients who receive conditioning regimens that do not lower absolute lymphocyte counts (ALCs) substantially may not experience a significant decrease in survival with ATLG.

These results were published in the Journal of Clinical Oncology. The study was sponsored by Neovii Pharmaceuticals AG, which is developing ATLG as Grafalon®.

The study was a prospective, randomized, double-blind trial conducted in North America and Australia (NCT01295710). It enrolled 254 patients, ages 18 to 65, who had acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndromes. All patients were undergoing myeloablative, HLA-matched, unrelated HSCT.

Patients were randomized in a 1:1 fashion to receive ATLG (given at 20 mg/kg/day, n=126) or placebo (250 ml of normal saline, n=128) on days -3, -2, and -1 prior to HSCT.

In addition, all patients received antihistamine and methylprednisolone (at 2 mg/kg on day -3 and 1 mg/kg on days -2 and -1).

Patients also received GVHD prophylaxis in the form of tacrolimus (with a target serum trough level of 5 to 15 ng/mL) and methotrexate (15 mg/m² on day 1, then 10 mg/m² on days 3, 6, and 11). If patients did not develop clinical GVHD, tacrolimus was tapered starting on day 50 or later over a minimum of 26 weeks and ultimately discontinued.

Patients received 1 of 3 conditioning regimens, which were declared prior to randomization and included:

• Cyclophosphamide at 120 mg/kg intravenously (IV) and fractionated total body irradiation (TBI, ≥12 Gy)
• Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and cyclophosphamide at 120 mg/kg IV
• Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and fludarabine at 120 mg/m2 IV.

Overall results

Compared to placebo-treated patients, those who received ATLG had a significant reduction in grade 2-4 acute GVHD—23% and 40%, respectively (P=0.004)—and moderate-to-severe chronic GVHD—12% and 33%, respectively (P<0.001).

However, there was no significant difference between the ATLG and placebo arms with regard to moderate-severe chronic GVHD-free survival. The 2-year estimate was 48% and 44%, respectively (P=0.47).

In addition, PFS and OS were significantly lower in patients who received ATLG. The estimated 2-year PFS was 47% in the ATLG arm and 65% in the placebo arm (P=0.04). The estimated 2-year OS was 59% and 74%, respectively (P=0.034).

In a multivariable analysis, ATLG remained significantly associated with inferior PFS (hazard ratio [HR]=1.55, P=0.026) and OS (hazard ratio=1.74, P=0.01).

Role of conditioning, ALC

The researchers found evidence to suggest that conditioning regimen and ALC played a role in patient outcomes.

For patients who received cyclophosphamide and TBI, 2-year moderate-severe chronic GVHD-free survival was 61% in the placebo arm and 38% in the ATLG arm (P=0.080). Two-year OS was 88% and 48%, respectively (P=0.006). And 2-year PFS was 75% and 29%, respectively (P=0.007).

For patients who received busulfan and cyclophosphamide, 2-year moderate-severe chronic GVHD-free survival was 47% in the placebo arm and 53% in the ATLG arm (P=0.650). Two-year OS was 77% and 71%, respectively (P=0.350). And 2-year PFS was 73% and 60%, respectively (P=0.460).

For patients who received busulfan and fludarabine, 2-year moderate-severe chronic GVHD-free survival was 33% in the placebo arm and 49% in the ATLG arm (P=0.047). Two-year OS was 66% and 53%, respectively (P=0.520). And 2-year PFS was 58% and 48%, respectively (P=0.540).

The researchers noted that the choice of conditioning regimen had a “profound effect” on ALC at day -3 (the time of ATLG/placebo initiation). More than 70% of patients who received TBI had an ALC <0.1 x 10⁹/L, compared to less than 35% of patients who received busulfan-based conditioning.

ALC, in turn, had an impact on PFS and OS. In patients with an ALC ≥ 0.1 x 10⁹/L on day -3, ATLG did not compromise PFS or OS, but PFS and OS were negatively affected in patients with an ALC < 0.1.

ATLG recipients with an ALC < 0.1 had significantly worse OS (HR=4.13, P<0.001) and PFS (HR=3.19, P<0.001) than patients with an ALC ≥ 0.1.

Older patients with acute myeloid leukemia (AML) tend to overestimate not only the risks of treatment, but also their likelihood of cure, according to the results of a 100-patient longitudinal study presented at the Palliative and Supportive Care in Oncology Symposium.

Compared with what their oncologists thought, patients were significantly more likely to believe they would die from treatment, said senior study author Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston.

Yet when surveyed again 1 month later, they were significantly more likely to overestimate the chances of being cured, versus the chances of cure given by their oncologists.

“We really need interventions to facilitate communication and ensure accurate prognostic understanding in this patient population, where understanding the treatment risk and prognosis can have a significant effect on their treatment choices and treatment decisions,” Dr. El-Jawahri said in a press conference from the symposium, which was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

Patients were first surveyed within 72 hours of starting chemotherapy.

At that point, 91% of patients said it was somewhat likely (63%) or extremely likely (28%) they would die as a result of their treatment, but among their oncologists, only 22% said death due to treatment was somewhat likely, and none thought it was very likely, according to the presented data.

A much different picture emerged 1 month later, when 90% of patients said they were somewhat or very likely to be cured of their leukemia, while only 26% of physicians said it was somewhat likely for the patient to be cured.

For both the question on treatment risk and the question on cure potential, the differences between patient responses and physician responses was significant (P less than .001), according to Dr. El-Jawahri.

Of note, half of the patients (n = 50) received intensive chemotherapy, while the other half received nonintensive (that is, palliative) chemotherapy. Patients receiving palliative therapy were even more likely to overestimate their chances of cure, Dr. El-Jawahi said.

This study highlights how stress and anxiety might shape a patient’s perception of treatment and prognosis, and provides new evidence that “accurate knowledge” can lead to “efficiencies on both sides of this [doctor-patient] interface,” said Andrew S. Epstein, MD, of Memorial Sloan-Kettering Cancer Center, New York.

A shared understanding of prognosis and treatment risk between clinician and patient is “crucial in informed consent” and can help patients make better-informed decisions with their doctor, said Dr. Epstein, who was not involved with the study.

This study was funded by a grant from the National Cancer Institute. Dr. El-Jawahri, the senior author, reported no relevant financial disclosures.

Older patients with acute myeloid leukemia (AML) tend to overestimate not only the risks of treatment, but also their likelihood of cure, according to the results of a 100-patient longitudinal study presented at the Palliative and Supportive Care in Oncology Symposium.

Compared with what their oncologists thought, patients were significantly more likely to believe they would die from treatment, said senior study author Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston.

Yet when surveyed again 1 month later, they were significantly more likely to overestimate the chances of being cured, versus the chances of cure given by their oncologists.

“We really need interventions to facilitate communication and ensure accurate prognostic understanding in this patient population, where understanding the treatment risk and prognosis can have a significant effect on their treatment choices and treatment decisions,” Dr. El-Jawahri said in a press conference from the symposium, which was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

Patients were first surveyed within 72 hours of starting chemotherapy.

At that point, 91% of patients said it was somewhat likely (63%) or extremely likely (28%) they would die as a result of their treatment, but among their oncologists, only 22% said death due to treatment was somewhat likely, and none thought it was very likely, according to the presented data.

A much different picture emerged 1 month later, when 90% of patients said they were somewhat or very likely to be cured of their leukemia, while only 26% of physicians said it was somewhat likely for the patient to be cured.

For both the question on treatment risk and the question on cure potential, the differences between patient responses and physician responses was significant (P less than .001), according to Dr. El-Jawahri.

Of note, half of the patients (n = 50) received intensive chemotherapy, while the other half received nonintensive (that is, palliative) chemotherapy. Patients receiving palliative therapy were even more likely to overestimate their chances of cure, Dr. El-Jawahi said.

This study highlights how stress and anxiety might shape a patient’s perception of treatment and prognosis, and provides new evidence that “accurate knowledge” can lead to “efficiencies on both sides of this [doctor-patient] interface,” said Andrew S. Epstein, MD, of Memorial Sloan-Kettering Cancer Center, New York.

A shared understanding of prognosis and treatment risk between clinician and patient is “crucial in informed consent” and can help patients make better-informed decisions with their doctor, said Dr. Epstein, who was not involved with the study.

This study was funded by a grant from the National Cancer Institute. Dr. El-Jawahri, the senior author, reported no relevant financial disclosures.

Older patients with acute myeloid leukemia (AML) tend to overestimate not only the risks of treatment, but also their likelihood of cure, according to the results of a 100-patient longitudinal study presented at the Palliative and Supportive Care in Oncology Symposium.

Compared with what their oncologists thought, patients were significantly more likely to believe they would die from treatment, said senior study author Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston.

Yet when surveyed again 1 month later, they were significantly more likely to overestimate the chances of being cured, versus the chances of cure given by their oncologists.

“We really need interventions to facilitate communication and ensure accurate prognostic understanding in this patient population, where understanding the treatment risk and prognosis can have a significant effect on their treatment choices and treatment decisions,” Dr. El-Jawahri said in a press conference from the symposium, which was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

Patients were first surveyed within 72 hours of starting chemotherapy.

At that point, 91% of patients said it was somewhat likely (63%) or extremely likely (28%) they would die as a result of their treatment, but among their oncologists, only 22% said death due to treatment was somewhat likely, and none thought it was very likely, according to the presented data.

A much different picture emerged 1 month later, when 90% of patients said they were somewhat or very likely to be cured of their leukemia, while only 26% of physicians said it was somewhat likely for the patient to be cured.

For both the question on treatment risk and the question on cure potential, the differences between patient responses and physician responses was significant (P less than .001), according to Dr. El-Jawahri.

Of note, half of the patients (n = 50) received intensive chemotherapy, while the other half received nonintensive (that is, palliative) chemotherapy. Patients receiving palliative therapy were even more likely to overestimate their chances of cure, Dr. El-Jawahi said.

This study highlights how stress and anxiety might shape a patient’s perception of treatment and prognosis, and provides new evidence that “accurate knowledge” can lead to “efficiencies on both sides of this [doctor-patient] interface,” said Andrew S. Epstein, MD, of Memorial Sloan-Kettering Cancer Center, New York.

A shared understanding of prognosis and treatment risk between clinician and patient is “crucial in informed consent” and can help patients make better-informed decisions with their doctor, said Dr. Epstein, who was not involved with the study.

This study was funded by a grant from the National Cancer Institute. Dr. El-Jawahri, the senior author, reported no relevant financial disclosures.

Photo by Bill Branson

Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.

CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.

Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.

The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.

The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).

Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).

Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.

Results

CCSs were more likely than siblings to report:

• Job lock—23.2% and 16.9%, respectively (P=0.16)
• Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
• Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).

In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).

In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).

The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.

“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”

“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”

Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.

Photo by Bill Branson

Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.

CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.

Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.

The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.

The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).

Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).

Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.

Results

CCSs were more likely than siblings to report:

• Job lock—23.2% and 16.9%, respectively (P=0.16)
• Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
• Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).

In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).

In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).

The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.

“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”

“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”

Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.

Photo by Bill Branson

Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.

CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.

Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.

The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.

The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).

Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).

Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.

Results

CCSs were more likely than siblings to report:

• Job lock—23.2% and 16.9%, respectively (P=0.16)
• Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
• Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).

In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).

In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).

The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.

“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”

“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”

Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.

Photo by Rhoda Baer

New research indicates that hospitalized patients with advanced cancer have a high burden of physical and psychological symptoms, and this burden is linked to longer hospital stays and a greater risk for unplanned hospital readmissions and death.

Researchers said these findings highlight the need to develop and test interventions to lessen patients’ symptoms.

Ryan Nipp, MD, of Massachusetts General Hospital in Boston, and his colleagues reported the findings in Cancer.

The researchers noted that patients with advanced cancer often experience frequent and prolonged hospitalizations for reasons that have not been fully explored.

To investigate, the team collected information from 1036 patients with advanced cancer as they were being admitted for an unplanned hospitalization.

The Edmonton Symptom Assessment System (ESAS) was used to assess patients’ physical symptoms, and the Patient Health Questionnaire 4 (PHQ-4) was used to assess their psychological symptoms.

The researchers examined the relationship between patients’ symptom burden and the duration of their hospital stay, risk of readmission, and death.

Many patients reported moderate or severe fatigue (86.7%), poor well-being (74.2%), drowsiness (71.7%), pain (67.7%), and lack of appetite (67.3%). Nearly 30% of patients had clinically significant symptoms of depression (28.8%) and anxiety (28.0%).

The patients’ mean hospital stay was 6.3 days, the readmission rate within 90 days of discharge was 43.1%, and the 90-day mortality rate was 41.6%.

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P=0.040), and depression symptoms (P=0.017) were significantly associated with longer hospital stays, but anxiety symptoms were not (P=0.190).

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P=0.072), and anxiety symptoms (P=0.045) were significantly associated with a higher likelihood of readmission within 90 days, but depression symptoms were not (P=0.219).

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P<0.001), depression symptoms (P<0.001), and anxiety symptoms (P=0.012) were all significantly associated with a higher likelihood of death or readmission within 90 days.

“We demonstrated that many hospitalized patients with advanced cancer experience an immense physical and psychological symptom burden,” Dr Nipp said.

“Interventions to identify and treat symptomatic patients hold great potential for improving patients’ experience with their illness, enhancing their quality of life, and reducing their healthcare utilization.”

Photo by Rhoda Baer

New research indicates that hospitalized patients with advanced cancer have a high burden of physical and psychological symptoms, and this burden is linked to longer hospital stays and a greater risk for unplanned hospital readmissions and death.

Researchers said these findings highlight the need to develop and test interventions to lessen patients’ symptoms.

Ryan Nipp, MD, of Massachusetts General Hospital in Boston, and his colleagues reported the findings in Cancer.

The researchers noted that patients with advanced cancer often experience frequent and prolonged hospitalizations for reasons that have not been fully explored.

To investigate, the team collected information from 1036 patients with advanced cancer as they were being admitted for an unplanned hospitalization.

The Edmonton Symptom Assessment System (ESAS) was used to assess patients’ physical symptoms, and the Patient Health Questionnaire 4 (PHQ-4) was used to assess their psychological symptoms.

The researchers examined the relationship between patients’ symptom burden and the duration of their hospital stay, risk of readmission, and death.

Many patients reported moderate or severe fatigue (86.7%), poor well-being (74.2%), drowsiness (71.7%), pain (67.7%), and lack of appetite (67.3%). Nearly 30% of patients had clinically significant symptoms of depression (28.8%) and anxiety (28.0%).

The patients’ mean hospital stay was 6.3 days, the readmission rate within 90 days of discharge was 43.1%, and the 90-day mortality rate was 41.6%.

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P=0.040), and depression symptoms (P=0.017) were significantly associated with longer hospital stays, but anxiety symptoms were not (P=0.190).

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P=0.072), and anxiety symptoms (P=0.045) were significantly associated with a higher likelihood of readmission within 90 days, but depression symptoms were not (P=0.219).

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P<0.001), depression symptoms (P<0.001), and anxiety symptoms (P=0.012) were all significantly associated with a higher likelihood of death or readmission within 90 days.

“We demonstrated that many hospitalized patients with advanced cancer experience an immense physical and psychological symptom burden,” Dr Nipp said.

“Interventions to identify and treat symptomatic patients hold great potential for improving patients’ experience with their illness, enhancing their quality of life, and reducing their healthcare utilization.”

Photo by Rhoda Baer

New research indicates that hospitalized patients with advanced cancer have a high burden of physical and psychological symptoms, and this burden is linked to longer hospital stays and a greater risk for unplanned hospital readmissions and death.

Researchers said these findings highlight the need to develop and test interventions to lessen patients’ symptoms.

Ryan Nipp, MD, of Massachusetts General Hospital in Boston, and his colleagues reported the findings in Cancer.

The researchers noted that patients with advanced cancer often experience frequent and prolonged hospitalizations for reasons that have not been fully explored.

To investigate, the team collected information from 1036 patients with advanced cancer as they were being admitted for an unplanned hospitalization.

The Edmonton Symptom Assessment System (ESAS) was used to assess patients’ physical symptoms, and the Patient Health Questionnaire 4 (PHQ-4) was used to assess their psychological symptoms.

The researchers examined the relationship between patients’ symptom burden and the duration of their hospital stay, risk of readmission, and death.

Many patients reported moderate or severe fatigue (86.7%), poor well-being (74.2%), drowsiness (71.7%), pain (67.7%), and lack of appetite (67.3%). Nearly 30% of patients had clinically significant symptoms of depression (28.8%) and anxiety (28.0%).

The patients’ mean hospital stay was 6.3 days, the readmission rate within 90 days of discharge was 43.1%, and the 90-day mortality rate was 41.6%.

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P=0.040), and depression symptoms (P=0.017) were significantly associated with longer hospital stays, but anxiety symptoms were not (P=0.190).

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P=0.072), and anxiety symptoms (P=0.045) were significantly associated with a higher likelihood of readmission within 90 days, but depression symptoms were not (P=0.219).

Physical symptoms (P<0.001), total ESAS score (P<0.001), total PHQ-4 score (P<0.001), depression symptoms (P<0.001), and anxiety symptoms (P=0.012) were all significantly associated with a higher likelihood of death or readmission within 90 days.

“We demonstrated that many hospitalized patients with advanced cancer experience an immense physical and psychological symptom burden,” Dr Nipp said.

“Interventions to identify and treat symptomatic patients hold great potential for improving patients’ experience with their illness, enhancing their quality of life, and reducing their healthcare utilization.”

Red blood cells

Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).

Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.

However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.

Researchers reported these findings in Nature Cell Biology.

The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.

The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.

“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.

“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”

“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.

“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”

“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.”

Red blood cells

Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).

Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.

However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.

Researchers reported these findings in Nature Cell Biology.

The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.

The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.

“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.

“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”

“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.

“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”

“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.”

Red blood cells

Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).

Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.

However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.

Researchers reported these findings in Nature Cell Biology.

The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.

The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.

“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.

“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”

“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.

“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”

“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.”