HT Staff

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.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

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.

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has accepted an investigational new drug application for SHP654 (also known as BAX 888) and granted the therapy orphan drug designation.

SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using an adeno-associated virus serotype 8 vector to deliver codon-optimized, B-domain-deleted FVIII specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.

Shire, the company developing SHP654, received FDA clearance for an investigational new drug application to initiate a global, phase 1/2 study of SHP654.

In this study, researchers will evaluate the safety and optimal dose of SHP654 needed to boost FVIII activity levels and affect hemophilic bleeding. Shire expects this study will begin by the end of this year.

The FDA also granted orphan designation to SHP654. The agency 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.

“This important orphan drug designation highlights Shire’s commitment to patients with rare diseases, and, for hemophilia patients specifically, our aim is to help them achieve zero bleeds,” said Paul Monahan, MD, senior medical director of gene therapy at Shire.

“We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has accepted an investigational new drug application for SHP654 (also known as BAX 888) and granted the therapy orphan drug designation.

SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using an adeno-associated virus serotype 8 vector to deliver codon-optimized, B-domain-deleted FVIII specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.

Shire, the company developing SHP654, received FDA clearance for an investigational new drug application to initiate a global, phase 1/2 study of SHP654.

In this study, researchers will evaluate the safety and optimal dose of SHP654 needed to boost FVIII activity levels and affect hemophilic bleeding. Shire expects this study will begin by the end of this year.

The FDA also granted orphan designation to SHP654. The agency 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.

“This important orphan drug designation highlights Shire’s commitment to patients with rare diseases, and, for hemophilia patients specifically, our aim is to help them achieve zero bleeds,” said Paul Monahan, MD, senior medical director of gene therapy at Shire.

“We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has accepted an investigational new drug application for SHP654 (also known as BAX 888) and granted the therapy orphan drug designation.

SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using an adeno-associated virus serotype 8 vector to deliver codon-optimized, B-domain-deleted FVIII specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.

Shire, the company developing SHP654, received FDA clearance for an investigational new drug application to initiate a global, phase 1/2 study of SHP654.

In this study, researchers will evaluate the safety and optimal dose of SHP654 needed to boost FVIII activity levels and affect hemophilic bleeding. Shire expects this study will begin by the end of this year.

The FDA also granted orphan designation to SHP654. The agency 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.

“This important orphan drug designation highlights Shire’s commitment to patients with rare diseases, and, for hemophilia patients specifically, our aim is to help them achieve zero bleeds,” said Paul Monahan, MD, senior medical director of gene therapy at Shire.

“We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”

Ortho Clinical Diagnostics

The China Food and Drug Administration has approved Ortho Clinical Diagnostics’ ORTHO VISION® Platform of fully automated blood analyzers for transfusion medicine laboratories.

The platform consists of ORTHO VISION and ORTHO VISION Max.

ORTHO VISION is a blood analyzer designed for small- to mid-sized transfusion labs, and ORTHO VISION Max is an analyzer developed for mid- to high-volume labs.

According to Ortho Clinical Diagnostics, the ORTHO VISION Platform automates more tests than ever before and takes less time to perform those tests.

The platform supports complex immunohematology testing such as serial dilutions for titration studies, reflex tests, and selected cell antibody identification.

The ORTHO VISION Platform also has scheduling intelligence, which allows a transfusion medicine department to process routine samples and STAT orders as they are received, rather than waiting for a complete batch before running the instrument.

The ORTHO VISION Platform offers dynamic workflow and lab standardization across instrumentation, technology, procedures, and training. These features are intended to help labs keep pace with growing industry pressure to increase productivity while remaining operationally efficient.

ORTHO VISION and ORTHO VISION Max are commercially available in countries other than China as well, including the US, Japan, and European countries.

“Around the world, transfusion medicine labs are facing increasing pressure to perform more tests with fewer resources, and yet their work in ensuring that all patients receive safe and appropriate blood remains critically important,” said Robert Yates, chief operating officer of Ortho Clinical Diagnostics.

“Ortho is committed to helping labs become more efficient while continuing to perform precise, accurate testing.” 

Ortho Clinical Diagnostics

The China Food and Drug Administration has approved Ortho Clinical Diagnostics’ ORTHO VISION® Platform of fully automated blood analyzers for transfusion medicine laboratories.

The platform consists of ORTHO VISION and ORTHO VISION Max.

ORTHO VISION is a blood analyzer designed for small- to mid-sized transfusion labs, and ORTHO VISION Max is an analyzer developed for mid- to high-volume labs.

According to Ortho Clinical Diagnostics, the ORTHO VISION Platform automates more tests than ever before and takes less time to perform those tests.

The platform supports complex immunohematology testing such as serial dilutions for titration studies, reflex tests, and selected cell antibody identification.

The ORTHO VISION Platform also has scheduling intelligence, which allows a transfusion medicine department to process routine samples and STAT orders as they are received, rather than waiting for a complete batch before running the instrument.

The ORTHO VISION Platform offers dynamic workflow and lab standardization across instrumentation, technology, procedures, and training. These features are intended to help labs keep pace with growing industry pressure to increase productivity while remaining operationally efficient.

ORTHO VISION and ORTHO VISION Max are commercially available in countries other than China as well, including the US, Japan, and European countries.

“Around the world, transfusion medicine labs are facing increasing pressure to perform more tests with fewer resources, and yet their work in ensuring that all patients receive safe and appropriate blood remains critically important,” said Robert Yates, chief operating officer of Ortho Clinical Diagnostics.

“Ortho is committed to helping labs become more efficient while continuing to perform precise, accurate testing.” 

Ortho Clinical Diagnostics

The China Food and Drug Administration has approved Ortho Clinical Diagnostics’ ORTHO VISION® Platform of fully automated blood analyzers for transfusion medicine laboratories.

The platform consists of ORTHO VISION and ORTHO VISION Max.

ORTHO VISION is a blood analyzer designed for small- to mid-sized transfusion labs, and ORTHO VISION Max is an analyzer developed for mid- to high-volume labs.

According to Ortho Clinical Diagnostics, the ORTHO VISION Platform automates more tests than ever before and takes less time to perform those tests.

The platform supports complex immunohematology testing such as serial dilutions for titration studies, reflex tests, and selected cell antibody identification.

The ORTHO VISION Platform also has scheduling intelligence, which allows a transfusion medicine department to process routine samples and STAT orders as they are received, rather than waiting for a complete batch before running the instrument.

The ORTHO VISION Platform offers dynamic workflow and lab standardization across instrumentation, technology, procedures, and training. These features are intended to help labs keep pace with growing industry pressure to increase productivity while remaining operationally efficient.

ORTHO VISION and ORTHO VISION Max are commercially available in countries other than China as well, including the US, Japan, and European countries.

“Around the world, transfusion medicine labs are facing increasing pressure to perform more tests with fewer resources, and yet their work in ensuring that all patients receive safe and appropriate blood remains critically important,” said Robert Yates, chief operating officer of Ortho Clinical Diagnostics.

“Ortho is committed to helping labs become more efficient while continuing to perform precise, accurate testing.” 

Photo from UAB Hospital

Early blood transfusion is associated with improved survival among people with severe trauma sustained during combat, according to research published in JAMA.

Researchers studied medically evacuated US military personnel fighting in Afghanistan and found that patients who received blood products prior to hospitalization or within 15 minutes of medical evacuation were more likely to be alive at 24 hours and 30 days, when compared to patients who had delayed transfusions or did not receive transfusions.

Stacy A. Shackelford, MD, of Ft. Sam Houston in San Antonio, Texas, and her colleagues conducted this study to examine the association of prehospital transfusion and time to initial transfusion with injury survival.

The study included US military combat casualties in Afghanistan between April 1, 2012, and August 7, 2015. Eligible patients were rescued alive by medical evacuation from the point of injury with either:

• A traumatic limb amputation at or above the knee or elbow
• Shock, defined as a systolic blood pressure of less than 90 mm Hg or a heart rate greater than 120 beats per minute.

The study included 502, mostly male (98%), patients with a median age of 25 (range, 22 to 29). There were 55 patients who received prehospital transfusions (of red blood cells and/or plasma) and 447 who did not.

The rate of death within 24 hours of medical evacuation was 5% (3/55) among prehospital transfusion recipients and 19% (85/447) among nonrecipients (P=0.01). The rate of death by day 30 was 11% (6/55) and 23% (102/447), respectively (P=0.04).

The researchers also matched nonrecipients and recipients of prehospital transfusion by mechanism of injury, prehospital shock, severity of limb amputation, head injury, and torso hemorrhage. And the team adjusted their analyses for patient age, injury year, transport team, tourniquet use, and time to medical evacuation.

There were 386 matched patients with complete covariate data. Among these patients, the association of survival with prehospital transfusion remained significant at 24 hours and 30 days.

At 24 hours, the adjusted hazard ratio (aHR) for mortality was 0.26 (P=0.02). There were 3 deaths among the 54 prehospital transfusion recipients and 67 deaths among the 332 matched nonrecipients.

At 30 days, the aHR was 0.39 (P=0.03). There were 6 deaths among the 54 prehospital transfusion recipients and 76 deaths among the 332 matched nonrecipients.

The researchers also found that shorter time to initial transfusion, whether it occurred prior to or during hospitalization, was associated with reduced 24-hour mortality.

Transfusions occurring within 15 minutes of medical evacuation (a median of 36 minutes after injury) were associated with reduced mortality at 24 hours.

The aHR was 0.17 (P=0.02). There were 2 deaths among the 62 patients who received a transfusion within 15 minutes of medical evacuation and 68 deaths among the 324 patients who received delayed transfusions or did not receive transfusions.

When the researchers eliminated patients who did not receive transfusions, the aHR was 0.23 (P=0.04). There were 47 deaths among the 303 patients who received delayed transfusions (compared to 2 deaths among the 62 patients who received a transfusion within 15 minutes of medical evacuation).

Photo from UAB Hospital

Early blood transfusion is associated with improved survival among people with severe trauma sustained during combat, according to research published in JAMA.

Researchers studied medically evacuated US military personnel fighting in Afghanistan and found that patients who received blood products prior to hospitalization or within 15 minutes of medical evacuation were more likely to be alive at 24 hours and 30 days, when compared to patients who had delayed transfusions or did not receive transfusions.

Stacy A. Shackelford, MD, of Ft. Sam Houston in San Antonio, Texas, and her colleagues conducted this study to examine the association of prehospital transfusion and time to initial transfusion with injury survival.

The study included US military combat casualties in Afghanistan between April 1, 2012, and August 7, 2015. Eligible patients were rescued alive by medical evacuation from the point of injury with either:

• A traumatic limb amputation at or above the knee or elbow
• Shock, defined as a systolic blood pressure of less than 90 mm Hg or a heart rate greater than 120 beats per minute.

The study included 502, mostly male (98%), patients with a median age of 25 (range, 22 to 29). There were 55 patients who received prehospital transfusions (of red blood cells and/or plasma) and 447 who did not.

The rate of death within 24 hours of medical evacuation was 5% (3/55) among prehospital transfusion recipients and 19% (85/447) among nonrecipients (P=0.01). The rate of death by day 30 was 11% (6/55) and 23% (102/447), respectively (P=0.04).

The researchers also matched nonrecipients and recipients of prehospital transfusion by mechanism of injury, prehospital shock, severity of limb amputation, head injury, and torso hemorrhage. And the team adjusted their analyses for patient age, injury year, transport team, tourniquet use, and time to medical evacuation.

There were 386 matched patients with complete covariate data. Among these patients, the association of survival with prehospital transfusion remained significant at 24 hours and 30 days.

At 24 hours, the adjusted hazard ratio (aHR) for mortality was 0.26 (P=0.02). There were 3 deaths among the 54 prehospital transfusion recipients and 67 deaths among the 332 matched nonrecipients.

At 30 days, the aHR was 0.39 (P=0.03). There were 6 deaths among the 54 prehospital transfusion recipients and 76 deaths among the 332 matched nonrecipients.

The researchers also found that shorter time to initial transfusion, whether it occurred prior to or during hospitalization, was associated with reduced 24-hour mortality.

Transfusions occurring within 15 minutes of medical evacuation (a median of 36 minutes after injury) were associated with reduced mortality at 24 hours.

The aHR was 0.17 (P=0.02). There were 2 deaths among the 62 patients who received a transfusion within 15 minutes of medical evacuation and 68 deaths among the 324 patients who received delayed transfusions or did not receive transfusions.

When the researchers eliminated patients who did not receive transfusions, the aHR was 0.23 (P=0.04). There were 47 deaths among the 303 patients who received delayed transfusions (compared to 2 deaths among the 62 patients who received a transfusion within 15 minutes of medical evacuation).

Photo from UAB Hospital

Early blood transfusion is associated with improved survival among people with severe trauma sustained during combat, according to research published in JAMA.

Researchers studied medically evacuated US military personnel fighting in Afghanistan and found that patients who received blood products prior to hospitalization or within 15 minutes of medical evacuation were more likely to be alive at 24 hours and 30 days, when compared to patients who had delayed transfusions or did not receive transfusions.

Stacy A. Shackelford, MD, of Ft. Sam Houston in San Antonio, Texas, and her colleagues conducted this study to examine the association of prehospital transfusion and time to initial transfusion with injury survival.

The study included US military combat casualties in Afghanistan between April 1, 2012, and August 7, 2015. Eligible patients were rescued alive by medical evacuation from the point of injury with either:

• A traumatic limb amputation at or above the knee or elbow
• Shock, defined as a systolic blood pressure of less than 90 mm Hg or a heart rate greater than 120 beats per minute.

The study included 502, mostly male (98%), patients with a median age of 25 (range, 22 to 29). There were 55 patients who received prehospital transfusions (of red blood cells and/or plasma) and 447 who did not.

The rate of death within 24 hours of medical evacuation was 5% (3/55) among prehospital transfusion recipients and 19% (85/447) among nonrecipients (P=0.01). The rate of death by day 30 was 11% (6/55) and 23% (102/447), respectively (P=0.04).

The researchers also matched nonrecipients and recipients of prehospital transfusion by mechanism of injury, prehospital shock, severity of limb amputation, head injury, and torso hemorrhage. And the team adjusted their analyses for patient age, injury year, transport team, tourniquet use, and time to medical evacuation.

There were 386 matched patients with complete covariate data. Among these patients, the association of survival with prehospital transfusion remained significant at 24 hours and 30 days.

At 24 hours, the adjusted hazard ratio (aHR) for mortality was 0.26 (P=0.02). There were 3 deaths among the 54 prehospital transfusion recipients and 67 deaths among the 332 matched nonrecipients.

At 30 days, the aHR was 0.39 (P=0.03). There were 6 deaths among the 54 prehospital transfusion recipients and 76 deaths among the 332 matched nonrecipients.

The researchers also found that shorter time to initial transfusion, whether it occurred prior to or during hospitalization, was associated with reduced 24-hour mortality.

Transfusions occurring within 15 minutes of medical evacuation (a median of 36 minutes after injury) were associated with reduced mortality at 24 hours.

The aHR was 0.17 (P=0.02). There were 2 deaths among the 62 patients who received a transfusion within 15 minutes of medical evacuation and 68 deaths among the 324 patients who received delayed transfusions or did not receive transfusions.

When the researchers eliminated patients who did not receive transfusions, the aHR was 0.23 (P=0.04). There were 47 deaths among the 303 patients who received delayed transfusions (compared to 2 deaths among the 62 patients who received a transfusion within 15 minutes of medical evacuation).

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 Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.

The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).

In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.

Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.

The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.

The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.

“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.

“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”

The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

*Data in the abstract differ from the data presented at the meeting.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.

The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).

In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.

Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.

The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.

The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.

“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.

“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”

The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

*Data in the abstract differ from the data presented at the meeting.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.

The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).

In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.

Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.

The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.

The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.

“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.

“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”

The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.

*Data in the abstract differ from the data presented at the meeting.

Photo courtesy of Amgen

Top-line results from the phase 3 A.R.R.O.W. trial support a 70 mg/m² weekly dose of carfilzomib in combination with dexamethasone for patients with relapsed and refractory multiple myeloma (MM).

The data suggest a weekly dose of carfilzomib at 70 mg/m² is more effective than, and just as safe as, a twice-weekly dose of carfilzomib at 27 mg/m².

These results were recently announced by Amgen, makers of carfilzomib.

The A.R.R.O.W. trial included 478 patients with relapsed and refractory MM who had received 2 to 3 prior therapies, including bortezomib and an immunomodulatory drug.

Patients were randomized to receive once-weekly carfilzomib (20 mg/m² on day 1 of cycle 1; 70 mg/m² on days 8 and 15 of cycle 1; and 70 mg/m² on days 1, 8 and 15 of subsequent cycles) with dexamethasone (40 mg) or twice-weekly carfilzomib (20 mg/m² on days 1 and 2 of cycle 1; 27 mg/m² on days 8, 9, 15 and 16 of cycle 1; and 27 mg/m² on days 1, 2, 8, 9, 15 and 16 of subsequent cycles) with dexamethasone (40 mg).

The study’s primary endpoint is progression-free survival (PFS).

Patients treated with the once-weekly regimen had significantly better PFS than patients who received carfilzomib twice weekly. The median PFS was 11.2 months and 7.6 months, respectively (hazard ratio=0.69, 95% confidence interval, 0.54–0.88).

The overall safety profile of the once-weekly regimen was comparable to that of the twice-weekly regimen.

The most frequently reported treatment-emergent adverse events (occurring in at least 20% of patients) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

Photo courtesy of Amgen

Top-line results from the phase 3 A.R.R.O.W. trial support a 70 mg/m² weekly dose of carfilzomib in combination with dexamethasone for patients with relapsed and refractory multiple myeloma (MM).

The data suggest a weekly dose of carfilzomib at 70 mg/m² is more effective than, and just as safe as, a twice-weekly dose of carfilzomib at 27 mg/m².

These results were recently announced by Amgen, makers of carfilzomib.

The A.R.R.O.W. trial included 478 patients with relapsed and refractory MM who had received 2 to 3 prior therapies, including bortezomib and an immunomodulatory drug.

Patients were randomized to receive once-weekly carfilzomib (20 mg/m² on day 1 of cycle 1; 70 mg/m² on days 8 and 15 of cycle 1; and 70 mg/m² on days 1, 8 and 15 of subsequent cycles) with dexamethasone (40 mg) or twice-weekly carfilzomib (20 mg/m² on days 1 and 2 of cycle 1; 27 mg/m² on days 8, 9, 15 and 16 of cycle 1; and 27 mg/m² on days 1, 2, 8, 9, 15 and 16 of subsequent cycles) with dexamethasone (40 mg).

The study’s primary endpoint is progression-free survival (PFS).

Patients treated with the once-weekly regimen had significantly better PFS than patients who received carfilzomib twice weekly. The median PFS was 11.2 months and 7.6 months, respectively (hazard ratio=0.69, 95% confidence interval, 0.54–0.88).

The overall safety profile of the once-weekly regimen was comparable to that of the twice-weekly regimen.

The most frequently reported treatment-emergent adverse events (occurring in at least 20% of patients) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

Photo courtesy of Amgen

Top-line results from the phase 3 A.R.R.O.W. trial support a 70 mg/m² weekly dose of carfilzomib in combination with dexamethasone for patients with relapsed and refractory multiple myeloma (MM).

The data suggest a weekly dose of carfilzomib at 70 mg/m² is more effective than, and just as safe as, a twice-weekly dose of carfilzomib at 27 mg/m².

These results were recently announced by Amgen, makers of carfilzomib.

The A.R.R.O.W. trial included 478 patients with relapsed and refractory MM who had received 2 to 3 prior therapies, including bortezomib and an immunomodulatory drug.

Patients were randomized to receive once-weekly carfilzomib (20 mg/m² on day 1 of cycle 1; 70 mg/m² on days 8 and 15 of cycle 1; and 70 mg/m² on days 1, 8 and 15 of subsequent cycles) with dexamethasone (40 mg) or twice-weekly carfilzomib (20 mg/m² on days 1 and 2 of cycle 1; 27 mg/m² on days 8, 9, 15 and 16 of cycle 1; and 27 mg/m² on days 1, 2, 8, 9, 15 and 16 of subsequent cycles) with dexamethasone (40 mg).

The study’s primary endpoint is progression-free survival (PFS).

Patients treated with the once-weekly regimen had significantly better PFS than patients who received carfilzomib twice weekly. The median PFS was 11.2 months and 7.6 months, respectively (hazard ratio=0.69, 95% confidence interval, 0.54–0.88).

The overall safety profile of the once-weekly regimen was comparable to that of the twice-weekly regimen.

The most frequently reported treatment-emergent adverse events (occurring in at least 20% of patients) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

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.”