HT Staff

Red blood cells

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for ALXN1210, a long-acting C5 complement inhibitor.

With this BLA, Alexion Pharmaceuticals, Inc., is seeking approval for ALXN1210 for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH).

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

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

The FDA expects to make a decision on the BLA for ALXN1210 by February 18, 2019.

The application is supported by data from a pair of phase 3 trials—PNH-301 and the Switch trial. Alexion released topline results from the PNH-301 trial in March and the Switch trial in April.

PNH-301 trial

This study enrolled 246 adults (age 18+) with PNH who were naïve to treatment with a complement inhibitor. Patients received ALXN1210 (n=125) or eculizumab (n=121).

Patients in the ALXN1210 arm received a single loading dose of ALXN1210, followed by regular maintenance weight-based dosing every 8 weeks. Patients in the eculizumab arm received 4 weekly induction doses, followed by regular maintenance dosing every 2 weeks.

Both arms were treated for 26 weeks. All patients enrolled in an extension study of up to 2 years, during which they will receive ALXN1210 every 8 weeks.

The study’s co-primary endpoints are:

• Transfusion avoidance, which was defined as the proportion of patients who remain transfusion-free and do not require a transfusion per protocol-specified guidelines through day 183
• Normalization of lactate dehydrogenase (LDH) levels as directly measured every 2 weeks by LDH levels ≤ 1 times the upper limit of normal from day 29 through day 183.

ALXN1210 proved non-inferior to eculizumab for both primary endpoints. Specifically, 73.6% of patients in the ALXN1210 arm and 66.1% in the eculizumab arm were able to avoid transfusion. LDH normalization occurred in 53.6% and 49.4%, respectively.

ALXN1210 also demonstrated non-inferiority to eculizumab on all 4 key secondary endpoints:

• Percentage change from baseline in LDH levels (-76.8% and -76.0%, respectively)
• Change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (7.1 and 6.4, respectively)
• Proportion of patients with breakthrough hemolysis (4.0% and 10.7%, respectively)
• Proportion of patients with stabilized hemoglobin levels (68.0% and 64.5%, respectively).

Alexion said there were no notable differences in the safety profiles for ALXN1210 and eculizumab. The most frequently observed adverse event (AE) was headache, and the most frequently observed serious AE was pyrexia.

One anti-drug antibody (ADA) was observed in the ALXN1210 arm and 1 in the eculizumab arm. There were no neutralizing antibodies detected and no cases of meningococcal infection.

Switch study

This study is a comparison of ALXN1210 and eculizumab in 195 adults (18+). At baseline, patients had a confirmed diagnosis of PNH, had LDH levels ≤ 1.5 times the upper limit of normal, and had been treated with eculizumab for at least the past 6 months.

ALXN1210 was administered every 8 weeks, and eculizumab was administered every 2 weeks. The 26-week treatment period is followed by an extension period, in which all patients will receive ALXN1210 every 8 weeks for up to 2 years.

Alexion did not provide any efficacy data in its announcement of results. However, the company said ALXN1210 proved non-inferior to eculizumab based on the primary endpoint of change in LDH levels.

Alexion also said ALXN1210 demonstrated non-inferiority on all 4 key secondary endpoints:

• The proportion of patients with breakthrough hemolysis
• The change from baseline in quality of life as assessed via the FACIT-Fatigue Scale
• The proportion of patients avoiding transfusion
• The proportion of patients with stabilized hemoglobin levels.

ALXN1210 had a safety profile that is consistent with that seen for eculizumab, according to Alexion. The most frequently observed AEs were headache and upper respiratory infection. The most frequently observed serious AEs were pyrexia and hemolysis.

There were no treatment-emergent ADAs in the ALXN1210 arm, but one patient in the eculizumab arm did have ADAs. There were no neutralizing antibodies and no cases of meningococcal infection in either arm.

Red blood cells

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for ALXN1210, a long-acting C5 complement inhibitor.

With this BLA, Alexion Pharmaceuticals, Inc., is seeking approval for ALXN1210 for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH).

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

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

The FDA expects to make a decision on the BLA for ALXN1210 by February 18, 2019.

The application is supported by data from a pair of phase 3 trials—PNH-301 and the Switch trial. Alexion released topline results from the PNH-301 trial in March and the Switch trial in April.

PNH-301 trial

This study enrolled 246 adults (age 18+) with PNH who were naïve to treatment with a complement inhibitor. Patients received ALXN1210 (n=125) or eculizumab (n=121).

Patients in the ALXN1210 arm received a single loading dose of ALXN1210, followed by regular maintenance weight-based dosing every 8 weeks. Patients in the eculizumab arm received 4 weekly induction doses, followed by regular maintenance dosing every 2 weeks.

Both arms were treated for 26 weeks. All patients enrolled in an extension study of up to 2 years, during which they will receive ALXN1210 every 8 weeks.

The study’s co-primary endpoints are:

• Transfusion avoidance, which was defined as the proportion of patients who remain transfusion-free and do not require a transfusion per protocol-specified guidelines through day 183
• Normalization of lactate dehydrogenase (LDH) levels as directly measured every 2 weeks by LDH levels ≤ 1 times the upper limit of normal from day 29 through day 183.

ALXN1210 proved non-inferior to eculizumab for both primary endpoints. Specifically, 73.6% of patients in the ALXN1210 arm and 66.1% in the eculizumab arm were able to avoid transfusion. LDH normalization occurred in 53.6% and 49.4%, respectively.

ALXN1210 also demonstrated non-inferiority to eculizumab on all 4 key secondary endpoints:

• Percentage change from baseline in LDH levels (-76.8% and -76.0%, respectively)
• Change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (7.1 and 6.4, respectively)
• Proportion of patients with breakthrough hemolysis (4.0% and 10.7%, respectively)
• Proportion of patients with stabilized hemoglobin levels (68.0% and 64.5%, respectively).

Alexion said there were no notable differences in the safety profiles for ALXN1210 and eculizumab. The most frequently observed adverse event (AE) was headache, and the most frequently observed serious AE was pyrexia.

One anti-drug antibody (ADA) was observed in the ALXN1210 arm and 1 in the eculizumab arm. There were no neutralizing antibodies detected and no cases of meningococcal infection.

Switch study

This study is a comparison of ALXN1210 and eculizumab in 195 adults (18+). At baseline, patients had a confirmed diagnosis of PNH, had LDH levels ≤ 1.5 times the upper limit of normal, and had been treated with eculizumab for at least the past 6 months.

ALXN1210 was administered every 8 weeks, and eculizumab was administered every 2 weeks. The 26-week treatment period is followed by an extension period, in which all patients will receive ALXN1210 every 8 weeks for up to 2 years.

Alexion did not provide any efficacy data in its announcement of results. However, the company said ALXN1210 proved non-inferior to eculizumab based on the primary endpoint of change in LDH levels.

Alexion also said ALXN1210 demonstrated non-inferiority on all 4 key secondary endpoints:

• The proportion of patients with breakthrough hemolysis
• The change from baseline in quality of life as assessed via the FACIT-Fatigue Scale
• The proportion of patients avoiding transfusion
• The proportion of patients with stabilized hemoglobin levels.

ALXN1210 had a safety profile that is consistent with that seen for eculizumab, according to Alexion. The most frequently observed AEs were headache and upper respiratory infection. The most frequently observed serious AEs were pyrexia and hemolysis.

There were no treatment-emergent ADAs in the ALXN1210 arm, but one patient in the eculizumab arm did have ADAs. There were no neutralizing antibodies and no cases of meningococcal infection in either arm.

Red blood cells

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for ALXN1210, a long-acting C5 complement inhibitor.

With this BLA, Alexion Pharmaceuticals, Inc., is seeking approval for ALXN1210 for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH).

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

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

The FDA expects to make a decision on the BLA for ALXN1210 by February 18, 2019.

The application is supported by data from a pair of phase 3 trials—PNH-301 and the Switch trial. Alexion released topline results from the PNH-301 trial in March and the Switch trial in April.

PNH-301 trial

This study enrolled 246 adults (age 18+) with PNH who were naïve to treatment with a complement inhibitor. Patients received ALXN1210 (n=125) or eculizumab (n=121).

Patients in the ALXN1210 arm received a single loading dose of ALXN1210, followed by regular maintenance weight-based dosing every 8 weeks. Patients in the eculizumab arm received 4 weekly induction doses, followed by regular maintenance dosing every 2 weeks.

Both arms were treated for 26 weeks. All patients enrolled in an extension study of up to 2 years, during which they will receive ALXN1210 every 8 weeks.

The study’s co-primary endpoints are:

• Transfusion avoidance, which was defined as the proportion of patients who remain transfusion-free and do not require a transfusion per protocol-specified guidelines through day 183
• Normalization of lactate dehydrogenase (LDH) levels as directly measured every 2 weeks by LDH levels ≤ 1 times the upper limit of normal from day 29 through day 183.

ALXN1210 proved non-inferior to eculizumab for both primary endpoints. Specifically, 73.6% of patients in the ALXN1210 arm and 66.1% in the eculizumab arm were able to avoid transfusion. LDH normalization occurred in 53.6% and 49.4%, respectively.

ALXN1210 also demonstrated non-inferiority to eculizumab on all 4 key secondary endpoints:

• Percentage change from baseline in LDH levels (-76.8% and -76.0%, respectively)
• Change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (7.1 and 6.4, respectively)
• Proportion of patients with breakthrough hemolysis (4.0% and 10.7%, respectively)
• Proportion of patients with stabilized hemoglobin levels (68.0% and 64.5%, respectively).

Alexion said there were no notable differences in the safety profiles for ALXN1210 and eculizumab. The most frequently observed adverse event (AE) was headache, and the most frequently observed serious AE was pyrexia.

One anti-drug antibody (ADA) was observed in the ALXN1210 arm and 1 in the eculizumab arm. There were no neutralizing antibodies detected and no cases of meningococcal infection.

Switch study

This study is a comparison of ALXN1210 and eculizumab in 195 adults (18+). At baseline, patients had a confirmed diagnosis of PNH, had LDH levels ≤ 1.5 times the upper limit of normal, and had been treated with eculizumab for at least the past 6 months.

ALXN1210 was administered every 8 weeks, and eculizumab was administered every 2 weeks. The 26-week treatment period is followed by an extension period, in which all patients will receive ALXN1210 every 8 weeks for up to 2 years.

Alexion did not provide any efficacy data in its announcement of results. However, the company said ALXN1210 proved non-inferior to eculizumab based on the primary endpoint of change in LDH levels.

Alexion also said ALXN1210 demonstrated non-inferiority on all 4 key secondary endpoints:

• The proportion of patients with breakthrough hemolysis
• The change from baseline in quality of life as assessed via the FACIT-Fatigue Scale
• The proportion of patients avoiding transfusion
• The proportion of patients with stabilized hemoglobin levels.

ALXN1210 had a safety profile that is consistent with that seen for eculizumab, according to Alexion. The most frequently observed AEs were headache and upper respiratory infection. The most frequently observed serious AEs were pyrexia and hemolysis.

There were no treatment-emergent ADAs in the ALXN1210 arm, but one patient in the eculizumab arm did have ADAs. There were no neutralizing antibodies and no cases of meningococcal infection in either arm.

Photo by Bill Branson

Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.

The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.

SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).

Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.

The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.

The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.

Survival differences by race/ethnicity

The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.

In addition, whites had a significant survival advantage over Hispanics for the following cancers.

Impact of SES

SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.

For black versus white patients, SES reduced the original association between race/ethnicity and survival by:

• 44% for ALL
• 28% for AML
• 49% for neuroblastoma
• 34% for NHL.

For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:

• 31% for ALL
• 73% for AML
• 48% for neuroblastoma
• 28% for NHL.

“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.

“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”

This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.

Photo by Bill Branson

Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.

The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.

SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).

Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.

The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.

The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.

Survival differences by race/ethnicity

The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.

In addition, whites had a significant survival advantage over Hispanics for the following cancers.

Impact of SES

SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.

For black versus white patients, SES reduced the original association between race/ethnicity and survival by:

• 44% for ALL
• 28% for AML
• 49% for neuroblastoma
• 34% for NHL.

For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:

• 31% for ALL
• 73% for AML
• 48% for neuroblastoma
• 28% for NHL.

“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.

“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”

This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.

Photo by Bill Branson

Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.

The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.

SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).

Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.

The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.

The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.

Survival differences by race/ethnicity

The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.

In addition, whites had a significant survival advantage over Hispanics for the following cancers.

Impact of SES

SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.

For black versus white patients, SES reduced the original association between race/ethnicity and survival by:

• 44% for ALL
• 28% for AML
• 49% for neuroblastoma
• 34% for NHL.

For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:

• 31% for ALL
• 73% for AML
• 48% for neuroblastoma
• 28% for NHL.

“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.

“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”

This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.

Catalyst Biosciences

BOSTON—The activated factor VIIa variant marzeptacog alfa has demonstrated efficacy as prophylaxis for patients with hemophilia A or B who also have inhibitors, according to researchers.

Three patients have completed dosing with marzeptacog alfa in a phase 2/3 study.

None of these patients experienced bleeding during treatment, and none have developed antidrug antibodies or reported injection site reactions.

As for the other 2 patients enrolled in this study, 1 withdrew consent, and 1 died of an adverse event unrelated to marzeptacog alfa.

Howard Levy, chief medical officer of Catalyst Biosciences, Inc., presented these data at the 2018 Hemophilia Drug Development Summit.

The trial is sponsored by Catalyst Biosciences, the company developing marzeptacog alfa.

Results

The goal of this ongoing trial is to determine whether daily subcutaneous injections of marzeptacog alfa can eliminate or minimize spontaneous bleeding episodes. The primary endpoint is a reduction in annualized bleed rate (ABR) compared to each individual’s recorded historical ABR.

Thus far, the trial has enrolled 5 patients with hemophilia A or B and inhibitors. (Catalyst would not disclose how many patients have hemophilia A and how many have hemophilia B).

One patient with a historic ABR of 26.7 completed the trial with no bleeds after 50 days of treatment with marzeptacog alfa at 60 µg/kg.

This patient had previously experienced a bleed on day 46 when receiving marzeptacog alfa at 30 µg/kg, and the patient experienced another bleed 16 days after the end of dosing at 60 µg/kg.

A second patient with a historic ABR of 16.6 had no bleeds when receiving marzeptacog alfa at 30 µg/kg for 50 days.

And a third patient with a historic ABR of 15.9 had no bleeds when receiving marzeptacog alfa at 30 µg/kg for 44 days.

“The data from these 3 individuals support the efficacy of [marzeptacog alfa] to reduce annualized bleed rates after daily subcutaneous injections,” said Nassim Usman, PhD, chief executive officer of Catalyst Biosciences.

“Importantly, to date, we have not observed any injection site reactions nor any anti-drug antibodies after more than 200 subcutaneous doses of [marzeptacog alfa].”

A fourth patient with a historic ABR of 18.3 had a fatal hemorrhagic stroke on day 11 that was considered unrelated to marzeptacog alfa. The patient had previously treated hypertension that was going untreated at the time of death.

A fifth patient with a historic ABR of 12.2 withdrew consent.

Catalyst Biosciences

BOSTON—The activated factor VIIa variant marzeptacog alfa has demonstrated efficacy as prophylaxis for patients with hemophilia A or B who also have inhibitors, according to researchers.

Three patients have completed dosing with marzeptacog alfa in a phase 2/3 study.

None of these patients experienced bleeding during treatment, and none have developed antidrug antibodies or reported injection site reactions.

As for the other 2 patients enrolled in this study, 1 withdrew consent, and 1 died of an adverse event unrelated to marzeptacog alfa.

Howard Levy, chief medical officer of Catalyst Biosciences, Inc., presented these data at the 2018 Hemophilia Drug Development Summit.

The trial is sponsored by Catalyst Biosciences, the company developing marzeptacog alfa.

Results

The goal of this ongoing trial is to determine whether daily subcutaneous injections of marzeptacog alfa can eliminate or minimize spontaneous bleeding episodes. The primary endpoint is a reduction in annualized bleed rate (ABR) compared to each individual’s recorded historical ABR.

Thus far, the trial has enrolled 5 patients with hemophilia A or B and inhibitors. (Catalyst would not disclose how many patients have hemophilia A and how many have hemophilia B).

One patient with a historic ABR of 26.7 completed the trial with no bleeds after 50 days of treatment with marzeptacog alfa at 60 µg/kg.

This patient had previously experienced a bleed on day 46 when receiving marzeptacog alfa at 30 µg/kg, and the patient experienced another bleed 16 days after the end of dosing at 60 µg/kg.

A second patient with a historic ABR of 16.6 had no bleeds when receiving marzeptacog alfa at 30 µg/kg for 50 days.

And a third patient with a historic ABR of 15.9 had no bleeds when receiving marzeptacog alfa at 30 µg/kg for 44 days.

“The data from these 3 individuals support the efficacy of [marzeptacog alfa] to reduce annualized bleed rates after daily subcutaneous injections,” said Nassim Usman, PhD, chief executive officer of Catalyst Biosciences.

“Importantly, to date, we have not observed any injection site reactions nor any anti-drug antibodies after more than 200 subcutaneous doses of [marzeptacog alfa].”

A fourth patient with a historic ABR of 18.3 had a fatal hemorrhagic stroke on day 11 that was considered unrelated to marzeptacog alfa. The patient had previously treated hypertension that was going untreated at the time of death.

A fifth patient with a historic ABR of 12.2 withdrew consent.

Catalyst Biosciences

BOSTON—The activated factor VIIa variant marzeptacog alfa has demonstrated efficacy as prophylaxis for patients with hemophilia A or B who also have inhibitors, according to researchers.

Three patients have completed dosing with marzeptacog alfa in a phase 2/3 study.

None of these patients experienced bleeding during treatment, and none have developed antidrug antibodies or reported injection site reactions.

As for the other 2 patients enrolled in this study, 1 withdrew consent, and 1 died of an adverse event unrelated to marzeptacog alfa.

Howard Levy, chief medical officer of Catalyst Biosciences, Inc., presented these data at the 2018 Hemophilia Drug Development Summit.

The trial is sponsored by Catalyst Biosciences, the company developing marzeptacog alfa.

Results

The goal of this ongoing trial is to determine whether daily subcutaneous injections of marzeptacog alfa can eliminate or minimize spontaneous bleeding episodes. The primary endpoint is a reduction in annualized bleed rate (ABR) compared to each individual’s recorded historical ABR.

Thus far, the trial has enrolled 5 patients with hemophilia A or B and inhibitors. (Catalyst would not disclose how many patients have hemophilia A and how many have hemophilia B).

One patient with a historic ABR of 26.7 completed the trial with no bleeds after 50 days of treatment with marzeptacog alfa at 60 µg/kg.

This patient had previously experienced a bleed on day 46 when receiving marzeptacog alfa at 30 µg/kg, and the patient experienced another bleed 16 days after the end of dosing at 60 µg/kg.

A second patient with a historic ABR of 16.6 had no bleeds when receiving marzeptacog alfa at 30 µg/kg for 50 days.

And a third patient with a historic ABR of 15.9 had no bleeds when receiving marzeptacog alfa at 30 µg/kg for 44 days.

“The data from these 3 individuals support the efficacy of [marzeptacog alfa] to reduce annualized bleed rates after daily subcutaneous injections,” said Nassim Usman, PhD, chief executive officer of Catalyst Biosciences.

“Importantly, to date, we have not observed any injection site reactions nor any anti-drug antibodies after more than 200 subcutaneous doses of [marzeptacog alfa].”

A fourth patient with a historic ABR of 18.3 had a fatal hemorrhagic stroke on day 11 that was considered unrelated to marzeptacog alfa. The patient had previously treated hypertension that was going untreated at the time of death.

A fifth patient with a historic ABR of 12.2 withdrew consent.

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan drug designation to ASLAN003 as a treatment for acute myeloid leukemia (AML).

ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme.

This second-generation DHODH inhibitor is being developed by ASLAN Pharmaceuticals.

The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML.

The goals of this trial are to determine the optimum dose of ASLAN003 as monotherapy and assess the drug’s efficacy by overall complete remission rate. ASLAN expects to report interim data from this trial in the second half of this year.

ASLAN has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers.

Results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to ASLAN, and the drug was considered well tolerated in the volunteers.

ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to ASLAN. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to 2 orders of magnitude stronger than first-generation DHODH inhibitors such as leflunomide and teriflunomide.

ASLAN also said ASLAN003 should not confer the same toxicities as first-generation DHODH inhibitors and other novel AML therapies.

For example, leflunomide and teriflunomide, which may cause significant liver toxicity, take between 3 and 4 weeks to build to therapeutic levels and 2 years to be cleared completely after treatment is stopped.

ASLAN003, on the other hand, reaches full exposure in 24 hours and has a half-life of 18 hours.

Finally, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.

Because of this research, ASLAN believes ASLAN003 may be effective in patients who do not respond to all-trans retinoic acid.

About orphan designation

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

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

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan drug designation to ASLAN003 as a treatment for acute myeloid leukemia (AML).

ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme.

This second-generation DHODH inhibitor is being developed by ASLAN Pharmaceuticals.

The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML.

The goals of this trial are to determine the optimum dose of ASLAN003 as monotherapy and assess the drug’s efficacy by overall complete remission rate. ASLAN expects to report interim data from this trial in the second half of this year.

ASLAN has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers.

Results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to ASLAN, and the drug was considered well tolerated in the volunteers.

ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to ASLAN. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to 2 orders of magnitude stronger than first-generation DHODH inhibitors such as leflunomide and teriflunomide.

ASLAN also said ASLAN003 should not confer the same toxicities as first-generation DHODH inhibitors and other novel AML therapies.

For example, leflunomide and teriflunomide, which may cause significant liver toxicity, take between 3 and 4 weeks to build to therapeutic levels and 2 years to be cleared completely after treatment is stopped.

ASLAN003, on the other hand, reaches full exposure in 24 hours and has a half-life of 18 hours.

Finally, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.

Because of this research, ASLAN believes ASLAN003 may be effective in patients who do not respond to all-trans retinoic acid.

About orphan designation

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

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

Henrique Orlandi Mourao

The US Food and Drug Administration (FDA) has granted orphan drug designation to ASLAN003 as a treatment for acute myeloid leukemia (AML).

ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme.

This second-generation DHODH inhibitor is being developed by ASLAN Pharmaceuticals.

The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML.

The goals of this trial are to determine the optimum dose of ASLAN003 as monotherapy and assess the drug’s efficacy by overall complete remission rate. ASLAN expects to report interim data from this trial in the second half of this year.

ASLAN has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers.

Results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to ASLAN, and the drug was considered well tolerated in the volunteers.

ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to ASLAN. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to 2 orders of magnitude stronger than first-generation DHODH inhibitors such as leflunomide and teriflunomide.

ASLAN also said ASLAN003 should not confer the same toxicities as first-generation DHODH inhibitors and other novel AML therapies.

For example, leflunomide and teriflunomide, which may cause significant liver toxicity, take between 3 and 4 weeks to build to therapeutic levels and 2 years to be cleared completely after treatment is stopped.

ASLAN003, on the other hand, reaches full exposure in 24 hours and has a half-life of 18 hours.

Finally, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.

Because of this research, ASLAN believes ASLAN003 may be effective in patients who do not respond to all-trans retinoic acid.

About orphan designation

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

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

Photo by Rhoda Baer

New research suggests that better access to quality care may reduce disparities in survival between cancer patients living in rural areas of the US and those living in urban areas.

The study showed that urban and rural cancer patients had similar survival outcomes when they were enrolled in clinical trials.

These results, published in JAMA Network Open, cast new light on decades of research showing that cancer patients living in rural areas don’t live as long as urban cancer patients.

“These findings were a surprise, since we thought we might find the same disparities others had found,” said study author Joseph Unger, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

“But clinical trials are a key difference here. In trials, patients are uniformly assessed, treated, and followed under a strict, guideline-driven protocol. This suggests that giving people with cancer access to uniform treatment strategies could help resolve the disparities in outcomes that we see between rural and urban patients.”

Dr Unger and his colleagues studied data on 36,995 patients who were enrolled in 44 phase 3 or phase 2/3 SWOG trials from 1986 through 2012. All 50 states were represented.

Patients had 17 different cancer types, including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM).

Using US Department of Agriculture population classifications known as Rural-Urban Continuum Codes, the researchers categorized the patients as either rural or urban and analyzed their outcomes.

A minority of patients (19.4%, n=7184) were from rural locations. They were significantly more likely than urban patients to be 65 or older (P<0.001) and significantly less likely to be black (vs all other races; P<0.001).

However, there was no significant between-group difference in sex (P=0.53), and all major US geographic regions (West, Midwest, South, and Northeast) were represented.

Results

The researchers limited their analysis of survival to the first 5 years after trial enrollment to emphasize outcomes related to cancer and its treatment. They looked at overall survival (OS) as well as cancer-specific survival.

The team found no meaningful difference in OS or cancer-specific survival between rural and urban patients for 16 of the 17 cancer types.

The exception was estrogen receptor-negative, progesterone receptor-negative breast cancer. Rural patients with this cancer didn’t live as long as their urban counterparts. The hazard ratio (HR) was 1.27 (95% CI, 1.06-1.51; P=0.008) for OS and 1.26 (95% CI, 1.04-1.52; P=0.02) for cancer-specific survival.

The researchers believe this finding could be attributed to a few factors, including timely access to follow-up chemotherapy after patients’ first round of cancer treatment.

Although there were no significant survival differences for patients with hematologic malignancies, rural patients had slightly better OS if they had advanced indolent NHL or AML but slightly worse OS if they had MM or advanced aggressive NHL. The HRs were as follows:

• Advanced indolent NHL—HR=0.91 (95% CI, 0.64-1.29; P=0.60)
• AML—HR=0.94 (95% CI, 0.83-1.06; P=0.29)
• MM—HR=1.05 (95% CI, 0.93-1.18, P=0.46)
• Advanced aggressive NHL—HR=1.05 (95% CI, 0.87-1.27; P=0.60).

Rural patients had slightly better cancer-specific survival if they had advanced indolent NHL but slightly worse cancer-specific survival if they had AML, MM, or advanced aggressive NHL. The HRs were as follows:

• Advanced indolent NHL—HR=0.98 (95% CI, 0.66-1.45; P=0.90)
• AML—HR=1.01 (95% CI, 0.86-1.20; P=0.87)
• MM—HR=1.04 (95% CI, 0.90-1.20; P=0.60)
• Advanced aggressive NHL—HR=1.08 (95% CI, 0.87-1.34; P=0.50).

The researchers said these findings suggest it is access to care, and not other characteristics, that drive the survival disparities typically observed between urban and rural cancer patients.

“If people diagnosed with cancer, regardless of where they live, receive similar care and have similar outcomes, then a reasonable inference is that the best way to improve outcomes for rural patients is to improve their access to quality care,” Dr Unger said.

This research was supported by the National Cancer Institute and the HOPE Foundation. The researchers reported financial relationships with various pharmaceutical companies.

Photo by Rhoda Baer

New research suggests that better access to quality care may reduce disparities in survival between cancer patients living in rural areas of the US and those living in urban areas.

The study showed that urban and rural cancer patients had similar survival outcomes when they were enrolled in clinical trials.

These results, published in JAMA Network Open, cast new light on decades of research showing that cancer patients living in rural areas don’t live as long as urban cancer patients.

“These findings were a surprise, since we thought we might find the same disparities others had found,” said study author Joseph Unger, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

“But clinical trials are a key difference here. In trials, patients are uniformly assessed, treated, and followed under a strict, guideline-driven protocol. This suggests that giving people with cancer access to uniform treatment strategies could help resolve the disparities in outcomes that we see between rural and urban patients.”

Dr Unger and his colleagues studied data on 36,995 patients who were enrolled in 44 phase 3 or phase 2/3 SWOG trials from 1986 through 2012. All 50 states were represented.

Patients had 17 different cancer types, including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM).

Using US Department of Agriculture population classifications known as Rural-Urban Continuum Codes, the researchers categorized the patients as either rural or urban and analyzed their outcomes.

A minority of patients (19.4%, n=7184) were from rural locations. They were significantly more likely than urban patients to be 65 or older (P<0.001) and significantly less likely to be black (vs all other races; P<0.001).

However, there was no significant between-group difference in sex (P=0.53), and all major US geographic regions (West, Midwest, South, and Northeast) were represented.

Results

The researchers limited their analysis of survival to the first 5 years after trial enrollment to emphasize outcomes related to cancer and its treatment. They looked at overall survival (OS) as well as cancer-specific survival.

The team found no meaningful difference in OS or cancer-specific survival between rural and urban patients for 16 of the 17 cancer types.

The exception was estrogen receptor-negative, progesterone receptor-negative breast cancer. Rural patients with this cancer didn’t live as long as their urban counterparts. The hazard ratio (HR) was 1.27 (95% CI, 1.06-1.51; P=0.008) for OS and 1.26 (95% CI, 1.04-1.52; P=0.02) for cancer-specific survival.

The researchers believe this finding could be attributed to a few factors, including timely access to follow-up chemotherapy after patients’ first round of cancer treatment.

Although there were no significant survival differences for patients with hematologic malignancies, rural patients had slightly better OS if they had advanced indolent NHL or AML but slightly worse OS if they had MM or advanced aggressive NHL. The HRs were as follows:

• Advanced indolent NHL—HR=0.91 (95% CI, 0.64-1.29; P=0.60)
• AML—HR=0.94 (95% CI, 0.83-1.06; P=0.29)
• MM—HR=1.05 (95% CI, 0.93-1.18, P=0.46)
• Advanced aggressive NHL—HR=1.05 (95% CI, 0.87-1.27; P=0.60).

Rural patients had slightly better cancer-specific survival if they had advanced indolent NHL but slightly worse cancer-specific survival if they had AML, MM, or advanced aggressive NHL. The HRs were as follows:

• Advanced indolent NHL—HR=0.98 (95% CI, 0.66-1.45; P=0.90)
• AML—HR=1.01 (95% CI, 0.86-1.20; P=0.87)
• MM—HR=1.04 (95% CI, 0.90-1.20; P=0.60)
• Advanced aggressive NHL—HR=1.08 (95% CI, 0.87-1.34; P=0.50).

The researchers said these findings suggest it is access to care, and not other characteristics, that drive the survival disparities typically observed between urban and rural cancer patients.

“If people diagnosed with cancer, regardless of where they live, receive similar care and have similar outcomes, then a reasonable inference is that the best way to improve outcomes for rural patients is to improve their access to quality care,” Dr Unger said.

This research was supported by the National Cancer Institute and the HOPE Foundation. The researchers reported financial relationships with various pharmaceutical companies.

Photo by Rhoda Baer

New research suggests that better access to quality care may reduce disparities in survival between cancer patients living in rural areas of the US and those living in urban areas.

The study showed that urban and rural cancer patients had similar survival outcomes when they were enrolled in clinical trials.

These results, published in JAMA Network Open, cast new light on decades of research showing that cancer patients living in rural areas don’t live as long as urban cancer patients.

“These findings were a surprise, since we thought we might find the same disparities others had found,” said study author Joseph Unger, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

“But clinical trials are a key difference here. In trials, patients are uniformly assessed, treated, and followed under a strict, guideline-driven protocol. This suggests that giving people with cancer access to uniform treatment strategies could help resolve the disparities in outcomes that we see between rural and urban patients.”

Dr Unger and his colleagues studied data on 36,995 patients who were enrolled in 44 phase 3 or phase 2/3 SWOG trials from 1986 through 2012. All 50 states were represented.

Patients had 17 different cancer types, including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM).

Using US Department of Agriculture population classifications known as Rural-Urban Continuum Codes, the researchers categorized the patients as either rural or urban and analyzed their outcomes.

A minority of patients (19.4%, n=7184) were from rural locations. They were significantly more likely than urban patients to be 65 or older (P<0.001) and significantly less likely to be black (vs all other races; P<0.001).

However, there was no significant between-group difference in sex (P=0.53), and all major US geographic regions (West, Midwest, South, and Northeast) were represented.

Results

The researchers limited their analysis of survival to the first 5 years after trial enrollment to emphasize outcomes related to cancer and its treatment. They looked at overall survival (OS) as well as cancer-specific survival.

The team found no meaningful difference in OS or cancer-specific survival between rural and urban patients for 16 of the 17 cancer types.

The exception was estrogen receptor-negative, progesterone receptor-negative breast cancer. Rural patients with this cancer didn’t live as long as their urban counterparts. The hazard ratio (HR) was 1.27 (95% CI, 1.06-1.51; P=0.008) for OS and 1.26 (95% CI, 1.04-1.52; P=0.02) for cancer-specific survival.

The researchers believe this finding could be attributed to a few factors, including timely access to follow-up chemotherapy after patients’ first round of cancer treatment.

Although there were no significant survival differences for patients with hematologic malignancies, rural patients had slightly better OS if they had advanced indolent NHL or AML but slightly worse OS if they had MM or advanced aggressive NHL. The HRs were as follows:

• Advanced indolent NHL—HR=0.91 (95% CI, 0.64-1.29; P=0.60)
• AML—HR=0.94 (95% CI, 0.83-1.06; P=0.29)
• MM—HR=1.05 (95% CI, 0.93-1.18, P=0.46)
• Advanced aggressive NHL—HR=1.05 (95% CI, 0.87-1.27; P=0.60).

Rural patients had slightly better cancer-specific survival if they had advanced indolent NHL but slightly worse cancer-specific survival if they had AML, MM, or advanced aggressive NHL. The HRs were as follows:

• Advanced indolent NHL—HR=0.98 (95% CI, 0.66-1.45; P=0.90)
• AML—HR=1.01 (95% CI, 0.86-1.20; P=0.87)
• MM—HR=1.04 (95% CI, 0.90-1.20; P=0.60)
• Advanced aggressive NHL—HR=1.08 (95% CI, 0.87-1.34; P=0.50).

The researchers said these findings suggest it is access to care, and not other characteristics, that drive the survival disparities typically observed between urban and rural cancer patients.

“If people diagnosed with cancer, regardless of where they live, receive similar care and have similar outcomes, then a reasonable inference is that the best way to improve outcomes for rural patients is to improve their access to quality care,” Dr Unger said.

This research was supported by the National Cancer Institute and the HOPE Foundation. The researchers reported financial relationships with various pharmaceutical companies.

Micrograph showing MDS

The US Food and Drug Administration (FDA) has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.

In this trial (NCT02576301), researchers are evaluating OXi4503, alone and in combination with cytarabine, in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The partial clinical hold applies to the 12.2 mg/m² dose of OXi4503.

The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m².

The agency said additional data on patients receiving OXi4503 at 9.76 mg/m² must be evaluated before dosing at 12.2 mg/m² can be resumed.

The partial clinical hold is a result of 2 potential dose-limiting toxicities (DLTs) observed at the 12.2 mg/m² dose level.

One DLT was hypotension, which occurred shortly after initial treatment with OXi4503. The other DLT was acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.

Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.

The study protocol generally defines a DLT as any grade 3 serious adverse event where a relationship to OXi4503 cannot be ruled out.

“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” said William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics, Inc., the company developing OXi4503.

About OXi4503

According to Mateon Therapeutics, OXi4503 has a dual mechanism of action that disrupts the shape of tumor bone marrow endothelial cells through reversible binding to tubulin at the colchicine binding site, downregulating intercellular adhesion molecules.

This alters the endothelial cell shape, releasing quiescent adherent tumor cells from bone marrow endothelial cells and activating the cell cycle, which makes the tumor cells vulnerable to chemotherapy.

OXi4503 also kills tumor cells directly via myeloperoxidase activation of an orthoquinone cytotoxic mediator.

In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.

Clinical trials

In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. The goals were to determine the safety profile, maximum tolerated dose, and biologic activity of OXi4503.

The researchers said OXi4503 demonstrated preliminary evidence of disease response in heavily pre-treated, refractory AML and advanced MDS.

The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.

Results from this study were presented at the 2013 ASH Annual Meeting.

In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.

The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS.

The phase 1 portion was also intended to determine the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.

The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.

Micrograph showing MDS

The US Food and Drug Administration (FDA) has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.

In this trial (NCT02576301), researchers are evaluating OXi4503, alone and in combination with cytarabine, in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The partial clinical hold applies to the 12.2 mg/m² dose of OXi4503.

The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m².

The agency said additional data on patients receiving OXi4503 at 9.76 mg/m² must be evaluated before dosing at 12.2 mg/m² can be resumed.

The partial clinical hold is a result of 2 potential dose-limiting toxicities (DLTs) observed at the 12.2 mg/m² dose level.

One DLT was hypotension, which occurred shortly after initial treatment with OXi4503. The other DLT was acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.

Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.

The study protocol generally defines a DLT as any grade 3 serious adverse event where a relationship to OXi4503 cannot be ruled out.

“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” said William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics, Inc., the company developing OXi4503.

About OXi4503

According to Mateon Therapeutics, OXi4503 has a dual mechanism of action that disrupts the shape of tumor bone marrow endothelial cells through reversible binding to tubulin at the colchicine binding site, downregulating intercellular adhesion molecules.

This alters the endothelial cell shape, releasing quiescent adherent tumor cells from bone marrow endothelial cells and activating the cell cycle, which makes the tumor cells vulnerable to chemotherapy.

OXi4503 also kills tumor cells directly via myeloperoxidase activation of an orthoquinone cytotoxic mediator.

In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.

Clinical trials

In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. The goals were to determine the safety profile, maximum tolerated dose, and biologic activity of OXi4503.

The researchers said OXi4503 demonstrated preliminary evidence of disease response in heavily pre-treated, refractory AML and advanced MDS.

The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.

Results from this study were presented at the 2013 ASH Annual Meeting.

In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.

The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS.

The phase 1 portion was also intended to determine the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.

The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.

Micrograph showing MDS

The US Food and Drug Administration (FDA) has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.

In this trial (NCT02576301), researchers are evaluating OXi4503, alone and in combination with cytarabine, in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The partial clinical hold applies to the 12.2 mg/m² dose of OXi4503.

The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m².

The agency said additional data on patients receiving OXi4503 at 9.76 mg/m² must be evaluated before dosing at 12.2 mg/m² can be resumed.

The partial clinical hold is a result of 2 potential dose-limiting toxicities (DLTs) observed at the 12.2 mg/m² dose level.

One DLT was hypotension, which occurred shortly after initial treatment with OXi4503. The other DLT was acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.

Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.

The study protocol generally defines a DLT as any grade 3 serious adverse event where a relationship to OXi4503 cannot be ruled out.

“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” said William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics, Inc., the company developing OXi4503.

About OXi4503

According to Mateon Therapeutics, OXi4503 has a dual mechanism of action that disrupts the shape of tumor bone marrow endothelial cells through reversible binding to tubulin at the colchicine binding site, downregulating intercellular adhesion molecules.

This alters the endothelial cell shape, releasing quiescent adherent tumor cells from bone marrow endothelial cells and activating the cell cycle, which makes the tumor cells vulnerable to chemotherapy.

OXi4503 also kills tumor cells directly via myeloperoxidase activation of an orthoquinone cytotoxic mediator.

In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.

Clinical trials

In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. The goals were to determine the safety profile, maximum tolerated dose, and biologic activity of OXi4503.

The researchers said OXi4503 demonstrated preliminary evidence of disease response in heavily pre-treated, refractory AML and advanced MDS.

The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.

Results from this study were presented at the 2013 ASH Annual Meeting.

In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.

The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS.

The phase 1 portion was also intended to determine the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.

The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.

Photo courtesy of CDC

A new study suggests that certain patients with acute pulmonary embolism (PE) may be better off receiving outpatient treatment.

Researchers tested outpatient anticoagulant therapy in 200 PE patients with a low risk of mortality.

At 90 days of follow-up, there were no deaths or recurrences of venous thromboembolism (VTE), but 1 patient experienced major bleeding after a traumatic injury.

A majority of patients said they were satisfied with outpatient care.

Joseph Bledsoe, MD, of Intermountain Medical Center in Salt Lake City, Utah, and his colleagues reported these results in CHEST.

The researchers tracked patients who were treated for acute PE in 5 Intermountain Healthcare emergency departments (EDs) from 2013 to 2016.

The patients had to have a low risk of mortality according to the Pulmonary Embolism Severity Index score (<86), echocardiography (no signs of right heart strain), and whole-leg compression ultrasound.

Patients could not have deep vein thrombosis proximal to the popliteal vein, hypoxia, hypotension, hepatic failure, or renal failure. They had to be eligible for therapeutic anticoagulation and not have any condition requiring hospitalization.

With these criteria, the researchers selected 200 patients. They were observed in the ED or hospital for 12 to 24 hours and then discharged with anticoagulant therapy.

Patients received rivaroxaban (n=149), enoxaparin transitioned to warfarin (n=26), apixaban (n=24), or enoxaparin alone (n=1).

Results

The study’s primary outcome was the 90-day composite rate of all-cause mortality, recurrent symptomatic VTE, and major bleeding.

There were no deaths and no cases of recurrent VTE. One patient did experience major bleeding at day 61 due to a traumatic thigh injury.

Within 7 days of study enrollment, there were 19 patients (9.5%) who returned to the ED and 2 patients (1%) who were admitted to the hospital. One patient with pulmonary infarct was admitted for pain control (day 2), and another was admitted for an elective coronary intervention (day 7) due to a positive cardiac stress test.

Within 30 days, 32 patients (16%) returned to the ED, and 5 (3%) were admitted to the hospital for events unrelated to their PE.

The study also showed that patients were largely satisfied with outpatient care. Of the 146 patients who completed a satisfaction survey at 90 days, 89% said they would choose outpatient management if they had another PE in the future.

“We found a large subset of patients with blood clots who’d do well at home; in fact, who probably did better at home,” Dr Bledsoe said. “When patients are sent home versus staying in the hospital, they’re at lower risk of getting another infection. It’s a lot less expensive, too.”

Currently, the standard of care in the US for acute PE is hospitalization for all patients. That’s recommended, in part, because their overall mortality rate is 17%.

However, the lower mortality rate among some appropriately risk-stratified patients suggests that at-home care, which has become the norm in some European countries, leads to better outcomes for those patients overall and less chance of a hospital-introduced infection, according to Dr Bledsoe.

“Our findings show that, if you appropriately risk-stratify patients, there are a lot of people with blood clots who are safe to go home,” he said.

Dr Bledsoe added that similar research should be conducted outside of the Intermountain Healthcare system to confirm the results of this study, and a larger group of patients should be studied.

Photo courtesy of CDC

A new study suggests that certain patients with acute pulmonary embolism (PE) may be better off receiving outpatient treatment.

Researchers tested outpatient anticoagulant therapy in 200 PE patients with a low risk of mortality.

At 90 days of follow-up, there were no deaths or recurrences of venous thromboembolism (VTE), but 1 patient experienced major bleeding after a traumatic injury.

A majority of patients said they were satisfied with outpatient care.

Joseph Bledsoe, MD, of Intermountain Medical Center in Salt Lake City, Utah, and his colleagues reported these results in CHEST.

The researchers tracked patients who were treated for acute PE in 5 Intermountain Healthcare emergency departments (EDs) from 2013 to 2016.

The patients had to have a low risk of mortality according to the Pulmonary Embolism Severity Index score (<86), echocardiography (no signs of right heart strain), and whole-leg compression ultrasound.

Patients could not have deep vein thrombosis proximal to the popliteal vein, hypoxia, hypotension, hepatic failure, or renal failure. They had to be eligible for therapeutic anticoagulation and not have any condition requiring hospitalization.

With these criteria, the researchers selected 200 patients. They were observed in the ED or hospital for 12 to 24 hours and then discharged with anticoagulant therapy.

Patients received rivaroxaban (n=149), enoxaparin transitioned to warfarin (n=26), apixaban (n=24), or enoxaparin alone (n=1).

Results

The study’s primary outcome was the 90-day composite rate of all-cause mortality, recurrent symptomatic VTE, and major bleeding.

There were no deaths and no cases of recurrent VTE. One patient did experience major bleeding at day 61 due to a traumatic thigh injury.

Within 7 days of study enrollment, there were 19 patients (9.5%) who returned to the ED and 2 patients (1%) who were admitted to the hospital. One patient with pulmonary infarct was admitted for pain control (day 2), and another was admitted for an elective coronary intervention (day 7) due to a positive cardiac stress test.

Within 30 days, 32 patients (16%) returned to the ED, and 5 (3%) were admitted to the hospital for events unrelated to their PE.

The study also showed that patients were largely satisfied with outpatient care. Of the 146 patients who completed a satisfaction survey at 90 days, 89% said they would choose outpatient management if they had another PE in the future.

“We found a large subset of patients with blood clots who’d do well at home; in fact, who probably did better at home,” Dr Bledsoe said. “When patients are sent home versus staying in the hospital, they’re at lower risk of getting another infection. It’s a lot less expensive, too.”

Currently, the standard of care in the US for acute PE is hospitalization for all patients. That’s recommended, in part, because their overall mortality rate is 17%.

However, the lower mortality rate among some appropriately risk-stratified patients suggests that at-home care, which has become the norm in some European countries, leads to better outcomes for those patients overall and less chance of a hospital-introduced infection, according to Dr Bledsoe.

“Our findings show that, if you appropriately risk-stratify patients, there are a lot of people with blood clots who are safe to go home,” he said.

Dr Bledsoe added that similar research should be conducted outside of the Intermountain Healthcare system to confirm the results of this study, and a larger group of patients should be studied.

Photo courtesy of CDC

A new study suggests that certain patients with acute pulmonary embolism (PE) may be better off receiving outpatient treatment.

Researchers tested outpatient anticoagulant therapy in 200 PE patients with a low risk of mortality.

At 90 days of follow-up, there were no deaths or recurrences of venous thromboembolism (VTE), but 1 patient experienced major bleeding after a traumatic injury.

A majority of patients said they were satisfied with outpatient care.

Joseph Bledsoe, MD, of Intermountain Medical Center in Salt Lake City, Utah, and his colleagues reported these results in CHEST.

The researchers tracked patients who were treated for acute PE in 5 Intermountain Healthcare emergency departments (EDs) from 2013 to 2016.

The patients had to have a low risk of mortality according to the Pulmonary Embolism Severity Index score (<86), echocardiography (no signs of right heart strain), and whole-leg compression ultrasound.

Patients could not have deep vein thrombosis proximal to the popliteal vein, hypoxia, hypotension, hepatic failure, or renal failure. They had to be eligible for therapeutic anticoagulation and not have any condition requiring hospitalization.

With these criteria, the researchers selected 200 patients. They were observed in the ED or hospital for 12 to 24 hours and then discharged with anticoagulant therapy.

Patients received rivaroxaban (n=149), enoxaparin transitioned to warfarin (n=26), apixaban (n=24), or enoxaparin alone (n=1).

Results

The study’s primary outcome was the 90-day composite rate of all-cause mortality, recurrent symptomatic VTE, and major bleeding.

There were no deaths and no cases of recurrent VTE. One patient did experience major bleeding at day 61 due to a traumatic thigh injury.

Within 7 days of study enrollment, there were 19 patients (9.5%) who returned to the ED and 2 patients (1%) who were admitted to the hospital. One patient with pulmonary infarct was admitted for pain control (day 2), and another was admitted for an elective coronary intervention (day 7) due to a positive cardiac stress test.

Within 30 days, 32 patients (16%) returned to the ED, and 5 (3%) were admitted to the hospital for events unrelated to their PE.

The study also showed that patients were largely satisfied with outpatient care. Of the 146 patients who completed a satisfaction survey at 90 days, 89% said they would choose outpatient management if they had another PE in the future.

“We found a large subset of patients with blood clots who’d do well at home; in fact, who probably did better at home,” Dr Bledsoe said. “When patients are sent home versus staying in the hospital, they’re at lower risk of getting another infection. It’s a lot less expensive, too.”

Currently, the standard of care in the US for acute PE is hospitalization for all patients. That’s recommended, in part, because their overall mortality rate is 17%.

However, the lower mortality rate among some appropriately risk-stratified patients suggests that at-home care, which has become the norm in some European countries, leads to better outcomes for those patients overall and less chance of a hospital-introduced infection, according to Dr Bledsoe.

“Our findings show that, if you appropriately risk-stratify patients, there are a lot of people with blood clots who are safe to go home,” he said.

Dr Bledsoe added that similar research should be conducted outside of the Intermountain Healthcare system to confirm the results of this study, and a larger group of patients should be studied.

Image by Michael Bonert

The US Food and Drug Administration (FDA) has granted orphan drug designation to CPI-613 for the treatment of peripheral T-cell lymphoma (PTCL).

CPI-613 is a novel lipoic acid analogue that inhibits multiple enzyme targets within the tricarboxylic acid cycle.

Rafael Pharmaceuticals, Inc., is developing CPI-613 as a treatment for hematologic malignancies and solid tumors.

CPI-613 is currently under investigation in combination with bendamustine in a phase 1 study of patients with relapsed or refractory T-cell lymphoma or classical Hodgkin lymphoma.

Results from this trial were presented at the 2016 ASH Annual Meeting.*

CPI-613 was given at escalating doses starting at 2000 mg/m² over 2 hours on days 1-4 as well as on days 8, 11, 15, and 18. Bendamustine was infused at 90 mg/m² on days 4 and 5 of each 4-week treatment cycle. The treatment cycles were repeated for up to 6 cycles. There was no intra-patient dose-escalation.

The ASH presentation included safety data on 8 patients. The most common grade 3 or higher toxicities—lymphopenia and neutropenia—occurred in 4 patients.

A patient dosed at 2750 mg/m² had a dose-limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. Because of this, the study protocol was amended to discontinue dose-escalation at doses of 2750 mg/m² or higher and to expand the 2500 mg/m² cohort.

Six patients were evaluable for efficacy, and the overall response rate was 83% (5/6).

There were 3 complete responses in patients with PTCL not otherwise specified, a partial response in a patient with mycosis fungoides, and a partial response in a patient with angioimmunoblastic T-cell lymphoma.

One patient with T-cell acute lymphoblastic leukemia experienced progressive disease.

About orphan designation

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

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

*The data presented differ from the abstract.

Image by Michael Bonert

The US Food and Drug Administration (FDA) has granted orphan drug designation to CPI-613 for the treatment of peripheral T-cell lymphoma (PTCL).

CPI-613 is a novel lipoic acid analogue that inhibits multiple enzyme targets within the tricarboxylic acid cycle.

Rafael Pharmaceuticals, Inc., is developing CPI-613 as a treatment for hematologic malignancies and solid tumors.

CPI-613 is currently under investigation in combination with bendamustine in a phase 1 study of patients with relapsed or refractory T-cell lymphoma or classical Hodgkin lymphoma.

Results from this trial were presented at the 2016 ASH Annual Meeting.*

CPI-613 was given at escalating doses starting at 2000 mg/m² over 2 hours on days 1-4 as well as on days 8, 11, 15, and 18. Bendamustine was infused at 90 mg/m² on days 4 and 5 of each 4-week treatment cycle. The treatment cycles were repeated for up to 6 cycles. There was no intra-patient dose-escalation.

The ASH presentation included safety data on 8 patients. The most common grade 3 or higher toxicities—lymphopenia and neutropenia—occurred in 4 patients.

A patient dosed at 2750 mg/m² had a dose-limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. Because of this, the study protocol was amended to discontinue dose-escalation at doses of 2750 mg/m² or higher and to expand the 2500 mg/m² cohort.

Six patients were evaluable for efficacy, and the overall response rate was 83% (5/6).

There were 3 complete responses in patients with PTCL not otherwise specified, a partial response in a patient with mycosis fungoides, and a partial response in a patient with angioimmunoblastic T-cell lymphoma.

One patient with T-cell acute lymphoblastic leukemia experienced progressive disease.

About orphan designation

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

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

*The data presented differ from the abstract.

Image by Michael Bonert

The US Food and Drug Administration (FDA) has granted orphan drug designation to CPI-613 for the treatment of peripheral T-cell lymphoma (PTCL).

CPI-613 is a novel lipoic acid analogue that inhibits multiple enzyme targets within the tricarboxylic acid cycle.

Rafael Pharmaceuticals, Inc., is developing CPI-613 as a treatment for hematologic malignancies and solid tumors.

CPI-613 is currently under investigation in combination with bendamustine in a phase 1 study of patients with relapsed or refractory T-cell lymphoma or classical Hodgkin lymphoma.

Results from this trial were presented at the 2016 ASH Annual Meeting.*

CPI-613 was given at escalating doses starting at 2000 mg/m² over 2 hours on days 1-4 as well as on days 8, 11, 15, and 18. Bendamustine was infused at 90 mg/m² on days 4 and 5 of each 4-week treatment cycle. The treatment cycles were repeated for up to 6 cycles. There was no intra-patient dose-escalation.

The ASH presentation included safety data on 8 patients. The most common grade 3 or higher toxicities—lymphopenia and neutropenia—occurred in 4 patients.

A patient dosed at 2750 mg/m² had a dose-limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. Because of this, the study protocol was amended to discontinue dose-escalation at doses of 2750 mg/m² or higher and to expand the 2500 mg/m² cohort.

Six patients were evaluable for efficacy, and the overall response rate was 83% (5/6).

There were 3 complete responses in patients with PTCL not otherwise specified, a partial response in a patient with mycosis fungoides, and a partial response in a patient with angioimmunoblastic T-cell lymphoma.

One patient with T-cell acute lymphoblastic leukemia experienced progressive disease.

About orphan designation

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

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

*The data presented differ from the abstract.

Photo by Marja Helander

The US Food and Drug Administration (FDA) has approved the Procleix® Zika Virus Assay for blood screening.

The assay is approved to detect Zika virus in individual or pooled plasma specimens from human donors, including volunteer donors of whole blood and blood components for transfusion.

The assay is also approved for testing plasma or serum specimens to screen other living or cadaveric organ donors and human cells, tissues, and cellular and tissue-based products.

The Procleix Zika Virus Assay, which was developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System. The Procleix Panther System automates all aspects of nucleic acid technology-based blood screening on a single, integrated platform.

The Procleix Zika Virus Assay has been in use in the US since June 2016, when it was authorized under an investigational new drug protocol to screen donated blood collected in the US.

Also in 2016, the assay was CE-marked for use in European countries conforming to CE Mark regulations.

Photo by Marja Helander

The US Food and Drug Administration (FDA) has approved the Procleix® Zika Virus Assay for blood screening.

The assay is approved to detect Zika virus in individual or pooled plasma specimens from human donors, including volunteer donors of whole blood and blood components for transfusion.

The assay is also approved for testing plasma or serum specimens to screen other living or cadaveric organ donors and human cells, tissues, and cellular and tissue-based products.

The Procleix Zika Virus Assay, which was developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System. The Procleix Panther System automates all aspects of nucleic acid technology-based blood screening on a single, integrated platform.

The Procleix Zika Virus Assay has been in use in the US since June 2016, when it was authorized under an investigational new drug protocol to screen donated blood collected in the US.

Also in 2016, the assay was CE-marked for use in European countries conforming to CE Mark regulations.

Photo by Marja Helander

The US Food and Drug Administration (FDA) has approved the Procleix® Zika Virus Assay for blood screening.

The assay is approved to detect Zika virus in individual or pooled plasma specimens from human donors, including volunteer donors of whole blood and blood components for transfusion.

The assay is also approved for testing plasma or serum specimens to screen other living or cadaveric organ donors and human cells, tissues, and cellular and tissue-based products.

The Procleix Zika Virus Assay, which was developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System. The Procleix Panther System automates all aspects of nucleic acid technology-based blood screening on a single, integrated platform.

The Procleix Zika Virus Assay has been in use in the US since June 2016, when it was authorized under an investigational new drug protocol to screen donated blood collected in the US.

Also in 2016, the assay was CE-marked for use in European countries conforming to CE Mark regulations.

Photo by Juan D. Alfonso

Researchers say they have determined which blood tests can help general practitioners (GPs) rule out a diagnosis of multiple myeloma (MM).

The team discovered that plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) were more helpful in ruling out MM than a C-reactive protein (CRP) test.

Furthermore, the possibility of MM “is extremely low” in patients with normal hemoglobin (Hb) and normal PV or ESR.

“Ordinarily, a GP will see a patient with myeloma every 5 years, and early diagnosis matters,” said study author William Hamilton, MD, of the University of Exeter Medical School in the UK.

“We report a simple way a GP can check patients presenting symptoms such as back, rib, and chest pain or recurrent chest infections and determine whether they have myeloma or not.”

Dr Hamilton and his colleagues reported their findings in the British Journal of General Practice.

The researchers analyzed blood tests performed on 2703 MM patients up to 5 years prior to diagnosis. The team then compared results in the MM cases to blood test results in 12,157 patients without MM, matched for age and other relevant parameters.

The researchers used likelihood ratios (LRs) to classify tests as useful for ruling in or ruling out MM.

The team explained that positive likelihood (LR+) tests indicate how many times more likely a positive test occurs in individuals with MM than in those without the disease. Negative likelihood (LR–) tests indicate how many times less likely a negative result will occur in individuals with MM than in those without MM.

A test was defined as useful for ruling in MM if the LR+ was ≥ 5 and useful for ruling out MM if the LR– was ≤ 0.2.

Results

None of the inflammatory markers analyzed proved useful (LR+ ≥ 5) for ruling in MM.

The LR+ was:

• 2.0 for raised PV
• 1.9 for raised ESR
• 1.2 for raised CRP.

Similarly, none of the tests alone was useful (LR– ≤ 0.2) for ruling out MM.

The LR– was:

• 0.42 for normal Hb
• 0.81 for normal calcium
• 0.80 for normal creatinine
• 0.28 for normal ESR
• 0.32 for normal PV
• 0.87 for normal CRP.

However, several combinations of tests were useful for ruling out MM.

Conclusions/implications

The researchers concluded that, with normal Hb and normal PV or ESR, the possibility of MM is very low, and assessing CRP or creatinine as well increases the sensitivity of testing only slightly.

“The combination of levels of hemoglobin . . . and 1 of 2 inflammatory markers [ESR or PV] are a sufficient test rule out myeloma,” said study author Constantinos Koshiaris, of the University of Oxford in the UK.

“If abnormalities are detected in this test, it should lead to urgent urine protein tests, which can help speed up diagnosis.”

The researchers also recommend adding calcium tests if patients have certain symptoms, such as back pain, rib pain, joint pain, and fracture.

Photo by Juan D. Alfonso

Researchers say they have determined which blood tests can help general practitioners (GPs) rule out a diagnosis of multiple myeloma (MM).

The team discovered that plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) were more helpful in ruling out MM than a C-reactive protein (CRP) test.

Furthermore, the possibility of MM “is extremely low” in patients with normal hemoglobin (Hb) and normal PV or ESR.

“Ordinarily, a GP will see a patient with myeloma every 5 years, and early diagnosis matters,” said study author William Hamilton, MD, of the University of Exeter Medical School in the UK.

“We report a simple way a GP can check patients presenting symptoms such as back, rib, and chest pain or recurrent chest infections and determine whether they have myeloma or not.”

Dr Hamilton and his colleagues reported their findings in the British Journal of General Practice.

The researchers analyzed blood tests performed on 2703 MM patients up to 5 years prior to diagnosis. The team then compared results in the MM cases to blood test results in 12,157 patients without MM, matched for age and other relevant parameters.

The researchers used likelihood ratios (LRs) to classify tests as useful for ruling in or ruling out MM.

The team explained that positive likelihood (LR+) tests indicate how many times more likely a positive test occurs in individuals with MM than in those without the disease. Negative likelihood (LR–) tests indicate how many times less likely a negative result will occur in individuals with MM than in those without MM.

A test was defined as useful for ruling in MM if the LR+ was ≥ 5 and useful for ruling out MM if the LR– was ≤ 0.2.

Results

None of the inflammatory markers analyzed proved useful (LR+ ≥ 5) for ruling in MM.

The LR+ was:

• 2.0 for raised PV
• 1.9 for raised ESR
• 1.2 for raised CRP.

Similarly, none of the tests alone was useful (LR– ≤ 0.2) for ruling out MM.

The LR– was:

• 0.42 for normal Hb
• 0.81 for normal calcium
• 0.80 for normal creatinine
• 0.28 for normal ESR
• 0.32 for normal PV
• 0.87 for normal CRP.

However, several combinations of tests were useful for ruling out MM.

Conclusions/implications

The researchers concluded that, with normal Hb and normal PV or ESR, the possibility of MM is very low, and assessing CRP or creatinine as well increases the sensitivity of testing only slightly.

“The combination of levels of hemoglobin . . . and 1 of 2 inflammatory markers [ESR or PV] are a sufficient test rule out myeloma,” said study author Constantinos Koshiaris, of the University of Oxford in the UK.

“If abnormalities are detected in this test, it should lead to urgent urine protein tests, which can help speed up diagnosis.”

The researchers also recommend adding calcium tests if patients have certain symptoms, such as back pain, rib pain, joint pain, and fracture.

Photo by Juan D. Alfonso

Researchers say they have determined which blood tests can help general practitioners (GPs) rule out a diagnosis of multiple myeloma (MM).

The team discovered that plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) were more helpful in ruling out MM than a C-reactive protein (CRP) test.

Furthermore, the possibility of MM “is extremely low” in patients with normal hemoglobin (Hb) and normal PV or ESR.

“Ordinarily, a GP will see a patient with myeloma every 5 years, and early diagnosis matters,” said study author William Hamilton, MD, of the University of Exeter Medical School in the UK.

“We report a simple way a GP can check patients presenting symptoms such as back, rib, and chest pain or recurrent chest infections and determine whether they have myeloma or not.”

Dr Hamilton and his colleagues reported their findings in the British Journal of General Practice.

The researchers analyzed blood tests performed on 2703 MM patients up to 5 years prior to diagnosis. The team then compared results in the MM cases to blood test results in 12,157 patients without MM, matched for age and other relevant parameters.

The researchers used likelihood ratios (LRs) to classify tests as useful for ruling in or ruling out MM.

The team explained that positive likelihood (LR+) tests indicate how many times more likely a positive test occurs in individuals with MM than in those without the disease. Negative likelihood (LR–) tests indicate how many times less likely a negative result will occur in individuals with MM than in those without MM.

A test was defined as useful for ruling in MM if the LR+ was ≥ 5 and useful for ruling out MM if the LR– was ≤ 0.2.

Results

None of the inflammatory markers analyzed proved useful (LR+ ≥ 5) for ruling in MM.

The LR+ was:

• 2.0 for raised PV
• 1.9 for raised ESR
• 1.2 for raised CRP.

Similarly, none of the tests alone was useful (LR– ≤ 0.2) for ruling out MM.

The LR– was:

• 0.42 for normal Hb
• 0.81 for normal calcium
• 0.80 for normal creatinine
• 0.28 for normal ESR
• 0.32 for normal PV
• 0.87 for normal CRP.

However, several combinations of tests were useful for ruling out MM.

Conclusions/implications

The researchers concluded that, with normal Hb and normal PV or ESR, the possibility of MM is very low, and assessing CRP or creatinine as well increases the sensitivity of testing only slightly.

“The combination of levels of hemoglobin . . . and 1 of 2 inflammatory markers [ESR or PV] are a sufficient test rule out myeloma,” said study author Constantinos Koshiaris, of the University of Oxford in the UK.

“If abnormalities are detected in this test, it should lead to urgent urine protein tests, which can help speed up diagnosis.”

The researchers also recommend adding calcium tests if patients have certain symptoms, such as back pain, rib pain, joint pain, and fracture.