Hematology Times

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

VIENNA—Millions of people throughout the world are dying from potentially treatable cancers because of a chronic underinvestment in radiotherapy resources, according to a new report.

The report suggests that expanding access to radiotherapy services will require a sizeable investment upfront, but that investment could bring economic benefits of up to $365 billion in developing countries over the next 20 years.

The report was published in The Lancet Oncology and presented at the 2015 European Cancer Congress.

The report estimates that 204 million fractions of radiotherapy will be needed to treat the 12 million cancer patients worldwide who could benefit from treatment in 2035.

But the cost per fraction is highly cost-effective and low compared to the price of many new cancer drugs, according to the report’s authors.

They estimate that full access to radiotherapy could be achieved for all patients in need in low-and middle income countries (LMIC) by 2035 for $97 billion, with potential health benefits of 27 million life-years saved and economic benefits ranging from $278 billion to $365 billion over the next 20 years.

“There is a widespread misconception that the costs of providing radiotherapy put it beyond the reach of all but the richest countries, [but] nothing could be further from the truth,” said Rifat Atun, MBBS, of Harvard University in Boston, Massachusetts.

“Our work . . .  clearly shows that not only can this essential service be deployed safely and high quality treatment delivered in low- and middle-income countries, but that scale-up of radiotherapy capacity is a feasible and highly cost-effective investment.”

The report provides details on access to radiotherapy services across the world, on a country-by-country basis. The authors calculated the costs and benefits of meeting the worldwide shortfall in resources and bridging the gap in access to effective treatment.

Estimates suggest that, at present, about 40% to 60% of cancer patients worldwide have access to radiotherapy. Even in high-income countries like Canada, Australia, and the UK, numbers of radiotherapy facilities, equipment, and trained staff are inadequate.

Access is worst in low-income countries, where as many as 9 out of 10 people cannot access radiotherapy. The problem of access is especially acute in Africa. In most African countries, radiotherapy is virtually non-existent. Forty countries have no radiotherapy facilities at all.

“The time has come to agree and implement immediate actions to tackle the global shortfall in radiotherapy services and the crisis of access to this highly effective treatment,” Dr Atun said.

With that in mind, he and his colleagues called for the following 6 targets to be met.

By 2020:

• 80% of countries to have comprehensive cancer plans that include radiotherapy.
• Each LMIC to create 1 new center for treatment and training.
• 80% of LMICs to include radiotherapy services in their universal health coverage plans.

By 2025:

• A 25% increase in radiotherapy treatment capacity.
• LMICs to train 7500 radiation oncologists, 20,000 radiotherapy radiographers, and 6000 medical physicists.
• $46 billion of upfront investment to be raised to establish radiotherapy infrastructure and training in LMICs (with help from international banks and the private sector).

“The evidence outlined in the [report] reinforces the case for investing in radiotherapy as an essential component of cancer control,” said Mary Gospodarowicz, MD, co-chair of the UICC Global Task Force on Radiotherapy for Cancer Control.

“The building of radiotherapy capacity will require large initial investment. However, the treatment is more cost-effective than chemotherapy and surgery for treating cancer, and the health and economic benefits will be realized in just 10 to 15 years.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

VIENNA—Millions of people throughout the world are dying from potentially treatable cancers because of a chronic underinvestment in radiotherapy resources, according to a new report.

The report suggests that expanding access to radiotherapy services will require a sizeable investment upfront, but that investment could bring economic benefits of up to $365 billion in developing countries over the next 20 years.

The report was published in The Lancet Oncology and presented at the 2015 European Cancer Congress.

The report estimates that 204 million fractions of radiotherapy will be needed to treat the 12 million cancer patients worldwide who could benefit from treatment in 2035.

But the cost per fraction is highly cost-effective and low compared to the price of many new cancer drugs, according to the report’s authors.

They estimate that full access to radiotherapy could be achieved for all patients in need in low-and middle income countries (LMIC) by 2035 for $97 billion, with potential health benefits of 27 million life-years saved and economic benefits ranging from $278 billion to $365 billion over the next 20 years.

“There is a widespread misconception that the costs of providing radiotherapy put it beyond the reach of all but the richest countries, [but] nothing could be further from the truth,” said Rifat Atun, MBBS, of Harvard University in Boston, Massachusetts.

“Our work . . .  clearly shows that not only can this essential service be deployed safely and high quality treatment delivered in low- and middle-income countries, but that scale-up of radiotherapy capacity is a feasible and highly cost-effective investment.”

The report provides details on access to radiotherapy services across the world, on a country-by-country basis. The authors calculated the costs and benefits of meeting the worldwide shortfall in resources and bridging the gap in access to effective treatment.

Estimates suggest that, at present, about 40% to 60% of cancer patients worldwide have access to radiotherapy. Even in high-income countries like Canada, Australia, and the UK, numbers of radiotherapy facilities, equipment, and trained staff are inadequate.

Access is worst in low-income countries, where as many as 9 out of 10 people cannot access radiotherapy. The problem of access is especially acute in Africa. In most African countries, radiotherapy is virtually non-existent. Forty countries have no radiotherapy facilities at all.

“The time has come to agree and implement immediate actions to tackle the global shortfall in radiotherapy services and the crisis of access to this highly effective treatment,” Dr Atun said.

With that in mind, he and his colleagues called for the following 6 targets to be met.

By 2020:

• 80% of countries to have comprehensive cancer plans that include radiotherapy.
• Each LMIC to create 1 new center for treatment and training.
• 80% of LMICs to include radiotherapy services in their universal health coverage plans.

By 2025:

• A 25% increase in radiotherapy treatment capacity.
• LMICs to train 7500 radiation oncologists, 20,000 radiotherapy radiographers, and 6000 medical physicists.
• $46 billion of upfront investment to be raised to establish radiotherapy infrastructure and training in LMICs (with help from international banks and the private sector).

“The evidence outlined in the [report] reinforces the case for investing in radiotherapy as an essential component of cancer control,” said Mary Gospodarowicz, MD, co-chair of the UICC Global Task Force on Radiotherapy for Cancer Control.

“The building of radiotherapy capacity will require large initial investment. However, the treatment is more cost-effective than chemotherapy and surgery for treating cancer, and the health and economic benefits will be realized in just 10 to 15 years.”

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

VIENNA—Millions of people throughout the world are dying from potentially treatable cancers because of a chronic underinvestment in radiotherapy resources, according to a new report.

The report suggests that expanding access to radiotherapy services will require a sizeable investment upfront, but that investment could bring economic benefits of up to $365 billion in developing countries over the next 20 years.

The report was published in The Lancet Oncology and presented at the 2015 European Cancer Congress.

The report estimates that 204 million fractions of radiotherapy will be needed to treat the 12 million cancer patients worldwide who could benefit from treatment in 2035.

But the cost per fraction is highly cost-effective and low compared to the price of many new cancer drugs, according to the report’s authors.

They estimate that full access to radiotherapy could be achieved for all patients in need in low-and middle income countries (LMIC) by 2035 for $97 billion, with potential health benefits of 27 million life-years saved and economic benefits ranging from $278 billion to $365 billion over the next 20 years.

“There is a widespread misconception that the costs of providing radiotherapy put it beyond the reach of all but the richest countries, [but] nothing could be further from the truth,” said Rifat Atun, MBBS, of Harvard University in Boston, Massachusetts.

“Our work . . .  clearly shows that not only can this essential service be deployed safely and high quality treatment delivered in low- and middle-income countries, but that scale-up of radiotherapy capacity is a feasible and highly cost-effective investment.”

The report provides details on access to radiotherapy services across the world, on a country-by-country basis. The authors calculated the costs and benefits of meeting the worldwide shortfall in resources and bridging the gap in access to effective treatment.

Estimates suggest that, at present, about 40% to 60% of cancer patients worldwide have access to radiotherapy. Even in high-income countries like Canada, Australia, and the UK, numbers of radiotherapy facilities, equipment, and trained staff are inadequate.

Access is worst in low-income countries, where as many as 9 out of 10 people cannot access radiotherapy. The problem of access is especially acute in Africa. In most African countries, radiotherapy is virtually non-existent. Forty countries have no radiotherapy facilities at all.

“The time has come to agree and implement immediate actions to tackle the global shortfall in radiotherapy services and the crisis of access to this highly effective treatment,” Dr Atun said.

With that in mind, he and his colleagues called for the following 6 targets to be met.

By 2020:

• 80% of countries to have comprehensive cancer plans that include radiotherapy.
• Each LMIC to create 1 new center for treatment and training.
• 80% of LMICs to include radiotherapy services in their universal health coverage plans.

By 2025:

• A 25% increase in radiotherapy treatment capacity.
• LMICs to train 7500 radiation oncologists, 20,000 radiotherapy radiographers, and 6000 medical physicists.
• $46 billion of upfront investment to be raised to establish radiotherapy infrastructure and training in LMICs (with help from international banks and the private sector).

“The evidence outlined in the [report] reinforces the case for investing in radiotherapy as an essential component of cancer control,” said Mary Gospodarowicz, MD, co-chair of the UICC Global Task Force on Radiotherapy for Cancer Control.

“The building of radiotherapy capacity will require large initial investment. However, the treatment is more cost-effective than chemotherapy and surgery for treating cancer, and the health and economic benefits will be realized in just 10 to 15 years.”

Patient undergoing CT scan

Photo by Angela Mary Butler

Clinicians should stratify patients with suspected acute pulmonary embolism (PE) to ensure use of the appropriate diagnostic strategy, according to guidelines from the American College of Physicians (ACP).

The ACP’s guidelines, published in Annals of Internal Medicine, are designed to help clinicians identify patients who should undergo diagnostic testing for PE—D-dimer and imaging—and those who should not.

“The use of computed tomography (CT) for the evaluation of patients with suspected pulmonary embolism is increasing, despite no evidence that this increased use has led to improved patient outcomes, while exposing patients to unnecessary risks and expense,” said ACP President Wayne J. Riley, MD.

“ACP’s advice is designed to help physicians identify patients for whom a PE is so unlikely that they need no further testing, for whom plasma D-dimer testing can provide additional risk stratification, and for whom imaging is indicated because of their high risk and clinical presentation.”

The guidelines say the first step for clinicians evaluating patients with suspected acute PE is to use a validated clinical prediction rule to estimate the patients’ pre-test probability of PE. The Wells and Geneva rules have been validated and are considered equally accurate in predicting the probability of PE.

In patients who have a low pre-test probability of PE, clinicians should apply the Pulmonary Embolism Rule-Out Criteria (PERC) rule. Clinicians should not obtain D-dimer tests or imaging studies in patients with a low pre-test probability of PE and who meet all 8 PERC.

Patients who have an intermediate pre-test probability of PE or patients with low pre-test probability of PE who do not meet all PERC should have a high sensitivity D-dimer test as the initial step in diagnosis.

Clinicians should not use imaging as the initial test in patients who have a low or intermediate pre-test probability of PE.

Since normal D-dimer levels increase with age, clinicians should use age-adjusted D-dimer thresholds (age times 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.

Clinicians should not use imaging in low- or intermediate-risk patients with a D-dimer below the age-adjusted cutoff.

“While highly sensitive, plasma D-dimer testing is nonspecific, and false-positives can lead to unnecessary imaging,” said guideline author Ali S. Raja, MD, of Massachusetts General Hospital in Boston.

“The use of an age-adjusted threshold resulted in maintenance of sensitivities with improved specificities in all age groups.”

Patients with high pre-test probability of PE should undergo imaging with CT pulmonary angiography. Clinicians should reserve V/Q scans for patients who have a contraindication for CT pulmonary angiography or if CT pulmonary angiography is not available.

Clinicians should avoid obtaining a D-dimer measurement in patients with a high pre-test probability of PE.

Patient undergoing CT scan

Photo by Angela Mary Butler

Clinicians should stratify patients with suspected acute pulmonary embolism (PE) to ensure use of the appropriate diagnostic strategy, according to guidelines from the American College of Physicians (ACP).

The ACP’s guidelines, published in Annals of Internal Medicine, are designed to help clinicians identify patients who should undergo diagnostic testing for PE—D-dimer and imaging—and those who should not.

“The use of computed tomography (CT) for the evaluation of patients with suspected pulmonary embolism is increasing, despite no evidence that this increased use has led to improved patient outcomes, while exposing patients to unnecessary risks and expense,” said ACP President Wayne J. Riley, MD.

“ACP’s advice is designed to help physicians identify patients for whom a PE is so unlikely that they need no further testing, for whom plasma D-dimer testing can provide additional risk stratification, and for whom imaging is indicated because of their high risk and clinical presentation.”

The guidelines say the first step for clinicians evaluating patients with suspected acute PE is to use a validated clinical prediction rule to estimate the patients’ pre-test probability of PE. The Wells and Geneva rules have been validated and are considered equally accurate in predicting the probability of PE.

In patients who have a low pre-test probability of PE, clinicians should apply the Pulmonary Embolism Rule-Out Criteria (PERC) rule. Clinicians should not obtain D-dimer tests or imaging studies in patients with a low pre-test probability of PE and who meet all 8 PERC.

Patients who have an intermediate pre-test probability of PE or patients with low pre-test probability of PE who do not meet all PERC should have a high sensitivity D-dimer test as the initial step in diagnosis.

Clinicians should not use imaging as the initial test in patients who have a low or intermediate pre-test probability of PE.

Since normal D-dimer levels increase with age, clinicians should use age-adjusted D-dimer thresholds (age times 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.

Clinicians should not use imaging in low- or intermediate-risk patients with a D-dimer below the age-adjusted cutoff.

“While highly sensitive, plasma D-dimer testing is nonspecific, and false-positives can lead to unnecessary imaging,” said guideline author Ali S. Raja, MD, of Massachusetts General Hospital in Boston.

“The use of an age-adjusted threshold resulted in maintenance of sensitivities with improved specificities in all age groups.”

Patients with high pre-test probability of PE should undergo imaging with CT pulmonary angiography. Clinicians should reserve V/Q scans for patients who have a contraindication for CT pulmonary angiography or if CT pulmonary angiography is not available.

Clinicians should avoid obtaining a D-dimer measurement in patients with a high pre-test probability of PE.

Patient undergoing CT scan

Photo by Angela Mary Butler

Clinicians should stratify patients with suspected acute pulmonary embolism (PE) to ensure use of the appropriate diagnostic strategy, according to guidelines from the American College of Physicians (ACP).

The ACP’s guidelines, published in Annals of Internal Medicine, are designed to help clinicians identify patients who should undergo diagnostic testing for PE—D-dimer and imaging—and those who should not.

“The use of computed tomography (CT) for the evaluation of patients with suspected pulmonary embolism is increasing, despite no evidence that this increased use has led to improved patient outcomes, while exposing patients to unnecessary risks and expense,” said ACP President Wayne J. Riley, MD.

“ACP’s advice is designed to help physicians identify patients for whom a PE is so unlikely that they need no further testing, for whom plasma D-dimer testing can provide additional risk stratification, and for whom imaging is indicated because of their high risk and clinical presentation.”

The guidelines say the first step for clinicians evaluating patients with suspected acute PE is to use a validated clinical prediction rule to estimate the patients’ pre-test probability of PE. The Wells and Geneva rules have been validated and are considered equally accurate in predicting the probability of PE.

In patients who have a low pre-test probability of PE, clinicians should apply the Pulmonary Embolism Rule-Out Criteria (PERC) rule. Clinicians should not obtain D-dimer tests or imaging studies in patients with a low pre-test probability of PE and who meet all 8 PERC.

Patients who have an intermediate pre-test probability of PE or patients with low pre-test probability of PE who do not meet all PERC should have a high sensitivity D-dimer test as the initial step in diagnosis.

Clinicians should not use imaging as the initial test in patients who have a low or intermediate pre-test probability of PE.

Since normal D-dimer levels increase with age, clinicians should use age-adjusted D-dimer thresholds (age times 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.

Clinicians should not use imaging in low- or intermediate-risk patients with a D-dimer below the age-adjusted cutoff.

“While highly sensitive, plasma D-dimer testing is nonspecific, and false-positives can lead to unnecessary imaging,” said guideline author Ali S. Raja, MD, of Massachusetts General Hospital in Boston.

“The use of an age-adjusted threshold resulted in maintenance of sensitivities with improved specificities in all age groups.”

Patients with high pre-test probability of PE should undergo imaging with CT pulmonary angiography. Clinicians should reserve V/Q scans for patients who have a contraindication for CT pulmonary angiography or if CT pulmonary angiography is not available.

Clinicians should avoid obtaining a D-dimer measurement in patients with a high pre-test probability of PE.

Laurence Cooper, MD, PhD

Photo courtesy of MDACC

NEW YORK—Researchers have used a nonviral approach to create chimeric antigen receptor (CAR) T cells and tested these cells in safety trials.

Patients with advanced lymphoma or leukemia were infused with the nonvirally modified CD19-directed CAR T cells after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

Eighty-six percent of autologous HSCT recipients were alive 24 months after infusion, and 53% of allogeneic HSCT recipients were alive with a median follow-up of 6.5 months.

“Gratifyingly, the patients have not demonstrated any acute or late toxicity to these CAR T-cell infusions,” said Laurence Cooper, MD, PhD, formerly of MD Anderson Cancer Center (MDACC) in Houston, Texas, and now with Ziopharm Oncology.

Dr Cooper presented these results at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Some of the technology he described was conducted at MDACC. Dr Cooper is currently a visiting scientist there and will continue to supervise the development of this technology.

Dr Cooper said the appeal of this nonviral approach, which is a modified Sleeping Beauty approach, “is it essentially avoids the complexity of making a virus, a lentivirus or a retrovirus, it can be done at quite low cost, and really allows for a nimbleness to this system.”

Using a simple blood draw of 200 cc of peripheral blood—the process does not require apheresis—the T cells can be expanded on a feeder cell layer and genetically reprogrammed.

Sleeping Beauty system

The researchers reprogrammed the T cells using a 2-plasmid Sleeping Beauty system, which is a transposon/transposase system.

The transposon DNA plasmid codes for the cargo load, which, in this case, is the CAR. At the same time, the transposase DNA plasmid is electroporated, “which is really the secret sauce of the transposition event,” Dr Cooper explained.

After electroporation, the transposon/transposase are co-cultured with K562-derived artificial antigen-presenting cells (aAPC) and expanded with the integrated transposon of K562-aAPC. In this case, CD19 is on the aAPC.

CD19 is co-expressed with other co-stimulatory molecules, CD86 and 4-1BB ligand.

In addition, the researchers added a molecule of interleukin 15 that’s sewn in frame to the Fc region of an immunoglobulin that then activates the T cell in the context of these co-stimulatory molecules.

The T cells that have stable integrants of the CAR grow out over time. And those that have transient expression of the CAR die by neglect.

“By day 14, most of the T cells have the CAR sewn into the genome and are stably expressed,” Dr Cooper said.

The CAR used for these safety trials at MDACC targets CD19 and uses mouse scFv held in frame with an immunoglobulin 4 Fc (IgG4Fc) stalk.

It’s tunneled through the T-cell membrane and has 2 costimulatory molecules, signal 1 delivered by phosphorylation of the immunoreceptor tyrosine-based activation motif in CD3ζ and signal 2 by the costimulatory domain CD28.

The researchers tested the CD19 CARs in 2 clinical settings—one with T cells that were patient-derived and infused after autologous HSCT, and the second with T cells that were derived from a third party and infused after allogeneic HSCT.

Infusion after autologous HSCT

The researchers first tried the CARs in 7 non-Hodgkin lymphoma patients who had an autologous HSCT. Their median age was 52 (range, 36-61).

Five patients received a starting CAR T-cell dose of 5x10⁸ cells/m², and 2 received 5x10⁹ cells/m².

Six patients (86%) remain alive and are in complete remission (CR) at a median follow-up of 24 months.

Infusion after allogeneic HSCT

The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.

Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).

All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.

Five patients received a CAR T-cell dose of 10⁶, 6 patients received 10⁷, 5 received 5x10⁷, and 3 received 5x10⁸ cells/m² based on recipient body surface area.

Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.

Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.

“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.

And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.

Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.

Persistence of infused T cells

The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.

“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.

He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center.

Laurence Cooper, MD, PhD

Photo courtesy of MDACC

NEW YORK—Researchers have used a nonviral approach to create chimeric antigen receptor (CAR) T cells and tested these cells in safety trials.

Patients with advanced lymphoma or leukemia were infused with the nonvirally modified CD19-directed CAR T cells after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

Eighty-six percent of autologous HSCT recipients were alive 24 months after infusion, and 53% of allogeneic HSCT recipients were alive with a median follow-up of 6.5 months.

“Gratifyingly, the patients have not demonstrated any acute or late toxicity to these CAR T-cell infusions,” said Laurence Cooper, MD, PhD, formerly of MD Anderson Cancer Center (MDACC) in Houston, Texas, and now with Ziopharm Oncology.

Dr Cooper presented these results at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Some of the technology he described was conducted at MDACC. Dr Cooper is currently a visiting scientist there and will continue to supervise the development of this technology.

Dr Cooper said the appeal of this nonviral approach, which is a modified Sleeping Beauty approach, “is it essentially avoids the complexity of making a virus, a lentivirus or a retrovirus, it can be done at quite low cost, and really allows for a nimbleness to this system.”

Using a simple blood draw of 200 cc of peripheral blood—the process does not require apheresis—the T cells can be expanded on a feeder cell layer and genetically reprogrammed.

Sleeping Beauty system

The researchers reprogrammed the T cells using a 2-plasmid Sleeping Beauty system, which is a transposon/transposase system.

The transposon DNA plasmid codes for the cargo load, which, in this case, is the CAR. At the same time, the transposase DNA plasmid is electroporated, “which is really the secret sauce of the transposition event,” Dr Cooper explained.

After electroporation, the transposon/transposase are co-cultured with K562-derived artificial antigen-presenting cells (aAPC) and expanded with the integrated transposon of K562-aAPC. In this case, CD19 is on the aAPC.

CD19 is co-expressed with other co-stimulatory molecules, CD86 and 4-1BB ligand.

In addition, the researchers added a molecule of interleukin 15 that’s sewn in frame to the Fc region of an immunoglobulin that then activates the T cell in the context of these co-stimulatory molecules.

The T cells that have stable integrants of the CAR grow out over time. And those that have transient expression of the CAR die by neglect.

“By day 14, most of the T cells have the CAR sewn into the genome and are stably expressed,” Dr Cooper said.

The CAR used for these safety trials at MDACC targets CD19 and uses mouse scFv held in frame with an immunoglobulin 4 Fc (IgG4Fc) stalk.

It’s tunneled through the T-cell membrane and has 2 costimulatory molecules, signal 1 delivered by phosphorylation of the immunoreceptor tyrosine-based activation motif in CD3ζ and signal 2 by the costimulatory domain CD28.

The researchers tested the CD19 CARs in 2 clinical settings—one with T cells that were patient-derived and infused after autologous HSCT, and the second with T cells that were derived from a third party and infused after allogeneic HSCT.

Infusion after autologous HSCT

The researchers first tried the CARs in 7 non-Hodgkin lymphoma patients who had an autologous HSCT. Their median age was 52 (range, 36-61).

Five patients received a starting CAR T-cell dose of 5x10⁸ cells/m², and 2 received 5x10⁹ cells/m².

Six patients (86%) remain alive and are in complete remission (CR) at a median follow-up of 24 months.

Infusion after allogeneic HSCT

The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.

Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).

All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.

Five patients received a CAR T-cell dose of 10⁶, 6 patients received 10⁷, 5 received 5x10⁷, and 3 received 5x10⁸ cells/m² based on recipient body surface area.

Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.

Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.

“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.

And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.

Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.

Persistence of infused T cells

The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.

“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.

He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center.

Laurence Cooper, MD, PhD

Photo courtesy of MDACC

NEW YORK—Researchers have used a nonviral approach to create chimeric antigen receptor (CAR) T cells and tested these cells in safety trials.

Patients with advanced lymphoma or leukemia were infused with the nonvirally modified CD19-directed CAR T cells after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

Eighty-six percent of autologous HSCT recipients were alive 24 months after infusion, and 53% of allogeneic HSCT recipients were alive with a median follow-up of 6.5 months.

“Gratifyingly, the patients have not demonstrated any acute or late toxicity to these CAR T-cell infusions,” said Laurence Cooper, MD, PhD, formerly of MD Anderson Cancer Center (MDACC) in Houston, Texas, and now with Ziopharm Oncology.

Dr Cooper presented these results at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Some of the technology he described was conducted at MDACC. Dr Cooper is currently a visiting scientist there and will continue to supervise the development of this technology.

Dr Cooper said the appeal of this nonviral approach, which is a modified Sleeping Beauty approach, “is it essentially avoids the complexity of making a virus, a lentivirus or a retrovirus, it can be done at quite low cost, and really allows for a nimbleness to this system.”

Using a simple blood draw of 200 cc of peripheral blood—the process does not require apheresis—the T cells can be expanded on a feeder cell layer and genetically reprogrammed.

Sleeping Beauty system

The researchers reprogrammed the T cells using a 2-plasmid Sleeping Beauty system, which is a transposon/transposase system.

The transposon DNA plasmid codes for the cargo load, which, in this case, is the CAR. At the same time, the transposase DNA plasmid is electroporated, “which is really the secret sauce of the transposition event,” Dr Cooper explained.

After electroporation, the transposon/transposase are co-cultured with K562-derived artificial antigen-presenting cells (aAPC) and expanded with the integrated transposon of K562-aAPC. In this case, CD19 is on the aAPC.

CD19 is co-expressed with other co-stimulatory molecules, CD86 and 4-1BB ligand.

In addition, the researchers added a molecule of interleukin 15 that’s sewn in frame to the Fc region of an immunoglobulin that then activates the T cell in the context of these co-stimulatory molecules.

The T cells that have stable integrants of the CAR grow out over time. And those that have transient expression of the CAR die by neglect.

“By day 14, most of the T cells have the CAR sewn into the genome and are stably expressed,” Dr Cooper said.

The CAR used for these safety trials at MDACC targets CD19 and uses mouse scFv held in frame with an immunoglobulin 4 Fc (IgG4Fc) stalk.

It’s tunneled through the T-cell membrane and has 2 costimulatory molecules, signal 1 delivered by phosphorylation of the immunoreceptor tyrosine-based activation motif in CD3ζ and signal 2 by the costimulatory domain CD28.

The researchers tested the CD19 CARs in 2 clinical settings—one with T cells that were patient-derived and infused after autologous HSCT, and the second with T cells that were derived from a third party and infused after allogeneic HSCT.

Infusion after autologous HSCT

The researchers first tried the CARs in 7 non-Hodgkin lymphoma patients who had an autologous HSCT. Their median age was 52 (range, 36-61).

Five patients received a starting CAR T-cell dose of 5x10⁸ cells/m², and 2 received 5x10⁹ cells/m².

Six patients (86%) remain alive and are in complete remission (CR) at a median follow-up of 24 months.

Infusion after allogeneic HSCT

The researchers expanded the investigation to a wider cohort of 19 patients who had undergone allogeneic HSCT.

Seventeen patients had advanced CD19-positive acute lymphoblastic leukemia, and 2 had non-Hodgkin lymphoma. Their median age was 35 (range, 21-56).

All patients were on graft-versus-host disease (GVHD) prophylaxis with tacrolimus at the time of CAR infusion. A subset of these allogeneic transplant patients had haploidentical donors rather than matched sibling donors.

Five patients received a CAR T-cell dose of 10⁶, 6 patients received 10⁷, 5 received 5x10⁷, and 3 received 5x10⁸ cells/m² based on recipient body surface area.

Fifty-eight percent of patients (11/19) achieved a CR, and 10 remain alive a median of 6.5 months after CAR T-cell infusion.

Three patients developed GVHD, 1 with steroid-refractory acute liver disease, 1 with grade 2 acute skin disease, and 1 with chronic limited skin disease. The incidence of GVHD was lower than historical controls at MDACC, Dr Cooper said.

“[G]ratifyingly, in this clinical setting of minimal disease, patients did not have any acute or late toxicity from these infusions,” he added.

And the rate of cytomegalovirus reactivation after CAR T-cell infusion was 24%, compared with 41% for patients after transplant at MDACC without CAR T-cell infusion.

Eight patients received haploidentical HSCT followed by CAR T-cell infusion, and 75% (6/8) remain in CR.

Persistence of infused T cells

The researchers used 2 forms of PCR—qPCR and droplet PCR—to map the fate of the CARs.

“Roughly speaking, for these patients, and this is in line with the literature, in terms of those T cells that are activated through CD28 in contrast to 4-1BB, these T cells are, on average, living about 28 or so days post-infusion,” Dr Cooper noted.

He said this is similar to results observed with CARs being tested at the National Cancer Institute and Memorial Sloan-Kettering Cancer Center.

Doctor and patient

Photo by Logan Tuttle

VIENNA—Despite progress made in recent years, there are “major problems” in pediatric oncology care in Europe, according to a report from the European Society for Paediatric Oncology (SIOPE).

Cancer is still the first cause of death by disease in children age 1 and older in Europe, and more than 300,000 European citizens are pediatric cancer survivors.

These individuals have a higher risk of death at 5 years after diagnosis than that of the general population.

“This is a serious problem for patients, their families, and for health services, with major inequalities existing across Europe,” said SIOPE President Gilles Vassal, MD, PhD, of the Institut Gustave Roussy in Villejuif, France.

“Add to this the fact that 35% of such cancers normally occur before the child is 5 years old and that many pediatric cancers are difficult to treat, and you will understand why we thought it essential to try to tackle this problem in a practical way.”

The resulting report, “The SIOPE Strategic Plan: A European Cancer Plan for Children and Adolescents,” was recently presented at the 2015 European Cancer Congress.

Problem-solving

The report was drawn up after widespread consultation, including discussions with parents, patients, and survivors. It sets out existing problems and proposes solutions to tackle them.

Among these problems are poor access to new drugs for pediatric patients; lack of funding; disparities across Europe in access to treatment and, hence, survival; and the fact that pediatric oncology has been relatively isolated from the adult oncology community.

With the goal of fixing these problems, the report sets out a number of goals and lists the key factors that will be necessary in order to achieve them.

These include a commitment of all funding bodies to finance projects and structures of relevance to pediatric oncology; a strong partnership with patients, parents, and survivors, including better communication and dissemination of information; better collaboration with adult oncology; and transparent partnerships with industry.

Understanding biology

“One of the most important objectives focuses on increasing our knowledge of the biology of pediatric tumors,” said SIOPE President-Elect Martin Schrappe, MD, of the University of Kiel, Germany.

“Cancers in adults result from a multistep process, usually after exposure to external carcinogens such as tobacco, alcohol, and diet, and often progress over many years. Pediatric malignancies develop early in life and over a much shorter time period. This suggests that fewer and stronger events are required for them to progress. Compared with adult cancers, most of them show fewer genetic defects and have a lower genetic complexity.”

“Major progress has been made in understanding pediatric tumor biology, and this has led to the discovery of some unique cancer hallmarks. Now, we need to use modern, innovative technologies to further decipher the mechanisms of pediatric tumor development, progression, and relapse, and speed up its translation to the clinic.”

To do this effectively and fairly, according to the report, interactions need to be strengthened at several levels—between networks of basic research teams, between basic scientists and clinical researchers, and by increasing the involvement of patients and parents in the search for personalized treatments. SIOPE plans to monitor progress through research into outcomes.

Improving quality of life

Another important issue for SIOPE is improving the quality of life for survivors.

“We believe that, in 2020, there will be nearly half a million European pediatric cancer survivors, and many of them will have side effects that are severe enough to affect their daily lives,” Dr Schrappe said. “While the fact that so many survive is a cause for rejoicing, we have a duty to provide them with optimal long-term care so that the rest of their lives may be as normal as possible.”

“One way of doing this would be the creation of a ‘survivorship passport’ for each child and adolescent cured of a cancer. This would contain a history of their disease and treatment, together with relevant follow-up measures aimed at improving their quality of life and a database for storing the clinical data [that would] facilitate monitoring and research.”

Doctor and patient

Photo by Logan Tuttle

VIENNA—Despite progress made in recent years, there are “major problems” in pediatric oncology care in Europe, according to a report from the European Society for Paediatric Oncology (SIOPE).

Cancer is still the first cause of death by disease in children age 1 and older in Europe, and more than 300,000 European citizens are pediatric cancer survivors.

These individuals have a higher risk of death at 5 years after diagnosis than that of the general population.

“This is a serious problem for patients, their families, and for health services, with major inequalities existing across Europe,” said SIOPE President Gilles Vassal, MD, PhD, of the Institut Gustave Roussy in Villejuif, France.

“Add to this the fact that 35% of such cancers normally occur before the child is 5 years old and that many pediatric cancers are difficult to treat, and you will understand why we thought it essential to try to tackle this problem in a practical way.”

The resulting report, “The SIOPE Strategic Plan: A European Cancer Plan for Children and Adolescents,” was recently presented at the 2015 European Cancer Congress.

Problem-solving

The report was drawn up after widespread consultation, including discussions with parents, patients, and survivors. It sets out existing problems and proposes solutions to tackle them.

Among these problems are poor access to new drugs for pediatric patients; lack of funding; disparities across Europe in access to treatment and, hence, survival; and the fact that pediatric oncology has been relatively isolated from the adult oncology community.

With the goal of fixing these problems, the report sets out a number of goals and lists the key factors that will be necessary in order to achieve them.

These include a commitment of all funding bodies to finance projects and structures of relevance to pediatric oncology; a strong partnership with patients, parents, and survivors, including better communication and dissemination of information; better collaboration with adult oncology; and transparent partnerships with industry.

Understanding biology

“One of the most important objectives focuses on increasing our knowledge of the biology of pediatric tumors,” said SIOPE President-Elect Martin Schrappe, MD, of the University of Kiel, Germany.

“Cancers in adults result from a multistep process, usually after exposure to external carcinogens such as tobacco, alcohol, and diet, and often progress over many years. Pediatric malignancies develop early in life and over a much shorter time period. This suggests that fewer and stronger events are required for them to progress. Compared with adult cancers, most of them show fewer genetic defects and have a lower genetic complexity.”

“Major progress has been made in understanding pediatric tumor biology, and this has led to the discovery of some unique cancer hallmarks. Now, we need to use modern, innovative technologies to further decipher the mechanisms of pediatric tumor development, progression, and relapse, and speed up its translation to the clinic.”

To do this effectively and fairly, according to the report, interactions need to be strengthened at several levels—between networks of basic research teams, between basic scientists and clinical researchers, and by increasing the involvement of patients and parents in the search for personalized treatments. SIOPE plans to monitor progress through research into outcomes.

Improving quality of life

Another important issue for SIOPE is improving the quality of life for survivors.

“We believe that, in 2020, there will be nearly half a million European pediatric cancer survivors, and many of them will have side effects that are severe enough to affect their daily lives,” Dr Schrappe said. “While the fact that so many survive is a cause for rejoicing, we have a duty to provide them with optimal long-term care so that the rest of their lives may be as normal as possible.”

“One way of doing this would be the creation of a ‘survivorship passport’ for each child and adolescent cured of a cancer. This would contain a history of their disease and treatment, together with relevant follow-up measures aimed at improving their quality of life and a database for storing the clinical data [that would] facilitate monitoring and research.”

Doctor and patient

Photo by Logan Tuttle

VIENNA—Despite progress made in recent years, there are “major problems” in pediatric oncology care in Europe, according to a report from the European Society for Paediatric Oncology (SIOPE).

Cancer is still the first cause of death by disease in children age 1 and older in Europe, and more than 300,000 European citizens are pediatric cancer survivors.

These individuals have a higher risk of death at 5 years after diagnosis than that of the general population.

“This is a serious problem for patients, their families, and for health services, with major inequalities existing across Europe,” said SIOPE President Gilles Vassal, MD, PhD, of the Institut Gustave Roussy in Villejuif, France.

“Add to this the fact that 35% of such cancers normally occur before the child is 5 years old and that many pediatric cancers are difficult to treat, and you will understand why we thought it essential to try to tackle this problem in a practical way.”

The resulting report, “The SIOPE Strategic Plan: A European Cancer Plan for Children and Adolescents,” was recently presented at the 2015 European Cancer Congress.

Problem-solving

The report was drawn up after widespread consultation, including discussions with parents, patients, and survivors. It sets out existing problems and proposes solutions to tackle them.

Among these problems are poor access to new drugs for pediatric patients; lack of funding; disparities across Europe in access to treatment and, hence, survival; and the fact that pediatric oncology has been relatively isolated from the adult oncology community.

With the goal of fixing these problems, the report sets out a number of goals and lists the key factors that will be necessary in order to achieve them.

These include a commitment of all funding bodies to finance projects and structures of relevance to pediatric oncology; a strong partnership with patients, parents, and survivors, including better communication and dissemination of information; better collaboration with adult oncology; and transparent partnerships with industry.

Understanding biology

“One of the most important objectives focuses on increasing our knowledge of the biology of pediatric tumors,” said SIOPE President-Elect Martin Schrappe, MD, of the University of Kiel, Germany.

“Cancers in adults result from a multistep process, usually after exposure to external carcinogens such as tobacco, alcohol, and diet, and often progress over many years. Pediatric malignancies develop early in life and over a much shorter time period. This suggests that fewer and stronger events are required for them to progress. Compared with adult cancers, most of them show fewer genetic defects and have a lower genetic complexity.”

“Major progress has been made in understanding pediatric tumor biology, and this has led to the discovery of some unique cancer hallmarks. Now, we need to use modern, innovative technologies to further decipher the mechanisms of pediatric tumor development, progression, and relapse, and speed up its translation to the clinic.”

To do this effectively and fairly, according to the report, interactions need to be strengthened at several levels—between networks of basic research teams, between basic scientists and clinical researchers, and by increasing the involvement of patients and parents in the search for personalized treatments. SIOPE plans to monitor progress through research into outcomes.

Improving quality of life

Another important issue for SIOPE is improving the quality of life for survivors.

“We believe that, in 2020, there will be nearly half a million European pediatric cancer survivors, and many of them will have side effects that are severe enough to affect their daily lives,” Dr Schrappe said. “While the fact that so many survive is a cause for rejoicing, we have a duty to provide them with optimal long-term care so that the rest of their lives may be as normal as possible.”

“One way of doing this would be the creation of a ‘survivorship passport’ for each child and adolescent cured of a cancer. This would contain a history of their disease and treatment, together with relevant follow-up measures aimed at improving their quality of life and a database for storing the clinical data [that would] facilitate monitoring and research.”

Micrograph showing AML

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).

The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.

The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.

AML-001 trial

The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.

Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.

Patients were then randomized to receive either azacitidine (75 mg/m²/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).

Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).

One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.

Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.

Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively. 

Micrograph showing AML

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).

The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.

The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.

AML-001 trial

The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.

Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.

Patients were then randomized to receive either azacitidine (75 mg/m²/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).

Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).

One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.

Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.

Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively. 

Micrograph showing AML

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).

The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.

The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.

The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.

AML-001 trial

The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.

Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.

Patients were then randomized to receive either azacitidine (75 mg/m²/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).

Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).

One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.

Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.

Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively. 

Pregnant woman

Photo by Nina Matthews

VIENNA—Women who are pregnant when diagnosed with cancer should carry their child to term but start cancer treatment immediately, according to researchers.

A study of young children suggested that exposure to cancer treatment in utero did not have detrimental effects on a child’s mental development or heart function.

Premature delivery, on the other hand, was associated with delayed cognitive development.

“Our results show that fear of cancer treatment is no reason to terminate a pregnancy, that maternal treatment should not be delayed, and that chemotherapy can be given,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.

“The study also shows that children suffer more from prematurity than from chemotherapy, so avoiding prematurity is more important than avoiding chemotherapy.”

Dr Amant presented these findings at the 2015 European Cancer Congress. The study was also published in NEJM.

The study included 129 children born to mothers with cancer, matched with 129 children of the same gestational age who were born to mothers unaffected by cancer.

The most common malignancies were breast (n=69) and hematologic cancers. This included acute myeloid leukemia (n=4), acute lymphoblastic leukemia (n=1), chronic myeloid leukemia (n=1), Hodgkin lymphoma (n=8), and non-Hodgkin lymphoma (n=6).

The researchers assessed the children’s general health and mental development when they were 18 months and 3 years old. At the age of 3, 47 of the children also had their heart function checked with electrocardiograms and echocardiography.

Ninety-six children (74.4%) were exposed to chemotherapy (alone or in combination with other treatment) before birth, 11 children (8.5%) were exposed to radiotherapy (alone or in combination), 13 (10.1%) were exposed to surgery alone, and 2 (1.6%) were exposed to drugs other than chemotherapeutic agents. Fourteen (10.9%) mothers did not receive cancer treatment during pregnancy.

Mental development

“Compared to the control group of children, we found no significant differences in mental development among children exposed to chemotherapy, radiotherapy, surgery alone, or no treatment,” Dr Amant said. “Nor was the number of chemotherapy cycles during pregnancy, which ranged from 1 to 10, related to the outcome of the children.”

To measure cognitive development, the researchers used the Bayley Scales of Infant Development. The median score was 101 (range, 56-145) in children exposed to cancer treatment and 100 (range, 50-145) in unexposed children.

When compared to controls, there was no significant difference in Bayley II or III score for all children born to mothers with cancer (P=0.08), children exposed to any chemotherapy (P=0.43), children exposed to anthracyclines (P=0.43), children exposed to taxanes (P=0.57), children exposed to platinum derivatives (P=0.95), children exposed to radiotherapy (P=0.69), children exposed to surgery alone (P=0.13), and children whose mothers did not undergo treatment (P=0.08).

Premature birth

Conversely, Bayley scores tended to increase by an average of 2.9 points for every week in gestational age. This was after the researchers controlled for a child’s age, gender, country, ethnicity, and parental education level.

“Delayed development of mental processes appeared to be related to premature birth,” Dr Amant said.

Premature birth was more frequent among children born to mothers with cancer, regardless of whether or not they received prenatal treatment, than in the general population in the countries participating in this study (Belgium, The Netherlands, Italy, and the Czech Republic).

The children born to mothers with cancer had a median gestational age of 36 weeks, ranging from 27 to 41 weeks. Seventy-nine (61.2%) children were born preterm, compared to 7% to 8% in the general population.

“In most cases, they were born prematurely due to a medical decision to induce preterm so as to continue cancer treatment after the delivery,” Dr Amant said.

“In some cases, preterm delivery was spontaneous, and it is possible that cancer treatment plays a role in this. But we do not know what exactly triggers preterm delivery. It could be that chemotherapy induces preterm contractions or vaginal inflammation with preterm rupture of the membranes.”

Cardiac function

The researchers assessed cardiac function in 47 three-year-olds whose mothers had cancer and 47 control children.

There were no significant differences between the exposed and control children for most measures of cardiac function, such as heart rate, ejection fraction, fractional shortening, global longitudinal strain, and circumferential strain.

The only exceptions were diastolic blood pressure, which was higher among exposed children (P=0.001), and tissue Doppler imaging measurements of the basal segment of the interventricular septum. There were higher mean peak systolic and early diastolic velocities in the control group than the exposed group (P=0.003 for both comparisons).

The researchers noted, however, that the differences in tissue Doppler velocities were not present when comparing the control group and the 26 children who were exposed to anthracyclines.

Next steps

Last year, Dr Amant reported similarly favorable results in 54 children exposed to chemotherapy or radiation in utero. The new report is a continuation of this work.

“These latest results are, again, reassuring,” Dr Amant said. “But given that we have a larger group of children . . . , the current data are much more robust.”

However, he also pointed out that this study has some limitations.

“Our data include many types of chemotherapy, but we cannot guarantee that all types of chemotherapy are safe,” Dr Amant said. “We need to look at larger numbers of children and larger numbers exposed to each drug in order to be able to document the potential effects of individual drugs.”

“In addition, we cannot extrapolate to newer drugs, including targeted drugs. We need longer follow-up to see if there are any long-term toxic effects in cases where cisplatin was administered before birth.”

“For these reasons, we will continue to follow these children until the age of 18 years, and we will enlarge the group. This will allow us to document longer-term effects and to draw conclusions for specific drugs. In addition, we will investigate to what extent anticancer drugs are diluted in the body during pregnancy and also [examine] the psycho-emotional needs of mothers and their partners.”

Pregnant woman

Photo by Nina Matthews

VIENNA—Women who are pregnant when diagnosed with cancer should carry their child to term but start cancer treatment immediately, according to researchers.

A study of young children suggested that exposure to cancer treatment in utero did not have detrimental effects on a child’s mental development or heart function.

Premature delivery, on the other hand, was associated with delayed cognitive development.

“Our results show that fear of cancer treatment is no reason to terminate a pregnancy, that maternal treatment should not be delayed, and that chemotherapy can be given,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.

“The study also shows that children suffer more from prematurity than from chemotherapy, so avoiding prematurity is more important than avoiding chemotherapy.”

Dr Amant presented these findings at the 2015 European Cancer Congress. The study was also published in NEJM.

The study included 129 children born to mothers with cancer, matched with 129 children of the same gestational age who were born to mothers unaffected by cancer.

The most common malignancies were breast (n=69) and hematologic cancers. This included acute myeloid leukemia (n=4), acute lymphoblastic leukemia (n=1), chronic myeloid leukemia (n=1), Hodgkin lymphoma (n=8), and non-Hodgkin lymphoma (n=6).

The researchers assessed the children’s general health and mental development when they were 18 months and 3 years old. At the age of 3, 47 of the children also had their heart function checked with electrocardiograms and echocardiography.

Ninety-six children (74.4%) were exposed to chemotherapy (alone or in combination with other treatment) before birth, 11 children (8.5%) were exposed to radiotherapy (alone or in combination), 13 (10.1%) were exposed to surgery alone, and 2 (1.6%) were exposed to drugs other than chemotherapeutic agents. Fourteen (10.9%) mothers did not receive cancer treatment during pregnancy.

Mental development

“Compared to the control group of children, we found no significant differences in mental development among children exposed to chemotherapy, radiotherapy, surgery alone, or no treatment,” Dr Amant said. “Nor was the number of chemotherapy cycles during pregnancy, which ranged from 1 to 10, related to the outcome of the children.”

To measure cognitive development, the researchers used the Bayley Scales of Infant Development. The median score was 101 (range, 56-145) in children exposed to cancer treatment and 100 (range, 50-145) in unexposed children.

When compared to controls, there was no significant difference in Bayley II or III score for all children born to mothers with cancer (P=0.08), children exposed to any chemotherapy (P=0.43), children exposed to anthracyclines (P=0.43), children exposed to taxanes (P=0.57), children exposed to platinum derivatives (P=0.95), children exposed to radiotherapy (P=0.69), children exposed to surgery alone (P=0.13), and children whose mothers did not undergo treatment (P=0.08).

Premature birth

Conversely, Bayley scores tended to increase by an average of 2.9 points for every week in gestational age. This was after the researchers controlled for a child’s age, gender, country, ethnicity, and parental education level.

“Delayed development of mental processes appeared to be related to premature birth,” Dr Amant said.

Premature birth was more frequent among children born to mothers with cancer, regardless of whether or not they received prenatal treatment, than in the general population in the countries participating in this study (Belgium, The Netherlands, Italy, and the Czech Republic).

The children born to mothers with cancer had a median gestational age of 36 weeks, ranging from 27 to 41 weeks. Seventy-nine (61.2%) children were born preterm, compared to 7% to 8% in the general population.

“In most cases, they were born prematurely due to a medical decision to induce preterm so as to continue cancer treatment after the delivery,” Dr Amant said.

“In some cases, preterm delivery was spontaneous, and it is possible that cancer treatment plays a role in this. But we do not know what exactly triggers preterm delivery. It could be that chemotherapy induces preterm contractions or vaginal inflammation with preterm rupture of the membranes.”

Cardiac function

The researchers assessed cardiac function in 47 three-year-olds whose mothers had cancer and 47 control children.

There were no significant differences between the exposed and control children for most measures of cardiac function, such as heart rate, ejection fraction, fractional shortening, global longitudinal strain, and circumferential strain.

The only exceptions were diastolic blood pressure, which was higher among exposed children (P=0.001), and tissue Doppler imaging measurements of the basal segment of the interventricular septum. There were higher mean peak systolic and early diastolic velocities in the control group than the exposed group (P=0.003 for both comparisons).

The researchers noted, however, that the differences in tissue Doppler velocities were not present when comparing the control group and the 26 children who were exposed to anthracyclines.

Next steps

Last year, Dr Amant reported similarly favorable results in 54 children exposed to chemotherapy or radiation in utero. The new report is a continuation of this work.

“These latest results are, again, reassuring,” Dr Amant said. “But given that we have a larger group of children . . . , the current data are much more robust.”

However, he also pointed out that this study has some limitations.

“Our data include many types of chemotherapy, but we cannot guarantee that all types of chemotherapy are safe,” Dr Amant said. “We need to look at larger numbers of children and larger numbers exposed to each drug in order to be able to document the potential effects of individual drugs.”

“In addition, we cannot extrapolate to newer drugs, including targeted drugs. We need longer follow-up to see if there are any long-term toxic effects in cases where cisplatin was administered before birth.”

“For these reasons, we will continue to follow these children until the age of 18 years, and we will enlarge the group. This will allow us to document longer-term effects and to draw conclusions for specific drugs. In addition, we will investigate to what extent anticancer drugs are diluted in the body during pregnancy and also [examine] the psycho-emotional needs of mothers and their partners.”

Pregnant woman

Photo by Nina Matthews

VIENNA—Women who are pregnant when diagnosed with cancer should carry their child to term but start cancer treatment immediately, according to researchers.

A study of young children suggested that exposure to cancer treatment in utero did not have detrimental effects on a child’s mental development or heart function.

Premature delivery, on the other hand, was associated with delayed cognitive development.

“Our results show that fear of cancer treatment is no reason to terminate a pregnancy, that maternal treatment should not be delayed, and that chemotherapy can be given,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.

“The study also shows that children suffer more from prematurity than from chemotherapy, so avoiding prematurity is more important than avoiding chemotherapy.”

Dr Amant presented these findings at the 2015 European Cancer Congress. The study was also published in NEJM.

The study included 129 children born to mothers with cancer, matched with 129 children of the same gestational age who were born to mothers unaffected by cancer.

The most common malignancies were breast (n=69) and hematologic cancers. This included acute myeloid leukemia (n=4), acute lymphoblastic leukemia (n=1), chronic myeloid leukemia (n=1), Hodgkin lymphoma (n=8), and non-Hodgkin lymphoma (n=6).

The researchers assessed the children’s general health and mental development when they were 18 months and 3 years old. At the age of 3, 47 of the children also had their heart function checked with electrocardiograms and echocardiography.

Ninety-six children (74.4%) were exposed to chemotherapy (alone or in combination with other treatment) before birth, 11 children (8.5%) were exposed to radiotherapy (alone or in combination), 13 (10.1%) were exposed to surgery alone, and 2 (1.6%) were exposed to drugs other than chemotherapeutic agents. Fourteen (10.9%) mothers did not receive cancer treatment during pregnancy.

Mental development

“Compared to the control group of children, we found no significant differences in mental development among children exposed to chemotherapy, radiotherapy, surgery alone, or no treatment,” Dr Amant said. “Nor was the number of chemotherapy cycles during pregnancy, which ranged from 1 to 10, related to the outcome of the children.”

To measure cognitive development, the researchers used the Bayley Scales of Infant Development. The median score was 101 (range, 56-145) in children exposed to cancer treatment and 100 (range, 50-145) in unexposed children.

When compared to controls, there was no significant difference in Bayley II or III score for all children born to mothers with cancer (P=0.08), children exposed to any chemotherapy (P=0.43), children exposed to anthracyclines (P=0.43), children exposed to taxanes (P=0.57), children exposed to platinum derivatives (P=0.95), children exposed to radiotherapy (P=0.69), children exposed to surgery alone (P=0.13), and children whose mothers did not undergo treatment (P=0.08).

Premature birth

Conversely, Bayley scores tended to increase by an average of 2.9 points for every week in gestational age. This was after the researchers controlled for a child’s age, gender, country, ethnicity, and parental education level.

“Delayed development of mental processes appeared to be related to premature birth,” Dr Amant said.

Premature birth was more frequent among children born to mothers with cancer, regardless of whether or not they received prenatal treatment, than in the general population in the countries participating in this study (Belgium, The Netherlands, Italy, and the Czech Republic).

The children born to mothers with cancer had a median gestational age of 36 weeks, ranging from 27 to 41 weeks. Seventy-nine (61.2%) children were born preterm, compared to 7% to 8% in the general population.

“In most cases, they were born prematurely due to a medical decision to induce preterm so as to continue cancer treatment after the delivery,” Dr Amant said.

“In some cases, preterm delivery was spontaneous, and it is possible that cancer treatment plays a role in this. But we do not know what exactly triggers preterm delivery. It could be that chemotherapy induces preterm contractions or vaginal inflammation with preterm rupture of the membranes.”

Cardiac function

The researchers assessed cardiac function in 47 three-year-olds whose mothers had cancer and 47 control children.

There were no significant differences between the exposed and control children for most measures of cardiac function, such as heart rate, ejection fraction, fractional shortening, global longitudinal strain, and circumferential strain.

The only exceptions were diastolic blood pressure, which was higher among exposed children (P=0.001), and tissue Doppler imaging measurements of the basal segment of the interventricular septum. There were higher mean peak systolic and early diastolic velocities in the control group than the exposed group (P=0.003 for both comparisons).

The researchers noted, however, that the differences in tissue Doppler velocities were not present when comparing the control group and the 26 children who were exposed to anthracyclines.

Next steps

Last year, Dr Amant reported similarly favorable results in 54 children exposed to chemotherapy or radiation in utero. The new report is a continuation of this work.

“These latest results are, again, reassuring,” Dr Amant said. “But given that we have a larger group of children . . . , the current data are much more robust.”

However, he also pointed out that this study has some limitations.

“Our data include many types of chemotherapy, but we cannot guarantee that all types of chemotherapy are safe,” Dr Amant said. “We need to look at larger numbers of children and larger numbers exposed to each drug in order to be able to document the potential effects of individual drugs.”

“In addition, we cannot extrapolate to newer drugs, including targeted drugs. We need longer follow-up to see if there are any long-term toxic effects in cases where cisplatin was administered before birth.”

“For these reasons, we will continue to follow these children until the age of 18 years, and we will enlarge the group. This will allow us to document longer-term effects and to draw conclusions for specific drugs. In addition, we will investigate to what extent anticancer drugs are diluted in the body during pregnancy and also [examine] the psycho-emotional needs of mothers and their partners.”

Micrograph showing MM

ROME—Early results of a pilot study indicate that a 3-agent combination regimen can produce responses in patients with relapsed or refractory multiple myeloma (MM).

The treatment consists of carfilzomib, dexamethasone, and pelareorep (Reolysin), a proprietary isolate of human reovirus (Type 3 Dearing strain).

All 8 evaluable patients treated with this regimen experienced an objective response, although 1 patient later progressed.

The investigators said the regimen has been relatively well tolerated, but most patients experience flu-like symptoms over the first week of treatment. And cytopenias, especially thrombocytopenia, are common.

Douglas Sborov, MD, of The Ohio State University in Columbus, and his colleagues presented this research at the 15th International Myeloma Workshop (poster #379).

The investigators noted that this is the first time a pelareorep-based combination has been tested in relapsed MM patients. A previous single-agent study indicated that pelareorep was well tolerated, and preclinical research has shown that reovirus and carfilzomib synergize to kill MM cells.

To expand upon these results, Dr Sborov and colleagues began testing pelareorep with carfilzomib and dexamethasone in patients with relapsed/refractory MM. The ongoing study, known as NCI-9603, is sponsored by the National Cancer Institute.

Of the 8 patients enrolled thus far, 5 had intermediate- or high-risk disease at baseline, and 1 patient was dialysis-dependent. The median age was 63 (range, 43-70).

Patients had received a median of 2 prior lines of therapy (range, 1-6) and a median of 4 prior treatments (range, 2-8). All of the patients had received lenalidomide, 1 had received carfilzomib, and 4 were refractory to bortezomib.

For the current study, patients were assigned to receive dexamethasone, carfilzomib over 10 minutes, and pelareorep over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment is set to repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients who achieve a minimal response or better may reduce treatment to days 1, 8, and 15 after 4 courses and to days 1 and 15 after 12 courses.

Treatment results

The investigators said the treatment produced a significant (P=0.005) increase in caspase-3, a marker associated with apoptotic cell death.

The combination was also associated with an increased infiltration of CD8+ T cells and the significant (P=0.005) upregulation of PD-L1, suggesting the addition of a PD-1 or PD-L1 inhibitor might further optimize the regimen.

All 8 patients experienced an objective response to treatment, as measured by changes in blood monoclonal protein. Two patients had a very good partial response, 3 had a partial response, and 3 had a minor response.

Five of the patients remain on study. The dialysis-dependent patient discontinued treatment due to progression after 3 treatment cycles. And 2 patients discontinued treatment due to dose-limiting toxicities after 2 doses.

One of the patients with dose-limiting toxicities had grade 4 myocarditis, grade 3 left ventricular dysfunction, and grade 4 respiratory failure possibly attributable to pelareorep and carfilzomib. The other patient had lower gastrointestinal bleeding that was not attributed to treatment.

Adverse events in cycle 1 that were possibly, likely, or definitely attributed to treatment included hypertension (n=5), thrombocytopenia (n=4), anemia (n=4), dyspnea on exertion (n=4), fatigue (n=4), myalgia (n=3), fever (n=2), leukopenia (n=2), lymphopenia (n=2), nausea (n=2), and diarrhea (n=2).

For more details, visit the Oncolytics Biotech Inc. website to view the poster. Oncolytics is the company developing pelareorep.

Micrograph showing MM

ROME—Early results of a pilot study indicate that a 3-agent combination regimen can produce responses in patients with relapsed or refractory multiple myeloma (MM).

The treatment consists of carfilzomib, dexamethasone, and pelareorep (Reolysin), a proprietary isolate of human reovirus (Type 3 Dearing strain).

All 8 evaluable patients treated with this regimen experienced an objective response, although 1 patient later progressed.

The investigators said the regimen has been relatively well tolerated, but most patients experience flu-like symptoms over the first week of treatment. And cytopenias, especially thrombocytopenia, are common.

Douglas Sborov, MD, of The Ohio State University in Columbus, and his colleagues presented this research at the 15th International Myeloma Workshop (poster #379).

The investigators noted that this is the first time a pelareorep-based combination has been tested in relapsed MM patients. A previous single-agent study indicated that pelareorep was well tolerated, and preclinical research has shown that reovirus and carfilzomib synergize to kill MM cells.

To expand upon these results, Dr Sborov and colleagues began testing pelareorep with carfilzomib and dexamethasone in patients with relapsed/refractory MM. The ongoing study, known as NCI-9603, is sponsored by the National Cancer Institute.

Of the 8 patients enrolled thus far, 5 had intermediate- or high-risk disease at baseline, and 1 patient was dialysis-dependent. The median age was 63 (range, 43-70).

Patients had received a median of 2 prior lines of therapy (range, 1-6) and a median of 4 prior treatments (range, 2-8). All of the patients had received lenalidomide, 1 had received carfilzomib, and 4 were refractory to bortezomib.

For the current study, patients were assigned to receive dexamethasone, carfilzomib over 10 minutes, and pelareorep over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment is set to repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients who achieve a minimal response or better may reduce treatment to days 1, 8, and 15 after 4 courses and to days 1 and 15 after 12 courses.

Treatment results

The investigators said the treatment produced a significant (P=0.005) increase in caspase-3, a marker associated with apoptotic cell death.

The combination was also associated with an increased infiltration of CD8+ T cells and the significant (P=0.005) upregulation of PD-L1, suggesting the addition of a PD-1 or PD-L1 inhibitor might further optimize the regimen.

All 8 patients experienced an objective response to treatment, as measured by changes in blood monoclonal protein. Two patients had a very good partial response, 3 had a partial response, and 3 had a minor response.

Five of the patients remain on study. The dialysis-dependent patient discontinued treatment due to progression after 3 treatment cycles. And 2 patients discontinued treatment due to dose-limiting toxicities after 2 doses.

One of the patients with dose-limiting toxicities had grade 4 myocarditis, grade 3 left ventricular dysfunction, and grade 4 respiratory failure possibly attributable to pelareorep and carfilzomib. The other patient had lower gastrointestinal bleeding that was not attributed to treatment.

Adverse events in cycle 1 that were possibly, likely, or definitely attributed to treatment included hypertension (n=5), thrombocytopenia (n=4), anemia (n=4), dyspnea on exertion (n=4), fatigue (n=4), myalgia (n=3), fever (n=2), leukopenia (n=2), lymphopenia (n=2), nausea (n=2), and diarrhea (n=2).

For more details, visit the Oncolytics Biotech Inc. website to view the poster. Oncolytics is the company developing pelareorep.

Micrograph showing MM

ROME—Early results of a pilot study indicate that a 3-agent combination regimen can produce responses in patients with relapsed or refractory multiple myeloma (MM).

The treatment consists of carfilzomib, dexamethasone, and pelareorep (Reolysin), a proprietary isolate of human reovirus (Type 3 Dearing strain).

All 8 evaluable patients treated with this regimen experienced an objective response, although 1 patient later progressed.

The investigators said the regimen has been relatively well tolerated, but most patients experience flu-like symptoms over the first week of treatment. And cytopenias, especially thrombocytopenia, are common.

Douglas Sborov, MD, of The Ohio State University in Columbus, and his colleagues presented this research at the 15th International Myeloma Workshop (poster #379).

The investigators noted that this is the first time a pelareorep-based combination has been tested in relapsed MM patients. A previous single-agent study indicated that pelareorep was well tolerated, and preclinical research has shown that reovirus and carfilzomib synergize to kill MM cells.

To expand upon these results, Dr Sborov and colleagues began testing pelareorep with carfilzomib and dexamethasone in patients with relapsed/refractory MM. The ongoing study, known as NCI-9603, is sponsored by the National Cancer Institute.

Of the 8 patients enrolled thus far, 5 had intermediate- or high-risk disease at baseline, and 1 patient was dialysis-dependent. The median age was 63 (range, 43-70).

Patients had received a median of 2 prior lines of therapy (range, 1-6) and a median of 4 prior treatments (range, 2-8). All of the patients had received lenalidomide, 1 had received carfilzomib, and 4 were refractory to bortezomib.

For the current study, patients were assigned to receive dexamethasone, carfilzomib over 10 minutes, and pelareorep over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment is set to repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients who achieve a minimal response or better may reduce treatment to days 1, 8, and 15 after 4 courses and to days 1 and 15 after 12 courses.

Treatment results

The investigators said the treatment produced a significant (P=0.005) increase in caspase-3, a marker associated with apoptotic cell death.

The combination was also associated with an increased infiltration of CD8+ T cells and the significant (P=0.005) upregulation of PD-L1, suggesting the addition of a PD-1 or PD-L1 inhibitor might further optimize the regimen.

All 8 patients experienced an objective response to treatment, as measured by changes in blood monoclonal protein. Two patients had a very good partial response, 3 had a partial response, and 3 had a minor response.

Five of the patients remain on study. The dialysis-dependent patient discontinued treatment due to progression after 3 treatment cycles. And 2 patients discontinued treatment due to dose-limiting toxicities after 2 doses.

One of the patients with dose-limiting toxicities had grade 4 myocarditis, grade 3 left ventricular dysfunction, and grade 4 respiratory failure possibly attributable to pelareorep and carfilzomib. The other patient had lower gastrointestinal bleeding that was not attributed to treatment.

Adverse events in cycle 1 that were possibly, likely, or definitely attributed to treatment included hypertension (n=5), thrombocytopenia (n=4), anemia (n=4), dyspnea on exertion (n=4), fatigue (n=4), myalgia (n=3), fever (n=2), leukopenia (n=2), lymphopenia (n=2), nausea (n=2), and diarrhea (n=2).

For more details, visit the Oncolytics Biotech Inc. website to view the poster. Oncolytics is the company developing pelareorep.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.

Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).

Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.

The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

The CHMP’s positive opinion was based on results with idarucizumab in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.

In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well tolerated.

In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.

Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.

Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).

Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.

The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

The CHMP’s positive opinion was based on results with idarucizumab in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.

In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well tolerated.

In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.

Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.

Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).

Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.

The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

The CHMP’s positive opinion was based on results with idarucizumab in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.

In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well tolerated.

In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.

Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”