Hematology Times

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

in the bone marrow

Targeting the protein Del-1 could potentially improve hematopoietic stem cell (HSC) transplants, according to researchers.

The team found that Del-1 promoted engraftment in murine transplant recipients, but the protein also promoted the retention of hematopoietic progenitors in the bone marrow of mice that received granulocyte colony-stimulating factor (G-CSF).

The researchers therefore believe that enhancing Del-1 in HSC transplant recipients might improve engraftment.

And inhibiting Del-1 could increase progenitor mobilization in transplant donors.

The researchers detailed these findings and theories in The Journal of Clinical Investigation.

“Because the hematopoietic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and easily manipulated, one can see that it could be a target in many potential applications,” said study author George Hajishengallis, DDS, PhD, of Penn Dental Medicine in Philadelphia, Pennsylvania.

For Dr Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine.

Dr Hajishengallis and Triantafyllos Chavakis, Dr med, of Technische Universität Dresden in Germany, identified Del-1 as a potential drug target for gum disease. (Del-1 prevents inflammatory cells from moving into the gums.)

Both of the researchers’ labs also discovered that Del-1 is expressed in bone marrow, so the groups began following up to examine the protein’s function there.

Their work revealed that Del-1 is a key regulator of the HSC niche.

Del-1 is expressed by cells that promote HSC maintenance under steady-state conditions. This includes arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage.

The researchers also found that Del-1 regulates long-term HSC proliferation and differentiation toward the myeloid lineage.

In mice that received HSC transplants, Del-1 promoted progenitor engraftment and the generation of both progenitors and mature myeloid cells. The researchers noted that this was dependent upon β3 integrin expression in hematopoietic cells.

The team also found that Del-1 promotes hematopoietic progenitors’ response to systemic inflammation (induced by lipopolysaccharide). And the protein promotes the retention of hematopoietic progenitors in the bone marrow after G-CSF administration.

Taken together, these findings suggest that manipulating Del-1 might enhance HSC transplants.

“It’s easy to think of practical applications,” Dr Hajishengallis said. “Now, we need to find out whether it works in practice, so our studies continue.”

in the bone marrow

Targeting the protein Del-1 could potentially improve hematopoietic stem cell (HSC) transplants, according to researchers.

The team found that Del-1 promoted engraftment in murine transplant recipients, but the protein also promoted the retention of hematopoietic progenitors in the bone marrow of mice that received granulocyte colony-stimulating factor (G-CSF).

The researchers therefore believe that enhancing Del-1 in HSC transplant recipients might improve engraftment.

And inhibiting Del-1 could increase progenitor mobilization in transplant donors.

The researchers detailed these findings and theories in The Journal of Clinical Investigation.

“Because the hematopoietic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and easily manipulated, one can see that it could be a target in many potential applications,” said study author George Hajishengallis, DDS, PhD, of Penn Dental Medicine in Philadelphia, Pennsylvania.

For Dr Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine.

Dr Hajishengallis and Triantafyllos Chavakis, Dr med, of Technische Universität Dresden in Germany, identified Del-1 as a potential drug target for gum disease. (Del-1 prevents inflammatory cells from moving into the gums.)

Both of the researchers’ labs also discovered that Del-1 is expressed in bone marrow, so the groups began following up to examine the protein’s function there.

Their work revealed that Del-1 is a key regulator of the HSC niche.

Del-1 is expressed by cells that promote HSC maintenance under steady-state conditions. This includes arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage.

The researchers also found that Del-1 regulates long-term HSC proliferation and differentiation toward the myeloid lineage.

In mice that received HSC transplants, Del-1 promoted progenitor engraftment and the generation of both progenitors and mature myeloid cells. The researchers noted that this was dependent upon β3 integrin expression in hematopoietic cells.

The team also found that Del-1 promotes hematopoietic progenitors’ response to systemic inflammation (induced by lipopolysaccharide). And the protein promotes the retention of hematopoietic progenitors in the bone marrow after G-CSF administration.

Taken together, these findings suggest that manipulating Del-1 might enhance HSC transplants.

“It’s easy to think of practical applications,” Dr Hajishengallis said. “Now, we need to find out whether it works in practice, so our studies continue.”

in the bone marrow

Targeting the protein Del-1 could potentially improve hematopoietic stem cell (HSC) transplants, according to researchers.

The team found that Del-1 promoted engraftment in murine transplant recipients, but the protein also promoted the retention of hematopoietic progenitors in the bone marrow of mice that received granulocyte colony-stimulating factor (G-CSF).

The researchers therefore believe that enhancing Del-1 in HSC transplant recipients might improve engraftment.

And inhibiting Del-1 could increase progenitor mobilization in transplant donors.

The researchers detailed these findings and theories in The Journal of Clinical Investigation.

“Because the hematopoietic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and easily manipulated, one can see that it could be a target in many potential applications,” said study author George Hajishengallis, DDS, PhD, of Penn Dental Medicine in Philadelphia, Pennsylvania.

For Dr Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine.

Dr Hajishengallis and Triantafyllos Chavakis, Dr med, of Technische Universität Dresden in Germany, identified Del-1 as a potential drug target for gum disease. (Del-1 prevents inflammatory cells from moving into the gums.)

Both of the researchers’ labs also discovered that Del-1 is expressed in bone marrow, so the groups began following up to examine the protein’s function there.

Their work revealed that Del-1 is a key regulator of the HSC niche.

Del-1 is expressed by cells that promote HSC maintenance under steady-state conditions. This includes arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage.

The researchers also found that Del-1 regulates long-term HSC proliferation and differentiation toward the myeloid lineage.

In mice that received HSC transplants, Del-1 promoted progenitor engraftment and the generation of both progenitors and mature myeloid cells. The researchers noted that this was dependent upon β3 integrin expression in hematopoietic cells.

The team also found that Del-1 promotes hematopoietic progenitors’ response to systemic inflammation (induced by lipopolysaccharide). And the protein promotes the retention of hematopoietic progenitors in the bone marrow after G-CSF administration.

Taken together, these findings suggest that manipulating Del-1 might enhance HSC transplants.

“It’s easy to think of practical applications,” Dr Hajishengallis said. “Now, we need to find out whether it works in practice, so our studies continue.”

Antihemophilic factor

New research suggests prophylaxis with a recombinant factor VIII Fc fusion protein (rFVIIIFc) can improve joint health over time in patients with hemophilia A.

Patients saw continuous improvement in joint health over a nearly 3-year period, regardless of prior treatment regimen, severity of joint damage, or target joints.

“Gradual joint destruction, which is the leading cause of morbidity for people with hemophilia, remains a significant challenge in the treatment of hemophilia A,” said Johannes Oldenburg, MD, of University Clinic Bonn in Germany.

“This is the first study to show that functional joint health can continue to improve using prophylactic treatment with an extended half-life factor therapy, even for those who have severe joint disease at the start of treatment.”

Dr Oldenburg and his colleagues reported these findings in Haemophilia. The research was sponsored by Biogen/Bioverativ and Sobi, the companies marketing rFVIIIFc (or efmoroctocog alfa) as Eloctate or Elocta.

This interim post hoc analysis was an evaluation of joint health in adults and adolescents who received rFVIIIFc prophylaxis in the A-LONG and ASPIRE studies.

In A-LONG, patients age 12 and older who had severe hemophilia A received rFVIIIFc at 25-65 IU/kg every 3 to 5 days (arm 1), at 65 IU/kg weekly (arm 2), or as episodic treatment (arm 3). Patients who completed A-LONG could then enroll in the ASPIRE extension study.

For the current analysis, Dr Oldenburg and his colleagues assessed joint health in ASPIRE enrollees using a modified version of the Hemophilia Joint Health Score (mHJHS). This tool grades joints by specific domains, including swelling, muscle atrophy, alignment, range of motion, joint pain, strength, and global gait.

The researchers examined mHJHS measurements (a decrease in score reflecting improvement) taken at A-LONG baseline, ASPIRE baseline, and annually thereafter for roughly 2.8 years of treatment.

There were 47 patients who had mHJHS data at both study baselines, ASPIRE year 1, and ASPIRE year 2.

These patients had a mean improvement in joint health score of -4.1 at ASPIRE year 2, compared with A-LONG baseline (P=0.001).

The mean improvement was -2.4 (P=0.09) for patients who received pre-study prophylaxis and -7.2 (P=0.003) for those who received pre-study episodic treatment.

The mean improvement was -5.6 (P=0.005) in patients with target joints and -8.8 (P=0.02) in those with severe joint destruction.

The mHJHS components with the greatest improvement at ASPIRE year 2 were swelling (-1.4, P=0.008), range of motion (-1.1, P=0.03), and strength (-0.8, P=0.04).

Antihemophilic factor

New research suggests prophylaxis with a recombinant factor VIII Fc fusion protein (rFVIIIFc) can improve joint health over time in patients with hemophilia A.

Patients saw continuous improvement in joint health over a nearly 3-year period, regardless of prior treatment regimen, severity of joint damage, or target joints.

“Gradual joint destruction, which is the leading cause of morbidity for people with hemophilia, remains a significant challenge in the treatment of hemophilia A,” said Johannes Oldenburg, MD, of University Clinic Bonn in Germany.

“This is the first study to show that functional joint health can continue to improve using prophylactic treatment with an extended half-life factor therapy, even for those who have severe joint disease at the start of treatment.”

Dr Oldenburg and his colleagues reported these findings in Haemophilia. The research was sponsored by Biogen/Bioverativ and Sobi, the companies marketing rFVIIIFc (or efmoroctocog alfa) as Eloctate or Elocta.

This interim post hoc analysis was an evaluation of joint health in adults and adolescents who received rFVIIIFc prophylaxis in the A-LONG and ASPIRE studies.

In A-LONG, patients age 12 and older who had severe hemophilia A received rFVIIIFc at 25-65 IU/kg every 3 to 5 days (arm 1), at 65 IU/kg weekly (arm 2), or as episodic treatment (arm 3). Patients who completed A-LONG could then enroll in the ASPIRE extension study.

For the current analysis, Dr Oldenburg and his colleagues assessed joint health in ASPIRE enrollees using a modified version of the Hemophilia Joint Health Score (mHJHS). This tool grades joints by specific domains, including swelling, muscle atrophy, alignment, range of motion, joint pain, strength, and global gait.

The researchers examined mHJHS measurements (a decrease in score reflecting improvement) taken at A-LONG baseline, ASPIRE baseline, and annually thereafter for roughly 2.8 years of treatment.

There were 47 patients who had mHJHS data at both study baselines, ASPIRE year 1, and ASPIRE year 2.

These patients had a mean improvement in joint health score of -4.1 at ASPIRE year 2, compared with A-LONG baseline (P=0.001).

The mean improvement was -2.4 (P=0.09) for patients who received pre-study prophylaxis and -7.2 (P=0.003) for those who received pre-study episodic treatment.

The mean improvement was -5.6 (P=0.005) in patients with target joints and -8.8 (P=0.02) in those with severe joint destruction.

The mHJHS components with the greatest improvement at ASPIRE year 2 were swelling (-1.4, P=0.008), range of motion (-1.1, P=0.03), and strength (-0.8, P=0.04).

Antihemophilic factor

New research suggests prophylaxis with a recombinant factor VIII Fc fusion protein (rFVIIIFc) can improve joint health over time in patients with hemophilia A.

Patients saw continuous improvement in joint health over a nearly 3-year period, regardless of prior treatment regimen, severity of joint damage, or target joints.

“Gradual joint destruction, which is the leading cause of morbidity for people with hemophilia, remains a significant challenge in the treatment of hemophilia A,” said Johannes Oldenburg, MD, of University Clinic Bonn in Germany.

“This is the first study to show that functional joint health can continue to improve using prophylactic treatment with an extended half-life factor therapy, even for those who have severe joint disease at the start of treatment.”

Dr Oldenburg and his colleagues reported these findings in Haemophilia. The research was sponsored by Biogen/Bioverativ and Sobi, the companies marketing rFVIIIFc (or efmoroctocog alfa) as Eloctate or Elocta.

This interim post hoc analysis was an evaluation of joint health in adults and adolescents who received rFVIIIFc prophylaxis in the A-LONG and ASPIRE studies.

In A-LONG, patients age 12 and older who had severe hemophilia A received rFVIIIFc at 25-65 IU/kg every 3 to 5 days (arm 1), at 65 IU/kg weekly (arm 2), or as episodic treatment (arm 3). Patients who completed A-LONG could then enroll in the ASPIRE extension study.

For the current analysis, Dr Oldenburg and his colleagues assessed joint health in ASPIRE enrollees using a modified version of the Hemophilia Joint Health Score (mHJHS). This tool grades joints by specific domains, including swelling, muscle atrophy, alignment, range of motion, joint pain, strength, and global gait.

The researchers examined mHJHS measurements (a decrease in score reflecting improvement) taken at A-LONG baseline, ASPIRE baseline, and annually thereafter for roughly 2.8 years of treatment.

There were 47 patients who had mHJHS data at both study baselines, ASPIRE year 1, and ASPIRE year 2.

These patients had a mean improvement in joint health score of -4.1 at ASPIRE year 2, compared with A-LONG baseline (P=0.001).

The mean improvement was -2.4 (P=0.09) for patients who received pre-study prophylaxis and -7.2 (P=0.003) for those who received pre-study episodic treatment.

The mean improvement was -5.6 (P=0.005) in patients with target joints and -8.8 (P=0.02) in those with severe joint destruction.

The mHJHS components with the greatest improvement at ASPIRE year 2 were swelling (-1.4, P=0.008), range of motion (-1.1, P=0.03), and strength (-0.8, P=0.04).

Pig-tailed macaque

Researchers say they have identified a subpopulation of hematopoietic stem cells (HSCs) that immediately contributes to long-term, multilineage hematopoietic reconstitution after transplant.

These HSCs were discovered in macaques, but the cells are similar to a subset of HSCs found in humans.

The researchers found the 2 sets of cells behaved identically when tested in vitro.

The team believes their findings will increase the efficiency of future efforts for HSC transplants, gene therapies, and gene editing.

Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues reported these findings in Science Translational Medicine.

The researchers performed HSC transplants in pig-tailed macaques, following hundreds of thousands of cells immediately after transplant and over the course of 7.5 years.

Previous reports had suggested that successive waves of progenitor cells expand and contract to establish the new bone marrow after transplant.

However, Dr Kiem and his colleagues homed in on a distinct group of HSCs that took hold early after transplant and went on to produce all cell lineages that constitute a complete blood system.

“These findings came as a surprise,” Dr Kiem said. “We had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system. This population does it all.”

The population is a subset of CD34+ cells expressing CD90 and lacking CD45RA markers.

“The gold standard target cell population for stem cell gene therapy are cells with the marker CD34,” said study author Stefan Radtke, PhD, of the Fred Hutchinson Cancer Research Center.

“But we used 2 additional markers to further distinguish the population from the other blood stem cells.”

The researchers noted that the CD34+ CD45RA- CD90+ HSCs started repopulating the hematopoietic system within 10 days of being infused in macaques undergoing transplant.

A year later, the researchers found strong molecular traces of the cells, suggesting they were responsible for the ongoing maintenance of the newly transplanted system.

The team also determined the minimum numbers of CD34+ CD45RA- CD90+ HSCs that were necessary for successful transplant (defined as sustained neutrophil and platelet recovery).

And the researchers found similar gene expression profiles between macaque and human CD34+ CD45RA- CD90+ HSCs.

The team therefore believes these findings could have implications for HSC transplants in humans.

The researchers are now working to move their findings into the clinic with the hopes of integrating them in ongoing clinical trials. The team is currently looking for commercial partners.

Pig-tailed macaque

Researchers say they have identified a subpopulation of hematopoietic stem cells (HSCs) that immediately contributes to long-term, multilineage hematopoietic reconstitution after transplant.

These HSCs were discovered in macaques, but the cells are similar to a subset of HSCs found in humans.

The researchers found the 2 sets of cells behaved identically when tested in vitro.

The team believes their findings will increase the efficiency of future efforts for HSC transplants, gene therapies, and gene editing.

Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues reported these findings in Science Translational Medicine.

The researchers performed HSC transplants in pig-tailed macaques, following hundreds of thousands of cells immediately after transplant and over the course of 7.5 years.

Previous reports had suggested that successive waves of progenitor cells expand and contract to establish the new bone marrow after transplant.

However, Dr Kiem and his colleagues homed in on a distinct group of HSCs that took hold early after transplant and went on to produce all cell lineages that constitute a complete blood system.

“These findings came as a surprise,” Dr Kiem said. “We had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system. This population does it all.”

The population is a subset of CD34+ cells expressing CD90 and lacking CD45RA markers.

“The gold standard target cell population for stem cell gene therapy are cells with the marker CD34,” said study author Stefan Radtke, PhD, of the Fred Hutchinson Cancer Research Center.

“But we used 2 additional markers to further distinguish the population from the other blood stem cells.”

The researchers noted that the CD34+ CD45RA- CD90+ HSCs started repopulating the hematopoietic system within 10 days of being infused in macaques undergoing transplant.

A year later, the researchers found strong molecular traces of the cells, suggesting they were responsible for the ongoing maintenance of the newly transplanted system.

The team also determined the minimum numbers of CD34+ CD45RA- CD90+ HSCs that were necessary for successful transplant (defined as sustained neutrophil and platelet recovery).

And the researchers found similar gene expression profiles between macaque and human CD34+ CD45RA- CD90+ HSCs.

The team therefore believes these findings could have implications for HSC transplants in humans.

The researchers are now working to move their findings into the clinic with the hopes of integrating them in ongoing clinical trials. The team is currently looking for commercial partners.

Pig-tailed macaque

Researchers say they have identified a subpopulation of hematopoietic stem cells (HSCs) that immediately contributes to long-term, multilineage hematopoietic reconstitution after transplant.

These HSCs were discovered in macaques, but the cells are similar to a subset of HSCs found in humans.

The researchers found the 2 sets of cells behaved identically when tested in vitro.

The team believes their findings will increase the efficiency of future efforts for HSC transplants, gene therapies, and gene editing.

Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues reported these findings in Science Translational Medicine.

The researchers performed HSC transplants in pig-tailed macaques, following hundreds of thousands of cells immediately after transplant and over the course of 7.5 years.

Previous reports had suggested that successive waves of progenitor cells expand and contract to establish the new bone marrow after transplant.

However, Dr Kiem and his colleagues homed in on a distinct group of HSCs that took hold early after transplant and went on to produce all cell lineages that constitute a complete blood system.

“These findings came as a surprise,” Dr Kiem said. “We had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system. This population does it all.”

The population is a subset of CD34+ cells expressing CD90 and lacking CD45RA markers.

“The gold standard target cell population for stem cell gene therapy are cells with the marker CD34,” said study author Stefan Radtke, PhD, of the Fred Hutchinson Cancer Research Center.

“But we used 2 additional markers to further distinguish the population from the other blood stem cells.”

The researchers noted that the CD34+ CD45RA- CD90+ HSCs started repopulating the hematopoietic system within 10 days of being infused in macaques undergoing transplant.

A year later, the researchers found strong molecular traces of the cells, suggesting they were responsible for the ongoing maintenance of the newly transplanted system.

The team also determined the minimum numbers of CD34+ CD45RA- CD90+ HSCs that were necessary for successful transplant (defined as sustained neutrophil and platelet recovery).

And the researchers found similar gene expression profiles between macaque and human CD34+ CD45RA- CD90+ HSCs.

The team therefore believes these findings could have implications for HSC transplants in humans.

The researchers are now working to move their findings into the clinic with the hopes of integrating them in ongoing clinical trials. The team is currently looking for commercial partners.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to GSK2857916, an anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F via a non-cleavable linker.

The designation is for GSK2857916 as monotherapy for patients with multiple myeloma (MM) who have failed at least 3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.

The designation is based on results from a phase 1, dose-escalation and expansion study in patients with relapsed/refractory MM, irrespective of BCMA expression (NCT02064387).

Data from this ongoing trial are scheduled to be presented December 11 in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.

GSK2857916 has also received orphan drug designation from the FDA and the European Medicines Agency (EMA) as well as PRIME designation from the EMA.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

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

Orphan and PRIME designations

The FDA grants orphan designation to therapies intended to treat conditions that affect fewer than 200,000 people in the US. The designation qualifies a drug’s sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing and 7 years of market exclusivity.

In Europe, sponsors who obtain orphan designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, 10 years of market exclusivity, and fee reductions.

The EMA grants PRIME designation to enhance support for the development of medicines that target an unmet medical need. The designation is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to GSK2857916, an anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F via a non-cleavable linker.

The designation is for GSK2857916 as monotherapy for patients with multiple myeloma (MM) who have failed at least 3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.

The designation is based on results from a phase 1, dose-escalation and expansion study in patients with relapsed/refractory MM, irrespective of BCMA expression (NCT02064387).

Data from this ongoing trial are scheduled to be presented December 11 in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.

GSK2857916 has also received orphan drug designation from the FDA and the European Medicines Agency (EMA) as well as PRIME designation from the EMA.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

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

Orphan and PRIME designations

The FDA grants orphan designation to therapies intended to treat conditions that affect fewer than 200,000 people in the US. The designation qualifies a drug’s sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing and 7 years of market exclusivity.

In Europe, sponsors who obtain orphan designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, 10 years of market exclusivity, and fee reductions.

The EMA grants PRIME designation to enhance support for the development of medicines that target an unmet medical need. The designation is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to GSK2857916, an anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F via a non-cleavable linker.

The designation is for GSK2857916 as monotherapy for patients with multiple myeloma (MM) who have failed at least 3 prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent.

The designation is based on results from a phase 1, dose-escalation and expansion study in patients with relapsed/refractory MM, irrespective of BCMA expression (NCT02064387).

Data from this ongoing trial are scheduled to be presented December 11 in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.

GSK2857916 has also received orphan drug designation from the FDA and the European Medicines Agency (EMA) as well as PRIME designation from the EMA.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions. The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

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

Orphan and PRIME designations

The FDA grants orphan designation to therapies intended to treat conditions that affect fewer than 200,000 people in the US. The designation qualifies a drug’s sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing and 7 years of market exclusivity.

In Europe, sponsors who obtain orphan designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, 10 years of market exclusivity, and fee reductions.

The EMA grants PRIME designation to enhance support for the development of medicines that target an unmet medical need. The designation is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

Photo courtesy of NIH

SAN DIEGO—A new study suggests patients with advanced cancer may prefer doctors who do not use a computer while communicating with them.

Most of the 120 patients studied said they preferred face-to-face consultations in which a doctor used a notepad rather than a computer.

Doctors who did not use a computer were perceived as more compassionate, communicative, and professional.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 26*).

“To our knowledge, this is the only study that compares exam room interactions between people with advanced cancer and their physicians, with or without a computer present,” said study investigator Ali Haider, MD, of the University of Texas MD Anderson Cancer Center in Houston.

For this study, Dr Haider and his colleagues enrolled 120 patients with localized, recurrent, or metastatic disease. The patients’ median ECOG performance status was 2.

All patients were English speakers, they had a median age of 58 (range, 44-66), and 55% were female. Sixty-seven percent of patients were white, 18% were Hispanic, 13% were African American, and 2% were “other.” Forty-one percent of patients had completed college.

According to the Edmonton Symptom Assessment System, patients’ median pain score was 5 (range, 2-7), and their median fatigue score was 4 (range, 3-7). According to the Hospital Anxiety and Depression Scale, patients’ median anxiety score was 6 (range, 4-8), and their median depression score was 6 (range, 4-9).

The intervention

The investigators randomly assigned patients to watch different videos showing doctor-patient interactions with and without computer use. The team had filmed 4 short videos that featured actors playing the parts of doctor and patient.

All study participants were blinded to the hypothesis of the study. The actors were carefully scripted and used the same gestures, expressions, and other nonverbal communication in each video to minimize bias.

Video 1 involved Doctor A in a face-to-face consultation with just a notepad in hand, and Video 2 involved Doctor A in a consultation using a computer.

Video 3 involved Doctor B in a face-to-face consultation with just a notepad in hand, and Video 4 involved Doctor B in a consultation using a computer.

Doctors A and B looked similar, which was intended to minimize bias.

After viewing their first video, patients completed a validated questionnaire rating the doctor’s communication skills, professionalism, and compassion.

Subsequently, each group was assigned to a video topic (face-to-face or computer) they had not viewed previously featuring the doctor they had not viewed in the first video.

A follow-up questionnaire was given after this round of viewing, and the patients were also asked to rate their overall physician preference.

Results

After the first round of viewing, the patients gave better ratings to doctors (A or B) in the face-to-face videos than in the computer videos. Face-to-face doctors were rated significantly higher for compassion (P=0.0003), communication skills (P=0.0012), and professionalism (P=0.0001).

After patients had watched both videos, doctors in the face-to-face videos still had better scores for compassion, communication, and professionalism (P<0.001 for all).

Most patients (72%) said they preferred the face-to-face consultation, while 8% said they preferred the computer consultation, and 20% said they had no preference.

Dr Haider said a possible explanation for these findings is that patients with serious chronic illnesses might value undivided attention from their physicians, and patients might perceive providers using computers as more distracted or multitasking during visits.

“We know that having a good rapport with patients can be extremely beneficial for their health,” Dr Haider said. “Patients with advanced disease need the cues that come with direct interaction to help them along with their care.”

However, Dr Haider also noted that additional research is needed to confirm these results. And he said perceptions might be different in a younger population with higher computer literacy.

*Data in the abstract differ from the presentation.

Photo courtesy of NIH

SAN DIEGO—A new study suggests patients with advanced cancer may prefer doctors who do not use a computer while communicating with them.

Most of the 120 patients studied said they preferred face-to-face consultations in which a doctor used a notepad rather than a computer.

Doctors who did not use a computer were perceived as more compassionate, communicative, and professional.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 26*).

“To our knowledge, this is the only study that compares exam room interactions between people with advanced cancer and their physicians, with or without a computer present,” said study investigator Ali Haider, MD, of the University of Texas MD Anderson Cancer Center in Houston.

For this study, Dr Haider and his colleagues enrolled 120 patients with localized, recurrent, or metastatic disease. The patients’ median ECOG performance status was 2.

All patients were English speakers, they had a median age of 58 (range, 44-66), and 55% were female. Sixty-seven percent of patients were white, 18% were Hispanic, 13% were African American, and 2% were “other.” Forty-one percent of patients had completed college.

According to the Edmonton Symptom Assessment System, patients’ median pain score was 5 (range, 2-7), and their median fatigue score was 4 (range, 3-7). According to the Hospital Anxiety and Depression Scale, patients’ median anxiety score was 6 (range, 4-8), and their median depression score was 6 (range, 4-9).

The intervention

The investigators randomly assigned patients to watch different videos showing doctor-patient interactions with and without computer use. The team had filmed 4 short videos that featured actors playing the parts of doctor and patient.

All study participants were blinded to the hypothesis of the study. The actors were carefully scripted and used the same gestures, expressions, and other nonverbal communication in each video to minimize bias.

Video 1 involved Doctor A in a face-to-face consultation with just a notepad in hand, and Video 2 involved Doctor A in a consultation using a computer.

Video 3 involved Doctor B in a face-to-face consultation with just a notepad in hand, and Video 4 involved Doctor B in a consultation using a computer.

Doctors A and B looked similar, which was intended to minimize bias.

After viewing their first video, patients completed a validated questionnaire rating the doctor’s communication skills, professionalism, and compassion.

Subsequently, each group was assigned to a video topic (face-to-face or computer) they had not viewed previously featuring the doctor they had not viewed in the first video.

A follow-up questionnaire was given after this round of viewing, and the patients were also asked to rate their overall physician preference.

Results

After the first round of viewing, the patients gave better ratings to doctors (A or B) in the face-to-face videos than in the computer videos. Face-to-face doctors were rated significantly higher for compassion (P=0.0003), communication skills (P=0.0012), and professionalism (P=0.0001).

After patients had watched both videos, doctors in the face-to-face videos still had better scores for compassion, communication, and professionalism (P<0.001 for all).

Most patients (72%) said they preferred the face-to-face consultation, while 8% said they preferred the computer consultation, and 20% said they had no preference.

Dr Haider said a possible explanation for these findings is that patients with serious chronic illnesses might value undivided attention from their physicians, and patients might perceive providers using computers as more distracted or multitasking during visits.

“We know that having a good rapport with patients can be extremely beneficial for their health,” Dr Haider said. “Patients with advanced disease need the cues that come with direct interaction to help them along with their care.”

However, Dr Haider also noted that additional research is needed to confirm these results. And he said perceptions might be different in a younger population with higher computer literacy.

*Data in the abstract differ from the presentation.

Photo courtesy of NIH

SAN DIEGO—A new study suggests patients with advanced cancer may prefer doctors who do not use a computer while communicating with them.

Most of the 120 patients studied said they preferred face-to-face consultations in which a doctor used a notepad rather than a computer.

Doctors who did not use a computer were perceived as more compassionate, communicative, and professional.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 26*).

“To our knowledge, this is the only study that compares exam room interactions between people with advanced cancer and their physicians, with or without a computer present,” said study investigator Ali Haider, MD, of the University of Texas MD Anderson Cancer Center in Houston.

For this study, Dr Haider and his colleagues enrolled 120 patients with localized, recurrent, or metastatic disease. The patients’ median ECOG performance status was 2.

All patients were English speakers, they had a median age of 58 (range, 44-66), and 55% were female. Sixty-seven percent of patients were white, 18% were Hispanic, 13% were African American, and 2% were “other.” Forty-one percent of patients had completed college.

According to the Edmonton Symptom Assessment System, patients’ median pain score was 5 (range, 2-7), and their median fatigue score was 4 (range, 3-7). According to the Hospital Anxiety and Depression Scale, patients’ median anxiety score was 6 (range, 4-8), and their median depression score was 6 (range, 4-9).

The intervention

The investigators randomly assigned patients to watch different videos showing doctor-patient interactions with and without computer use. The team had filmed 4 short videos that featured actors playing the parts of doctor and patient.

All study participants were blinded to the hypothesis of the study. The actors were carefully scripted and used the same gestures, expressions, and other nonverbal communication in each video to minimize bias.

Video 1 involved Doctor A in a face-to-face consultation with just a notepad in hand, and Video 2 involved Doctor A in a consultation using a computer.

Video 3 involved Doctor B in a face-to-face consultation with just a notepad in hand, and Video 4 involved Doctor B in a consultation using a computer.

Doctors A and B looked similar, which was intended to minimize bias.

After viewing their first video, patients completed a validated questionnaire rating the doctor’s communication skills, professionalism, and compassion.

Subsequently, each group was assigned to a video topic (face-to-face or computer) they had not viewed previously featuring the doctor they had not viewed in the first video.

A follow-up questionnaire was given after this round of viewing, and the patients were also asked to rate their overall physician preference.

Results

After the first round of viewing, the patients gave better ratings to doctors (A or B) in the face-to-face videos than in the computer videos. Face-to-face doctors were rated significantly higher for compassion (P=0.0003), communication skills (P=0.0012), and professionalism (P=0.0001).

After patients had watched both videos, doctors in the face-to-face videos still had better scores for compassion, communication, and professionalism (P<0.001 for all).

Most patients (72%) said they preferred the face-to-face consultation, while 8% said they preferred the computer consultation, and 20% said they had no preference.

Dr Haider said a possible explanation for these findings is that patients with serious chronic illnesses might value undivided attention from their physicians, and patients might perceive providers using computers as more distracted or multitasking during visits.

“We know that having a good rapport with patients can be extremely beneficial for their health,” Dr Haider said. “Patients with advanced disease need the cues that come with direct interaction to help them along with their care.”

However, Dr Haider also noted that additional research is needed to confirm these results. And he said perceptions might be different in a younger population with higher computer literacy.

*Data in the abstract differ from the presentation.

Bone marrow aspirate showing plasma cells of multiple myeloma

NEW YORK, NY—The B-cell maturation antigen (BCMA) is emerging as a promising target in multiple myeloma (MM), according to Adam D. Cohen, MD, of the University of Pennsylvania in Philadelphia.

BCMA is highly expressed on MM cells and, with its 2 ligands, is responsible for maintaining normal plasma cell homeostasis.

“And it’s really not expressed on any other normal tissues of the body,” Dr Cohen said.

“Importantly, BCMA is not just sitting on the cell surface as a target but actually promotes myeloma pathogenesis.”

Dr Cohen reviewed the progress being made using BCMA as a target in MM, paying particular attention to chimeric antigen receptor (CAR) T cells. He presented the update at Lymphoma & Myeloma 2017.

NCI BCMA-specific CARs

The first CAR to specifically target BCMA in MM was developed at the National Cancer Institute (NCI). It consisted of a murine single-chain variable fragment (scFv), CD3/CD28 signaling domains, and a gamma-retroviral vector.

Investigators conducted the first-in-human trial of this CAR T-cell therapy in 12 relapsed/refractory MM patients.

All patients received a lymphodepleting conditioning regimen of cyclophosphamide and fludarabine and a single infusion of 1 of 4 doses of the CAR T-cell therapy.

At higher dose levels, the BCMA-CAR produced objective responses “even in these highly refractory patients,” Dr Cohen said. “Some responses lasted 4 to 6 months.”

Patients who had the greatest degree of expansion of CAR T cells were the ones who had the best responses.

The BCMA-CAR is associated with the same toxicities as the CD19-directed CAR T-cell therapies now approved in acute lymphoblastic leukemia and non-Hodgkin lymphoma—cytokine release syndrome (CRS) and neurotoxicity.

The NCI study (NCT02215967) is ongoing.

Penn BCMA-specific CAR

A different BCMA CAR is being investigated at the University of Pennsylvania. It is a fully human CAR that consists of a human scFv, CD3/4-1BB costimulatory domains, and a lentiviral vector.

Investigators designed the first-in-human trial* (NCT02546167) with 3 different cohorts.

Patients in cohort 1 received 5 x 10⁸ CAR T cells without any lymphodepleting chemotherapy.

The remaining patients received cyclophosphamide, followed by 5 x 10⁷ CAR T cells in cohort 2 and 5 x 10⁸ CAR T cells in cohort 3.

Dr Cohen reviewed current data from cohort 1, which included 9 patients. They were a median age of 57 (range, 44-70), and 67% were male. They were heavily pretreated with a median of 9 prior lines of therapy (range, 4-11).

All had high-risk cytogenetics, 67% had deletion 17p or TP53 mutation, and they had a median of 80% bone marrow plasma cells (range, 15%-95%).

“Despite this,” Dr Cohen said, “we were able to generate, successfully, CAR T cells from all patients, although 1 patient did require a second apheresis and manufacturing attempt.”

Four of the 9 patients achieved very good partial responses, and an additional 2 patients had minimal responses.

One patient had a stringent CR (sCR) for close to 2 years without having any intervening therapy.

“[The sCR] shows the potential for this [therapy] to create a durable remission in a patient without any other therapy,” Dr Cohen said. “And this patient still has circulating CAR cells detectable.”

Most of the other patients did not have as durable a response. Responses lasted a median of 3 to 5 months before the patients relapsed.

Dr Cohen noted that the Penn data confirm the NCI experience showing proof of principle.

“You can target BCMA with these cells and get objective responses that can lead to a durable one in a subset of patients,” he added.

Dr Cohen is scheduled to report the preliminary data on the cyclophosphamide cohorts (cohorts 2 and 3) at ASH 2017. Those cohorts, he said, are showing a bit more persistence and increased frequency of responses.

Other BCMA-specific CAR trials

Another BCMA CAR, bb2121, consists of a human anti-BCMA scFv, a lentiviral vector, and a CD3/4-1BB costimulatory domain.

In the first-in-human trial of bb2121* (NCT02658929), all 21 patients received cyclophosphamide and fludarabine conditioning first.

There were “very impressive response rates in this study,” Dr Cohen said.

Once patients were dosed at the higher levels of 150 million cells or greater, every patient responded.

“Many responses are still durable,” he pointed out, “some approaching a year.”

LCAR-B38M is structurally different from the other BCMA-specific CARs. It has 2 binding sites for BCMA.

Thirty-five patients enrolled on the trial of LCAR-B38M (NCT03090659), and 19 were evaluable for response.

Patients had a median of 3 or 4 lines of prior therapy. All received cyclophosphamide alone as conditioning.

All 19 evaluable patients responded, and 14 (74%) achieved an sCR.

Dr Cohen noted the differences among the 4 trials: costimulatory domains varied, the Penn study did not require a pre-existing level of BCMA on the MM cells, other studies excluded patients who didn’t meet a certain threshold level of BCMA expression, median lines of prior therapy differed, and conditioning regimens differed as well.

All trials, however, presented data on fewer than 20 patients.

“And so I think it’s a little too early to compare head-to-head between all of these, but they all are really demonstrating promising results so far,” he observed.

Toxicities

“Unfortunately, there’s no free lunch with CAR T cells,” Dr Cohen stated, “and these extraordinary responses do come at the cost of several somewhat unique toxicities that can be serious.”

Toxicities have included:

• Tumor lysis syndrome, which is expected and manageable
• B-cell aplasia, which is not as much of an issue with BCMA as with CD19-directed CAR Ts, since most B cells don’t express BCMA
• Hypogammaglobulinemia, which can be mitigated with IVIG
• CRS, which can be alleviated with tocilizumab
• Neurotoxicity and encephalopathy, which do not occur as frequently as CRS.

“These, I think, are things we still obviously need to learn more about and try to mitigate before this [BCMA-directed CAR therapy] is expanded and brought earlier to patients,” Dr Cohen said.

“The other issues with CAR T cells are logistical. Limited access (the procedure is available at only a few centers); manufacturing can take 2 to 4 weeks, during which time it is difficult to maintain disease control; and the cost is significant.”

“We are really in the early days of CAR cells for myeloma, but, certainly, this appears very bright in terms of its future.” 

* Data from the presentation differ from the abstract.

Bone marrow aspirate showing plasma cells of multiple myeloma

NEW YORK, NY—The B-cell maturation antigen (BCMA) is emerging as a promising target in multiple myeloma (MM), according to Adam D. Cohen, MD, of the University of Pennsylvania in Philadelphia.

BCMA is highly expressed on MM cells and, with its 2 ligands, is responsible for maintaining normal plasma cell homeostasis.

“And it’s really not expressed on any other normal tissues of the body,” Dr Cohen said.

“Importantly, BCMA is not just sitting on the cell surface as a target but actually promotes myeloma pathogenesis.”

Dr Cohen reviewed the progress being made using BCMA as a target in MM, paying particular attention to chimeric antigen receptor (CAR) T cells. He presented the update at Lymphoma & Myeloma 2017.

NCI BCMA-specific CARs

The first CAR to specifically target BCMA in MM was developed at the National Cancer Institute (NCI). It consisted of a murine single-chain variable fragment (scFv), CD3/CD28 signaling domains, and a gamma-retroviral vector.

Investigators conducted the first-in-human trial of this CAR T-cell therapy in 12 relapsed/refractory MM patients.

All patients received a lymphodepleting conditioning regimen of cyclophosphamide and fludarabine and a single infusion of 1 of 4 doses of the CAR T-cell therapy.

At higher dose levels, the BCMA-CAR produced objective responses “even in these highly refractory patients,” Dr Cohen said. “Some responses lasted 4 to 6 months.”

Patients who had the greatest degree of expansion of CAR T cells were the ones who had the best responses.

The BCMA-CAR is associated with the same toxicities as the CD19-directed CAR T-cell therapies now approved in acute lymphoblastic leukemia and non-Hodgkin lymphoma—cytokine release syndrome (CRS) and neurotoxicity.

The NCI study (NCT02215967) is ongoing.

Penn BCMA-specific CAR

A different BCMA CAR is being investigated at the University of Pennsylvania. It is a fully human CAR that consists of a human scFv, CD3/4-1BB costimulatory domains, and a lentiviral vector.

Investigators designed the first-in-human trial* (NCT02546167) with 3 different cohorts.

Patients in cohort 1 received 5 x 10⁸ CAR T cells without any lymphodepleting chemotherapy.

The remaining patients received cyclophosphamide, followed by 5 x 10⁷ CAR T cells in cohort 2 and 5 x 10⁸ CAR T cells in cohort 3.

Dr Cohen reviewed current data from cohort 1, which included 9 patients. They were a median age of 57 (range, 44-70), and 67% were male. They were heavily pretreated with a median of 9 prior lines of therapy (range, 4-11).

All had high-risk cytogenetics, 67% had deletion 17p or TP53 mutation, and they had a median of 80% bone marrow plasma cells (range, 15%-95%).

“Despite this,” Dr Cohen said, “we were able to generate, successfully, CAR T cells from all patients, although 1 patient did require a second apheresis and manufacturing attempt.”

Four of the 9 patients achieved very good partial responses, and an additional 2 patients had minimal responses.

One patient had a stringent CR (sCR) for close to 2 years without having any intervening therapy.

“[The sCR] shows the potential for this [therapy] to create a durable remission in a patient without any other therapy,” Dr Cohen said. “And this patient still has circulating CAR cells detectable.”

Most of the other patients did not have as durable a response. Responses lasted a median of 3 to 5 months before the patients relapsed.

Dr Cohen noted that the Penn data confirm the NCI experience showing proof of principle.

“You can target BCMA with these cells and get objective responses that can lead to a durable one in a subset of patients,” he added.

Dr Cohen is scheduled to report the preliminary data on the cyclophosphamide cohorts (cohorts 2 and 3) at ASH 2017. Those cohorts, he said, are showing a bit more persistence and increased frequency of responses.

Other BCMA-specific CAR trials

Another BCMA CAR, bb2121, consists of a human anti-BCMA scFv, a lentiviral vector, and a CD3/4-1BB costimulatory domain.

In the first-in-human trial of bb2121* (NCT02658929), all 21 patients received cyclophosphamide and fludarabine conditioning first.

There were “very impressive response rates in this study,” Dr Cohen said.

Once patients were dosed at the higher levels of 150 million cells or greater, every patient responded.

“Many responses are still durable,” he pointed out, “some approaching a year.”

LCAR-B38M is structurally different from the other BCMA-specific CARs. It has 2 binding sites for BCMA.

Thirty-five patients enrolled on the trial of LCAR-B38M (NCT03090659), and 19 were evaluable for response.

Patients had a median of 3 or 4 lines of prior therapy. All received cyclophosphamide alone as conditioning.

All 19 evaluable patients responded, and 14 (74%) achieved an sCR.

Dr Cohen noted the differences among the 4 trials: costimulatory domains varied, the Penn study did not require a pre-existing level of BCMA on the MM cells, other studies excluded patients who didn’t meet a certain threshold level of BCMA expression, median lines of prior therapy differed, and conditioning regimens differed as well.

All trials, however, presented data on fewer than 20 patients.

“And so I think it’s a little too early to compare head-to-head between all of these, but they all are really demonstrating promising results so far,” he observed.

Toxicities

“Unfortunately, there’s no free lunch with CAR T cells,” Dr Cohen stated, “and these extraordinary responses do come at the cost of several somewhat unique toxicities that can be serious.”

Toxicities have included:

• Tumor lysis syndrome, which is expected and manageable
• B-cell aplasia, which is not as much of an issue with BCMA as with CD19-directed CAR Ts, since most B cells don’t express BCMA
• Hypogammaglobulinemia, which can be mitigated with IVIG
• CRS, which can be alleviated with tocilizumab
• Neurotoxicity and encephalopathy, which do not occur as frequently as CRS.

“These, I think, are things we still obviously need to learn more about and try to mitigate before this [BCMA-directed CAR therapy] is expanded and brought earlier to patients,” Dr Cohen said.

“The other issues with CAR T cells are logistical. Limited access (the procedure is available at only a few centers); manufacturing can take 2 to 4 weeks, during which time it is difficult to maintain disease control; and the cost is significant.”

“We are really in the early days of CAR cells for myeloma, but, certainly, this appears very bright in terms of its future.” 

* Data from the presentation differ from the abstract.

Bone marrow aspirate showing plasma cells of multiple myeloma

NEW YORK, NY—The B-cell maturation antigen (BCMA) is emerging as a promising target in multiple myeloma (MM), according to Adam D. Cohen, MD, of the University of Pennsylvania in Philadelphia.

BCMA is highly expressed on MM cells and, with its 2 ligands, is responsible for maintaining normal plasma cell homeostasis.

“And it’s really not expressed on any other normal tissues of the body,” Dr Cohen said.

“Importantly, BCMA is not just sitting on the cell surface as a target but actually promotes myeloma pathogenesis.”

Dr Cohen reviewed the progress being made using BCMA as a target in MM, paying particular attention to chimeric antigen receptor (CAR) T cells. He presented the update at Lymphoma & Myeloma 2017.

NCI BCMA-specific CARs

The first CAR to specifically target BCMA in MM was developed at the National Cancer Institute (NCI). It consisted of a murine single-chain variable fragment (scFv), CD3/CD28 signaling domains, and a gamma-retroviral vector.

Investigators conducted the first-in-human trial of this CAR T-cell therapy in 12 relapsed/refractory MM patients.

All patients received a lymphodepleting conditioning regimen of cyclophosphamide and fludarabine and a single infusion of 1 of 4 doses of the CAR T-cell therapy.

At higher dose levels, the BCMA-CAR produced objective responses “even in these highly refractory patients,” Dr Cohen said. “Some responses lasted 4 to 6 months.”

Patients who had the greatest degree of expansion of CAR T cells were the ones who had the best responses.

The BCMA-CAR is associated with the same toxicities as the CD19-directed CAR T-cell therapies now approved in acute lymphoblastic leukemia and non-Hodgkin lymphoma—cytokine release syndrome (CRS) and neurotoxicity.

The NCI study (NCT02215967) is ongoing.

Penn BCMA-specific CAR

A different BCMA CAR is being investigated at the University of Pennsylvania. It is a fully human CAR that consists of a human scFv, CD3/4-1BB costimulatory domains, and a lentiviral vector.

Investigators designed the first-in-human trial* (NCT02546167) with 3 different cohorts.

Patients in cohort 1 received 5 x 10⁸ CAR T cells without any lymphodepleting chemotherapy.

The remaining patients received cyclophosphamide, followed by 5 x 10⁷ CAR T cells in cohort 2 and 5 x 10⁸ CAR T cells in cohort 3.

Dr Cohen reviewed current data from cohort 1, which included 9 patients. They were a median age of 57 (range, 44-70), and 67% were male. They were heavily pretreated with a median of 9 prior lines of therapy (range, 4-11).

All had high-risk cytogenetics, 67% had deletion 17p or TP53 mutation, and they had a median of 80% bone marrow plasma cells (range, 15%-95%).

“Despite this,” Dr Cohen said, “we were able to generate, successfully, CAR T cells from all patients, although 1 patient did require a second apheresis and manufacturing attempt.”

Four of the 9 patients achieved very good partial responses, and an additional 2 patients had minimal responses.

One patient had a stringent CR (sCR) for close to 2 years without having any intervening therapy.

“[The sCR] shows the potential for this [therapy] to create a durable remission in a patient without any other therapy,” Dr Cohen said. “And this patient still has circulating CAR cells detectable.”

Most of the other patients did not have as durable a response. Responses lasted a median of 3 to 5 months before the patients relapsed.

Dr Cohen noted that the Penn data confirm the NCI experience showing proof of principle.

“You can target BCMA with these cells and get objective responses that can lead to a durable one in a subset of patients,” he added.

Dr Cohen is scheduled to report the preliminary data on the cyclophosphamide cohorts (cohorts 2 and 3) at ASH 2017. Those cohorts, he said, are showing a bit more persistence and increased frequency of responses.

Other BCMA-specific CAR trials

Another BCMA CAR, bb2121, consists of a human anti-BCMA scFv, a lentiviral vector, and a CD3/4-1BB costimulatory domain.

In the first-in-human trial of bb2121* (NCT02658929), all 21 patients received cyclophosphamide and fludarabine conditioning first.

There were “very impressive response rates in this study,” Dr Cohen said.

Once patients were dosed at the higher levels of 150 million cells or greater, every patient responded.

“Many responses are still durable,” he pointed out, “some approaching a year.”

LCAR-B38M is structurally different from the other BCMA-specific CARs. It has 2 binding sites for BCMA.

Thirty-five patients enrolled on the trial of LCAR-B38M (NCT03090659), and 19 were evaluable for response.

Patients had a median of 3 or 4 lines of prior therapy. All received cyclophosphamide alone as conditioning.

All 19 evaluable patients responded, and 14 (74%) achieved an sCR.

Dr Cohen noted the differences among the 4 trials: costimulatory domains varied, the Penn study did not require a pre-existing level of BCMA on the MM cells, other studies excluded patients who didn’t meet a certain threshold level of BCMA expression, median lines of prior therapy differed, and conditioning regimens differed as well.

All trials, however, presented data on fewer than 20 patients.

“And so I think it’s a little too early to compare head-to-head between all of these, but they all are really demonstrating promising results so far,” he observed.

Toxicities

“Unfortunately, there’s no free lunch with CAR T cells,” Dr Cohen stated, “and these extraordinary responses do come at the cost of several somewhat unique toxicities that can be serious.”

Toxicities have included:

• Tumor lysis syndrome, which is expected and manageable
• B-cell aplasia, which is not as much of an issue with BCMA as with CD19-directed CAR Ts, since most B cells don’t express BCMA
• Hypogammaglobulinemia, which can be mitigated with IVIG
• CRS, which can be alleviated with tocilizumab
• Neurotoxicity and encephalopathy, which do not occur as frequently as CRS.

“These, I think, are things we still obviously need to learn more about and try to mitigate before this [BCMA-directed CAR therapy] is expanded and brought earlier to patients,” Dr Cohen said.

“The other issues with CAR T cells are logistical. Limited access (the procedure is available at only a few centers); manufacturing can take 2 to 4 weeks, during which time it is difficult to maintain disease control; and the cost is significant.”

“We are really in the early days of CAR cells for myeloma, but, certainly, this appears very bright in terms of its future.” 

* Data from the presentation differ from the abstract.

Photo by Rhoda Baer

SAN DIEGO—A study of acute myeloid leukemia (AML) patients has revealed misperceptions about treatment risks and the likelihood of cure.

Investigators surveyed 100 AML patients receiving intensive and non-intensive chemotherapy, as well as the patients’ oncologists.

The results showed that patients tended to overestimate both the risk of dying due to treatment and the likelihood of cure.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 43).

“Patients with AML face very challenging treatment decisions that are often placed upon them within days after being diagnosed,” said study investigator Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston.

“Because they face a grave decision, they need to understand what the risks of treatment are versus the possibility of a cure.”

For this study, Dr El-Jawahri and her colleagues enrolled 50 patients who were receiving intensive care for AML (which usually meant hospitalization for 4 to 6 weeks) and 50 patients who were receiving non-intensive care (often given as outpatient treatment).

The patients’ median age was 71 (range, 60-100), and 92% were white. Six percent of patients had low-risk disease, 48% had intermediate-risk, and 46% had high-risk disease.

Within 3 days of starting treatment, both the patients and their physicians were given a questionnaire to assess how they perceived the likelihood of the patient dying from treatment.

One month later, patients and physicians completed a follow-up questionnaire to assess perceptions of patient prognosis. Within that time frame, most patients received laboratory results that more definitively established the type and stage of cancer.

At 24 weeks, the investigators asked patients if they had discussed their end-of-life wishes with their oncologists.

Results

Initially, most of the patient population (91.3%) thought it was “somewhat” or “extremely” likely they would die from their treatment. However, only 22% of treating oncologists said the same.

One month later, a majority of patients in both treatment groups thought it was “somewhat” or “extremely” likely they would be cured of their AML.

Specifically, 82.1% of patients receiving non-intensive chemotherapy said it was “somewhat” or “extremely” likely they would be cured, while 10% of their oncologists said the same.

Meanwhile, 97.6% of patients receiving intensive chemotherapy said it was “somewhat” or “extremely” likely they would be cured, and 42% of their oncologists said the same.

Overall, 77.8% of patients said they had not discussed their end-of-life wishes with their oncologists at 24 weeks.

“There were several very important factors we were not able to capture in our study, including what was actually discussed between patients and their oncologists and whether patients simply misunderstood or misheard the information conveyed to them,” Dr El-Jawahri said.

“Perhaps most importantly, we did not audio-record the discussions between the patients and their physicians, which could provide additional details regarding barriers to accurate prognostic understanding in these conversations.”

Related research and next steps

Prior to this study, Dr El-Jawahri and her colleagues had looked at similar perceptions in patients with solid tumor malignancies as well as in patients with hematologic malignancies who were receiving hematopoietic stem cell transplants.

The gaps in perception of treatment risk and cure for patients compared to their physicians were not as large in those cases as in the AML patients in this study. The investigators attribute this to higher levels of distress seen in AML patients due to the urgency of their treatment decisions.

Dr El-Jawahri and her colleagues have found that early consideration of palliative care in a treatment plan for patients with solid tumors improves patients’ understanding of the prognosis. The team hopes to implement a similar study in patients with AML.

“Clearly, there are important communication gaps between oncologists and their patients,” Dr El-Jawahri said. “We need to find ways to help physicians do a better job of communicating with their patients, especially in diseases like AML where stress levels are remarkably high.”

Photo by Rhoda Baer

SAN DIEGO—A study of acute myeloid leukemia (AML) patients has revealed misperceptions about treatment risks and the likelihood of cure.

Investigators surveyed 100 AML patients receiving intensive and non-intensive chemotherapy, as well as the patients’ oncologists.

The results showed that patients tended to overestimate both the risk of dying due to treatment and the likelihood of cure.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 43).

“Patients with AML face very challenging treatment decisions that are often placed upon them within days after being diagnosed,” said study investigator Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston.

“Because they face a grave decision, they need to understand what the risks of treatment are versus the possibility of a cure.”

For this study, Dr El-Jawahri and her colleagues enrolled 50 patients who were receiving intensive care for AML (which usually meant hospitalization for 4 to 6 weeks) and 50 patients who were receiving non-intensive care (often given as outpatient treatment).

The patients’ median age was 71 (range, 60-100), and 92% were white. Six percent of patients had low-risk disease, 48% had intermediate-risk, and 46% had high-risk disease.

Within 3 days of starting treatment, both the patients and their physicians were given a questionnaire to assess how they perceived the likelihood of the patient dying from treatment.

One month later, patients and physicians completed a follow-up questionnaire to assess perceptions of patient prognosis. Within that time frame, most patients received laboratory results that more definitively established the type and stage of cancer.

At 24 weeks, the investigators asked patients if they had discussed their end-of-life wishes with their oncologists.

Results

Initially, most of the patient population (91.3%) thought it was “somewhat” or “extremely” likely they would die from their treatment. However, only 22% of treating oncologists said the same.

One month later, a majority of patients in both treatment groups thought it was “somewhat” or “extremely” likely they would be cured of their AML.

Specifically, 82.1% of patients receiving non-intensive chemotherapy said it was “somewhat” or “extremely” likely they would be cured, while 10% of their oncologists said the same.

Meanwhile, 97.6% of patients receiving intensive chemotherapy said it was “somewhat” or “extremely” likely they would be cured, and 42% of their oncologists said the same.

Overall, 77.8% of patients said they had not discussed their end-of-life wishes with their oncologists at 24 weeks.

“There were several very important factors we were not able to capture in our study, including what was actually discussed between patients and their oncologists and whether patients simply misunderstood or misheard the information conveyed to them,” Dr El-Jawahri said.

“Perhaps most importantly, we did not audio-record the discussions between the patients and their physicians, which could provide additional details regarding barriers to accurate prognostic understanding in these conversations.”

Related research and next steps

Prior to this study, Dr El-Jawahri and her colleagues had looked at similar perceptions in patients with solid tumor malignancies as well as in patients with hematologic malignancies who were receiving hematopoietic stem cell transplants.

The gaps in perception of treatment risk and cure for patients compared to their physicians were not as large in those cases as in the AML patients in this study. The investigators attribute this to higher levels of distress seen in AML patients due to the urgency of their treatment decisions.

Dr El-Jawahri and her colleagues have found that early consideration of palliative care in a treatment plan for patients with solid tumors improves patients’ understanding of the prognosis. The team hopes to implement a similar study in patients with AML.

“Clearly, there are important communication gaps between oncologists and their patients,” Dr El-Jawahri said. “We need to find ways to help physicians do a better job of communicating with their patients, especially in diseases like AML where stress levels are remarkably high.”

Photo by Rhoda Baer

SAN DIEGO—A study of acute myeloid leukemia (AML) patients has revealed misperceptions about treatment risks and the likelihood of cure.

Investigators surveyed 100 AML patients receiving intensive and non-intensive chemotherapy, as well as the patients’ oncologists.

The results showed that patients tended to overestimate both the risk of dying due to treatment and the likelihood of cure.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 43).

“Patients with AML face very challenging treatment decisions that are often placed upon them within days after being diagnosed,” said study investigator Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston.

“Because they face a grave decision, they need to understand what the risks of treatment are versus the possibility of a cure.”

For this study, Dr El-Jawahri and her colleagues enrolled 50 patients who were receiving intensive care for AML (which usually meant hospitalization for 4 to 6 weeks) and 50 patients who were receiving non-intensive care (often given as outpatient treatment).

The patients’ median age was 71 (range, 60-100), and 92% were white. Six percent of patients had low-risk disease, 48% had intermediate-risk, and 46% had high-risk disease.

Within 3 days of starting treatment, both the patients and their physicians were given a questionnaire to assess how they perceived the likelihood of the patient dying from treatment.

One month later, patients and physicians completed a follow-up questionnaire to assess perceptions of patient prognosis. Within that time frame, most patients received laboratory results that more definitively established the type and stage of cancer.

At 24 weeks, the investigators asked patients if they had discussed their end-of-life wishes with their oncologists.

Results

Initially, most of the patient population (91.3%) thought it was “somewhat” or “extremely” likely they would die from their treatment. However, only 22% of treating oncologists said the same.

One month later, a majority of patients in both treatment groups thought it was “somewhat” or “extremely” likely they would be cured of their AML.

Specifically, 82.1% of patients receiving non-intensive chemotherapy said it was “somewhat” or “extremely” likely they would be cured, while 10% of their oncologists said the same.

Meanwhile, 97.6% of patients receiving intensive chemotherapy said it was “somewhat” or “extremely” likely they would be cured, and 42% of their oncologists said the same.

Overall, 77.8% of patients said they had not discussed their end-of-life wishes with their oncologists at 24 weeks.

“There were several very important factors we were not able to capture in our study, including what was actually discussed between patients and their oncologists and whether patients simply misunderstood or misheard the information conveyed to them,” Dr El-Jawahri said.

“Perhaps most importantly, we did not audio-record the discussions between the patients and their physicians, which could provide additional details regarding barriers to accurate prognostic understanding in these conversations.”

Related research and next steps

Prior to this study, Dr El-Jawahri and her colleagues had looked at similar perceptions in patients with solid tumor malignancies as well as in patients with hematologic malignancies who were receiving hematopoietic stem cell transplants.

The gaps in perception of treatment risk and cure for patients compared to their physicians were not as large in those cases as in the AML patients in this study. The investigators attribute this to higher levels of distress seen in AML patients due to the urgency of their treatment decisions.

Dr El-Jawahri and her colleagues have found that early consideration of palliative care in a treatment plan for patients with solid tumors improves patients’ understanding of the prognosis. The team hopes to implement a similar study in patients with AML.

“Clearly, there are important communication gaps between oncologists and their patients,” Dr El-Jawahri said. “We need to find ways to help physicians do a better job of communicating with their patients, especially in diseases like AML where stress levels are remarkably high.”

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted fast track designation to the telomerase inhibitor imetelstat.

The designation is for imetelstat as a potential treatment for adults who have transfusion-dependent anemia due to low or intermediate-1 risk myelodysplastic syndromes (MDS), do not have 5q deletion, and are refractory or resistant to treatment with an erythropoiesis-stimulating agent (ESA).

Imetelstat was initially developed by Geron Corporation and exclusively licensed to Janssen Biotech, Inc.

Janssen sponsored the application for fast track designation using preliminary data from IMerge, a trial in which researchers are studying transfusion-dependent patients with low- or intermediate-1 risk MDS who have relapsed after or are refractory to treatment with an ESA.

Part 1 of IMerge is a phase 2, single-arm trial. Part 2 is a phase 3, randomized, placebo-controlled trial.

Thirty-two patients have been enrolled in part 1 of IMerge. However, this part of the trial is expanding to enroll approximately 20 additional patients who do not have 5q deletion and are naïve to treatment with a hypomethylating agent and lenalidomide.

The expansion is based on results observed in a subset of the original 32 patients who had not received prior treatment with a hypomethylating agent or lenalidomide and did not have 5q deletion.

As of May 2017, this 13-patient subset showed an increased durability and rate of red blood cell transfusion-independence compared to the overall trial population.

Results in these patients and the rest of the original 32 patients are expected to be presented at an upcoming medical conference.

About fast track designation

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted fast track designation to the telomerase inhibitor imetelstat.

The designation is for imetelstat as a potential treatment for adults who have transfusion-dependent anemia due to low or intermediate-1 risk myelodysplastic syndromes (MDS), do not have 5q deletion, and are refractory or resistant to treatment with an erythropoiesis-stimulating agent (ESA).

Imetelstat was initially developed by Geron Corporation and exclusively licensed to Janssen Biotech, Inc.

Janssen sponsored the application for fast track designation using preliminary data from IMerge, a trial in which researchers are studying transfusion-dependent patients with low- or intermediate-1 risk MDS who have relapsed after or are refractory to treatment with an ESA.

Part 1 of IMerge is a phase 2, single-arm trial. Part 2 is a phase 3, randomized, placebo-controlled trial.

Thirty-two patients have been enrolled in part 1 of IMerge. However, this part of the trial is expanding to enroll approximately 20 additional patients who do not have 5q deletion and are naïve to treatment with a hypomethylating agent and lenalidomide.

The expansion is based on results observed in a subset of the original 32 patients who had not received prior treatment with a hypomethylating agent or lenalidomide and did not have 5q deletion.

As of May 2017, this 13-patient subset showed an increased durability and rate of red blood cell transfusion-independence compared to the overall trial population.

Results in these patients and the rest of the original 32 patients are expected to be presented at an upcoming medical conference.

About fast track designation

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted fast track designation to the telomerase inhibitor imetelstat.

The designation is for imetelstat as a potential treatment for adults who have transfusion-dependent anemia due to low or intermediate-1 risk myelodysplastic syndromes (MDS), do not have 5q deletion, and are refractory or resistant to treatment with an erythropoiesis-stimulating agent (ESA).

Imetelstat was initially developed by Geron Corporation and exclusively licensed to Janssen Biotech, Inc.

Janssen sponsored the application for fast track designation using preliminary data from IMerge, a trial in which researchers are studying transfusion-dependent patients with low- or intermediate-1 risk MDS who have relapsed after or are refractory to treatment with an ESA.

Part 1 of IMerge is a phase 2, single-arm trial. Part 2 is a phase 3, randomized, placebo-controlled trial.

Thirty-two patients have been enrolled in part 1 of IMerge. However, this part of the trial is expanding to enroll approximately 20 additional patients who do not have 5q deletion and are naïve to treatment with a hypomethylating agent and lenalidomide.

The expansion is based on results observed in a subset of the original 32 patients who had not received prior treatment with a hypomethylating agent or lenalidomide and did not have 5q deletion.

As of May 2017, this 13-patient subset showed an increased durability and rate of red blood cell transfusion-independence compared to the overall trial population.

Results in these patients and the rest of the original 32 patients are expected to be presented at an upcoming medical conference.

About fast track designation

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.