Hodgkin Lymphoma

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Replacing bleomycin with brentuximab vedotin in the classic ABVD regimen improved a measure of progression-free survival and reduced pulmonary toxicity in patients with previously untreated Hodgkin lymphoma, findings from a randomized, phase 3 trial suggest.

Patients receiving brentuximab plus chemotherapy had a “statistically significant and clinically meaningful improvement” in the rate of modified progression-free survival, according to results published in the New England Journal of Medicine.

Pulmonary toxicity also occurred at a lower rate with the regimen containing brentuximab, an anti-CD30 antibody–drug conjugate, wrote Joseph M. Connors, MD, of the British Columbia Cancer Agency, Vancouver, and his coauthors.

Taken together, these findings suggest brentuximab vedotin and chemotherapy had “substantially less pulmonary toxicity and appears to be more effective for frontline treatment of advanced-stage classic Hodgkin lymphoma,” the researchers wrote.

Bleomycin is often omitted from later cycles of chemotherapy for patients with Hodgkin lymphoma due to pulmonary symptoms, and is sometimes associated with unpredictable or even fatal pulmonary toxicity, the researchers noted.

The brentuximab vedotin arm of the trial did have more neurotoxicity, which was largely reversible, and more myelotoxicity, though that “can be ameliorated with prophylactic granulocyte colony-stimulating factor (G-CSF),” the researchers wrote.

The study by Dr. Connors and colleagues, known as ECHELON-1, was an open-label, multicenter, randomized phase 3 trial including patients with previously untreated stage III or IV classic Hodgkin lymphoma. Among enrolled patients, 664 received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and 670 received standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

The study used a primary endpoint of progression-free survival augmented to include not only time to disease progression or death, but also “modified progression,” which the researchers defined as evidence of noncomplete response at the end of frontline chemotherapy.

It is accepted practice to give more chemotherapy or radiotherapy in Hodgkin lymphoma patients who have a positive PET scan at the end of frontline therapy, since metabolically detectable residual disease reliably predicts imminent progression, Dr. Connors and coauthors wrote.

“In this context, the conventional endpoint of progression-free survival does not accurately assess the curative intent of frontline chemotherapy,” they wrote.

With a median 24.9-month follow-up, modified 2-year progression-free survival in the trial was 82.1% for patients receiving brentuximab plus AVD, versus 77.2% for ABVD (P = .03), a 23% risk reduction.

Pulmonary toxicity of grade 3 or higher occurred in less than 1% of patients in the brentuximab vedotin plus AVD arm of the trial and in 3% of the ABVD arm.

Neutropenia was reported in 58% and 45% in the brentuximab vedotin plus AVD and ABVD arms, respectively, while febrile neutropenia was reported in 19% and 8%, respectively.

In the brentuximab plus AVD group, the rate of febrile neutropenia was 11% for those patients who received primary prophylaxis with G-CSF, and 21% for patients who did not, the researchers noted.

Peripheral neuropathy was seen in 67% and 43% of the brentuximab vedotin plus AVD and ABVD arms, respectively, and about two-thirds of the patients in the brentuximab vedotin plus AVD arm had improvement or resolution at the final follow-up visit.

The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.

[email protected]

SOURCE: Connors JM et al. N Engl J Med. 2018;378:331-44.

Replacing bleomycin with brentuximab vedotin in the classic ABVD regimen improved a measure of progression-free survival and reduced pulmonary toxicity in patients with previously untreated Hodgkin lymphoma, findings from a randomized, phase 3 trial suggest.

Patients receiving brentuximab plus chemotherapy had a “statistically significant and clinically meaningful improvement” in the rate of modified progression-free survival, according to results published in the New England Journal of Medicine.

Pulmonary toxicity also occurred at a lower rate with the regimen containing brentuximab, an anti-CD30 antibody–drug conjugate, wrote Joseph M. Connors, MD, of the British Columbia Cancer Agency, Vancouver, and his coauthors.

Taken together, these findings suggest brentuximab vedotin and chemotherapy had “substantially less pulmonary toxicity and appears to be more effective for frontline treatment of advanced-stage classic Hodgkin lymphoma,” the researchers wrote.

Bleomycin is often omitted from later cycles of chemotherapy for patients with Hodgkin lymphoma due to pulmonary symptoms, and is sometimes associated with unpredictable or even fatal pulmonary toxicity, the researchers noted.

The brentuximab vedotin arm of the trial did have more neurotoxicity, which was largely reversible, and more myelotoxicity, though that “can be ameliorated with prophylactic granulocyte colony-stimulating factor (G-CSF),” the researchers wrote.

The study by Dr. Connors and colleagues, known as ECHELON-1, was an open-label, multicenter, randomized phase 3 trial including patients with previously untreated stage III or IV classic Hodgkin lymphoma. Among enrolled patients, 664 received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and 670 received standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

The study used a primary endpoint of progression-free survival augmented to include not only time to disease progression or death, but also “modified progression,” which the researchers defined as evidence of noncomplete response at the end of frontline chemotherapy.

It is accepted practice to give more chemotherapy or radiotherapy in Hodgkin lymphoma patients who have a positive PET scan at the end of frontline therapy, since metabolically detectable residual disease reliably predicts imminent progression, Dr. Connors and coauthors wrote.

“In this context, the conventional endpoint of progression-free survival does not accurately assess the curative intent of frontline chemotherapy,” they wrote.

With a median 24.9-month follow-up, modified 2-year progression-free survival in the trial was 82.1% for patients receiving brentuximab plus AVD, versus 77.2% for ABVD (P = .03), a 23% risk reduction.

Pulmonary toxicity of grade 3 or higher occurred in less than 1% of patients in the brentuximab vedotin plus AVD arm of the trial and in 3% of the ABVD arm.

Neutropenia was reported in 58% and 45% in the brentuximab vedotin plus AVD and ABVD arms, respectively, while febrile neutropenia was reported in 19% and 8%, respectively.

In the brentuximab plus AVD group, the rate of febrile neutropenia was 11% for those patients who received primary prophylaxis with G-CSF, and 21% for patients who did not, the researchers noted.

Peripheral neuropathy was seen in 67% and 43% of the brentuximab vedotin plus AVD and ABVD arms, respectively, and about two-thirds of the patients in the brentuximab vedotin plus AVD arm had improvement or resolution at the final follow-up visit.

The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.

[email protected]

SOURCE: Connors JM et al. N Engl J Med. 2018;378:331-44.

Replacing bleomycin with brentuximab vedotin in the classic ABVD regimen improved a measure of progression-free survival and reduced pulmonary toxicity in patients with previously untreated Hodgkin lymphoma, findings from a randomized, phase 3 trial suggest.

Patients receiving brentuximab plus chemotherapy had a “statistically significant and clinically meaningful improvement” in the rate of modified progression-free survival, according to results published in the New England Journal of Medicine.

Pulmonary toxicity also occurred at a lower rate with the regimen containing brentuximab, an anti-CD30 antibody–drug conjugate, wrote Joseph M. Connors, MD, of the British Columbia Cancer Agency, Vancouver, and his coauthors.

Taken together, these findings suggest brentuximab vedotin and chemotherapy had “substantially less pulmonary toxicity and appears to be more effective for frontline treatment of advanced-stage classic Hodgkin lymphoma,” the researchers wrote.

Bleomycin is often omitted from later cycles of chemotherapy for patients with Hodgkin lymphoma due to pulmonary symptoms, and is sometimes associated with unpredictable or even fatal pulmonary toxicity, the researchers noted.

The brentuximab vedotin arm of the trial did have more neurotoxicity, which was largely reversible, and more myelotoxicity, though that “can be ameliorated with prophylactic granulocyte colony-stimulating factor (G-CSF),” the researchers wrote.

The study by Dr. Connors and colleagues, known as ECHELON-1, was an open-label, multicenter, randomized phase 3 trial including patients with previously untreated stage III or IV classic Hodgkin lymphoma. Among enrolled patients, 664 received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and 670 received standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

The study used a primary endpoint of progression-free survival augmented to include not only time to disease progression or death, but also “modified progression,” which the researchers defined as evidence of noncomplete response at the end of frontline chemotherapy.

It is accepted practice to give more chemotherapy or radiotherapy in Hodgkin lymphoma patients who have a positive PET scan at the end of frontline therapy, since metabolically detectable residual disease reliably predicts imminent progression, Dr. Connors and coauthors wrote.

“In this context, the conventional endpoint of progression-free survival does not accurately assess the curative intent of frontline chemotherapy,” they wrote.

With a median 24.9-month follow-up, modified 2-year progression-free survival in the trial was 82.1% for patients receiving brentuximab plus AVD, versus 77.2% for ABVD (P = .03), a 23% risk reduction.

Pulmonary toxicity of grade 3 or higher occurred in less than 1% of patients in the brentuximab vedotin plus AVD arm of the trial and in 3% of the ABVD arm.

Neutropenia was reported in 58% and 45% in the brentuximab vedotin plus AVD and ABVD arms, respectively, while febrile neutropenia was reported in 19% and 8%, respectively.

In the brentuximab plus AVD group, the rate of febrile neutropenia was 11% for those patients who received primary prophylaxis with G-CSF, and 21% for patients who did not, the researchers noted.

Peripheral neuropathy was seen in 67% and 43% of the brentuximab vedotin plus AVD and ABVD arms, respectively, and about two-thirds of the patients in the brentuximab vedotin plus AVD arm had improvement or resolution at the final follow-up visit.

The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.

[email protected]

SOURCE: Connors JM et al. N Engl J Med. 2018;378:331-44.

NextSource Pharma recently hiked the price for Gleostine (lomustine), a treatment approved for Hodgkin lymphoma and brain cancer, by 1,400%, adding it to a growing list of drugs without competition that have seen significant price increases.

In this case, the price tag for Gleostine jumped from about $50 to $786 in the 3 years since it was acquired by NextSource Pharma.

PCMA

[email protected]

NextSource Pharma recently hiked the price for Gleostine (lomustine), a treatment approved for Hodgkin lymphoma and brain cancer, by 1,400%, adding it to a growing list of drugs without competition that have seen significant price increases.

In this case, the price tag for Gleostine jumped from about $50 to $786 in the 3 years since it was acquired by NextSource Pharma.

PCMA

[email protected]

NextSource Pharma recently hiked the price for Gleostine (lomustine), a treatment approved for Hodgkin lymphoma and brain cancer, by 1,400%, adding it to a growing list of drugs without competition that have seen significant price increases.

In this case, the price tag for Gleostine jumped from about $50 to $786 in the 3 years since it was acquired by NextSource Pharma.

PCMA

[email protected]

Image from NIAID

Engineered T cells can produce durable responses in patients with Epstein Barr virus–positive (EBV+), relapsed/refractory Hodgkin lymphoma (HL), according to research published in the Journal of Clinical Oncology.

These T cells, known as DNRII-LSTs, produced responses in 4 of the 8 patients studied.

This included 3 complete responses (CRs), the longest of which has exceeded 7 years.

What’s more, these responses were achieved without the use of lymphodepleting chemotherapy.

“While the study is small, its findings are incredibly encouraging for our [patients’] families and for the cancer field,” said study author Catherine M. Bollard, MD, MBChB, of Children’s National Health System in Washington, DC.

To engineer the DNRII-LSTs, Dr Bollard and her colleagues forced expression of a dominant-negative TGF-beta receptor type 2 (DNRII) on LMP-specific T cells (LSTs), which are T cells directed to the EBV latency-associated antigens LMP-1 and LMP-2.

The goal of forcing DNRII expression was to enable the LSTs to resist the hostile tumor environment so they could seek out and kill the tumor cells.

Dr Bollard and her colleagues administered DNRII-LSTs to 8 patients with EBV+ HL. The patients ranged in age from 27 to 47.

Seven of the 8 patients had active disease at the time of DNRII-LST infusion. Two patients had stage IVB HL, 1 had stage IIIB, and 2 had stage IIB. Four patients had nodular-sclerosing HL.

Six patients had relapsed twice. The remaining 2 patients had relapsed 3 and 4 times, respectively. All patients had previously received an autologous stem cell transplant and a range of multi-agent chemotherapy regimens (eg, ABVD, R-ICE, and MOPP).

For this study, the patients received 2 to 12 infusions of DNRII-LSTs, at doses ranging from 2 × 10⁷ to 1.5 × 10⁸ cells/m².

Results

The researchers found that autologous DNRII-LSTs (given to 7 patients) did not cause autoimmunity, and donor-derived DNRII-LSTs (n=1) did not induce graft-vs-host disease.

The team also noted there were no toxicities resulting from cytokine release syndrome.

Four patients achieved a response to treatment—3 CRs and a partial response.

All complete responders are still in CR, but the partial responder progressed at 19 months and ultimately died of sepsis (2 years after the first dose of DNRII-LSTs).

The other 4 patients had stable disease (SD) for 4 months to 13 months after treatment with DNRII-LSTs.

One patient with SD died of disease progression 2 years after receiving DNRII-LSTs, and another died of transplant complications less than 2 years after the last dose of DNRII-LSTs.

One patient with SD went on to receive additional therapy and is still alive more than 6 years after receiving DNRII-LSTs (currently receiving nivolumab). Another SD patient went on to receive additional therapy, achieved a CR, and is still alive.

One of the patients who achieved a CR to DNRII-LSTs remains in CR more than 7 years after the last dose. Another patient’s CR has exceeded 2 years, and another’s has exceeded 5 years.

All 3 of these patients received doses of 2 × 10⁷ cells/m². The patients with the longest and shortest CRs each received 2 infusions of DNRII-LSTs. The patient with the CR exceeding 5 years received 12 infusions.

“These results come 18 years after this revolutionary approach was first conceptualized,” Dr Bollard said. “I started work in this area in 2000. At that time, the oncology community had little enthusiasm for the use of T-cell therapies to treat cancer.”

“Even then, when T-cell therapy was in its relative infancy, some research institutions began to see more than 90% complete responses and cure rates in some settings. This most recent study points to the potential of specialized T cells to fight even more types of immune-evading tumors.”

Image from NIAID

Engineered T cells can produce durable responses in patients with Epstein Barr virus–positive (EBV+), relapsed/refractory Hodgkin lymphoma (HL), according to research published in the Journal of Clinical Oncology.

These T cells, known as DNRII-LSTs, produced responses in 4 of the 8 patients studied.

This included 3 complete responses (CRs), the longest of which has exceeded 7 years.

What’s more, these responses were achieved without the use of lymphodepleting chemotherapy.

“While the study is small, its findings are incredibly encouraging for our [patients’] families and for the cancer field,” said study author Catherine M. Bollard, MD, MBChB, of Children’s National Health System in Washington, DC.

To engineer the DNRII-LSTs, Dr Bollard and her colleagues forced expression of a dominant-negative TGF-beta receptor type 2 (DNRII) on LMP-specific T cells (LSTs), which are T cells directed to the EBV latency-associated antigens LMP-1 and LMP-2.

The goal of forcing DNRII expression was to enable the LSTs to resist the hostile tumor environment so they could seek out and kill the tumor cells.

Dr Bollard and her colleagues administered DNRII-LSTs to 8 patients with EBV+ HL. The patients ranged in age from 27 to 47.

Seven of the 8 patients had active disease at the time of DNRII-LST infusion. Two patients had stage IVB HL, 1 had stage IIIB, and 2 had stage IIB. Four patients had nodular-sclerosing HL.

Six patients had relapsed twice. The remaining 2 patients had relapsed 3 and 4 times, respectively. All patients had previously received an autologous stem cell transplant and a range of multi-agent chemotherapy regimens (eg, ABVD, R-ICE, and MOPP).

For this study, the patients received 2 to 12 infusions of DNRII-LSTs, at doses ranging from 2 × 10⁷ to 1.5 × 10⁸ cells/m².

Results

The researchers found that autologous DNRII-LSTs (given to 7 patients) did not cause autoimmunity, and donor-derived DNRII-LSTs (n=1) did not induce graft-vs-host disease.

The team also noted there were no toxicities resulting from cytokine release syndrome.

Four patients achieved a response to treatment—3 CRs and a partial response.

All complete responders are still in CR, but the partial responder progressed at 19 months and ultimately died of sepsis (2 years after the first dose of DNRII-LSTs).

The other 4 patients had stable disease (SD) for 4 months to 13 months after treatment with DNRII-LSTs.

One patient with SD died of disease progression 2 years after receiving DNRII-LSTs, and another died of transplant complications less than 2 years after the last dose of DNRII-LSTs.

One patient with SD went on to receive additional therapy and is still alive more than 6 years after receiving DNRII-LSTs (currently receiving nivolumab). Another SD patient went on to receive additional therapy, achieved a CR, and is still alive.

One of the patients who achieved a CR to DNRII-LSTs remains in CR more than 7 years after the last dose. Another patient’s CR has exceeded 2 years, and another’s has exceeded 5 years.

All 3 of these patients received doses of 2 × 10⁷ cells/m². The patients with the longest and shortest CRs each received 2 infusions of DNRII-LSTs. The patient with the CR exceeding 5 years received 12 infusions.

“These results come 18 years after this revolutionary approach was first conceptualized,” Dr Bollard said. “I started work in this area in 2000. At that time, the oncology community had little enthusiasm for the use of T-cell therapies to treat cancer.”

“Even then, when T-cell therapy was in its relative infancy, some research institutions began to see more than 90% complete responses and cure rates in some settings. This most recent study points to the potential of specialized T cells to fight even more types of immune-evading tumors.”

Image from NIAID

Engineered T cells can produce durable responses in patients with Epstein Barr virus–positive (EBV+), relapsed/refractory Hodgkin lymphoma (HL), according to research published in the Journal of Clinical Oncology.

These T cells, known as DNRII-LSTs, produced responses in 4 of the 8 patients studied.

This included 3 complete responses (CRs), the longest of which has exceeded 7 years.

What’s more, these responses were achieved without the use of lymphodepleting chemotherapy.

“While the study is small, its findings are incredibly encouraging for our [patients’] families and for the cancer field,” said study author Catherine M. Bollard, MD, MBChB, of Children’s National Health System in Washington, DC.

To engineer the DNRII-LSTs, Dr Bollard and her colleagues forced expression of a dominant-negative TGF-beta receptor type 2 (DNRII) on LMP-specific T cells (LSTs), which are T cells directed to the EBV latency-associated antigens LMP-1 and LMP-2.

The goal of forcing DNRII expression was to enable the LSTs to resist the hostile tumor environment so they could seek out and kill the tumor cells.

Dr Bollard and her colleagues administered DNRII-LSTs to 8 patients with EBV+ HL. The patients ranged in age from 27 to 47.

Seven of the 8 patients had active disease at the time of DNRII-LST infusion. Two patients had stage IVB HL, 1 had stage IIIB, and 2 had stage IIB. Four patients had nodular-sclerosing HL.

Six patients had relapsed twice. The remaining 2 patients had relapsed 3 and 4 times, respectively. All patients had previously received an autologous stem cell transplant and a range of multi-agent chemotherapy regimens (eg, ABVD, R-ICE, and MOPP).

For this study, the patients received 2 to 12 infusions of DNRII-LSTs, at doses ranging from 2 × 10⁷ to 1.5 × 10⁸ cells/m².

Results

The researchers found that autologous DNRII-LSTs (given to 7 patients) did not cause autoimmunity, and donor-derived DNRII-LSTs (n=1) did not induce graft-vs-host disease.

The team also noted there were no toxicities resulting from cytokine release syndrome.

Four patients achieved a response to treatment—3 CRs and a partial response.

All complete responders are still in CR, but the partial responder progressed at 19 months and ultimately died of sepsis (2 years after the first dose of DNRII-LSTs).

The other 4 patients had stable disease (SD) for 4 months to 13 months after treatment with DNRII-LSTs.

One patient with SD died of disease progression 2 years after receiving DNRII-LSTs, and another died of transplant complications less than 2 years after the last dose of DNRII-LSTs.

One patient with SD went on to receive additional therapy and is still alive more than 6 years after receiving DNRII-LSTs (currently receiving nivolumab). Another SD patient went on to receive additional therapy, achieved a CR, and is still alive.

One of the patients who achieved a CR to DNRII-LSTs remains in CR more than 7 years after the last dose. Another patient’s CR has exceeded 2 years, and another’s has exceeded 5 years.

All 3 of these patients received doses of 2 × 10⁷ cells/m². The patients with the longest and shortest CRs each received 2 infusions of DNRII-LSTs. The patient with the CR exceeding 5 years received 12 infusions.

“These results come 18 years after this revolutionary approach was first conceptualized,” Dr Bollard said. “I started work in this area in 2000. At that time, the oncology community had little enthusiasm for the use of T-cell therapies to treat cancer.”

“Even then, when T-cell therapy was in its relative infancy, some research institutions began to see more than 90% complete responses and cure rates in some settings. This most recent study points to the potential of specialized T cells to fight even more types of immune-evading tumors.”

Photo by Rhoda Baer

A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.

The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.

The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).

For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).

For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.

“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.

That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”

According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.

Survival data for patients with hematologic malignancies were as follows.

Acute lymphoblastic leukemia

There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.

Five-year survival was similar between males (43%) and females (41%).

Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).

Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).

Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).

Acute myeloid leukemia

There were 1195 cases of acute myeloid leukemia—641 males and 554 females.

Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).

Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).

Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).

Chronic myeloid leukemia

There were 655 cases of chronic myeloid leukemia—408 males and 247 females.

Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).

Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).

Hodgkin lymphoma

There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.

The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).

Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).

And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).

Non-Hodkgin lymphoma

There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period­—3064 males and 1421 females.

The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).

Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).

And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).

“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.

“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”

Photo by Rhoda Baer

A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.

The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.

The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).

For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).

For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.

“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.

That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”

According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.

Survival data for patients with hematologic malignancies were as follows.

Acute lymphoblastic leukemia

There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.

Five-year survival was similar between males (43%) and females (41%).

Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).

Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).

Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).

Acute myeloid leukemia

There were 1195 cases of acute myeloid leukemia—641 males and 554 females.

Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).

Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).

Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).

Chronic myeloid leukemia

There were 655 cases of chronic myeloid leukemia—408 males and 247 females.

Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).

Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).

Hodgkin lymphoma

There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.

The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).

Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).

And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).

Non-Hodkgin lymphoma

There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period­—3064 males and 1421 females.

The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).

Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).

And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).

“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.

“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”

Photo by Rhoda Baer

A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.

The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.

The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).

For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).

For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.

“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.

That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”

According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.

Survival data for patients with hematologic malignancies were as follows.

Acute lymphoblastic leukemia

There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.

Five-year survival was similar between males (43%) and females (41%).

Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).

Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).

Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).

Acute myeloid leukemia

There were 1195 cases of acute myeloid leukemia—641 males and 554 females.

Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).

Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).

Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).

Chronic myeloid leukemia

There were 655 cases of chronic myeloid leukemia—408 males and 247 females.

Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).

Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).

Hodgkin lymphoma

There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.

The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).

Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).

And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).

Non-Hodkgin lymphoma

There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period­—3064 males and 1421 females.

The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).

Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).

And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).

“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.

“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”

Photo from Business Wire

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental biologics license application (sBLA) for brentuximab vedotin (ADCETRIS).

With this sBLA, Seattle Genetics, Inc., is seeking approval for brentuximab vedotin in combination with chemotherapy for frontline treatment of patients with advanced classical Hodgkin lymphoma (HL).

The FDA expects to make a decision on the sBLA by May 1, 2018.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

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

The priority review for this sBLA is based on positive results from the phase 3 ECHELON-1 trial.

The FDA previously granted brentuximab vedotin breakthrough therapy designation based on ECHELON-1 results.

Breakthrough therapy designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies in one or more clinically significant endpoints.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The study’s primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

About brentuximab vedotin

Brentuximab vedotin is already FDA-approved to treat adults with:

• Classical HL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens.
• Classical HL at high risk of relapse or progression as post-auto-HSCT consolidation.
• Primary cutaneous anaplastic large-cell lymphoma (ALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.
• Systemic ALCL who have failed at least 1 prior multi-agent chemotherapy regimen. (The drug has accelerated approval for this indication, based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.)
  

Photo from Business Wire

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental biologics license application (sBLA) for brentuximab vedotin (ADCETRIS).

With this sBLA, Seattle Genetics, Inc., is seeking approval for brentuximab vedotin in combination with chemotherapy for frontline treatment of patients with advanced classical Hodgkin lymphoma (HL).

The FDA expects to make a decision on the sBLA by May 1, 2018.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

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

The priority review for this sBLA is based on positive results from the phase 3 ECHELON-1 trial.

The FDA previously granted brentuximab vedotin breakthrough therapy designation based on ECHELON-1 results.

Breakthrough therapy designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies in one or more clinically significant endpoints.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The study’s primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

About brentuximab vedotin

Brentuximab vedotin is already FDA-approved to treat adults with:

• Classical HL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens.
• Classical HL at high risk of relapse or progression as post-auto-HSCT consolidation.
• Primary cutaneous anaplastic large-cell lymphoma (ALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.
• Systemic ALCL who have failed at least 1 prior multi-agent chemotherapy regimen. (The drug has accelerated approval for this indication, based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.)
  

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The US Food and Drug Administration (FDA) has accepted for priority review a supplemental biologics license application (sBLA) for brentuximab vedotin (ADCETRIS).

With this sBLA, Seattle Genetics, Inc., is seeking approval for brentuximab vedotin in combination with chemotherapy for frontline treatment of patients with advanced classical Hodgkin lymphoma (HL).

The FDA expects to make a decision on the sBLA by May 1, 2018.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

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

The priority review for this sBLA is based on positive results from the phase 3 ECHELON-1 trial.

The FDA previously granted brentuximab vedotin breakthrough therapy designation based on ECHELON-1 results.

Breakthrough therapy designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies in one or more clinically significant endpoints.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The study’s primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

About brentuximab vedotin

Brentuximab vedotin is already FDA-approved to treat adults with:

• Classical HL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens.
• Classical HL at high risk of relapse or progression as post-auto-HSCT consolidation.
• Primary cutaneous anaplastic large-cell lymphoma (ALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.
• Systemic ALCL who have failed at least 1 prior multi-agent chemotherapy regimen. (The drug has accelerated approval for this indication, based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.)
  

Image from NIDCD

Researchers have gained new insight into hearing loss caused by cisplatin.

By measuring and mapping cisplatin retention in mouse and human inner ear tissues, the researchers found that cisplatin builds up in the inner ear and can remain there for years.

The team also found that a region in the inner ear called the stria vascularis could be targeted to prevent hearing loss resulting from cisplatin.

Lisa L. Cunningham, PhD, of the National Institute on Deafness and other Communications Disorders (NIDCD) in Bethesda, Maryland, and her colleagues reported these findings in Nature Communications.

The researchers noted that cisplatin can cause permanent hearing loss in 40% to 80% of treated patients. The team’s new findings help explain why.

The researchers found that, in most areas of the body, cisplatin is eliminated within days or weeks of treatment, but, in the inner ear, the drug remains much longer.

The team developed a mouse model that represents cisplatin-induced hearing loss seen in human patients.

By looking at inner ear tissue of mice after the first, second, and third cisplatin treatment, the researchers saw that cisplatin remained in the mouse inner ear much longer than in most other body tissues, and the drug builds up with each successive treatment.

The team also studied inner ear tissue donated by deceased adults who had been treated with cisplatin and found the drug is retained in the inner ear months or years after treatment.

When the researchers examined inner ear tissue from a child, they found cisplatin buildup that was even higher than that seen in adults.

Taken together, these results suggest the inner ear readily takes up cisplatin but has limited ability to remove the drug.

In mice and human tissues, the researchers saw the highest buildup of cisplatin in a part of the inner ear called the stria vascularis, which helps maintain the positive electrical charge in inner ear fluid that certain cells need to detect sound.

The team found the accumulation of cisplatin in the stria vascularis contributed to cisplatin-related hearing loss.

“Our findings suggest that if we can prevent cisplatin from entering the stria vascularis in the inner ear during treatment, we may be able to protect cancer patients from developing cisplatin-induced hearing loss,” Dr Cunningham said.

Image from NIDCD

Researchers have gained new insight into hearing loss caused by cisplatin.

By measuring and mapping cisplatin retention in mouse and human inner ear tissues, the researchers found that cisplatin builds up in the inner ear and can remain there for years.

The team also found that a region in the inner ear called the stria vascularis could be targeted to prevent hearing loss resulting from cisplatin.

Lisa L. Cunningham, PhD, of the National Institute on Deafness and other Communications Disorders (NIDCD) in Bethesda, Maryland, and her colleagues reported these findings in Nature Communications.

The researchers noted that cisplatin can cause permanent hearing loss in 40% to 80% of treated patients. The team’s new findings help explain why.

The researchers found that, in most areas of the body, cisplatin is eliminated within days or weeks of treatment, but, in the inner ear, the drug remains much longer.

The team developed a mouse model that represents cisplatin-induced hearing loss seen in human patients.

By looking at inner ear tissue of mice after the first, second, and third cisplatin treatment, the researchers saw that cisplatin remained in the mouse inner ear much longer than in most other body tissues, and the drug builds up with each successive treatment.

The team also studied inner ear tissue donated by deceased adults who had been treated with cisplatin and found the drug is retained in the inner ear months or years after treatment.

When the researchers examined inner ear tissue from a child, they found cisplatin buildup that was even higher than that seen in adults.

Taken together, these results suggest the inner ear readily takes up cisplatin but has limited ability to remove the drug.

In mice and human tissues, the researchers saw the highest buildup of cisplatin in a part of the inner ear called the stria vascularis, which helps maintain the positive electrical charge in inner ear fluid that certain cells need to detect sound.

The team found the accumulation of cisplatin in the stria vascularis contributed to cisplatin-related hearing loss.

“Our findings suggest that if we can prevent cisplatin from entering the stria vascularis in the inner ear during treatment, we may be able to protect cancer patients from developing cisplatin-induced hearing loss,” Dr Cunningham said.

Image from NIDCD

Researchers have gained new insight into hearing loss caused by cisplatin.

By measuring and mapping cisplatin retention in mouse and human inner ear tissues, the researchers found that cisplatin builds up in the inner ear and can remain there for years.

The team also found that a region in the inner ear called the stria vascularis could be targeted to prevent hearing loss resulting from cisplatin.

Lisa L. Cunningham, PhD, of the National Institute on Deafness and other Communications Disorders (NIDCD) in Bethesda, Maryland, and her colleagues reported these findings in Nature Communications.

The researchers noted that cisplatin can cause permanent hearing loss in 40% to 80% of treated patients. The team’s new findings help explain why.

The researchers found that, in most areas of the body, cisplatin is eliminated within days or weeks of treatment, but, in the inner ear, the drug remains much longer.

The team developed a mouse model that represents cisplatin-induced hearing loss seen in human patients.

By looking at inner ear tissue of mice after the first, second, and third cisplatin treatment, the researchers saw that cisplatin remained in the mouse inner ear much longer than in most other body tissues, and the drug builds up with each successive treatment.

The team also studied inner ear tissue donated by deceased adults who had been treated with cisplatin and found the drug is retained in the inner ear months or years after treatment.

When the researchers examined inner ear tissue from a child, they found cisplatin buildup that was even higher than that seen in adults.

Taken together, these results suggest the inner ear readily takes up cisplatin but has limited ability to remove the drug.

In mice and human tissues, the researchers saw the highest buildup of cisplatin in a part of the inner ear called the stria vascularis, which helps maintain the positive electrical charge in inner ear fluid that certain cells need to detect sound.

The team found the accumulation of cisplatin in the stria vascularis contributed to cisplatin-related hearing loss.

“Our findings suggest that if we can prevent cisplatin from entering the stria vascularis in the inner ear during treatment, we may be able to protect cancer patients from developing cisplatin-induced hearing loss,” Dr Cunningham said.