Hodgkin Lymphoma

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.)
  

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.)
  

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.

Photo courtesy of ASH

ATLANTA—Phase 3 trial results suggest one 4-drug combination may be more effective than another as frontline treatment for advanced Hodgkin lymphoma (HL).

In the ECHELON-1 trial, treatment with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) staved off progression, death, and the need for subsequent therapy more effectively than treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

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

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

These data were presented at the 2017 ASH Annual Meeting (abstract 6) and simultaneously published in The New England Journal of Medicine. The trial was funded by Millennium Pharmaceuticals and Seattle Genetics, Inc.

“The standard of care in the treatment of Hodgkin lymphoma has not changed over the last several decades, and there remains an unmet need for additional regimens in frontline treatment,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

With this in mind, he and his colleagues conducted ECHELON-1. The study enrolled 1334 patients who had stage III or IV HL and had not previously received systemic chemotherapy or radiotherapy.

Fifty-eight percent of patients were male, and the median age was 36 (range, 18-83). Sixty-four percent of patients had stage IV disease, 62% had extranodal involvement at diagnosis, and 58% had B symptoms.

The patients were randomized to receive A+AVD (n=664) or ABVD (n=670) on days 1 and 15 of each 28-day cycle for up to 6 cycles. Baseline characteristics were well-balanced between the treatment arms.

The median follow-up was 24.9 months (range, 0-49.3).

Primary endpoint

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

“Reducing the risk of relapse is an important concern for patients and their physicians,” Dr Connors noted. “In the trial, 33% fewer patients [in the A+AVD arm] required subsequent salvage chemotherapy or high-dose chemotherapy and transplant compared to the patients treated with ABVD.”

According to the independent review facility, the 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

Certain pre-specified subgroups of patients appeared to benefit more with A+AVD than with ABVD, including:

• Males
• Patients treated in North America
• Patients with involvement of more than 1 extranodal site
• Patients with International Prognostic Scores of 4 to 7
• Patients with stage IV disease
• Patients younger than 60.

Secondary endpoints

Secondary endpoints trended in favor of the A+AVD arm, although there were no significant differences between the treatment arms.

The objective response rate at the end of the randomized regimen 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 proportion of patients with a Deauville score ≤2 after the completion of frontline therapy was 85% in the A+AVD arm and 80% in the ABVD arm (P=0.03).

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).

Safety

“[T]he safety profile [of A+AVD] was generally consistent with that known for the single-agent components of the regimen,” Dr Connors said.

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.

Common AEs (in the A+AVD and ABVD arms, respectively) included neutropenia (58% and 45%), constipation (42% and 37%), vomiting (33% and 28%), fatigue (both 32%), diarrhea (27% and 18%), pyrexia (27% and 22%), abdominal pain (21% and 10%), and stomatitis (21% and 16%).

Peripheral neuropathy events were observed in 67% of patients in the A+AVD arm and 43% in the ABVD arm. Grade 3 or higher peripheral neuropathy was reported in 11% and 2%, respectively.

Febrile neutropenia occurred in 19% of patients in the A+AVD arm and 8% of those in the ABVD arm. However, prophylaxis with granulocyte colony-stimulating factor (G-CSF) was able to reduce the incidence of febrile neutropenia. In the A+AVD arm, the rate of febrile neutropenia was 11% among patients who received G-CSF and 21% among patients who did not.

Pulmonary toxicity occurred in 2% of patients in the A+AVD arm and 7% of those in the ABVD arm. Grade 3 or higher pulmonary toxicity was reported in 0.76% and 3%, respectively.

There were 9 deaths during treatment in the A+AVD arm. Seven were due to neutropenia or associated complications, and 2 were due to myocardial infarction. One of the patients who died of neutropenia had the condition prior to trial enrollment. The remaining 6 patients did not receive G-CSF prophylaxis.

In the ABVD arm, there were 13 deaths during treatment. Eleven were due to or associated with pulmonary-related toxicity, 1 was due to cardiopulmonary failure, and 1 death had an unknown cause.

Photo courtesy of ASH

ATLANTA—Phase 3 trial results suggest one 4-drug combination may be more effective than another as frontline treatment for advanced Hodgkin lymphoma (HL).

In the ECHELON-1 trial, treatment with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) staved off progression, death, and the need for subsequent therapy more effectively than treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

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

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

These data were presented at the 2017 ASH Annual Meeting (abstract 6) and simultaneously published in The New England Journal of Medicine. The trial was funded by Millennium Pharmaceuticals and Seattle Genetics, Inc.

“The standard of care in the treatment of Hodgkin lymphoma has not changed over the last several decades, and there remains an unmet need for additional regimens in frontline treatment,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

With this in mind, he and his colleagues conducted ECHELON-1. The study enrolled 1334 patients who had stage III or IV HL and had not previously received systemic chemotherapy or radiotherapy.

Fifty-eight percent of patients were male, and the median age was 36 (range, 18-83). Sixty-four percent of patients had stage IV disease, 62% had extranodal involvement at diagnosis, and 58% had B symptoms.

The patients were randomized to receive A+AVD (n=664) or ABVD (n=670) on days 1 and 15 of each 28-day cycle for up to 6 cycles. Baseline characteristics were well-balanced between the treatment arms.

The median follow-up was 24.9 months (range, 0-49.3).

Primary endpoint

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

“Reducing the risk of relapse is an important concern for patients and their physicians,” Dr Connors noted. “In the trial, 33% fewer patients [in the A+AVD arm] required subsequent salvage chemotherapy or high-dose chemotherapy and transplant compared to the patients treated with ABVD.”

According to the independent review facility, the 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

Certain pre-specified subgroups of patients appeared to benefit more with A+AVD than with ABVD, including:

• Males
• Patients treated in North America
• Patients with involvement of more than 1 extranodal site
• Patients with International Prognostic Scores of 4 to 7
• Patients with stage IV disease
• Patients younger than 60.

Secondary endpoints

Secondary endpoints trended in favor of the A+AVD arm, although there were no significant differences between the treatment arms.

The objective response rate at the end of the randomized regimen 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 proportion of patients with a Deauville score ≤2 after the completion of frontline therapy was 85% in the A+AVD arm and 80% in the ABVD arm (P=0.03).

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).

Safety

“[T]he safety profile [of A+AVD] was generally consistent with that known for the single-agent components of the regimen,” Dr Connors said.

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.

Common AEs (in the A+AVD and ABVD arms, respectively) included neutropenia (58% and 45%), constipation (42% and 37%), vomiting (33% and 28%), fatigue (both 32%), diarrhea (27% and 18%), pyrexia (27% and 22%), abdominal pain (21% and 10%), and stomatitis (21% and 16%).

Peripheral neuropathy events were observed in 67% of patients in the A+AVD arm and 43% in the ABVD arm. Grade 3 or higher peripheral neuropathy was reported in 11% and 2%, respectively.

Febrile neutropenia occurred in 19% of patients in the A+AVD arm and 8% of those in the ABVD arm. However, prophylaxis with granulocyte colony-stimulating factor (G-CSF) was able to reduce the incidence of febrile neutropenia. In the A+AVD arm, the rate of febrile neutropenia was 11% among patients who received G-CSF and 21% among patients who did not.

Pulmonary toxicity occurred in 2% of patients in the A+AVD arm and 7% of those in the ABVD arm. Grade 3 or higher pulmonary toxicity was reported in 0.76% and 3%, respectively.

There were 9 deaths during treatment in the A+AVD arm. Seven were due to neutropenia or associated complications, and 2 were due to myocardial infarction. One of the patients who died of neutropenia had the condition prior to trial enrollment. The remaining 6 patients did not receive G-CSF prophylaxis.

In the ABVD arm, there were 13 deaths during treatment. Eleven were due to or associated with pulmonary-related toxicity, 1 was due to cardiopulmonary failure, and 1 death had an unknown cause.

Photo courtesy of ASH

ATLANTA—Phase 3 trial results suggest one 4-drug combination may be more effective than another as frontline treatment for advanced Hodgkin lymphoma (HL).

In the ECHELON-1 trial, treatment with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) staved off progression, death, and the need for subsequent therapy more effectively than treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

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

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

These data were presented at the 2017 ASH Annual Meeting (abstract 6) and simultaneously published in The New England Journal of Medicine. The trial was funded by Millennium Pharmaceuticals and Seattle Genetics, Inc.

“The standard of care in the treatment of Hodgkin lymphoma has not changed over the last several decades, and there remains an unmet need for additional regimens in frontline treatment,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

With this in mind, he and his colleagues conducted ECHELON-1. The study enrolled 1334 patients who had stage III or IV HL and had not previously received systemic chemotherapy or radiotherapy.

Fifty-eight percent of patients were male, and the median age was 36 (range, 18-83). Sixty-four percent of patients had stage IV disease, 62% had extranodal involvement at diagnosis, and 58% had B symptoms.

The patients were randomized to receive A+AVD (n=664) or ABVD (n=670) on days 1 and 15 of each 28-day cycle for up to 6 cycles. Baseline characteristics were well-balanced between the treatment arms.

The median follow-up was 24.9 months (range, 0-49.3).

Primary endpoint

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

“Reducing the risk of relapse is an important concern for patients and their physicians,” Dr Connors noted. “In the trial, 33% fewer patients [in the A+AVD arm] required subsequent salvage chemotherapy or high-dose chemotherapy and transplant compared to the patients treated with ABVD.”

According to the independent review facility, the 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

Certain pre-specified subgroups of patients appeared to benefit more with A+AVD than with ABVD, including:

• Males
• Patients treated in North America
• Patients with involvement of more than 1 extranodal site
• Patients with International Prognostic Scores of 4 to 7
• Patients with stage IV disease
• Patients younger than 60.

Secondary endpoints

Secondary endpoints trended in favor of the A+AVD arm, although there were no significant differences between the treatment arms.

The objective response rate at the end of the randomized regimen 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 proportion of patients with a Deauville score ≤2 after the completion of frontline therapy was 85% in the A+AVD arm and 80% in the ABVD arm (P=0.03).

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).

Safety

“[T]he safety profile [of A+AVD] was generally consistent with that known for the single-agent components of the regimen,” Dr Connors said.

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.

Common AEs (in the A+AVD and ABVD arms, respectively) included neutropenia (58% and 45%), constipation (42% and 37%), vomiting (33% and 28%), fatigue (both 32%), diarrhea (27% and 18%), pyrexia (27% and 22%), abdominal pain (21% and 10%), and stomatitis (21% and 16%).

Peripheral neuropathy events were observed in 67% of patients in the A+AVD arm and 43% in the ABVD arm. Grade 3 or higher peripheral neuropathy was reported in 11% and 2%, respectively.

Febrile neutropenia occurred in 19% of patients in the A+AVD arm and 8% of those in the ABVD arm. However, prophylaxis with granulocyte colony-stimulating factor (G-CSF) was able to reduce the incidence of febrile neutropenia. In the A+AVD arm, the rate of febrile neutropenia was 11% among patients who received G-CSF and 21% among patients who did not.

Pulmonary toxicity occurred in 2% of patients in the A+AVD arm and 7% of those in the ABVD arm. Grade 3 or higher pulmonary toxicity was reported in 0.76% and 3%, respectively.

There were 9 deaths during treatment in the A+AVD arm. Seven were due to neutropenia or associated complications, and 2 were due to myocardial infarction. One of the patients who died of neutropenia had the condition prior to trial enrollment. The remaining 6 patients did not receive G-CSF prophylaxis.

In the ABVD arm, there were 13 deaths during treatment. Eleven were due to or associated with pulmonary-related toxicity, 1 was due to cardiopulmonary failure, and 1 death had an unknown cause.

Micrograph showing DLBCL

Preclinical research suggests the dual PI3K/mTOR inhibitor PQR309 has activity against several types of lymphoma and works well in combination with other agents.

PQR309 exhibited anti-lymphoma activity as a single agent and in combination with venetoclax, panobinostat, ibrutinib, lenalidomide, ARV-825, marizomib, and rituximab.

PQR309 demonstrated greater activity against B-cell lymphoma than T-cell lymphoma, and the inhibitor was able to overcome both primary and acquired resistance to idelalisib.

Francesco Bertoni, MD, of the Institute of Oncology Research in Bellinzona, Switzerland, and his colleagues conducted this research and reported the results in Clinical Cancer Research.

The work was funded by PIQUR Therapeutics AG, the company developing PQR309, and some study authors are PIQUR employees.

The researchers tested PQR309 in 49 human lymphoma cell lines—7 activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), 18 germinal center B-cell (GCB) DLBCL, 10 mantle cell lymphoma (MCL), 3 splenic marginal zone lymphoma (SMZL), 2 chronic lymphocytic leukemia (CLL), 4 Hodgkin lymphoma, and 5 anaplastic large-cell lymphoma (ALCL).

In most cell lines, PQR309 halted proliferation, mainly due to cell-cycle arrest with a block in G1. However, PQR309 induced apoptosis in 2 cell lines tested—SU-DHL-4 and TMD8.

The researchers noted that PQR309 was significantly more active in the B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell lymphoma cell line ALCL (P=0.028).

PQR309 exhibited similar activity in ABC and GCB DLBCL cell lines, de novo DLBCL, and DLBCL derived from transformed follicular lymphoma. TP53, MYC, and BCL2 status also had no significant effect on PQR309 activity.

The researchers compared cell lines that were very sensitive to PQR309 to those with low sensitivity to the drug and identified differences.

The team said that transcripts preferentially expressed in PQR309-sensitive cell lines were significantly enriched of genes involved in BCR pathway/signaling and BLIMP1 targets. Transcripts associated with less sensitive cell lines were enriched of members of proteasome pathway, response to unfolded proteins, MYC targets, XBP1 targets, genes downregulated by mTOR inhibitors, and genes involved in oxidative phosphorylation.

PQR309 demonstrated synergistic effects when combined with the BTK inhibitor ibrutinib, the immunomodulatory drug lenalidomide, the anti-CD20 monoclonal antibody rituximab, and the proteasome inhibitor marizomib.

PQR309 demonstrated synergistic or additive effects when combined with the BCL2 inhibitor venetoclax, the HDAC inhibitor panobinostat, and the PROTAC BET inhibitor ARV-825.

In addition, PQR309 was active in lymphoma cell lines with primary and secondary resistance to the PI3K inhibitor idelalisib.

The researchers believe the results of this study, together with ongoing clinical studies of PQR309, can lead to better treatments for lymphoma patients and better understanding of the mechanisms of anti-lymphoma agents.

Micrograph showing DLBCL

Preclinical research suggests the dual PI3K/mTOR inhibitor PQR309 has activity against several types of lymphoma and works well in combination with other agents.

PQR309 exhibited anti-lymphoma activity as a single agent and in combination with venetoclax, panobinostat, ibrutinib, lenalidomide, ARV-825, marizomib, and rituximab.

PQR309 demonstrated greater activity against B-cell lymphoma than T-cell lymphoma, and the inhibitor was able to overcome both primary and acquired resistance to idelalisib.

Francesco Bertoni, MD, of the Institute of Oncology Research in Bellinzona, Switzerland, and his colleagues conducted this research and reported the results in Clinical Cancer Research.

The work was funded by PIQUR Therapeutics AG, the company developing PQR309, and some study authors are PIQUR employees.

The researchers tested PQR309 in 49 human lymphoma cell lines—7 activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), 18 germinal center B-cell (GCB) DLBCL, 10 mantle cell lymphoma (MCL), 3 splenic marginal zone lymphoma (SMZL), 2 chronic lymphocytic leukemia (CLL), 4 Hodgkin lymphoma, and 5 anaplastic large-cell lymphoma (ALCL).

In most cell lines, PQR309 halted proliferation, mainly due to cell-cycle arrest with a block in G1. However, PQR309 induced apoptosis in 2 cell lines tested—SU-DHL-4 and TMD8.

The researchers noted that PQR309 was significantly more active in the B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell lymphoma cell line ALCL (P=0.028).

PQR309 exhibited similar activity in ABC and GCB DLBCL cell lines, de novo DLBCL, and DLBCL derived from transformed follicular lymphoma. TP53, MYC, and BCL2 status also had no significant effect on PQR309 activity.

The researchers compared cell lines that were very sensitive to PQR309 to those with low sensitivity to the drug and identified differences.

The team said that transcripts preferentially expressed in PQR309-sensitive cell lines were significantly enriched of genes involved in BCR pathway/signaling and BLIMP1 targets. Transcripts associated with less sensitive cell lines were enriched of members of proteasome pathway, response to unfolded proteins, MYC targets, XBP1 targets, genes downregulated by mTOR inhibitors, and genes involved in oxidative phosphorylation.

PQR309 demonstrated synergistic effects when combined with the BTK inhibitor ibrutinib, the immunomodulatory drug lenalidomide, the anti-CD20 monoclonal antibody rituximab, and the proteasome inhibitor marizomib.

PQR309 demonstrated synergistic or additive effects when combined with the BCL2 inhibitor venetoclax, the HDAC inhibitor panobinostat, and the PROTAC BET inhibitor ARV-825.

In addition, PQR309 was active in lymphoma cell lines with primary and secondary resistance to the PI3K inhibitor idelalisib.

The researchers believe the results of this study, together with ongoing clinical studies of PQR309, can lead to better treatments for lymphoma patients and better understanding of the mechanisms of anti-lymphoma agents.

Micrograph showing DLBCL

Preclinical research suggests the dual PI3K/mTOR inhibitor PQR309 has activity against several types of lymphoma and works well in combination with other agents.

PQR309 exhibited anti-lymphoma activity as a single agent and in combination with venetoclax, panobinostat, ibrutinib, lenalidomide, ARV-825, marizomib, and rituximab.

PQR309 demonstrated greater activity against B-cell lymphoma than T-cell lymphoma, and the inhibitor was able to overcome both primary and acquired resistance to idelalisib.

Francesco Bertoni, MD, of the Institute of Oncology Research in Bellinzona, Switzerland, and his colleagues conducted this research and reported the results in Clinical Cancer Research.

The work was funded by PIQUR Therapeutics AG, the company developing PQR309, and some study authors are PIQUR employees.

The researchers tested PQR309 in 49 human lymphoma cell lines—7 activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), 18 germinal center B-cell (GCB) DLBCL, 10 mantle cell lymphoma (MCL), 3 splenic marginal zone lymphoma (SMZL), 2 chronic lymphocytic leukemia (CLL), 4 Hodgkin lymphoma, and 5 anaplastic large-cell lymphoma (ALCL).

In most cell lines, PQR309 halted proliferation, mainly due to cell-cycle arrest with a block in G1. However, PQR309 induced apoptosis in 2 cell lines tested—SU-DHL-4 and TMD8.

The researchers noted that PQR309 was significantly more active in the B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell lymphoma cell line ALCL (P=0.028).

PQR309 exhibited similar activity in ABC and GCB DLBCL cell lines, de novo DLBCL, and DLBCL derived from transformed follicular lymphoma. TP53, MYC, and BCL2 status also had no significant effect on PQR309 activity.

The researchers compared cell lines that were very sensitive to PQR309 to those with low sensitivity to the drug and identified differences.

The team said that transcripts preferentially expressed in PQR309-sensitive cell lines were significantly enriched of genes involved in BCR pathway/signaling and BLIMP1 targets. Transcripts associated with less sensitive cell lines were enriched of members of proteasome pathway, response to unfolded proteins, MYC targets, XBP1 targets, genes downregulated by mTOR inhibitors, and genes involved in oxidative phosphorylation.

PQR309 demonstrated synergistic effects when combined with the BTK inhibitor ibrutinib, the immunomodulatory drug lenalidomide, the anti-CD20 monoclonal antibody rituximab, and the proteasome inhibitor marizomib.

PQR309 demonstrated synergistic or additive effects when combined with the BCL2 inhibitor venetoclax, the HDAC inhibitor panobinostat, and the PROTAC BET inhibitor ARV-825.

In addition, PQR309 was active in lymphoma cell lines with primary and secondary resistance to the PI3K inhibitor idelalisib.

The researchers believe the results of this study, together with ongoing clinical studies of PQR309, can lead to better treatments for lymphoma patients and better understanding of the mechanisms of anti-lymphoma agents.

Photo from NIH

A study of childhood cancer survivors (CCSs) suggests these individuals have an increased risk of developing hypertension as adults.

The CCSs studied had more than double the rate of hypertension observed in the matched general population.

Sex, age, race, and weight were all significantly associated with hypertension among CCSs, but most treatment types were not.

The exception was nephrectomy, which was associated with an increased risk of hypertension.

Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported the results in Cancer Epidemiology, Biomarkers & Prevention.

“High blood pressure is an important modifiable risk factor that increases the risk of heart problems in everyone,” Dr Gibson said. “Research has shown that high blood pressure can have an even greater negative impact on survivors of childhood cancer who were treated with cardiotoxic therapies such as anthracyclines or chest radiation.”

To assess the prevalence of hypertension among CCSs, Dr Gibson and his colleagues examined 3016 adults who were 10-year survivors of childhood cancers. The subjects were enrolled in the St. Jude Lifetime Cohort Study, which provides ongoing medical assessments of CCSs to advance knowledge of their long-term health outcomes.

The subjects’ mean age at the initial study assessment was 32, and 52% were male. Most (83%) were non-Hispanic white, 14% were non-Hispanic black, 2% were Hispanic, and 1% were “other.”

Thirty-seven percent of subjects had leukemia, 12% had Hodgkin lymphoma, and 7% had non-Hodgkin lymphoma.

Eighty-six percent of subjects had received chemotherapy, and 59% received radiation.

Results

Subjects were considered to have hypertension if their systolic blood pressure was 140 or greater, their diastolic blood pressure was 90 or greater, or if they had been previously diagnosed with hypertension and were taking antihypertensive medication.

The prevalence of hypertension was 2.6 times higher among CCSs than expected, based on age-, sex-, race- and body mass index-specific rates in the general population.

In addition, the incidence of hypertension increased for CCSs over time. Thirteen percent of CCSs had hypertension at age 30, 37% had it at age 40, and more than 70% had it at age 50.

Dr Gibson said rates of hypertension in CCSs matched rates in the general population of people about a decade older.

The researchers identified several factors that were significantly associated with hypertension among CCSs, including:

• Male sex (odd ratio [OR], 1.38; 95% CI, 1.14–1.67)
• Non-Hispanic black race (OR, 1.66; 95% CI, 1.28–2.16)
• Older age at assessment (OR per 1 year of age, 1.10; 95% CI, 1.08–1.11)
• Being overweight (OR, 1.58; 95% CI, 1.21–2.07)
• Obesity (OR, 3.02; 95% CI, 2.34–3.88).

Exposure to any type of radiation or chemotherapy was not significantly associated with hypertension, but nephrectomy was (OR, 1.68; 95% CI, 1.11–2.53).

Dr Gibson said the lack of an association between hypertension and radiation/chemotherapy was surprising. It suggests the connection between childhood cancer survival and adult hypertension is multifactorial and worthy of future research.

In the meantime, he said, clinicians should be mindful that CCSs are more likely than the general public to develop hypertension.

“The good news is that, unlike prior cancer therapy, high blood pressure is a modifiable risk factor,” Dr Gibson noted. “Research is needed to identify effective interventions to prevent hypertension in survivors, but our results emphasize the importance of blood pressure surveillance and management.”

Dr Gibson said a limitation of this study is that it was based on blood pressure measurements taken at a single study visit. A clinical diagnosis of hypertension typically requires measurements taken at multiple intervals.

In addition, the St. Jude Lifetime Cohort is a group of CCSs who undergo frequent clinical follow-up, so its participants may have benefited from being monitored and may therefore be in better health than CCSs who have less comprehensive follow-up.

Photo from NIH

A study of childhood cancer survivors (CCSs) suggests these individuals have an increased risk of developing hypertension as adults.

The CCSs studied had more than double the rate of hypertension observed in the matched general population.

Sex, age, race, and weight were all significantly associated with hypertension among CCSs, but most treatment types were not.

The exception was nephrectomy, which was associated with an increased risk of hypertension.

Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported the results in Cancer Epidemiology, Biomarkers & Prevention.

“High blood pressure is an important modifiable risk factor that increases the risk of heart problems in everyone,” Dr Gibson said. “Research has shown that high blood pressure can have an even greater negative impact on survivors of childhood cancer who were treated with cardiotoxic therapies such as anthracyclines or chest radiation.”

To assess the prevalence of hypertension among CCSs, Dr Gibson and his colleagues examined 3016 adults who were 10-year survivors of childhood cancers. The subjects were enrolled in the St. Jude Lifetime Cohort Study, which provides ongoing medical assessments of CCSs to advance knowledge of their long-term health outcomes.

The subjects’ mean age at the initial study assessment was 32, and 52% were male. Most (83%) were non-Hispanic white, 14% were non-Hispanic black, 2% were Hispanic, and 1% were “other.”

Thirty-seven percent of subjects had leukemia, 12% had Hodgkin lymphoma, and 7% had non-Hodgkin lymphoma.

Eighty-six percent of subjects had received chemotherapy, and 59% received radiation.

Results

Subjects were considered to have hypertension if their systolic blood pressure was 140 or greater, their diastolic blood pressure was 90 or greater, or if they had been previously diagnosed with hypertension and were taking antihypertensive medication.

The prevalence of hypertension was 2.6 times higher among CCSs than expected, based on age-, sex-, race- and body mass index-specific rates in the general population.

In addition, the incidence of hypertension increased for CCSs over time. Thirteen percent of CCSs had hypertension at age 30, 37% had it at age 40, and more than 70% had it at age 50.

Dr Gibson said rates of hypertension in CCSs matched rates in the general population of people about a decade older.

The researchers identified several factors that were significantly associated with hypertension among CCSs, including:

• Male sex (odd ratio [OR], 1.38; 95% CI, 1.14–1.67)
• Non-Hispanic black race (OR, 1.66; 95% CI, 1.28–2.16)
• Older age at assessment (OR per 1 year of age, 1.10; 95% CI, 1.08–1.11)
• Being overweight (OR, 1.58; 95% CI, 1.21–2.07)
• Obesity (OR, 3.02; 95% CI, 2.34–3.88).

Exposure to any type of radiation or chemotherapy was not significantly associated with hypertension, but nephrectomy was (OR, 1.68; 95% CI, 1.11–2.53).

Dr Gibson said the lack of an association between hypertension and radiation/chemotherapy was surprising. It suggests the connection between childhood cancer survival and adult hypertension is multifactorial and worthy of future research.

In the meantime, he said, clinicians should be mindful that CCSs are more likely than the general public to develop hypertension.

“The good news is that, unlike prior cancer therapy, high blood pressure is a modifiable risk factor,” Dr Gibson noted. “Research is needed to identify effective interventions to prevent hypertension in survivors, but our results emphasize the importance of blood pressure surveillance and management.”

Dr Gibson said a limitation of this study is that it was based on blood pressure measurements taken at a single study visit. A clinical diagnosis of hypertension typically requires measurements taken at multiple intervals.

In addition, the St. Jude Lifetime Cohort is a group of CCSs who undergo frequent clinical follow-up, so its participants may have benefited from being monitored and may therefore be in better health than CCSs who have less comprehensive follow-up.

Photo from NIH

A study of childhood cancer survivors (CCSs) suggests these individuals have an increased risk of developing hypertension as adults.

The CCSs studied had more than double the rate of hypertension observed in the matched general population.

Sex, age, race, and weight were all significantly associated with hypertension among CCSs, but most treatment types were not.

The exception was nephrectomy, which was associated with an increased risk of hypertension.

Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported the results in Cancer Epidemiology, Biomarkers & Prevention.

“High blood pressure is an important modifiable risk factor that increases the risk of heart problems in everyone,” Dr Gibson said. “Research has shown that high blood pressure can have an even greater negative impact on survivors of childhood cancer who were treated with cardiotoxic therapies such as anthracyclines or chest radiation.”

To assess the prevalence of hypertension among CCSs, Dr Gibson and his colleagues examined 3016 adults who were 10-year survivors of childhood cancers. The subjects were enrolled in the St. Jude Lifetime Cohort Study, which provides ongoing medical assessments of CCSs to advance knowledge of their long-term health outcomes.

The subjects’ mean age at the initial study assessment was 32, and 52% were male. Most (83%) were non-Hispanic white, 14% were non-Hispanic black, 2% were Hispanic, and 1% were “other.”

Thirty-seven percent of subjects had leukemia, 12% had Hodgkin lymphoma, and 7% had non-Hodgkin lymphoma.

Eighty-six percent of subjects had received chemotherapy, and 59% received radiation.

Results

Subjects were considered to have hypertension if their systolic blood pressure was 140 or greater, their diastolic blood pressure was 90 or greater, or if they had been previously diagnosed with hypertension and were taking antihypertensive medication.

The prevalence of hypertension was 2.6 times higher among CCSs than expected, based on age-, sex-, race- and body mass index-specific rates in the general population.

In addition, the incidence of hypertension increased for CCSs over time. Thirteen percent of CCSs had hypertension at age 30, 37% had it at age 40, and more than 70% had it at age 50.

Dr Gibson said rates of hypertension in CCSs matched rates in the general population of people about a decade older.

The researchers identified several factors that were significantly associated with hypertension among CCSs, including:

• Male sex (odd ratio [OR], 1.38; 95% CI, 1.14–1.67)
• Non-Hispanic black race (OR, 1.66; 95% CI, 1.28–2.16)
• Older age at assessment (OR per 1 year of age, 1.10; 95% CI, 1.08–1.11)
• Being overweight (OR, 1.58; 95% CI, 1.21–2.07)
• Obesity (OR, 3.02; 95% CI, 2.34–3.88).

Exposure to any type of radiation or chemotherapy was not significantly associated with hypertension, but nephrectomy was (OR, 1.68; 95% CI, 1.11–2.53).

Dr Gibson said the lack of an association between hypertension and radiation/chemotherapy was surprising. It suggests the connection between childhood cancer survival and adult hypertension is multifactorial and worthy of future research.

In the meantime, he said, clinicians should be mindful that CCSs are more likely than the general public to develop hypertension.

“The good news is that, unlike prior cancer therapy, high blood pressure is a modifiable risk factor,” Dr Gibson noted. “Research is needed to identify effective interventions to prevent hypertension in survivors, but our results emphasize the importance of blood pressure surveillance and management.”

Dr Gibson said a limitation of this study is that it was based on blood pressure measurements taken at a single study visit. A clinical diagnosis of hypertension typically requires measurements taken at multiple intervals.

In addition, the St. Jude Lifetime Cohort is a group of CCSs who undergo frequent clinical follow-up, so its participants may have benefited from being monitored and may therefore be in better health than CCSs who have less comprehensive follow-up.

SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.

Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).

juststock

[email protected]

On Twitter @karioakes

*Correction 11/14/17: An earlier version of this article misstated the P values.

SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.

Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).

juststock

[email protected]

On Twitter @karioakes

*Correction 11/14/17: An earlier version of this article misstated the P values.

SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.

Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).

juststock

[email protected]

On Twitter @karioakes

*Correction 11/14/17: An earlier version of this article misstated the P values.