M. Alexander Otto

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

The U.S. Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer.

The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy.

Patients with BCG-unresponsive disease “have historically had limited treatment options other than bladder removal surgery. The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option,” Steven Boorjian, MD, a Mayo Clinic urologist and lead investigator on that agent’s approval trial, said in a press release Dec. 16 from gene therapy developer Ferring Pharmaceuticals.

Nadofaragene firadenovec is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein.

Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

The most common adverse events were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to adverse events was 1.9%.

Ferring expects the gene therapy to be commercially available in the United States in the second half of 2023.

The cost of the gene therapy has not yet been announced, but a cost effectiveness analysis from the Institute for Clinical and Economic Review, published last year, put the range for the annual cost between $158,600 and $262,000.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer.

The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy.

Patients with BCG-unresponsive disease “have historically had limited treatment options other than bladder removal surgery. The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option,” Steven Boorjian, MD, a Mayo Clinic urologist and lead investigator on that agent’s approval trial, said in a press release Dec. 16 from gene therapy developer Ferring Pharmaceuticals.

Nadofaragene firadenovec is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein.

Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

The most common adverse events were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to adverse events was 1.9%.

Ferring expects the gene therapy to be commercially available in the United States in the second half of 2023.

The cost of the gene therapy has not yet been announced, but a cost effectiveness analysis from the Institute for Clinical and Economic Review, published last year, put the range for the annual cost between $158,600 and $262,000.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved nadofaragene firadenovec-vncg (Adstiladrin), the first gene therapy for adults with bladder cancer.

The adenovirus vector based gene therapy is indicated for adults with high-risk non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors who are unresponsive to Bacillus Calmette-Guérin (BCG) therapy.

Patients with BCG-unresponsive disease “have historically had limited treatment options other than bladder removal surgery. The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option,” Steven Boorjian, MD, a Mayo Clinic urologist and lead investigator on that agent’s approval trial, said in a press release Dec. 16 from gene therapy developer Ferring Pharmaceuticals.

Nadofaragene firadenovec is instilled into the bladder via urinary catheter once every 3 months for up to a year. The adenovirus vector enters the cells of the bladder wall, releasing a gene that directs the cells to secrete high quantities of interferon alfa-2b, a naturally occurring cancer-fighting protein.

Approval was based on a multicenter clinical study that included 98 evaluable patients with high-risk, BCG-unresponsive disease. Overall, 51% achieved a complete response with a disappearance of all signs of cancer on cystoscopy, biopsied tissue, and urine. The median duration of response was 9.7 months. Overall, 46% of responding patients remained in complete response for at least 1 year.

The most common adverse events were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to adverse events was 1.9%.

Ferring expects the gene therapy to be commercially available in the United States in the second half of 2023.

The cost of the gene therapy has not yet been announced, but a cost effectiveness analysis from the Institute for Clinical and Economic Review, published last year, put the range for the annual cost between $158,600 and $262,000.

A version of this article first appeared on Medscape.com.

Nearly 90% of beta-thalassemia patients were transfusion free for up to 8 years after treatment with the one-time gene therapy betibeglogene autotemcel (beti-cel), according to a report at the American Society of Hematology annual meeting.

Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.

The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.

The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.

The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.

As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.

“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.

Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.

The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.

As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.

When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.

There were also improvements on various quality of life scales, including in physical functioning and mental health.

Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.

On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.

As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.

No malignancies, insertional oncogenesis, or lentivirus replication have been observed.

The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.

Nearly 90% of beta-thalassemia patients were transfusion free for up to 8 years after treatment with the one-time gene therapy betibeglogene autotemcel (beti-cel), according to a report at the American Society of Hematology annual meeting.

Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.

The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.

The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.

The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.

As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.

“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.

Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.

The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.

As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.

When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.

There were also improvements on various quality of life scales, including in physical functioning and mental health.

Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.

On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.

As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.

No malignancies, insertional oncogenesis, or lentivirus replication have been observed.

The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.

Nearly 90% of beta-thalassemia patients were transfusion free for up to 8 years after treatment with the one-time gene therapy betibeglogene autotemcel (beti-cel), according to a report at the American Society of Hematology annual meeting.

Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.

The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.

The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.

The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.

As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.

“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.

Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.

The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.

As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.

When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.

There were also improvements on various quality of life scales, including in physical functioning and mental health.

Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.

On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.

As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.

No malignancies, insertional oncogenesis, or lentivirus replication have been observed.

The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.

Non-European ancestry is a risk factor for receiving the “most complex” bone marrow transplantations, and this factor is related to socioeconomic status, according to a report presented at the American Society of Hematology annual meeting.

There is “an intersectionality between ancestry and socioeconomic status and an association with donor type, with the most vulnerable patients” – those of non-European ancestry with low socioeconomic status (SES), especially people of African ancestry – “receiving the most complex [i.e., human leukocyte antigen (HLA)–disparate] transplants,” said lead investigator Warren Fingrut, MD, a research fellow in the Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center, New York.

“Successful extension of transplant access to minority patients will be contingent on addressing [their] financial hardship,” said Dr. Fingrut, who presented the findings at the meeting.

To better channel support services and ensure that resources are available, he also noted that centers will have to do a better job of identifying patients with financial struggles.

“Household income data is not collected at our center, and neither is it collected at most centers,” hence assessments of SES are based on imperfect surrogates, such as neighborhood poverty by zip code. “Interventions to advance equity will require better SES classifications or detailed recording of household income,” Dr. Fingrut said.

Overall, the study highlights “inequities in the delivery of stem cell transplants,” pointing to opportunities “to improve access to this potentially curative treatment,” said hematologist/oncologist Chancellor Donald, MD, of Tulane University, New Orleans, who moderated the study presentation.

Dr. Donald said that the new research shows “how interactions between racial backgrounds and socioeconomic status relate to the type of allogenic stem cell transplant patients receive.” The team “identified that [people] of non-European ancestry and especially those of low SES, are more likely to receive the most specialized type of allogeneic stem cell transplantation, which notably require the highest level of care,” Dr. Donald said.

The investigators reviewed 372 consecutive adults transplanted at MSKCC from March 2020 to February 2022, mostly for myeloid malignancies.

Thirty-one percent of patients had non-European ancestry, including 11% of African, 9% of Asian, and 8% of White Hispanic descent.

With no information about household income, the team used neighborhood poverty (which affected 5% of patients); Medicaid as the primary insurance (6% of patients), and financial support for living and medical expenses (19%) as surrogates of lower SES. Classification depended largely on what criteria were used, with only 20 patients meeting two criteria and only one patient meeting all three.

Overall, more than half (58%) of non-European ancestry patients received HLA-disparate grafts, compared with 24% of people with European ancestry, including 48% of White Hispanic patients, 58% of Asian patients, and 78% of patients of African decent.

Markers of lower SES were more common among non-European patients. For instance, among people of European ancestry, 4% were on Medicaid and 15% were on financial aid, versus 10% on Medicaid and 29% on financial support among people of other ancestries. Medicaid use (12.5%) and financial aid (42.5%) were highest among patients of African descent.

Among patients who received HLA-disparate grafts, patients of non-European descent were three times more likely to be on Medicaid (12% versus 4%) and more than twice as likely to be on financial support (33% versus 15%).

People of African ancestry who received HLA-disparate grafts had the highest proportions of Medicaid reliance (16%) and financial support (45%).

Non-European ancestry is a risk factor for receiving the “most complex” bone marrow transplantations, and this factor is related to socioeconomic status, according to a report presented at the American Society of Hematology annual meeting.

There is “an intersectionality between ancestry and socioeconomic status and an association with donor type, with the most vulnerable patients” – those of non-European ancestry with low socioeconomic status (SES), especially people of African ancestry – “receiving the most complex [i.e., human leukocyte antigen (HLA)–disparate] transplants,” said lead investigator Warren Fingrut, MD, a research fellow in the Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center, New York.

“Successful extension of transplant access to minority patients will be contingent on addressing [their] financial hardship,” said Dr. Fingrut, who presented the findings at the meeting.

To better channel support services and ensure that resources are available, he also noted that centers will have to do a better job of identifying patients with financial struggles.

“Household income data is not collected at our center, and neither is it collected at most centers,” hence assessments of SES are based on imperfect surrogates, such as neighborhood poverty by zip code. “Interventions to advance equity will require better SES classifications or detailed recording of household income,” Dr. Fingrut said.

Overall, the study highlights “inequities in the delivery of stem cell transplants,” pointing to opportunities “to improve access to this potentially curative treatment,” said hematologist/oncologist Chancellor Donald, MD, of Tulane University, New Orleans, who moderated the study presentation.

Dr. Donald said that the new research shows “how interactions between racial backgrounds and socioeconomic status relate to the type of allogenic stem cell transplant patients receive.” The team “identified that [people] of non-European ancestry and especially those of low SES, are more likely to receive the most specialized type of allogeneic stem cell transplantation, which notably require the highest level of care,” Dr. Donald said.

The investigators reviewed 372 consecutive adults transplanted at MSKCC from March 2020 to February 2022, mostly for myeloid malignancies.

Thirty-one percent of patients had non-European ancestry, including 11% of African, 9% of Asian, and 8% of White Hispanic descent.

With no information about household income, the team used neighborhood poverty (which affected 5% of patients); Medicaid as the primary insurance (6% of patients), and financial support for living and medical expenses (19%) as surrogates of lower SES. Classification depended largely on what criteria were used, with only 20 patients meeting two criteria and only one patient meeting all three.

Overall, more than half (58%) of non-European ancestry patients received HLA-disparate grafts, compared with 24% of people with European ancestry, including 48% of White Hispanic patients, 58% of Asian patients, and 78% of patients of African decent.

Markers of lower SES were more common among non-European patients. For instance, among people of European ancestry, 4% were on Medicaid and 15% were on financial aid, versus 10% on Medicaid and 29% on financial support among people of other ancestries. Medicaid use (12.5%) and financial aid (42.5%) were highest among patients of African descent.

Among patients who received HLA-disparate grafts, patients of non-European descent were three times more likely to be on Medicaid (12% versus 4%) and more than twice as likely to be on financial support (33% versus 15%).

People of African ancestry who received HLA-disparate grafts had the highest proportions of Medicaid reliance (16%) and financial support (45%).

Non-European ancestry is a risk factor for receiving the “most complex” bone marrow transplantations, and this factor is related to socioeconomic status, according to a report presented at the American Society of Hematology annual meeting.

There is “an intersectionality between ancestry and socioeconomic status and an association with donor type, with the most vulnerable patients” – those of non-European ancestry with low socioeconomic status (SES), especially people of African ancestry – “receiving the most complex [i.e., human leukocyte antigen (HLA)–disparate] transplants,” said lead investigator Warren Fingrut, MD, a research fellow in the Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center, New York.

“Successful extension of transplant access to minority patients will be contingent on addressing [their] financial hardship,” said Dr. Fingrut, who presented the findings at the meeting.

To better channel support services and ensure that resources are available, he also noted that centers will have to do a better job of identifying patients with financial struggles.

“Household income data is not collected at our center, and neither is it collected at most centers,” hence assessments of SES are based on imperfect surrogates, such as neighborhood poverty by zip code. “Interventions to advance equity will require better SES classifications or detailed recording of household income,” Dr. Fingrut said.

Overall, the study highlights “inequities in the delivery of stem cell transplants,” pointing to opportunities “to improve access to this potentially curative treatment,” said hematologist/oncologist Chancellor Donald, MD, of Tulane University, New Orleans, who moderated the study presentation.

Dr. Donald said that the new research shows “how interactions between racial backgrounds and socioeconomic status relate to the type of allogenic stem cell transplant patients receive.” The team “identified that [people] of non-European ancestry and especially those of low SES, are more likely to receive the most specialized type of allogeneic stem cell transplantation, which notably require the highest level of care,” Dr. Donald said.

The investigators reviewed 372 consecutive adults transplanted at MSKCC from March 2020 to February 2022, mostly for myeloid malignancies.

Thirty-one percent of patients had non-European ancestry, including 11% of African, 9% of Asian, and 8% of White Hispanic descent.

With no information about household income, the team used neighborhood poverty (which affected 5% of patients); Medicaid as the primary insurance (6% of patients), and financial support for living and medical expenses (19%) as surrogates of lower SES. Classification depended largely on what criteria were used, with only 20 patients meeting two criteria and only one patient meeting all three.

Overall, more than half (58%) of non-European ancestry patients received HLA-disparate grafts, compared with 24% of people with European ancestry, including 48% of White Hispanic patients, 58% of Asian patients, and 78% of patients of African decent.

Markers of lower SES were more common among non-European patients. For instance, among people of European ancestry, 4% were on Medicaid and 15% were on financial aid, versus 10% on Medicaid and 29% on financial support among people of other ancestries. Medicaid use (12.5%) and financial aid (42.5%) were highest among patients of African descent.

Among patients who received HLA-disparate grafts, patients of non-European descent were three times more likely to be on Medicaid (12% versus 4%) and more than twice as likely to be on financial support (33% versus 15%).

People of African ancestry who received HLA-disparate grafts had the highest proportions of Medicaid reliance (16%) and financial support (45%).

The U.S. Food and Drug Administration has approved etranacogene dezaparvovec (Hemgenix), the first gene therapy option for adults with hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.*

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.

The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.

Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.

Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.

Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.

Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.

The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.

Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.

This article was updated 11/23/22.

Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.

The U.S. Food and Drug Administration has approved etranacogene dezaparvovec (Hemgenix), the first gene therapy option for adults with hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.*

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.

The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.

Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.

Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.

Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.

Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.

The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.

Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.

This article was updated 11/23/22.

Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.

The U.S. Food and Drug Administration has approved etranacogene dezaparvovec (Hemgenix), the first gene therapy option for adults with hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.*

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.

The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.

Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.

Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.

Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.

Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.

The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.

Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.

This article was updated 11/23/22.

Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.

The Food and Drug Administration has granted accelerated approval to mirvetuximab soravtansine (Elahere) for use in pretreated patients with folate receptor (FR) alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancer. These patients can have received one to three prior lines of treatment.

“Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial,” according to labeling.

Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) with an antibody directed against FR alpha that is linked to a microtubule inhibitor conjugate.

This product is a first-in-class ADC directed against FR alpha, a cell-surface protein highly expressed in ovarian cancer, and is the first FDA-approved ADC for platinum-resistant disease, said the manufacturer, ImmunoGen.

Patients are selected for treatment with this drug using a diagnostic test that the FDA approved along with the agent: the VENTANA FOLR1 (FOLR-2.1) RxDx Assay.

FR alpha–positive platinum-resistant ovarian cancer is characterized by limited treatment options and poor outcomes, commented Ursula Matulonis, MD, chief of the division of gynecologic oncology at the Dana-Farber Cancer Institute, Boston, and co–principal investigator of the SORAYA trial that led to the approval. In a company press release, she said results from this trial show that mirvetuximab soravtansine has “impressive antitumor activity, durability of response, and overall tolerability ... [which] demonstrate the benefit of this new therapeutic option.”

The SORAYA trial (also known as Study 0417 [NCT04296890]) was a single-arm trial of 106 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

These patients were identified as FR alpha positive by using the assay. They were permitted to receive up to three prior lines of systemic therapy, and all patients were required to have received bevacizumab.

All patients received mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.

The approval was based on an investigator-assessed overall response rate of 31.7%, which included five complete responses, and a median duration of response of 6.9 months.

Safety was evaluated in a pooled analysis from three studies among a total of 464 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received at least one dose of the drug.

The most common adverse events, occurring in 20% or more of study participants, were vision impairment, fatigue, increased AST level, nausea, increased alanine aminotransferase level, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase level, dry eye, decreased magnesium level, decreased leukocyte count, decreased neutrophil count, and decreased hemoglobin level.

Potential participants were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, peripheral neuropathy above grade 1, or noninfectious interstitial lung disease.

The product labeling contains a boxed warning of ocular toxicity. Full prescribing information is available.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to mirvetuximab soravtansine (Elahere) for use in pretreated patients with folate receptor (FR) alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancer. These patients can have received one to three prior lines of treatment.

“Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial,” according to labeling.

Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) with an antibody directed against FR alpha that is linked to a microtubule inhibitor conjugate.

This product is a first-in-class ADC directed against FR alpha, a cell-surface protein highly expressed in ovarian cancer, and is the first FDA-approved ADC for platinum-resistant disease, said the manufacturer, ImmunoGen.

Patients are selected for treatment with this drug using a diagnostic test that the FDA approved along with the agent: the VENTANA FOLR1 (FOLR-2.1) RxDx Assay.

FR alpha–positive platinum-resistant ovarian cancer is characterized by limited treatment options and poor outcomes, commented Ursula Matulonis, MD, chief of the division of gynecologic oncology at the Dana-Farber Cancer Institute, Boston, and co–principal investigator of the SORAYA trial that led to the approval. In a company press release, she said results from this trial show that mirvetuximab soravtansine has “impressive antitumor activity, durability of response, and overall tolerability ... [which] demonstrate the benefit of this new therapeutic option.”

The SORAYA trial (also known as Study 0417 [NCT04296890]) was a single-arm trial of 106 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

These patients were identified as FR alpha positive by using the assay. They were permitted to receive up to three prior lines of systemic therapy, and all patients were required to have received bevacizumab.

All patients received mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.

The approval was based on an investigator-assessed overall response rate of 31.7%, which included five complete responses, and a median duration of response of 6.9 months.

Safety was evaluated in a pooled analysis from three studies among a total of 464 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received at least one dose of the drug.

The most common adverse events, occurring in 20% or more of study participants, were vision impairment, fatigue, increased AST level, nausea, increased alanine aminotransferase level, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase level, dry eye, decreased magnesium level, decreased leukocyte count, decreased neutrophil count, and decreased hemoglobin level.

Potential participants were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, peripheral neuropathy above grade 1, or noninfectious interstitial lung disease.

The product labeling contains a boxed warning of ocular toxicity. Full prescribing information is available.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to mirvetuximab soravtansine (Elahere) for use in pretreated patients with folate receptor (FR) alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancer. These patients can have received one to three prior lines of treatment.

“Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial,” according to labeling.

Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) with an antibody directed against FR alpha that is linked to a microtubule inhibitor conjugate.

This product is a first-in-class ADC directed against FR alpha, a cell-surface protein highly expressed in ovarian cancer, and is the first FDA-approved ADC for platinum-resistant disease, said the manufacturer, ImmunoGen.

Patients are selected for treatment with this drug using a diagnostic test that the FDA approved along with the agent: the VENTANA FOLR1 (FOLR-2.1) RxDx Assay.

FR alpha–positive platinum-resistant ovarian cancer is characterized by limited treatment options and poor outcomes, commented Ursula Matulonis, MD, chief of the division of gynecologic oncology at the Dana-Farber Cancer Institute, Boston, and co–principal investigator of the SORAYA trial that led to the approval. In a company press release, she said results from this trial show that mirvetuximab soravtansine has “impressive antitumor activity, durability of response, and overall tolerability ... [which] demonstrate the benefit of this new therapeutic option.”

The SORAYA trial (also known as Study 0417 [NCT04296890]) was a single-arm trial of 106 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

These patients were identified as FR alpha positive by using the assay. They were permitted to receive up to three prior lines of systemic therapy, and all patients were required to have received bevacizumab.

All patients received mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.

The approval was based on an investigator-assessed overall response rate of 31.7%, which included five complete responses, and a median duration of response of 6.9 months.

Safety was evaluated in a pooled analysis from three studies among a total of 464 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received at least one dose of the drug.

The most common adverse events, occurring in 20% or more of study participants, were vision impairment, fatigue, increased AST level, nausea, increased alanine aminotransferase level, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase level, dry eye, decreased magnesium level, decreased leukocyte count, decreased neutrophil count, and decreased hemoglobin level.

Potential participants were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, peripheral neuropathy above grade 1, or noninfectious interstitial lung disease.

The product labeling contains a boxed warning of ocular toxicity. Full prescribing information is available.

A version of this article first appeared on Medscape.com.

The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

The hemophilia A treatment paradigm has shifted away from simply maintaining a prophylaxis trough level of 1% towards a focus on patient outcomes and leading healthy, active lives, according to a recent report in The Journal of Medicine in Life.

To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.

“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.

The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.

They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.

About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.

However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.

“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.

There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.

The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.

“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.

In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.

For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.

Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.

Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.

The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.

Just about every patient-reported outcome favors adding immunotherapy to standard chemotherapy for patients with metastatic non-small cell lung cancer, according to an analysis presented at the annual European Lung Cancer Congress (ELCC) on March 30.

“Overall, it is very clear that chemotherapy plus immunotherapy prolongs the time to symptom deterioration and actually improves symptoms” in this patient population, said study discussant Luis Paz-Ares, MD, PhD, chair of medical oncology at the Hospital Universitario 12 de Octubre, Madrid, who was not involved in the research.

Last September, investigators reported efficacy outcomes from the phase 3 POSEIDON trial, which randomized 1,013 patients with EGFR/ALK wild-type mNSCLC to one of three first-line options: chemotherapy alone, chemotherapy plus the checkpoint inhibitor durvalumab, or chemotherapy plus two check-point inhibitors, durvalumab and tremelimumab. The analysis showed improved progression-free survival in both immunotherapy arms as well as a significant 2.3-month overall survival advantage with dual immunotherapy and a nonsignificant 1.6-month advantage with single agent durvalumab.

At the ELCC meeting, study presenter and lead investigator Edward Garon, MD, reported the latest data on the trial’s secondary endpoints: patient-reported outcomes. Global health status, functioning, and symptom scores were assessed using two questionnaires, the EORTC QLQ-C30 and EORTC QLQ-LC13.

Overall, Dr. Garon and colleagues reported a longer time to deterioration in all three areas – global health status, functioning, and symptoms – for patients who received immunotherapy versus chemotherapy alone, with similar results in both immunotherapy arms.

Time to deterioration in global health status, for instance, was a median of about 8 months on both immunotherapy regimens versus 5.6 months with chemotherapy alone. The positive findings held for many patient-reported treatment side effects, including dyspnea, hemoptysis, nausea/vomiting, and insomnia, but the benefits of adding immunotherapy weren’t always statistically significant.

Adding one or both checkpoint inhibitors to chemotherapy “improved efficacy while delaying deterioration in symptoms, functioning, and [health-related quality of life] versus chemotherapy alone in patients with mNSCLC,” concluded Dr. Garon, a thoracic medical oncologist at the University of California, Los Angeles. Plus, he added, “the pattern was observed across nearly all prespecified symptoms and domains of interest.”

According to study discussant Dr. Paz-Ares, “the data seem to be very consistent with all the trials asking similar questions.” The important thing here is figuring out the ideal candidates for dual inhibitor therapy, he said.

With positive efficacy and patient-reported outcomes for single and dual immunotherapy in this trial, it’s a “relatively straightforward” decision to add immunotherapy to chemotherapy for patients with mNSCLC, Massimo Di Maio, a medical oncologist at the University of Turin, Italy, said in an editorial on the ELCC’s news site.

However, that’s not always the case for every cancer type, which makes patient-reported outcomes “crucial” for determining the right treatment for each patient. Some might opt for a modest survival benefit regardless of the side effects, while others might favor a less toxic approach, even it means not living quite as long, he said.

The problem, he stressed, is that trials often release efficacy data well before patient-reported outcomes, which makes weighing the benefits and risks of a treat-ment option more difficult. The delay between efficacy and patient-reported outcome data was about 6 months in the POSEIDON trial.

“Timing is key when it comes to using [patient reported outcomes] for decision-making in oncology,” Dr. Di Maio said. “In fact, to enable a full assessment of a treatment, results should be published concurrently with the efficacy and safety data. Unfortunately, this is generally not the case.”

POSEIDON was funded by AstraZeneca, which markets durvalumab and is developing tremelimumab. Dr. Garon reported grants from the company. Dr. Paz-Ares reported honoraria and institutional research grants from AstraZeneca. Dr. Di Maio is a consultant for AstraZeneca and reported receiving honoraria and personal fees from the company.

Just about every patient-reported outcome favors adding immunotherapy to standard chemotherapy for patients with metastatic non-small cell lung cancer, according to an analysis presented at the annual European Lung Cancer Congress (ELCC) on March 30.

“Overall, it is very clear that chemotherapy plus immunotherapy prolongs the time to symptom deterioration and actually improves symptoms” in this patient population, said study discussant Luis Paz-Ares, MD, PhD, chair of medical oncology at the Hospital Universitario 12 de Octubre, Madrid, who was not involved in the research.

Last September, investigators reported efficacy outcomes from the phase 3 POSEIDON trial, which randomized 1,013 patients with EGFR/ALK wild-type mNSCLC to one of three first-line options: chemotherapy alone, chemotherapy plus the checkpoint inhibitor durvalumab, or chemotherapy plus two check-point inhibitors, durvalumab and tremelimumab. The analysis showed improved progression-free survival in both immunotherapy arms as well as a significant 2.3-month overall survival advantage with dual immunotherapy and a nonsignificant 1.6-month advantage with single agent durvalumab.

At the ELCC meeting, study presenter and lead investigator Edward Garon, MD, reported the latest data on the trial’s secondary endpoints: patient-reported outcomes. Global health status, functioning, and symptom scores were assessed using two questionnaires, the EORTC QLQ-C30 and EORTC QLQ-LC13.

Overall, Dr. Garon and colleagues reported a longer time to deterioration in all three areas – global health status, functioning, and symptoms – for patients who received immunotherapy versus chemotherapy alone, with similar results in both immunotherapy arms.

Time to deterioration in global health status, for instance, was a median of about 8 months on both immunotherapy regimens versus 5.6 months with chemotherapy alone. The positive findings held for many patient-reported treatment side effects, including dyspnea, hemoptysis, nausea/vomiting, and insomnia, but the benefits of adding immunotherapy weren’t always statistically significant.

Adding one or both checkpoint inhibitors to chemotherapy “improved efficacy while delaying deterioration in symptoms, functioning, and [health-related quality of life] versus chemotherapy alone in patients with mNSCLC,” concluded Dr. Garon, a thoracic medical oncologist at the University of California, Los Angeles. Plus, he added, “the pattern was observed across nearly all prespecified symptoms and domains of interest.”

According to study discussant Dr. Paz-Ares, “the data seem to be very consistent with all the trials asking similar questions.” The important thing here is figuring out the ideal candidates for dual inhibitor therapy, he said.

With positive efficacy and patient-reported outcomes for single and dual immunotherapy in this trial, it’s a “relatively straightforward” decision to add immunotherapy to chemotherapy for patients with mNSCLC, Massimo Di Maio, a medical oncologist at the University of Turin, Italy, said in an editorial on the ELCC’s news site.

However, that’s not always the case for every cancer type, which makes patient-reported outcomes “crucial” for determining the right treatment for each patient. Some might opt for a modest survival benefit regardless of the side effects, while others might favor a less toxic approach, even it means not living quite as long, he said.

The problem, he stressed, is that trials often release efficacy data well before patient-reported outcomes, which makes weighing the benefits and risks of a treat-ment option more difficult. The delay between efficacy and patient-reported outcome data was about 6 months in the POSEIDON trial.

“Timing is key when it comes to using [patient reported outcomes] for decision-making in oncology,” Dr. Di Maio said. “In fact, to enable a full assessment of a treatment, results should be published concurrently with the efficacy and safety data. Unfortunately, this is generally not the case.”

POSEIDON was funded by AstraZeneca, which markets durvalumab and is developing tremelimumab. Dr. Garon reported grants from the company. Dr. Paz-Ares reported honoraria and institutional research grants from AstraZeneca. Dr. Di Maio is a consultant for AstraZeneca and reported receiving honoraria and personal fees from the company.

Just about every patient-reported outcome favors adding immunotherapy to standard chemotherapy for patients with metastatic non-small cell lung cancer, according to an analysis presented at the annual European Lung Cancer Congress (ELCC) on March 30.

“Overall, it is very clear that chemotherapy plus immunotherapy prolongs the time to symptom deterioration and actually improves symptoms” in this patient population, said study discussant Luis Paz-Ares, MD, PhD, chair of medical oncology at the Hospital Universitario 12 de Octubre, Madrid, who was not involved in the research.

Last September, investigators reported efficacy outcomes from the phase 3 POSEIDON trial, which randomized 1,013 patients with EGFR/ALK wild-type mNSCLC to one of three first-line options: chemotherapy alone, chemotherapy plus the checkpoint inhibitor durvalumab, or chemotherapy plus two check-point inhibitors, durvalumab and tremelimumab. The analysis showed improved progression-free survival in both immunotherapy arms as well as a significant 2.3-month overall survival advantage with dual immunotherapy and a nonsignificant 1.6-month advantage with single agent durvalumab.

At the ELCC meeting, study presenter and lead investigator Edward Garon, MD, reported the latest data on the trial’s secondary endpoints: patient-reported outcomes. Global health status, functioning, and symptom scores were assessed using two questionnaires, the EORTC QLQ-C30 and EORTC QLQ-LC13.

Overall, Dr. Garon and colleagues reported a longer time to deterioration in all three areas – global health status, functioning, and symptoms – for patients who received immunotherapy versus chemotherapy alone, with similar results in both immunotherapy arms.

Time to deterioration in global health status, for instance, was a median of about 8 months on both immunotherapy regimens versus 5.6 months with chemotherapy alone. The positive findings held for many patient-reported treatment side effects, including dyspnea, hemoptysis, nausea/vomiting, and insomnia, but the benefits of adding immunotherapy weren’t always statistically significant.

Adding one or both checkpoint inhibitors to chemotherapy “improved efficacy while delaying deterioration in symptoms, functioning, and [health-related quality of life] versus chemotherapy alone in patients with mNSCLC,” concluded Dr. Garon, a thoracic medical oncologist at the University of California, Los Angeles. Plus, he added, “the pattern was observed across nearly all prespecified symptoms and domains of interest.”

According to study discussant Dr. Paz-Ares, “the data seem to be very consistent with all the trials asking similar questions.” The important thing here is figuring out the ideal candidates for dual inhibitor therapy, he said.

With positive efficacy and patient-reported outcomes for single and dual immunotherapy in this trial, it’s a “relatively straightforward” decision to add immunotherapy to chemotherapy for patients with mNSCLC, Massimo Di Maio, a medical oncologist at the University of Turin, Italy, said in an editorial on the ELCC’s news site.

However, that’s not always the case for every cancer type, which makes patient-reported outcomes “crucial” for determining the right treatment for each patient. Some might opt for a modest survival benefit regardless of the side effects, while others might favor a less toxic approach, even it means not living quite as long, he said.

The problem, he stressed, is that trials often release efficacy data well before patient-reported outcomes, which makes weighing the benefits and risks of a treat-ment option more difficult. The delay between efficacy and patient-reported outcome data was about 6 months in the POSEIDON trial.

“Timing is key when it comes to using [patient reported outcomes] for decision-making in oncology,” Dr. Di Maio said. “In fact, to enable a full assessment of a treatment, results should be published concurrently with the efficacy and safety data. Unfortunately, this is generally not the case.”

POSEIDON was funded by AstraZeneca, which markets durvalumab and is developing tremelimumab. Dr. Garon reported grants from the company. Dr. Paz-Ares reported honoraria and institutional research grants from AstraZeneca. Dr. Di Maio is a consultant for AstraZeneca and reported receiving honoraria and personal fees from the company.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.