User login
Abecma Approved for Earlier Lines in Relapsed/Refractory Multiple Myeloma
The approval expands the chimeric antigen receptor (CAR) T-cell therapy’s indications to earlier lines of treatment after exposure to these other main therapy classes, Bristol Myers Squibb said in a press release.
Approval was based on the KarMMa-3 trial, in which 254 patients were randomly assigned to ide-cel and 132 to investigators’ choice of standard regimens, consisting of combinations of daratumumab, dexamethasone, and other agents.
After a median follow-up of 15.9 months, median progression-free survival was three times higher in the ide-cel arm: 13.3 months with the CAR T-cell therapy vs 4.4 months with standard treatment. Overall, 39% of patients on ide-cel had a complete response vs 5% on standard regimens.
The approval includes a new recommended dose range of 300-510 x 106 CAR-positive T cells.
Ide-cel carries a boxed warning for cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, prolonged cytopenia, and secondary hematologic cancers.
In trials, cytokine release syndrome occurred in 89% (310 of 349) of patients in the KarMMa-3 and KarMMa studies, which included grade 3 syndrome in 7% (23 of 349) and fatal cases in 0.9% (3 of 349) of patients.
A one-time treatment is over $500,000, according to drugs.com.
A version of this article appeared on Medscape.com.
The approval expands the chimeric antigen receptor (CAR) T-cell therapy’s indications to earlier lines of treatment after exposure to these other main therapy classes, Bristol Myers Squibb said in a press release.
Approval was based on the KarMMa-3 trial, in which 254 patients were randomly assigned to ide-cel and 132 to investigators’ choice of standard regimens, consisting of combinations of daratumumab, dexamethasone, and other agents.
After a median follow-up of 15.9 months, median progression-free survival was three times higher in the ide-cel arm: 13.3 months with the CAR T-cell therapy vs 4.4 months with standard treatment. Overall, 39% of patients on ide-cel had a complete response vs 5% on standard regimens.
The approval includes a new recommended dose range of 300-510 x 106 CAR-positive T cells.
Ide-cel carries a boxed warning for cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, prolonged cytopenia, and secondary hematologic cancers.
In trials, cytokine release syndrome occurred in 89% (310 of 349) of patients in the KarMMa-3 and KarMMa studies, which included grade 3 syndrome in 7% (23 of 349) and fatal cases in 0.9% (3 of 349) of patients.
A one-time treatment is over $500,000, according to drugs.com.
A version of this article appeared on Medscape.com.
The approval expands the chimeric antigen receptor (CAR) T-cell therapy’s indications to earlier lines of treatment after exposure to these other main therapy classes, Bristol Myers Squibb said in a press release.
Approval was based on the KarMMa-3 trial, in which 254 patients were randomly assigned to ide-cel and 132 to investigators’ choice of standard regimens, consisting of combinations of daratumumab, dexamethasone, and other agents.
After a median follow-up of 15.9 months, median progression-free survival was three times higher in the ide-cel arm: 13.3 months with the CAR T-cell therapy vs 4.4 months with standard treatment. Overall, 39% of patients on ide-cel had a complete response vs 5% on standard regimens.
The approval includes a new recommended dose range of 300-510 x 106 CAR-positive T cells.
Ide-cel carries a boxed warning for cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, prolonged cytopenia, and secondary hematologic cancers.
In trials, cytokine release syndrome occurred in 89% (310 of 349) of patients in the KarMMa-3 and KarMMa studies, which included grade 3 syndrome in 7% (23 of 349) and fatal cases in 0.9% (3 of 349) of patients.
A one-time treatment is over $500,000, according to drugs.com.
A version of this article appeared on Medscape.com.
Eliminating H pylori Lowers CRC Incidence, Mortality Risk
TOPLINE:
METHODOLOGY:
- H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
- Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
- To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
- Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.
TAKEAWAY:
- H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
- Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
- Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
- Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.
IN PRACTICE:
“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”
SOURCE:
The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.
LIMITATIONS:
The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.
DISCLOSURES:
The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
- Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
- To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
- Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.
TAKEAWAY:
- H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
- Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
- Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
- Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.
IN PRACTICE:
“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”
SOURCE:
The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.
LIMITATIONS:
The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.
DISCLOSURES:
The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
- Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
- To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
- Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.
TAKEAWAY:
- H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
- Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
- Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
- Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.
IN PRACTICE:
“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”
SOURCE:
The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.
LIMITATIONS:
The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.
DISCLOSURES:
The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.
A version of this article appeared on Medscape.com.
Polygenic Risk Scores Improve Breast Cancer Screening
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
FDA OKs Danicopan Add-On for Extravascular Hemolysis in Adults With PNH
PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.
Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.
Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.
Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.
Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.
Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.
Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.
A version of this article appeared on Medscape.com.
PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.
Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.
Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.
Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.
Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.
Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.
Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.
A version of this article appeared on Medscape.com.
PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.
Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.
Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.
Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.
Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.
Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.
Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.
A version of this article appeared on Medscape.com.
Upfront Low-Dose Radiation Improves Advanced SCLC Outcomes
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ELCC 2024
FDA Approves Ponatinib for Upfront Ph+ ALL
The approval makes the third-generation tyrosine kinase inhibitor (TKI) the first targeted treatment approved for upfront use in adults with Ph+ ALL, Takeda said in a press release.
Ponatinib was previously approved as monotherapy for Ph+ ALL when no other kinase inhibitors are indicated or for T315I-positive Ph+ ALL, as well as for chronic myeloid leukemia.
Approval for the new indication was based on the PhALLCON trial. In the trial, 245 patients were randomized 2:1 to either ponatinib 30 mg once daily or the first-generation TKI imatinib (Gleevec, Novartis) 600 mg once daily on a chemotherapy background consisting of three cycles of vincristine/dexamethasone induction, six cycles methotrexate/cytarabine consolidation, and 11 cycles of vincristine/prednisone maintenance.
At the end of induction, 12% of patients in the imatinib arm vs 30% in the ponatinib group were in complete remission with no minimal residual disease. Event-free survival data are not yet mature.
At the 2023 American Society of Clinical Oncology annual meeting, an investigator on the trial said that ponatinib plus low-intensity chemotherapy has the potential to become the new standard of care for upfront Ph+ All. However, continued approval for the new indication may depend on trials confirming clinical benefit, Takeda said.
Ponatinib carries a boxed warning of arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity.
The most common adverse reactions reported in the PhALLCON trial were hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily until the end of induction, dropping down to 15 mg once daily in patients who go into remission with no minimal residual disease after induction, for up to 20 cycles or until loss of response or unacceptable toxicity.
Thirty tablets of 30 mg or 15 mg cost $21,944.54, according to Drugs.com.
A version of this article appeared on Medscape.com.
The approval makes the third-generation tyrosine kinase inhibitor (TKI) the first targeted treatment approved for upfront use in adults with Ph+ ALL, Takeda said in a press release.
Ponatinib was previously approved as monotherapy for Ph+ ALL when no other kinase inhibitors are indicated or for T315I-positive Ph+ ALL, as well as for chronic myeloid leukemia.
Approval for the new indication was based on the PhALLCON trial. In the trial, 245 patients were randomized 2:1 to either ponatinib 30 mg once daily or the first-generation TKI imatinib (Gleevec, Novartis) 600 mg once daily on a chemotherapy background consisting of three cycles of vincristine/dexamethasone induction, six cycles methotrexate/cytarabine consolidation, and 11 cycles of vincristine/prednisone maintenance.
At the end of induction, 12% of patients in the imatinib arm vs 30% in the ponatinib group were in complete remission with no minimal residual disease. Event-free survival data are not yet mature.
At the 2023 American Society of Clinical Oncology annual meeting, an investigator on the trial said that ponatinib plus low-intensity chemotherapy has the potential to become the new standard of care for upfront Ph+ All. However, continued approval for the new indication may depend on trials confirming clinical benefit, Takeda said.
Ponatinib carries a boxed warning of arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity.
The most common adverse reactions reported in the PhALLCON trial were hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily until the end of induction, dropping down to 15 mg once daily in patients who go into remission with no minimal residual disease after induction, for up to 20 cycles or until loss of response or unacceptable toxicity.
Thirty tablets of 30 mg or 15 mg cost $21,944.54, according to Drugs.com.
A version of this article appeared on Medscape.com.
The approval makes the third-generation tyrosine kinase inhibitor (TKI) the first targeted treatment approved for upfront use in adults with Ph+ ALL, Takeda said in a press release.
Ponatinib was previously approved as monotherapy for Ph+ ALL when no other kinase inhibitors are indicated or for T315I-positive Ph+ ALL, as well as for chronic myeloid leukemia.
Approval for the new indication was based on the PhALLCON trial. In the trial, 245 patients were randomized 2:1 to either ponatinib 30 mg once daily or the first-generation TKI imatinib (Gleevec, Novartis) 600 mg once daily on a chemotherapy background consisting of three cycles of vincristine/dexamethasone induction, six cycles methotrexate/cytarabine consolidation, and 11 cycles of vincristine/prednisone maintenance.
At the end of induction, 12% of patients in the imatinib arm vs 30% in the ponatinib group were in complete remission with no minimal residual disease. Event-free survival data are not yet mature.
At the 2023 American Society of Clinical Oncology annual meeting, an investigator on the trial said that ponatinib plus low-intensity chemotherapy has the potential to become the new standard of care for upfront Ph+ All. However, continued approval for the new indication may depend on trials confirming clinical benefit, Takeda said.
Ponatinib carries a boxed warning of arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity.
The most common adverse reactions reported in the PhALLCON trial were hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily until the end of induction, dropping down to 15 mg once daily in patients who go into remission with no minimal residual disease after induction, for up to 20 cycles or until loss of response or unacceptable toxicity.
Thirty tablets of 30 mg or 15 mg cost $21,944.54, according to Drugs.com.
A version of this article appeared on Medscape.com.
Zanubrutinib Label Expands to Include RR Follicular Lymphoma
Approval was based on the ROSEWOOD trial, which included 217 adults with relapsed or refractory follicular lymphoma randomized 2:1 to obinutuzumab plus zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity or to obinutuzumab alone. Participants had a median of three prior lines of treatment and as many as 11.
The overall response rate was 69% with zanubrutinib add-on vs 46% with stand-alone obinutuzumab (P = .0012). After a median follow-up of 19 months, the median duration of response was 14 months with obinutuzumab alone but not reached in the combination arm and estimated to be 69% at 18 months.
Across clinical trials, the most common adverse events with zanubrutinib were decreased neutrophil counts (51%), decreased platelet counts (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Serious adverse reactions occurred in 35% of patients.
The recommended zanubrutinib dose is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.
Previously approved indications for the kinase inhibitor include mantle cell lymphoma, Waldenström’s macroglobulinemia, chronic lymphocytic leukemia, and small lymphocytic lymphoma.
According to drugs.com, 120 80-mg capsules cost $15,874.
A version of this article appeared on Medscape.com .
Approval was based on the ROSEWOOD trial, which included 217 adults with relapsed or refractory follicular lymphoma randomized 2:1 to obinutuzumab plus zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity or to obinutuzumab alone. Participants had a median of three prior lines of treatment and as many as 11.
The overall response rate was 69% with zanubrutinib add-on vs 46% with stand-alone obinutuzumab (P = .0012). After a median follow-up of 19 months, the median duration of response was 14 months with obinutuzumab alone but not reached in the combination arm and estimated to be 69% at 18 months.
Across clinical trials, the most common adverse events with zanubrutinib were decreased neutrophil counts (51%), decreased platelet counts (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Serious adverse reactions occurred in 35% of patients.
The recommended zanubrutinib dose is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.
Previously approved indications for the kinase inhibitor include mantle cell lymphoma, Waldenström’s macroglobulinemia, chronic lymphocytic leukemia, and small lymphocytic lymphoma.
According to drugs.com, 120 80-mg capsules cost $15,874.
A version of this article appeared on Medscape.com .
Approval was based on the ROSEWOOD trial, which included 217 adults with relapsed or refractory follicular lymphoma randomized 2:1 to obinutuzumab plus zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity or to obinutuzumab alone. Participants had a median of three prior lines of treatment and as many as 11.
The overall response rate was 69% with zanubrutinib add-on vs 46% with stand-alone obinutuzumab (P = .0012). After a median follow-up of 19 months, the median duration of response was 14 months with obinutuzumab alone but not reached in the combination arm and estimated to be 69% at 18 months.
Across clinical trials, the most common adverse events with zanubrutinib were decreased neutrophil counts (51%), decreased platelet counts (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Serious adverse reactions occurred in 35% of patients.
The recommended zanubrutinib dose is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.
Previously approved indications for the kinase inhibitor include mantle cell lymphoma, Waldenström’s macroglobulinemia, chronic lymphocytic leukemia, and small lymphocytic lymphoma.
According to drugs.com, 120 80-mg capsules cost $15,874.
A version of this article appeared on Medscape.com .
Nivolumab Wins First-Line Indication in Metastatic Urothelial Carcinoma
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Pfizer Antibody-Drug Conjugate Picks Up Pediatric ALL Indication
The CD22-directed antibody and cytotoxic drug conjugate was previously approved only for adults with the condition.
Pediatric approval was based on a single-arm study of 53 children, of whom 12 were treated with an initial dose of 1.4 mg/m2 per cycle and the rest with an initial dose of 1.8 mg/m2 per cycle for a median of two cycles and a range of one to four cycles.
Premedications included methylprednisolone plus an antipyretic and antihistamine.
Overall, 22 children (42%) had a complete remission, defined as < 5% blasts in the bone marrow, no leukemia blasts in peripheral blood, full recovery of peripheral blood counts, and resolution of extramedullary disease. The median duration of complete remission was 8.2 months.
All but one child who went into complete remission (95.5%) had no minimal residual disease (MRD) by flow cytometry, and 19 (86.4%) were MRD negative by real-time quantitative polymerase chain reaction.
Adverse events in ≥ 20% of participants included thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
The antibody-drug conjugate carries a black box warning of hepatotoxicity, including hepatic veno-occlusive and post-hematopoietic stem cell transplant mortality.
The initial recommended dose is 1.8 mg/m2 per cycle, divided into 0.8 mg/m2 on day 1, followed by 0.5 mg/m2 on day 9 and 0.5 mg/m2 on day 15. The initial 3-week cycle can be extended to 4 weeks for patients who have a complete remission or a complete remission with incomplete hematologic recovery and/or to recover from toxicities.
According to drugs.com, 0.9 mg costs $23,423.47.
A version of this article appeared on Medscape.com.
The CD22-directed antibody and cytotoxic drug conjugate was previously approved only for adults with the condition.
Pediatric approval was based on a single-arm study of 53 children, of whom 12 were treated with an initial dose of 1.4 mg/m2 per cycle and the rest with an initial dose of 1.8 mg/m2 per cycle for a median of two cycles and a range of one to four cycles.
Premedications included methylprednisolone plus an antipyretic and antihistamine.
Overall, 22 children (42%) had a complete remission, defined as < 5% blasts in the bone marrow, no leukemia blasts in peripheral blood, full recovery of peripheral blood counts, and resolution of extramedullary disease. The median duration of complete remission was 8.2 months.
All but one child who went into complete remission (95.5%) had no minimal residual disease (MRD) by flow cytometry, and 19 (86.4%) were MRD negative by real-time quantitative polymerase chain reaction.
Adverse events in ≥ 20% of participants included thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
The antibody-drug conjugate carries a black box warning of hepatotoxicity, including hepatic veno-occlusive and post-hematopoietic stem cell transplant mortality.
The initial recommended dose is 1.8 mg/m2 per cycle, divided into 0.8 mg/m2 on day 1, followed by 0.5 mg/m2 on day 9 and 0.5 mg/m2 on day 15. The initial 3-week cycle can be extended to 4 weeks for patients who have a complete remission or a complete remission with incomplete hematologic recovery and/or to recover from toxicities.
According to drugs.com, 0.9 mg costs $23,423.47.
A version of this article appeared on Medscape.com.
The CD22-directed antibody and cytotoxic drug conjugate was previously approved only for adults with the condition.
Pediatric approval was based on a single-arm study of 53 children, of whom 12 were treated with an initial dose of 1.4 mg/m2 per cycle and the rest with an initial dose of 1.8 mg/m2 per cycle for a median of two cycles and a range of one to four cycles.
Premedications included methylprednisolone plus an antipyretic and antihistamine.
Overall, 22 children (42%) had a complete remission, defined as < 5% blasts in the bone marrow, no leukemia blasts in peripheral blood, full recovery of peripheral blood counts, and resolution of extramedullary disease. The median duration of complete remission was 8.2 months.
All but one child who went into complete remission (95.5%) had no minimal residual disease (MRD) by flow cytometry, and 19 (86.4%) were MRD negative by real-time quantitative polymerase chain reaction.
Adverse events in ≥ 20% of participants included thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
The antibody-drug conjugate carries a black box warning of hepatotoxicity, including hepatic veno-occlusive and post-hematopoietic stem cell transplant mortality.
The initial recommended dose is 1.8 mg/m2 per cycle, divided into 0.8 mg/m2 on day 1, followed by 0.5 mg/m2 on day 9 and 0.5 mg/m2 on day 15. The initial 3-week cycle can be extended to 4 weeks for patients who have a complete remission or a complete remission with incomplete hematologic recovery and/or to recover from toxicities.
According to drugs.com, 0.9 mg costs $23,423.47.
A version of this article appeared on Medscape.com.
Doxorubicin Increases Breast Cancer Risk in Women With Hodgkin Lymphoma
TOPLINE:
METHODOLOGY:
- Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
- Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
- To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
- Patients had survived for at least 5 years, and 57% received doxorubicin.
TAKEAWAY:
- Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
- The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
- The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
- After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.
IN PRACTICE:
The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.
SOURCE:
The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology.
LIMITATIONS:
Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.
DISCLOSURES:
The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
- Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
- To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
- Patients had survived for at least 5 years, and 57% received doxorubicin.
TAKEAWAY:
- Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
- The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
- The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
- After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.
IN PRACTICE:
The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.
SOURCE:
The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology.
LIMITATIONS:
Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.
DISCLOSURES:
The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
- Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
- To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
- Patients had survived for at least 5 years, and 57% received doxorubicin.
TAKEAWAY:
- Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
- The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
- The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
- After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.
IN PRACTICE:
The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.
SOURCE:
The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology.
LIMITATIONS:
Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.
DISCLOSURES:
The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
A version of this article appeared on Medscape.com.