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Jennifer Smith is the editor of Oncology Practice, part of MDedge Hematology/Oncology. She was previously the editor of Hematology Times, an editor at Principal Investigators Association, and a reporter at The Oneida Daily Dispatch. She has a BS in journalism.
Blood banking experts nab leadership positions at AABB
Beth Shaz, MD, has started her term as president of AABB (formerly the American Association of Blood Banks). Dr. Shaz, who will be president for the 2019-2020 term, was inaugurated during the 2019 AABB annual meeting. She succeeds Michael Murphy, MD, as president.
Dr. Shaz is the executive vice president and chief medical and scientific officer at the New York Blood Center in New York. She is a scientific member of Biomedical Excellence for Safer Transfusion, an associate editor of Transfusion, and an editorial board member of Blood. She received her medical degree from University of Michigan in Ann Arbor and a bachelor’s degree in chemical engineering from Cornell University in Ithaca, N.Y.
AABB also has a new president-elect, David Green. Mr. Green is president and chief executive officer of Vitalant, and he is based in Scottsdale, Ariz. Mr. Green previously led the Vitalant blood services division. Before that, he was president and chief executive officer of Mississippi Valley Regional Blood Center in Davenport, Iowa.
Mr. Green has served as chairman of Blood Centers of America and president of America’s Blood Centers. He earned a bachelor’s degree from Knox College in Gallesburg, Ill., and a master’s degree from Central Michigan University in Mount Pleasant, Mich.
Dana Devine, PhD, is the new vice president of AABB. Dr. Devine is the chief medical and scientific officer at Canadian Blood Services. She is also a professor at the University of British Columbia in Vancouver and a founding member of the university’s Centre for Blood Research.
Dr. Devine’s research is focused on platelet biology, complement biochemistry, coagulation, and blood product processing and storage. Dr. Devine is the editor in chief of Vox Sanguinis. She earned her PhD from Duke University in Durham, N.C.
Steven Sloan, MD, PhD, is the new secretary of AABB. Dr. Sloan is an associate professor at Harvard Medical School in Boston and blood bank medical director at Children’s Hospital Boston.
Dr. Sloan’s research is focused on intracellular signaling and transcription regulation in B cells during immune responses. Dr. Sloan attended medical school at New York University in New York, and completed his residency and fellowship at the Hospital of the University of Pennsylvania in Philadelphia.
Beth Shaz, MD, has started her term as president of AABB (formerly the American Association of Blood Banks). Dr. Shaz, who will be president for the 2019-2020 term, was inaugurated during the 2019 AABB annual meeting. She succeeds Michael Murphy, MD, as president.
Dr. Shaz is the executive vice president and chief medical and scientific officer at the New York Blood Center in New York. She is a scientific member of Biomedical Excellence for Safer Transfusion, an associate editor of Transfusion, and an editorial board member of Blood. She received her medical degree from University of Michigan in Ann Arbor and a bachelor’s degree in chemical engineering from Cornell University in Ithaca, N.Y.
AABB also has a new president-elect, David Green. Mr. Green is president and chief executive officer of Vitalant, and he is based in Scottsdale, Ariz. Mr. Green previously led the Vitalant blood services division. Before that, he was president and chief executive officer of Mississippi Valley Regional Blood Center in Davenport, Iowa.
Mr. Green has served as chairman of Blood Centers of America and president of America’s Blood Centers. He earned a bachelor’s degree from Knox College in Gallesburg, Ill., and a master’s degree from Central Michigan University in Mount Pleasant, Mich.
Dana Devine, PhD, is the new vice president of AABB. Dr. Devine is the chief medical and scientific officer at Canadian Blood Services. She is also a professor at the University of British Columbia in Vancouver and a founding member of the university’s Centre for Blood Research.
Dr. Devine’s research is focused on platelet biology, complement biochemistry, coagulation, and blood product processing and storage. Dr. Devine is the editor in chief of Vox Sanguinis. She earned her PhD from Duke University in Durham, N.C.
Steven Sloan, MD, PhD, is the new secretary of AABB. Dr. Sloan is an associate professor at Harvard Medical School in Boston and blood bank medical director at Children’s Hospital Boston.
Dr. Sloan’s research is focused on intracellular signaling and transcription regulation in B cells during immune responses. Dr. Sloan attended medical school at New York University in New York, and completed his residency and fellowship at the Hospital of the University of Pennsylvania in Philadelphia.
Beth Shaz, MD, has started her term as president of AABB (formerly the American Association of Blood Banks). Dr. Shaz, who will be president for the 2019-2020 term, was inaugurated during the 2019 AABB annual meeting. She succeeds Michael Murphy, MD, as president.
Dr. Shaz is the executive vice president and chief medical and scientific officer at the New York Blood Center in New York. She is a scientific member of Biomedical Excellence for Safer Transfusion, an associate editor of Transfusion, and an editorial board member of Blood. She received her medical degree from University of Michigan in Ann Arbor and a bachelor’s degree in chemical engineering from Cornell University in Ithaca, N.Y.
AABB also has a new president-elect, David Green. Mr. Green is president and chief executive officer of Vitalant, and he is based in Scottsdale, Ariz. Mr. Green previously led the Vitalant blood services division. Before that, he was president and chief executive officer of Mississippi Valley Regional Blood Center in Davenport, Iowa.
Mr. Green has served as chairman of Blood Centers of America and president of America’s Blood Centers. He earned a bachelor’s degree from Knox College in Gallesburg, Ill., and a master’s degree from Central Michigan University in Mount Pleasant, Mich.
Dana Devine, PhD, is the new vice president of AABB. Dr. Devine is the chief medical and scientific officer at Canadian Blood Services. She is also a professor at the University of British Columbia in Vancouver and a founding member of the university’s Centre for Blood Research.
Dr. Devine’s research is focused on platelet biology, complement biochemistry, coagulation, and blood product processing and storage. Dr. Devine is the editor in chief of Vox Sanguinis. She earned her PhD from Duke University in Durham, N.C.
Steven Sloan, MD, PhD, is the new secretary of AABB. Dr. Sloan is an associate professor at Harvard Medical School in Boston and blood bank medical director at Children’s Hospital Boston.
Dr. Sloan’s research is focused on intracellular signaling and transcription regulation in B cells during immune responses. Dr. Sloan attended medical school at New York University in New York, and completed his residency and fellowship at the Hospital of the University of Pennsylvania in Philadelphia.
Macitentan produces similar results in PAH-SSc and IPAH/HPAH
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
REPORTING FROM CHEST 2019
Omalizumab results for asthma varied with fixed airflow obstruction, reversibility
NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
Nicola Hanania, MD, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (NCT00314574). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.869.
NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
Nicola Hanania, MD, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (NCT00314574). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.869.
NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
Nicola Hanania, MD, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (NCT00314574). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.869.
REPORTING FROM CHEST 2019
Macitentan, tadalafil combo found effective for newly diagnosed PAH
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
REPORTING FROM CHEST 2019
Physician-researcher who promoted industry collaboration dies unexpectedly
Thomas Peter Stossel, MD, a physician-researcher known for his discovery of cellular proteins and advocacy for academic-industry relationships, died unexpectedly on Sept. 29 at the age of 78.
Dr. Stossel’s research was largely focused on cell motility. He is known for discovering the cellular proteins filamin and gelsolin, which regulate the assembly of actin. Dr. Stossel is also known for promoting relationships between physicians and industry. He believed these relationships accelerate medical innovation.
Dr. Stossel graduated from Princeton University and Harvard Medical School. He served as chief of the hematology-oncology unit at Massachusetts General Hospital, head of experimental medicine and codirector of the hematology and translational medicine units at Brigham and Women’s Hospital, and a professor at Harvard Medical School. When he died, Dr. Stossel was chief scientific officer of BioAegis Therapeutics, a company he cofounded.
Dr. Stossel also cofounded Options for Children in Zambia, a charity that works with Zambian partners to provide preventive dental and medical care. And he helped establish a sickle cell disease clinical and research center at University Teaching Hospital in Lusaka.
In happier news, Jeff Vacirca, MD, recently won the 2019 American Red Cross Greater New York Region’s Humanitarian Award. Dr. Vacirca received the award at the 2019 Heroes Among Us Gala on Oct. 16.
Dr. Vacirca is chief executive officer of New York Cancer & Blood Specialists. He is also a consulting physician for the Long Island Association for AIDS Care, medical director for AmerisourceBergen specialty group, a scientific advisory board member for Caris Life Sciences, director at OneOncology, director at Spectrum Pharmaceuticals, a medical board adviser for Flatiron Health, and vice-chairman of the board for Odonate Therapeutics, a company he cofounded in 2016. In 2014, Dr. Vacirca founded the New York Cancer Foundation, which provides financial assistance to patients undergoing cancer treatment.
Another award winner is Richard J. Bleicher, MD, who has won the 2020 Jamie Brooke Lieberman Remembrance Award from Susan G. Komen Philadelphia for his work related to breast cancer. Dr. Bleicher is scheduled to receive his award at the Susan G. Komen Philadelphia MORE THAN PINK Walk Kickoff event on March 18, 2020.
Dr. Bleicher is a professor, breast cancer surgeon, and clinical researcher at Fox Chase Cancer Center in Philadelphia. He is director of the breast fellowship and leader of the breast cancer program at Fox Chase. He sits on the board of the National Accreditation Program for Breast Centers and the Quality Improvement Committee, sits on the Commission for Cancer’s Operative Standards Committee, and is the vice-chair for the Society of Surgical Oncology’s breast fellowship programs for the United States and Canada.
Thomas Peter Stossel, MD, a physician-researcher known for his discovery of cellular proteins and advocacy for academic-industry relationships, died unexpectedly on Sept. 29 at the age of 78.
Dr. Stossel’s research was largely focused on cell motility. He is known for discovering the cellular proteins filamin and gelsolin, which regulate the assembly of actin. Dr. Stossel is also known for promoting relationships between physicians and industry. He believed these relationships accelerate medical innovation.
Dr. Stossel graduated from Princeton University and Harvard Medical School. He served as chief of the hematology-oncology unit at Massachusetts General Hospital, head of experimental medicine and codirector of the hematology and translational medicine units at Brigham and Women’s Hospital, and a professor at Harvard Medical School. When he died, Dr. Stossel was chief scientific officer of BioAegis Therapeutics, a company he cofounded.
Dr. Stossel also cofounded Options for Children in Zambia, a charity that works with Zambian partners to provide preventive dental and medical care. And he helped establish a sickle cell disease clinical and research center at University Teaching Hospital in Lusaka.
In happier news, Jeff Vacirca, MD, recently won the 2019 American Red Cross Greater New York Region’s Humanitarian Award. Dr. Vacirca received the award at the 2019 Heroes Among Us Gala on Oct. 16.
Dr. Vacirca is chief executive officer of New York Cancer & Blood Specialists. He is also a consulting physician for the Long Island Association for AIDS Care, medical director for AmerisourceBergen specialty group, a scientific advisory board member for Caris Life Sciences, director at OneOncology, director at Spectrum Pharmaceuticals, a medical board adviser for Flatiron Health, and vice-chairman of the board for Odonate Therapeutics, a company he cofounded in 2016. In 2014, Dr. Vacirca founded the New York Cancer Foundation, which provides financial assistance to patients undergoing cancer treatment.
Another award winner is Richard J. Bleicher, MD, who has won the 2020 Jamie Brooke Lieberman Remembrance Award from Susan G. Komen Philadelphia for his work related to breast cancer. Dr. Bleicher is scheduled to receive his award at the Susan G. Komen Philadelphia MORE THAN PINK Walk Kickoff event on March 18, 2020.
Dr. Bleicher is a professor, breast cancer surgeon, and clinical researcher at Fox Chase Cancer Center in Philadelphia. He is director of the breast fellowship and leader of the breast cancer program at Fox Chase. He sits on the board of the National Accreditation Program for Breast Centers and the Quality Improvement Committee, sits on the Commission for Cancer’s Operative Standards Committee, and is the vice-chair for the Society of Surgical Oncology’s breast fellowship programs for the United States and Canada.
Thomas Peter Stossel, MD, a physician-researcher known for his discovery of cellular proteins and advocacy for academic-industry relationships, died unexpectedly on Sept. 29 at the age of 78.
Dr. Stossel’s research was largely focused on cell motility. He is known for discovering the cellular proteins filamin and gelsolin, which regulate the assembly of actin. Dr. Stossel is also known for promoting relationships between physicians and industry. He believed these relationships accelerate medical innovation.
Dr. Stossel graduated from Princeton University and Harvard Medical School. He served as chief of the hematology-oncology unit at Massachusetts General Hospital, head of experimental medicine and codirector of the hematology and translational medicine units at Brigham and Women’s Hospital, and a professor at Harvard Medical School. When he died, Dr. Stossel was chief scientific officer of BioAegis Therapeutics, a company he cofounded.
Dr. Stossel also cofounded Options for Children in Zambia, a charity that works with Zambian partners to provide preventive dental and medical care. And he helped establish a sickle cell disease clinical and research center at University Teaching Hospital in Lusaka.
In happier news, Jeff Vacirca, MD, recently won the 2019 American Red Cross Greater New York Region’s Humanitarian Award. Dr. Vacirca received the award at the 2019 Heroes Among Us Gala on Oct. 16.
Dr. Vacirca is chief executive officer of New York Cancer & Blood Specialists. He is also a consulting physician for the Long Island Association for AIDS Care, medical director for AmerisourceBergen specialty group, a scientific advisory board member for Caris Life Sciences, director at OneOncology, director at Spectrum Pharmaceuticals, a medical board adviser for Flatiron Health, and vice-chairman of the board for Odonate Therapeutics, a company he cofounded in 2016. In 2014, Dr. Vacirca founded the New York Cancer Foundation, which provides financial assistance to patients undergoing cancer treatment.
Another award winner is Richard J. Bleicher, MD, who has won the 2020 Jamie Brooke Lieberman Remembrance Award from Susan G. Komen Philadelphia for his work related to breast cancer. Dr. Bleicher is scheduled to receive his award at the Susan G. Komen Philadelphia MORE THAN PINK Walk Kickoff event on March 18, 2020.
Dr. Bleicher is a professor, breast cancer surgeon, and clinical researcher at Fox Chase Cancer Center in Philadelphia. He is director of the breast fellowship and leader of the breast cancer program at Fox Chase. He sits on the board of the National Accreditation Program for Breast Centers and the Quality Improvement Committee, sits on the Commission for Cancer’s Operative Standards Committee, and is the vice-chair for the Society of Surgical Oncology’s breast fellowship programs for the United States and Canada.
Digital inhaler reveals uncontrolled asthma
NEW ORLEANS – Data collected by the ProAir Digihaler suggest .
Researchers studied asthma patients who had experienced exacerbations in the previous year. Patients who also had exacerbations while on study used the ProAir Digihaler about twice a day, on average. Patients without on-study exacerbations used the ProAir Digihaler an average of 1.14 times per day.
The daily use among patients without exacerbations suggests their asthma is “still quite uncontrolled,” and, according to guidelines, they may require additional therapy, said Roy Pleasants, PharmD, of the University of North Carolina at Chapel Hill.
Dr. Pleasants presented these findings at the annual meeting of the American College of Chest Physicians.
He and his colleagues conducted a phase 3 study (NCT02969408) of ProAir Digihaler use in adults who had at least one severe clinical asthma exacerbation in the previous 12 months. They had an Asthma Control Questionnaire score of 1.5 or greater, were on moderate-dose inhaled corticosteroids (with or without a long-acting beta-agonist), and had stable asthma controller dosing for at least 3 months.
For this study, the ProAir Digihaler replaced patients’ other rescue medications. The ProAir Digihaler is a digital inhaler that delivers 90 mcg of albuterol per dose, detects the date and time a dose was prepared, and records the inhalation profile. Over a 12-week period, the ProAir Digihaler recorded each use, which was defined as consecutive inhalations within 60 seconds.
Of the 381 patients enrolled in the study, 360 (94.5%) made at least one valid inhalation. The mean age of these patients was 50 years, and 80.6% were female. Of the 360 patients, 64 experienced 78 exacerbations while on study.
Most episodes of inhaler use consisted of a single inhalation (58.9%), although 35.8% consisted of two inhalations, 3.5% consisted of three inhalations, and 1.8% consisted of four or more inhalations.
The mean peak inspiratory flow was 73.18 L/min (standard deviation [SD] 20.33) in patients without exacerbations. Among patients with exacerbations, the mean peak inspiratory flow was 71.36 (SD 23.80) during exacerbation and 74.71 L/min (SD 22.46) outside the exacerbation window, which was 14 days before and after the exacerbation peak.
The mean inhalation volume was 1.45 L (SD 0.75) among patients without exacerbations, 1.44 L (SD 0.66) outside the exacerbation window, and 1.44 L (SD 0.76) during exacerbation. The mean inhalation duration was 1.62 sec (SD 0.88), 1.59 sec (SD 0.77), and 1.61 sec (SD 0.82), respectively.
“If you look at the inhalation volume in the 64 patients who exacerbated, it really didn’t change during exacerbation,” Dr. Pleasants noted. “Essentially, you can say the same thing about inhalation duration.”
Patients without exacerbations used the ProAir Digihaler an average of 1.14 (SD 2.35) times per day. Patients who had at least one exacerbation used the ProAir Digihaler an average of 1.87 (SD 2.78) times per day outside the exacerbation window and 2.43 (SD 3.67) times during exacerbation.
“As you would predict, those exacerbating patients were using more albuterol than patients who were not exacerbating,” Dr. Pleasants said. “Even when they weren’t exacerbating, that frequency of daily albuterol use is pretty much indicating these patients were not so well controlled.”
Dr. Pleasants went on to say that data from the ProAir Digihaler could help identify, in real time, patients with poor asthma control and those with impending exacerbations.
This study was sponsored by Teva, makers of the ProAir Digihaler. Dr. Pleasants disclosed relationships with Teva, Grifols, Sunovion, and Boehringer Ingelheim.
SOURCE: Pleasants R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.273.
NEW ORLEANS – Data collected by the ProAir Digihaler suggest .
Researchers studied asthma patients who had experienced exacerbations in the previous year. Patients who also had exacerbations while on study used the ProAir Digihaler about twice a day, on average. Patients without on-study exacerbations used the ProAir Digihaler an average of 1.14 times per day.
The daily use among patients without exacerbations suggests their asthma is “still quite uncontrolled,” and, according to guidelines, they may require additional therapy, said Roy Pleasants, PharmD, of the University of North Carolina at Chapel Hill.
Dr. Pleasants presented these findings at the annual meeting of the American College of Chest Physicians.
He and his colleagues conducted a phase 3 study (NCT02969408) of ProAir Digihaler use in adults who had at least one severe clinical asthma exacerbation in the previous 12 months. They had an Asthma Control Questionnaire score of 1.5 or greater, were on moderate-dose inhaled corticosteroids (with or without a long-acting beta-agonist), and had stable asthma controller dosing for at least 3 months.
For this study, the ProAir Digihaler replaced patients’ other rescue medications. The ProAir Digihaler is a digital inhaler that delivers 90 mcg of albuterol per dose, detects the date and time a dose was prepared, and records the inhalation profile. Over a 12-week period, the ProAir Digihaler recorded each use, which was defined as consecutive inhalations within 60 seconds.
Of the 381 patients enrolled in the study, 360 (94.5%) made at least one valid inhalation. The mean age of these patients was 50 years, and 80.6% were female. Of the 360 patients, 64 experienced 78 exacerbations while on study.
Most episodes of inhaler use consisted of a single inhalation (58.9%), although 35.8% consisted of two inhalations, 3.5% consisted of three inhalations, and 1.8% consisted of four or more inhalations.
The mean peak inspiratory flow was 73.18 L/min (standard deviation [SD] 20.33) in patients without exacerbations. Among patients with exacerbations, the mean peak inspiratory flow was 71.36 (SD 23.80) during exacerbation and 74.71 L/min (SD 22.46) outside the exacerbation window, which was 14 days before and after the exacerbation peak.
The mean inhalation volume was 1.45 L (SD 0.75) among patients without exacerbations, 1.44 L (SD 0.66) outside the exacerbation window, and 1.44 L (SD 0.76) during exacerbation. The mean inhalation duration was 1.62 sec (SD 0.88), 1.59 sec (SD 0.77), and 1.61 sec (SD 0.82), respectively.
“If you look at the inhalation volume in the 64 patients who exacerbated, it really didn’t change during exacerbation,” Dr. Pleasants noted. “Essentially, you can say the same thing about inhalation duration.”
Patients without exacerbations used the ProAir Digihaler an average of 1.14 (SD 2.35) times per day. Patients who had at least one exacerbation used the ProAir Digihaler an average of 1.87 (SD 2.78) times per day outside the exacerbation window and 2.43 (SD 3.67) times during exacerbation.
“As you would predict, those exacerbating patients were using more albuterol than patients who were not exacerbating,” Dr. Pleasants said. “Even when they weren’t exacerbating, that frequency of daily albuterol use is pretty much indicating these patients were not so well controlled.”
Dr. Pleasants went on to say that data from the ProAir Digihaler could help identify, in real time, patients with poor asthma control and those with impending exacerbations.
This study was sponsored by Teva, makers of the ProAir Digihaler. Dr. Pleasants disclosed relationships with Teva, Grifols, Sunovion, and Boehringer Ingelheim.
SOURCE: Pleasants R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.273.
NEW ORLEANS – Data collected by the ProAir Digihaler suggest .
Researchers studied asthma patients who had experienced exacerbations in the previous year. Patients who also had exacerbations while on study used the ProAir Digihaler about twice a day, on average. Patients without on-study exacerbations used the ProAir Digihaler an average of 1.14 times per day.
The daily use among patients without exacerbations suggests their asthma is “still quite uncontrolled,” and, according to guidelines, they may require additional therapy, said Roy Pleasants, PharmD, of the University of North Carolina at Chapel Hill.
Dr. Pleasants presented these findings at the annual meeting of the American College of Chest Physicians.
He and his colleagues conducted a phase 3 study (NCT02969408) of ProAir Digihaler use in adults who had at least one severe clinical asthma exacerbation in the previous 12 months. They had an Asthma Control Questionnaire score of 1.5 or greater, were on moderate-dose inhaled corticosteroids (with or without a long-acting beta-agonist), and had stable asthma controller dosing for at least 3 months.
For this study, the ProAir Digihaler replaced patients’ other rescue medications. The ProAir Digihaler is a digital inhaler that delivers 90 mcg of albuterol per dose, detects the date and time a dose was prepared, and records the inhalation profile. Over a 12-week period, the ProAir Digihaler recorded each use, which was defined as consecutive inhalations within 60 seconds.
Of the 381 patients enrolled in the study, 360 (94.5%) made at least one valid inhalation. The mean age of these patients was 50 years, and 80.6% were female. Of the 360 patients, 64 experienced 78 exacerbations while on study.
Most episodes of inhaler use consisted of a single inhalation (58.9%), although 35.8% consisted of two inhalations, 3.5% consisted of three inhalations, and 1.8% consisted of four or more inhalations.
The mean peak inspiratory flow was 73.18 L/min (standard deviation [SD] 20.33) in patients without exacerbations. Among patients with exacerbations, the mean peak inspiratory flow was 71.36 (SD 23.80) during exacerbation and 74.71 L/min (SD 22.46) outside the exacerbation window, which was 14 days before and after the exacerbation peak.
The mean inhalation volume was 1.45 L (SD 0.75) among patients without exacerbations, 1.44 L (SD 0.66) outside the exacerbation window, and 1.44 L (SD 0.76) during exacerbation. The mean inhalation duration was 1.62 sec (SD 0.88), 1.59 sec (SD 0.77), and 1.61 sec (SD 0.82), respectively.
“If you look at the inhalation volume in the 64 patients who exacerbated, it really didn’t change during exacerbation,” Dr. Pleasants noted. “Essentially, you can say the same thing about inhalation duration.”
Patients without exacerbations used the ProAir Digihaler an average of 1.14 (SD 2.35) times per day. Patients who had at least one exacerbation used the ProAir Digihaler an average of 1.87 (SD 2.78) times per day outside the exacerbation window and 2.43 (SD 3.67) times during exacerbation.
“As you would predict, those exacerbating patients were using more albuterol than patients who were not exacerbating,” Dr. Pleasants said. “Even when they weren’t exacerbating, that frequency of daily albuterol use is pretty much indicating these patients were not so well controlled.”
Dr. Pleasants went on to say that data from the ProAir Digihaler could help identify, in real time, patients with poor asthma control and those with impending exacerbations.
This study was sponsored by Teva, makers of the ProAir Digihaler. Dr. Pleasants disclosed relationships with Teva, Grifols, Sunovion, and Boehringer Ingelheim.
SOURCE: Pleasants R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.273.
REPORTING FROM CHEST 2019
Study suggests physicians and patients overestimate asthma control
NEW ORLEANS – according to an observational study.
More than half (53%) of cases physicians rated as controlled were actually uncontrolled according to the Asthma Control Test (ACT), and 30% of patients who considered their asthma controlled actually had uncontrolled asthma according to the ACT.
Reynold A. Panettieri Jr., MD, of Rutgers University in New Brunswick, N.J., presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from the CHRONICLE study, an ongoing observational study of adults with severe asthma who are being treated by U.S. allergists or pulmonologists. The study enrolled 796 patients from Feb. 2018 to Feb. 2019, and 482 of them were evaluable because they completed the necessary surveys.
The patients’ median age at enrollment was 55 years, and 68% of patients were female. Most were white (82%), 12% were black, 6% were an “other” race, and 7% had Hispanic ethnicity. The median body mass index was 31 kg/m2.
Patients received care from an allergist (49%), a pulmonologist (38%), or both (13%). Patients were treated with biologics (n = 370), maintenance systemic corticosteroids (n = 64), or high-dosage inhaled corticosteroids with additional controllers (n = 90).
At patient enrollment, physicians reported their assessment of patients’ asthma control and completed the 5-point Global Evaluation of Treatment Effectiveness (GETE). The physicians’ assessments of patients were informed by patients’ verbal reports (50%), lung function testing (44%), in-office ACT (41%), and recent exacerbations (39%).
Patients also completed the ACT and GETE online at the time of enrollment. Neither patients nor physicians were privy to the other group’s responses.
Overall, physicians said 279 patients had controlled asthma. However, according to the ACT, 27% of these cases were very poorly controlled, 26% were not well controlled, and 47% were well controlled.
“So [when] we as a provider say the patient’s controlled, we’re wrong half the time,” Dr. Panettieri said.
However, physicians were more accurate when deeming patients’ asthma uncontrolled. Physicians said 201 cases of asthma were uncontrolled, and the ACT said 64% of these cases were very poorly controlled, 22% were not well controlled, and 13% were well controlled.
Compared with the physicians’ results, the patients’ reports were more in line with ACT results. However, the patients still overestimated control.
In all, 222 patients said their asthma was controlled. According to the ACT, 70% of these cases were well controlled, 23% were not well controlled, and 7% were very poorly controlled.
Patients were even more accurate when deeming their asthma uncontrolled. A total of 258 patients said their asthma was uncontrolled. According to the ACT, 74% of these cases were very poorly controlled, 25% were not well controlled, and 1% were well controlled.
“About 99% of the time, when a patient tells you they’re uncontrolled, they’re uncontrolled by the ACT,” Dr. Panettieri said.
Though patients were fairly accurate when assessing asthma control, they were less accurate when gauging treatment effectiveness. A majority of patients overestimated the effectiveness of treatment.
There were 124 patients who did not have any improvement after treatment, according to physicians. Although 23% of the patients concurred with this assessment, 77% said they did experience some improvement.
On the other hand, there were 355 patients who had some improvement after treatment according to physicians, and most of these patients (96%) agreed that they had some improvement.
Dr. Panettieri said these results support use of the ACT and similar tools. When using these tools isn’t feasible, Dr. Panettieri recommends simply asking patients how they are feeling. However, he said, providers should not rely on a patient’s report of treatment effectiveness to assess asthma control.
This study is supported by AstraZeneca. Dr. Panettieri disclosed relationships with AstraZeneca, Sanofi, Regeneron, Genentech, and Novartis.
SOURCE: Panettieri R et al. CHEST 2019. Abstract, doi. 10.1016/j.chest.2019.08.272.
NEW ORLEANS – according to an observational study.
More than half (53%) of cases physicians rated as controlled were actually uncontrolled according to the Asthma Control Test (ACT), and 30% of patients who considered their asthma controlled actually had uncontrolled asthma according to the ACT.
Reynold A. Panettieri Jr., MD, of Rutgers University in New Brunswick, N.J., presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from the CHRONICLE study, an ongoing observational study of adults with severe asthma who are being treated by U.S. allergists or pulmonologists. The study enrolled 796 patients from Feb. 2018 to Feb. 2019, and 482 of them were evaluable because they completed the necessary surveys.
The patients’ median age at enrollment was 55 years, and 68% of patients were female. Most were white (82%), 12% were black, 6% were an “other” race, and 7% had Hispanic ethnicity. The median body mass index was 31 kg/m2.
Patients received care from an allergist (49%), a pulmonologist (38%), or both (13%). Patients were treated with biologics (n = 370), maintenance systemic corticosteroids (n = 64), or high-dosage inhaled corticosteroids with additional controllers (n = 90).
At patient enrollment, physicians reported their assessment of patients’ asthma control and completed the 5-point Global Evaluation of Treatment Effectiveness (GETE). The physicians’ assessments of patients were informed by patients’ verbal reports (50%), lung function testing (44%), in-office ACT (41%), and recent exacerbations (39%).
Patients also completed the ACT and GETE online at the time of enrollment. Neither patients nor physicians were privy to the other group’s responses.
Overall, physicians said 279 patients had controlled asthma. However, according to the ACT, 27% of these cases were very poorly controlled, 26% were not well controlled, and 47% were well controlled.
“So [when] we as a provider say the patient’s controlled, we’re wrong half the time,” Dr. Panettieri said.
However, physicians were more accurate when deeming patients’ asthma uncontrolled. Physicians said 201 cases of asthma were uncontrolled, and the ACT said 64% of these cases were very poorly controlled, 22% were not well controlled, and 13% were well controlled.
Compared with the physicians’ results, the patients’ reports were more in line with ACT results. However, the patients still overestimated control.
In all, 222 patients said their asthma was controlled. According to the ACT, 70% of these cases were well controlled, 23% were not well controlled, and 7% were very poorly controlled.
Patients were even more accurate when deeming their asthma uncontrolled. A total of 258 patients said their asthma was uncontrolled. According to the ACT, 74% of these cases were very poorly controlled, 25% were not well controlled, and 1% were well controlled.
“About 99% of the time, when a patient tells you they’re uncontrolled, they’re uncontrolled by the ACT,” Dr. Panettieri said.
Though patients were fairly accurate when assessing asthma control, they were less accurate when gauging treatment effectiveness. A majority of patients overestimated the effectiveness of treatment.
There were 124 patients who did not have any improvement after treatment, according to physicians. Although 23% of the patients concurred with this assessment, 77% said they did experience some improvement.
On the other hand, there were 355 patients who had some improvement after treatment according to physicians, and most of these patients (96%) agreed that they had some improvement.
Dr. Panettieri said these results support use of the ACT and similar tools. When using these tools isn’t feasible, Dr. Panettieri recommends simply asking patients how they are feeling. However, he said, providers should not rely on a patient’s report of treatment effectiveness to assess asthma control.
This study is supported by AstraZeneca. Dr. Panettieri disclosed relationships with AstraZeneca, Sanofi, Regeneron, Genentech, and Novartis.
SOURCE: Panettieri R et al. CHEST 2019. Abstract, doi. 10.1016/j.chest.2019.08.272.
NEW ORLEANS – according to an observational study.
More than half (53%) of cases physicians rated as controlled were actually uncontrolled according to the Asthma Control Test (ACT), and 30% of patients who considered their asthma controlled actually had uncontrolled asthma according to the ACT.
Reynold A. Panettieri Jr., MD, of Rutgers University in New Brunswick, N.J., presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from the CHRONICLE study, an ongoing observational study of adults with severe asthma who are being treated by U.S. allergists or pulmonologists. The study enrolled 796 patients from Feb. 2018 to Feb. 2019, and 482 of them were evaluable because they completed the necessary surveys.
The patients’ median age at enrollment was 55 years, and 68% of patients were female. Most were white (82%), 12% were black, 6% were an “other” race, and 7% had Hispanic ethnicity. The median body mass index was 31 kg/m2.
Patients received care from an allergist (49%), a pulmonologist (38%), or both (13%). Patients were treated with biologics (n = 370), maintenance systemic corticosteroids (n = 64), or high-dosage inhaled corticosteroids with additional controllers (n = 90).
At patient enrollment, physicians reported their assessment of patients’ asthma control and completed the 5-point Global Evaluation of Treatment Effectiveness (GETE). The physicians’ assessments of patients were informed by patients’ verbal reports (50%), lung function testing (44%), in-office ACT (41%), and recent exacerbations (39%).
Patients also completed the ACT and GETE online at the time of enrollment. Neither patients nor physicians were privy to the other group’s responses.
Overall, physicians said 279 patients had controlled asthma. However, according to the ACT, 27% of these cases were very poorly controlled, 26% were not well controlled, and 47% were well controlled.
“So [when] we as a provider say the patient’s controlled, we’re wrong half the time,” Dr. Panettieri said.
However, physicians were more accurate when deeming patients’ asthma uncontrolled. Physicians said 201 cases of asthma were uncontrolled, and the ACT said 64% of these cases were very poorly controlled, 22% were not well controlled, and 13% were well controlled.
Compared with the physicians’ results, the patients’ reports were more in line with ACT results. However, the patients still overestimated control.
In all, 222 patients said their asthma was controlled. According to the ACT, 70% of these cases were well controlled, 23% were not well controlled, and 7% were very poorly controlled.
Patients were even more accurate when deeming their asthma uncontrolled. A total of 258 patients said their asthma was uncontrolled. According to the ACT, 74% of these cases were very poorly controlled, 25% were not well controlled, and 1% were well controlled.
“About 99% of the time, when a patient tells you they’re uncontrolled, they’re uncontrolled by the ACT,” Dr. Panettieri said.
Though patients were fairly accurate when assessing asthma control, they were less accurate when gauging treatment effectiveness. A majority of patients overestimated the effectiveness of treatment.
There were 124 patients who did not have any improvement after treatment, according to physicians. Although 23% of the patients concurred with this assessment, 77% said they did experience some improvement.
On the other hand, there were 355 patients who had some improvement after treatment according to physicians, and most of these patients (96%) agreed that they had some improvement.
Dr. Panettieri said these results support use of the ACT and similar tools. When using these tools isn’t feasible, Dr. Panettieri recommends simply asking patients how they are feeling. However, he said, providers should not rely on a patient’s report of treatment effectiveness to assess asthma control.
This study is supported by AstraZeneca. Dr. Panettieri disclosed relationships with AstraZeneca, Sanofi, Regeneron, Genentech, and Novartis.
SOURCE: Panettieri R et al. CHEST 2019. Abstract, doi. 10.1016/j.chest.2019.08.272.
REPORTING FROM CHEST 2019
Best treatment approach for early stage follicular lymphoma is unclear
Randomized trials are needed to determine the optimal treatment approach for early stage follicular lymphoma (FL), according to researchers.
A retrospective study showed similar outcomes among patients who received radiotherapy, immunochemotherapy, combined modality treatment (CMT), and watchful waiting (WW).
There were some differences in progression-free survival (PFS) according to treatment approach. However, there were no significant differences in overall survival (OS) between any of the active treatments or between patients who received active treatment and those managed with WW.
Joshua W. D. Tobin, MD, of Princess Alexandra Hospital in Brisbane, Queensland, Australia, and colleagues conducted this research and reported the results in Blood Advances.
The researchers analyzed 365 patients with newly diagnosed, stage I/II FL. The patients had a median age of 63 years and more than half were men. They were diagnosed between 2005 and 2017, and the median follow-up was 45 months.
Most patients (n = 280) received active treatment, but 85 were managed with WW. The WW patients were older and had more extranodal involvement.
Types of active treatment included radiotherapy alone (n = 171), immunochemotherapy alone (n = 63), and CMT (n = 46). Compared with the other groups, patients who received radiotherapy alone had less bulk, fewer nodal sites, and fewer B symptoms, and were more likely to have stage I disease. Patients who received CMT had fewer B symptoms and lower FLIPI scores compared with patients who received immunochemotherapy.
The immunochemotherapy regimens used were largely rituximab based. In all, 106 patients received rituximab (alone or in combination) for induction, and 49 received maintenance rituximab (37 in the immunochemotherapy group and 12 in the CMT group).
Results
Response rates were similar among the active treatment groups. The overall response rate was 95% in the radiotherapy group, 96% in the immunochemotherapy group, and 95% in the CMT group (P = .87).
There was a significant difference in PFS between the radiotherapy, immunochemotherapy, and CMT groups (P = .023), but there was no difference in OS between these groups (P = .38).
There was no significant difference in PFS between the immunochemotherapy and CMT groups (hazard ratio [HR], 1.78; P = .24), so the researchers combined these groups into a single group called “systemic therapy.” The patients treated with systemic therapy had PFS (HR, 1.32; P = .96) and OS (HR, 0.46; P = .21) similar to that of patients treated with radiotherapy alone.
Maintenance rituximab was associated with prolonged PFS among patients treated with systemic therapy (HR, 0.24; P = .017). However, there was no significant difference in OS between patients who received maintenance and those who did not (HR, 0.89; P = .90).
Relapse was less common among patients who received maintenance, and there were no cases of transformation in that group. Relapse occurred in 24.6% of the radiotherapy group, 18.3% of the systemic therapy group, and 4.1% of the group that received systemic therapy plus maintenance (P = .006). Transformation was less likely in the systemic therapy group (1.8%) than in the radiotherapy (6.4%) and WW (9.4%) groups (HR, 0.20; P = .034).
Overall, the active treatment group had better PFS than the WW group (HR, 0.52; P = .002), but there was no significant difference in OS between the groups (HR, 0.94; P = .90).
“Based on our comparable OS between WW and actively treated patients, WW could be considered as an initial management strategy in early stage FL,” Dr. Tobin and colleagues wrote. “However, long-term follow-up is required to determine if a survival benefit exists favoring active treatment.”
The researchers reported relationships with many pharmaceutical companies.
SOURCE: Tobin JWD et al. Blood Adv. 2019 Oct 8;3(19):2804-11.
Randomized trials are needed to determine the optimal treatment approach for early stage follicular lymphoma (FL), according to researchers.
A retrospective study showed similar outcomes among patients who received radiotherapy, immunochemotherapy, combined modality treatment (CMT), and watchful waiting (WW).
There were some differences in progression-free survival (PFS) according to treatment approach. However, there were no significant differences in overall survival (OS) between any of the active treatments or between patients who received active treatment and those managed with WW.
Joshua W. D. Tobin, MD, of Princess Alexandra Hospital in Brisbane, Queensland, Australia, and colleagues conducted this research and reported the results in Blood Advances.
The researchers analyzed 365 patients with newly diagnosed, stage I/II FL. The patients had a median age of 63 years and more than half were men. They were diagnosed between 2005 and 2017, and the median follow-up was 45 months.
Most patients (n = 280) received active treatment, but 85 were managed with WW. The WW patients were older and had more extranodal involvement.
Types of active treatment included radiotherapy alone (n = 171), immunochemotherapy alone (n = 63), and CMT (n = 46). Compared with the other groups, patients who received radiotherapy alone had less bulk, fewer nodal sites, and fewer B symptoms, and were more likely to have stage I disease. Patients who received CMT had fewer B symptoms and lower FLIPI scores compared with patients who received immunochemotherapy.
The immunochemotherapy regimens used were largely rituximab based. In all, 106 patients received rituximab (alone or in combination) for induction, and 49 received maintenance rituximab (37 in the immunochemotherapy group and 12 in the CMT group).
Results
Response rates were similar among the active treatment groups. The overall response rate was 95% in the radiotherapy group, 96% in the immunochemotherapy group, and 95% in the CMT group (P = .87).
There was a significant difference in PFS between the radiotherapy, immunochemotherapy, and CMT groups (P = .023), but there was no difference in OS between these groups (P = .38).
There was no significant difference in PFS between the immunochemotherapy and CMT groups (hazard ratio [HR], 1.78; P = .24), so the researchers combined these groups into a single group called “systemic therapy.” The patients treated with systemic therapy had PFS (HR, 1.32; P = .96) and OS (HR, 0.46; P = .21) similar to that of patients treated with radiotherapy alone.
Maintenance rituximab was associated with prolonged PFS among patients treated with systemic therapy (HR, 0.24; P = .017). However, there was no significant difference in OS between patients who received maintenance and those who did not (HR, 0.89; P = .90).
Relapse was less common among patients who received maintenance, and there were no cases of transformation in that group. Relapse occurred in 24.6% of the radiotherapy group, 18.3% of the systemic therapy group, and 4.1% of the group that received systemic therapy plus maintenance (P = .006). Transformation was less likely in the systemic therapy group (1.8%) than in the radiotherapy (6.4%) and WW (9.4%) groups (HR, 0.20; P = .034).
Overall, the active treatment group had better PFS than the WW group (HR, 0.52; P = .002), but there was no significant difference in OS between the groups (HR, 0.94; P = .90).
“Based on our comparable OS between WW and actively treated patients, WW could be considered as an initial management strategy in early stage FL,” Dr. Tobin and colleagues wrote. “However, long-term follow-up is required to determine if a survival benefit exists favoring active treatment.”
The researchers reported relationships with many pharmaceutical companies.
SOURCE: Tobin JWD et al. Blood Adv. 2019 Oct 8;3(19):2804-11.
Randomized trials are needed to determine the optimal treatment approach for early stage follicular lymphoma (FL), according to researchers.
A retrospective study showed similar outcomes among patients who received radiotherapy, immunochemotherapy, combined modality treatment (CMT), and watchful waiting (WW).
There were some differences in progression-free survival (PFS) according to treatment approach. However, there were no significant differences in overall survival (OS) between any of the active treatments or between patients who received active treatment and those managed with WW.
Joshua W. D. Tobin, MD, of Princess Alexandra Hospital in Brisbane, Queensland, Australia, and colleagues conducted this research and reported the results in Blood Advances.
The researchers analyzed 365 patients with newly diagnosed, stage I/II FL. The patients had a median age of 63 years and more than half were men. They were diagnosed between 2005 and 2017, and the median follow-up was 45 months.
Most patients (n = 280) received active treatment, but 85 were managed with WW. The WW patients were older and had more extranodal involvement.
Types of active treatment included radiotherapy alone (n = 171), immunochemotherapy alone (n = 63), and CMT (n = 46). Compared with the other groups, patients who received radiotherapy alone had less bulk, fewer nodal sites, and fewer B symptoms, and were more likely to have stage I disease. Patients who received CMT had fewer B symptoms and lower FLIPI scores compared with patients who received immunochemotherapy.
The immunochemotherapy regimens used were largely rituximab based. In all, 106 patients received rituximab (alone or in combination) for induction, and 49 received maintenance rituximab (37 in the immunochemotherapy group and 12 in the CMT group).
Results
Response rates were similar among the active treatment groups. The overall response rate was 95% in the radiotherapy group, 96% in the immunochemotherapy group, and 95% in the CMT group (P = .87).
There was a significant difference in PFS between the radiotherapy, immunochemotherapy, and CMT groups (P = .023), but there was no difference in OS between these groups (P = .38).
There was no significant difference in PFS between the immunochemotherapy and CMT groups (hazard ratio [HR], 1.78; P = .24), so the researchers combined these groups into a single group called “systemic therapy.” The patients treated with systemic therapy had PFS (HR, 1.32; P = .96) and OS (HR, 0.46; P = .21) similar to that of patients treated with radiotherapy alone.
Maintenance rituximab was associated with prolonged PFS among patients treated with systemic therapy (HR, 0.24; P = .017). However, there was no significant difference in OS between patients who received maintenance and those who did not (HR, 0.89; P = .90).
Relapse was less common among patients who received maintenance, and there were no cases of transformation in that group. Relapse occurred in 24.6% of the radiotherapy group, 18.3% of the systemic therapy group, and 4.1% of the group that received systemic therapy plus maintenance (P = .006). Transformation was less likely in the systemic therapy group (1.8%) than in the radiotherapy (6.4%) and WW (9.4%) groups (HR, 0.20; P = .034).
Overall, the active treatment group had better PFS than the WW group (HR, 0.52; P = .002), but there was no significant difference in OS between the groups (HR, 0.94; P = .90).
“Based on our comparable OS between WW and actively treated patients, WW could be considered as an initial management strategy in early stage FL,” Dr. Tobin and colleagues wrote. “However, long-term follow-up is required to determine if a survival benefit exists favoring active treatment.”
The researchers reported relationships with many pharmaceutical companies.
SOURCE: Tobin JWD et al. Blood Adv. 2019 Oct 8;3(19):2804-11.
FROM BLOOD ADVANCES
Follow-up shows favorable results with acalabrutinib in MCL
Acalabrutinib monotherapy can produce durable responses in relapsed/refractory mantle cell lymphoma (MCL), according to updated results from a phase 2 trial.
The drug produced an overall response rate (ORR) of 81%, and the median duration of response was 26 months.
These are the highest such figures reported “among all approved single-agent therapies for the treatment of relapsed/refractory MCL,” Michael Wang, MD, of the MD Anderson Cancer Center at the University of Texas in Houston and colleagues wrote in a letter in Leukemia.
Dr. Wang and colleagues reported updated results in 124 patients treated on the ACE-LY-004 trial. At baseline, the patients had a median age of 68 years (range, 42-90 years), and 80% were men. Three-quarters of patients had stage IV disease, 72% had extranodal disease, 21% had blastoid/pleomorphic MCL, and 26% had a Ki-67 proliferation index of 50% or greater.
At a median follow-up of 26 months, 40% (n = 49) of patients were still on acalabrutinib, and 61% (n = 76) were still in follow-up for survival. Six patients went on to allogeneic transplant at a median of 19 days after stopping acalabrutinib.
The ORR was 81% (100/124), and the complete response (CR) rate was 43% (n = 53). Four patients who initially had a partial response converted to a CR with longer follow-up. The estimated 24-month duration of response was 52.4%.
“ORR was consistent across patients with refractory disease and those with blastoid/pleomorphic MCL, despite those patients having a higher mean Ki-67 index [of 50% or greater], suggesting that some patients with poorer prognosis may also benefit from acalabrutinib,” Dr. Wang and colleagues wrote.
There were 29 patients evaluable for minimal residual disease (MRD) assessment. Seven patients (24%) had MRD-negative disease in the peripheral blood after they achieved a CR. An additional patient with a CR became MRD negative when a second blood sample was taken about 6 months after the first.
“Despite limited samples, these results demonstrate that continued use of acalabrutinib can lead to undetectable MRD in patients with CR,” Dr. Wang and his colleagues wrote. “Since most patients with MRD data are still on treatment (27/29), relationships between MRD negativity and durability of response cannot be made at this time.”
The median progression-free survival was 20 months, and the median overall survival was not reached. The estimated 24-month progression-free survival rate was 49.0%, and the estimated 24-month overall survival rate was 72.4%. Patients with low/intermediate Mantle Cell Lymphoma International Prognostic Index scores, classical MCL, and a Ki-67 index less than 50% had a longer duration of response and survival.
The adverse event profile was “largely consistent with earlier reporting,” Dr. Wang and colleagues wrote. The most frequent adverse events were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). The most common grade 3/4 adverse events were anemia (10%), neutropenia (10%), and pneumonia (6%).
Ten patients developed second primary cancers. There were no new atrial fibrillation events and no new hypertension events. The frequency of infections decreased over time, as did the number of bleeding events. However, two of three major hemorrhage events occurred after the previous report was published.
There were 43 deaths (35%), 29 of them because of disease progression. Six patients died of adverse events, two died of unknown causes, and two died of secondary acute myeloid leukemia. Other causes of death included multiorgan failure, intestinal obstruction, lung cancer, and graft-versus-host disease.
This study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. The researchers reported relationships with AstraZeneca/Acerta Pharma and many other companies.
SOURCE: Wang M et al. Leukemia. 2019 Sep 26. doi: 10.1038/s41375-019-0575-9.
Acalabrutinib monotherapy can produce durable responses in relapsed/refractory mantle cell lymphoma (MCL), according to updated results from a phase 2 trial.
The drug produced an overall response rate (ORR) of 81%, and the median duration of response was 26 months.
These are the highest such figures reported “among all approved single-agent therapies for the treatment of relapsed/refractory MCL,” Michael Wang, MD, of the MD Anderson Cancer Center at the University of Texas in Houston and colleagues wrote in a letter in Leukemia.
Dr. Wang and colleagues reported updated results in 124 patients treated on the ACE-LY-004 trial. At baseline, the patients had a median age of 68 years (range, 42-90 years), and 80% were men. Three-quarters of patients had stage IV disease, 72% had extranodal disease, 21% had blastoid/pleomorphic MCL, and 26% had a Ki-67 proliferation index of 50% or greater.
At a median follow-up of 26 months, 40% (n = 49) of patients were still on acalabrutinib, and 61% (n = 76) were still in follow-up for survival. Six patients went on to allogeneic transplant at a median of 19 days after stopping acalabrutinib.
The ORR was 81% (100/124), and the complete response (CR) rate was 43% (n = 53). Four patients who initially had a partial response converted to a CR with longer follow-up. The estimated 24-month duration of response was 52.4%.
“ORR was consistent across patients with refractory disease and those with blastoid/pleomorphic MCL, despite those patients having a higher mean Ki-67 index [of 50% or greater], suggesting that some patients with poorer prognosis may also benefit from acalabrutinib,” Dr. Wang and colleagues wrote.
There were 29 patients evaluable for minimal residual disease (MRD) assessment. Seven patients (24%) had MRD-negative disease in the peripheral blood after they achieved a CR. An additional patient with a CR became MRD negative when a second blood sample was taken about 6 months after the first.
“Despite limited samples, these results demonstrate that continued use of acalabrutinib can lead to undetectable MRD in patients with CR,” Dr. Wang and his colleagues wrote. “Since most patients with MRD data are still on treatment (27/29), relationships between MRD negativity and durability of response cannot be made at this time.”
The median progression-free survival was 20 months, and the median overall survival was not reached. The estimated 24-month progression-free survival rate was 49.0%, and the estimated 24-month overall survival rate was 72.4%. Patients with low/intermediate Mantle Cell Lymphoma International Prognostic Index scores, classical MCL, and a Ki-67 index less than 50% had a longer duration of response and survival.
The adverse event profile was “largely consistent with earlier reporting,” Dr. Wang and colleagues wrote. The most frequent adverse events were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). The most common grade 3/4 adverse events were anemia (10%), neutropenia (10%), and pneumonia (6%).
Ten patients developed second primary cancers. There were no new atrial fibrillation events and no new hypertension events. The frequency of infections decreased over time, as did the number of bleeding events. However, two of three major hemorrhage events occurred after the previous report was published.
There were 43 deaths (35%), 29 of them because of disease progression. Six patients died of adverse events, two died of unknown causes, and two died of secondary acute myeloid leukemia. Other causes of death included multiorgan failure, intestinal obstruction, lung cancer, and graft-versus-host disease.
This study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. The researchers reported relationships with AstraZeneca/Acerta Pharma and many other companies.
SOURCE: Wang M et al. Leukemia. 2019 Sep 26. doi: 10.1038/s41375-019-0575-9.
Acalabrutinib monotherapy can produce durable responses in relapsed/refractory mantle cell lymphoma (MCL), according to updated results from a phase 2 trial.
The drug produced an overall response rate (ORR) of 81%, and the median duration of response was 26 months.
These are the highest such figures reported “among all approved single-agent therapies for the treatment of relapsed/refractory MCL,” Michael Wang, MD, of the MD Anderson Cancer Center at the University of Texas in Houston and colleagues wrote in a letter in Leukemia.
Dr. Wang and colleagues reported updated results in 124 patients treated on the ACE-LY-004 trial. At baseline, the patients had a median age of 68 years (range, 42-90 years), and 80% were men. Three-quarters of patients had stage IV disease, 72% had extranodal disease, 21% had blastoid/pleomorphic MCL, and 26% had a Ki-67 proliferation index of 50% or greater.
At a median follow-up of 26 months, 40% (n = 49) of patients were still on acalabrutinib, and 61% (n = 76) were still in follow-up for survival. Six patients went on to allogeneic transplant at a median of 19 days after stopping acalabrutinib.
The ORR was 81% (100/124), and the complete response (CR) rate was 43% (n = 53). Four patients who initially had a partial response converted to a CR with longer follow-up. The estimated 24-month duration of response was 52.4%.
“ORR was consistent across patients with refractory disease and those with blastoid/pleomorphic MCL, despite those patients having a higher mean Ki-67 index [of 50% or greater], suggesting that some patients with poorer prognosis may also benefit from acalabrutinib,” Dr. Wang and colleagues wrote.
There were 29 patients evaluable for minimal residual disease (MRD) assessment. Seven patients (24%) had MRD-negative disease in the peripheral blood after they achieved a CR. An additional patient with a CR became MRD negative when a second blood sample was taken about 6 months after the first.
“Despite limited samples, these results demonstrate that continued use of acalabrutinib can lead to undetectable MRD in patients with CR,” Dr. Wang and his colleagues wrote. “Since most patients with MRD data are still on treatment (27/29), relationships between MRD negativity and durability of response cannot be made at this time.”
The median progression-free survival was 20 months, and the median overall survival was not reached. The estimated 24-month progression-free survival rate was 49.0%, and the estimated 24-month overall survival rate was 72.4%. Patients with low/intermediate Mantle Cell Lymphoma International Prognostic Index scores, classical MCL, and a Ki-67 index less than 50% had a longer duration of response and survival.
The adverse event profile was “largely consistent with earlier reporting,” Dr. Wang and colleagues wrote. The most frequent adverse events were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). The most common grade 3/4 adverse events were anemia (10%), neutropenia (10%), and pneumonia (6%).
Ten patients developed second primary cancers. There were no new atrial fibrillation events and no new hypertension events. The frequency of infections decreased over time, as did the number of bleeding events. However, two of three major hemorrhage events occurred after the previous report was published.
There were 43 deaths (35%), 29 of them because of disease progression. Six patients died of adverse events, two died of unknown causes, and two died of secondary acute myeloid leukemia. Other causes of death included multiorgan failure, intestinal obstruction, lung cancer, and graft-versus-host disease.
This study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. The researchers reported relationships with AstraZeneca/Acerta Pharma and many other companies.
SOURCE: Wang M et al. Leukemia. 2019 Sep 26. doi: 10.1038/s41375-019-0575-9.
FROM LEUKEMIA
What is the optimal duration of maintenance in myeloma?
SAN FRANCISCO – Should patients with multiple myeloma receive maintenance therapy until progression?
Yvonne A. Efebera, MD, of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital in Columbus, and Nina Shah, MD, of the University of California San Francisco Health, faced off on this question at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.
Dr. Shah said maintenance therapy improves survival in myeloma patients, so it follows that treating them until progression would confer a survival advantage. While Dr. Efebera agreed that maintenance can improve survival, she said the optimal duration of that treatment is unknown.
Treat until progression
Dr. Shah cited studies suggesting that maintenance improves progression-free survival (PFS) and may prolong overall survival (OS) in multiple myeloma.
A meta-analysis of data from the IFM 2005-02, CALGB 100104, and GIMEMA RV-MM-PI-209 trials showed that lenalidomide maintenance prolonged PFS and OS. The median PFS was 52.8 months in patients who received maintenance and 23.5 months in those who received placebo or observation (hazard ratio [HR], 0.48). At a median follow-up of 79.5 months, the median OS was not reached for the maintenance group and was 86.0 months for the no-maintenance group (HR, 0.75; P = .001; J Clin Oncol. 2017 Oct 10;35[29]:3279-89).
In the Myeloma XI trial, maintenance improved PFS, but not OS, in both transplant-eligible and ineligible patients. Overall, the median PFS was 39 months in the lenalidomide maintenance arm and 20 months in the observation arm (P less than .0001). Among transplant-eligible patients, the median PFS was 57 months and 30 months, respectively (P less than .0001). Among transplant-ineligible patients, the median PFS was 26 months and 11 months, respectively (P less than .0001; Lancet Oncol. 2019 Jan;20[1]:57-73).
These data suggest maintenance can improve survival, “but the question is, how long should we have therapy,” Dr. Shah said. “No one has looked at this in a prospective manner, so we really have to look at our retrospective data.”
One study suggested a longer duration of lenalidomide maintenance improves PFS. The HR for progression or death was 0.39 for patients who received maintenance for 12-24 months, compared with those who received maintenance for less than 12 months. The HR was 0.13 for patients who received maintenance for more than 24 months, compared with less than 12 months (Leuk Lymphoma. 2019 Feb;60[2]:511-4).
Dr. Shah also cited a pooled analysis of three phase 3 trials suggesting that continuous therapy is superior to fixed-duration therapy in patients with newly diagnosed myeloma. The median PFS was 32 months with continuous therapy and 16 months with fixed-duration therapy (P less than .001). The 4-year OS was 69% and 60%, respectively (P = .003; J Clin Oncol. 2015 Oct 20;33[30]:3459-66).
These data suggest that “continuous therapy, more therapy, has a survival advantage,” Dr. Shah said.
Don’t treat until progression
Dr. Efebera also discussed data from studies showing that lenalidomide maintenance can prolong survival in multiple myeloma. However, she said, it’s unclear how long maintenance should last.
Different durations of maintenance have proved effective in different trials. In the CALGB 100104 trial, the median duration of maintenance was 31 months (Lancet Haematol. 2017 Sep;4[9]:e431-e442). In the meta-analysis of the CALGB, IFM, and GIMEMA trials, the median duration was 22 months. And in Myeloma XI, the median duration was 18 months.
As there is no randomized trial comparing different durations of maintenance, Dr. Efebera proposed that researchers conduct one. She said this “perfect study” would involve induction with an immunomodulatory agent, a proteasome inhibitor, dexamethasone, and perhaps an anti-CD38 therapy. Transplant-eligible patients would receive four cycles of induction before transplant. Transplant-ineligible patients would receive eight cycles of induction. Then, all patients would be randomized to lenalidomide maintenance for 3 years, 5 years, or 7-10 years.
Until a trial like this reveals the optimal duration of maintenance, we cannot conclude that treating patients until progression is better, Dr. Efebera said.
She added that maintenance has been shown to have detrimental effects, and these should be taken into consideration. For instance, neutropenia, other hematologic adverse events, and second primary malignancies have been shown to be more common among patients who receive lenalidomide maintenance (N Engl J Med. 2012; 366:1782-91).
The cost of maintenance is another factor to consider. Researchers analyzed data from the CALGB 100104 and IFM 2005-02 trials to compare the cost of lenalidomide maintenance with no maintenance. In the CALGB 100104 trial, patients who received lenalidomide maintenance had 5.72 quality-adjusted life years (QALYs), and those who received no maintenance had 4.61 QALYs. The incremental cost-utility ratio (ICUR) was more than 277,000 euros per QALY.
In the IFM2005-02 trial, patients in the lenalidomide group had 5.13 QALYs, and those who didn’t receive maintenance had 4.98 QALYs. The ICUR was more than 1.5 million euros per QALY. The researchers said the high ICURs and budgetary impact add “uncertainty about the maximum prudent duration of the treatment” (Bone Marrow Transplant. 2019 May 31. doi: 10.1038/s41409-019-0574-5).
Dr. Efebera reported relationships with Akcea Therapeutics, Janssen, and Takeda. Dr. Shah reported having no relevant financial relationships.
SAN FRANCISCO – Should patients with multiple myeloma receive maintenance therapy until progression?
Yvonne A. Efebera, MD, of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital in Columbus, and Nina Shah, MD, of the University of California San Francisco Health, faced off on this question at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.
Dr. Shah said maintenance therapy improves survival in myeloma patients, so it follows that treating them until progression would confer a survival advantage. While Dr. Efebera agreed that maintenance can improve survival, she said the optimal duration of that treatment is unknown.
Treat until progression
Dr. Shah cited studies suggesting that maintenance improves progression-free survival (PFS) and may prolong overall survival (OS) in multiple myeloma.
A meta-analysis of data from the IFM 2005-02, CALGB 100104, and GIMEMA RV-MM-PI-209 trials showed that lenalidomide maintenance prolonged PFS and OS. The median PFS was 52.8 months in patients who received maintenance and 23.5 months in those who received placebo or observation (hazard ratio [HR], 0.48). At a median follow-up of 79.5 months, the median OS was not reached for the maintenance group and was 86.0 months for the no-maintenance group (HR, 0.75; P = .001; J Clin Oncol. 2017 Oct 10;35[29]:3279-89).
In the Myeloma XI trial, maintenance improved PFS, but not OS, in both transplant-eligible and ineligible patients. Overall, the median PFS was 39 months in the lenalidomide maintenance arm and 20 months in the observation arm (P less than .0001). Among transplant-eligible patients, the median PFS was 57 months and 30 months, respectively (P less than .0001). Among transplant-ineligible patients, the median PFS was 26 months and 11 months, respectively (P less than .0001; Lancet Oncol. 2019 Jan;20[1]:57-73).
These data suggest maintenance can improve survival, “but the question is, how long should we have therapy,” Dr. Shah said. “No one has looked at this in a prospective manner, so we really have to look at our retrospective data.”
One study suggested a longer duration of lenalidomide maintenance improves PFS. The HR for progression or death was 0.39 for patients who received maintenance for 12-24 months, compared with those who received maintenance for less than 12 months. The HR was 0.13 for patients who received maintenance for more than 24 months, compared with less than 12 months (Leuk Lymphoma. 2019 Feb;60[2]:511-4).
Dr. Shah also cited a pooled analysis of three phase 3 trials suggesting that continuous therapy is superior to fixed-duration therapy in patients with newly diagnosed myeloma. The median PFS was 32 months with continuous therapy and 16 months with fixed-duration therapy (P less than .001). The 4-year OS was 69% and 60%, respectively (P = .003; J Clin Oncol. 2015 Oct 20;33[30]:3459-66).
These data suggest that “continuous therapy, more therapy, has a survival advantage,” Dr. Shah said.
Don’t treat until progression
Dr. Efebera also discussed data from studies showing that lenalidomide maintenance can prolong survival in multiple myeloma. However, she said, it’s unclear how long maintenance should last.
Different durations of maintenance have proved effective in different trials. In the CALGB 100104 trial, the median duration of maintenance was 31 months (Lancet Haematol. 2017 Sep;4[9]:e431-e442). In the meta-analysis of the CALGB, IFM, and GIMEMA trials, the median duration was 22 months. And in Myeloma XI, the median duration was 18 months.
As there is no randomized trial comparing different durations of maintenance, Dr. Efebera proposed that researchers conduct one. She said this “perfect study” would involve induction with an immunomodulatory agent, a proteasome inhibitor, dexamethasone, and perhaps an anti-CD38 therapy. Transplant-eligible patients would receive four cycles of induction before transplant. Transplant-ineligible patients would receive eight cycles of induction. Then, all patients would be randomized to lenalidomide maintenance for 3 years, 5 years, or 7-10 years.
Until a trial like this reveals the optimal duration of maintenance, we cannot conclude that treating patients until progression is better, Dr. Efebera said.
She added that maintenance has been shown to have detrimental effects, and these should be taken into consideration. For instance, neutropenia, other hematologic adverse events, and second primary malignancies have been shown to be more common among patients who receive lenalidomide maintenance (N Engl J Med. 2012; 366:1782-91).
The cost of maintenance is another factor to consider. Researchers analyzed data from the CALGB 100104 and IFM 2005-02 trials to compare the cost of lenalidomide maintenance with no maintenance. In the CALGB 100104 trial, patients who received lenalidomide maintenance had 5.72 quality-adjusted life years (QALYs), and those who received no maintenance had 4.61 QALYs. The incremental cost-utility ratio (ICUR) was more than 277,000 euros per QALY.
In the IFM2005-02 trial, patients in the lenalidomide group had 5.13 QALYs, and those who didn’t receive maintenance had 4.98 QALYs. The ICUR was more than 1.5 million euros per QALY. The researchers said the high ICURs and budgetary impact add “uncertainty about the maximum prudent duration of the treatment” (Bone Marrow Transplant. 2019 May 31. doi: 10.1038/s41409-019-0574-5).
Dr. Efebera reported relationships with Akcea Therapeutics, Janssen, and Takeda. Dr. Shah reported having no relevant financial relationships.
SAN FRANCISCO – Should patients with multiple myeloma receive maintenance therapy until progression?
Yvonne A. Efebera, MD, of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital in Columbus, and Nina Shah, MD, of the University of California San Francisco Health, faced off on this question at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.
Dr. Shah said maintenance therapy improves survival in myeloma patients, so it follows that treating them until progression would confer a survival advantage. While Dr. Efebera agreed that maintenance can improve survival, she said the optimal duration of that treatment is unknown.
Treat until progression
Dr. Shah cited studies suggesting that maintenance improves progression-free survival (PFS) and may prolong overall survival (OS) in multiple myeloma.
A meta-analysis of data from the IFM 2005-02, CALGB 100104, and GIMEMA RV-MM-PI-209 trials showed that lenalidomide maintenance prolonged PFS and OS. The median PFS was 52.8 months in patients who received maintenance and 23.5 months in those who received placebo or observation (hazard ratio [HR], 0.48). At a median follow-up of 79.5 months, the median OS was not reached for the maintenance group and was 86.0 months for the no-maintenance group (HR, 0.75; P = .001; J Clin Oncol. 2017 Oct 10;35[29]:3279-89).
In the Myeloma XI trial, maintenance improved PFS, but not OS, in both transplant-eligible and ineligible patients. Overall, the median PFS was 39 months in the lenalidomide maintenance arm and 20 months in the observation arm (P less than .0001). Among transplant-eligible patients, the median PFS was 57 months and 30 months, respectively (P less than .0001). Among transplant-ineligible patients, the median PFS was 26 months and 11 months, respectively (P less than .0001; Lancet Oncol. 2019 Jan;20[1]:57-73).
These data suggest maintenance can improve survival, “but the question is, how long should we have therapy,” Dr. Shah said. “No one has looked at this in a prospective manner, so we really have to look at our retrospective data.”
One study suggested a longer duration of lenalidomide maintenance improves PFS. The HR for progression or death was 0.39 for patients who received maintenance for 12-24 months, compared with those who received maintenance for less than 12 months. The HR was 0.13 for patients who received maintenance for more than 24 months, compared with less than 12 months (Leuk Lymphoma. 2019 Feb;60[2]:511-4).
Dr. Shah also cited a pooled analysis of three phase 3 trials suggesting that continuous therapy is superior to fixed-duration therapy in patients with newly diagnosed myeloma. The median PFS was 32 months with continuous therapy and 16 months with fixed-duration therapy (P less than .001). The 4-year OS was 69% and 60%, respectively (P = .003; J Clin Oncol. 2015 Oct 20;33[30]:3459-66).
These data suggest that “continuous therapy, more therapy, has a survival advantage,” Dr. Shah said.
Don’t treat until progression
Dr. Efebera also discussed data from studies showing that lenalidomide maintenance can prolong survival in multiple myeloma. However, she said, it’s unclear how long maintenance should last.
Different durations of maintenance have proved effective in different trials. In the CALGB 100104 trial, the median duration of maintenance was 31 months (Lancet Haematol. 2017 Sep;4[9]:e431-e442). In the meta-analysis of the CALGB, IFM, and GIMEMA trials, the median duration was 22 months. And in Myeloma XI, the median duration was 18 months.
As there is no randomized trial comparing different durations of maintenance, Dr. Efebera proposed that researchers conduct one. She said this “perfect study” would involve induction with an immunomodulatory agent, a proteasome inhibitor, dexamethasone, and perhaps an anti-CD38 therapy. Transplant-eligible patients would receive four cycles of induction before transplant. Transplant-ineligible patients would receive eight cycles of induction. Then, all patients would be randomized to lenalidomide maintenance for 3 years, 5 years, or 7-10 years.
Until a trial like this reveals the optimal duration of maintenance, we cannot conclude that treating patients until progression is better, Dr. Efebera said.
She added that maintenance has been shown to have detrimental effects, and these should be taken into consideration. For instance, neutropenia, other hematologic adverse events, and second primary malignancies have been shown to be more common among patients who receive lenalidomide maintenance (N Engl J Med. 2012; 366:1782-91).
The cost of maintenance is another factor to consider. Researchers analyzed data from the CALGB 100104 and IFM 2005-02 trials to compare the cost of lenalidomide maintenance with no maintenance. In the CALGB 100104 trial, patients who received lenalidomide maintenance had 5.72 quality-adjusted life years (QALYs), and those who received no maintenance had 4.61 QALYs. The incremental cost-utility ratio (ICUR) was more than 277,000 euros per QALY.
In the IFM2005-02 trial, patients in the lenalidomide group had 5.13 QALYs, and those who didn’t receive maintenance had 4.98 QALYs. The ICUR was more than 1.5 million euros per QALY. The researchers said the high ICURs and budgetary impact add “uncertainty about the maximum prudent duration of the treatment” (Bone Marrow Transplant. 2019 May 31. doi: 10.1038/s41409-019-0574-5).
Dr. Efebera reported relationships with Akcea Therapeutics, Janssen, and Takeda. Dr. Shah reported having no relevant financial relationships.
EXPERT ANALYSIS FROM NCCN HEMATOLOGIC MALIGNANCIES