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MEDALIST: Erythroid maturation agent reduced transfusion burden in MDS
SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.
Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said Alan F. List, MD, of Moffitt Cancer Center, Tampa.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of the MEDALIST trial, said in a press conference at the annual meeting of the American Society of Hematology.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan, reported that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.
The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed sideroblasts who were RBC transfusion–dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomly allocated to luspatercept 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days. The primary end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).
There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.
The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.
That study also included a small number of patients who had not previously received an ESA. Currently underway is a phase 3 trial looking at luspatercept in ESA-naive, lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, who represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.
“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
Dr. List reported research funding from Celgene.
SOURCE: List AF et al. ASH 2018, Abstract 1.
SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.
Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said Alan F. List, MD, of Moffitt Cancer Center, Tampa.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of the MEDALIST trial, said in a press conference at the annual meeting of the American Society of Hematology.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan, reported that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.
The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed sideroblasts who were RBC transfusion–dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomly allocated to luspatercept 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days. The primary end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).
There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.
The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.
That study also included a small number of patients who had not previously received an ESA. Currently underway is a phase 3 trial looking at luspatercept in ESA-naive, lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, who represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.
“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
Dr. List reported research funding from Celgene.
SOURCE: List AF et al. ASH 2018, Abstract 1.
SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.
Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said Alan F. List, MD, of Moffitt Cancer Center, Tampa.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of the MEDALIST trial, said in a press conference at the annual meeting of the American Society of Hematology.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan, reported that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.
The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed sideroblasts who were RBC transfusion–dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomly allocated to luspatercept 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days. The primary end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).
There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.
The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.
That study also included a small number of patients who had not previously received an ESA. Currently underway is a phase 3 trial looking at luspatercept in ESA-naive, lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, who represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.
“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
Dr. List reported research funding from Celgene.
SOURCE: List AF et al. ASH 2018, Abstract 1.
REPORTING FROM ASH 2018
Key clinical point: Luspatercept, a novel erythroid maturation agent, significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes and ringed sideroblasts.
Major finding: The proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment was 37.9% for luspatercept and 13.2% for placebo (P less than .0001).
Study details: A randomized, phase 3 trial including 220 lower-risk myelodysplastic syndromes patients with ringed sideroblasts who were RBC transfusion–dependent.
Disclosures: Dr. List reported research funding from Celgene.
Source: List AF et al. ASH 2018, abstract 1.
Heavy menstrual bleeding in teens often linked to bleeding disorders
Over one-third of adolescents presenting with heavy menstrual bleeding were diagnosed with a bleeding disorder after screening, according to results of a retrospective study.
The high incidence of bleeding disorders detected argues for routine screening of adolescents with heavy menstrual bleeding (HMB), Brooke O’Brien, MD, of the University of Queensland, Brisbane, Australia, and her colleagues wrote in the Journal of Pediatric & Adolescent Gynecology.
“These findings support comprehensive and systematic hemostatic evaluation in adolescents with HMB,” Dr. O’Brien and her colleagues wrote. “A higher level of awareness of bleeding disorders as a cause for HMB in adolescence, especially [von Willebrand disease] and platelet function disorders, is needed and close multidisciplinary collaboration between the pediatric and adolescent gynecologist and hematologist in a specialized tertiary center should be established in the management of these patients.”
In their study, Dr. O’Brien and her colleagues retrospectively evaluated 124 adolescents with HMB at a pediatric and adolescent gynecology tertiary care center between July 2007 and July 2017. Of these, 77 patients (62.1%) underwent screening for blood disorders.
The researchers found 27 adolescents overall were diagnosed with a blood disorder, which consisted of 35.0% of patients screened and 21.7% of all patients studied. Specifically, 14 of 27 patients (51.6%) screened were diagnosed with von Willebrand disease, 9 of 27 patients (33.3%) screened were found to have inherited platelet function disorders, 3 of 27 patients (11.1%) had inherited or acquired thrombocytopenia, and 1 of 27 patients (3.7%) had factor IX deficiency. The researchers also screened for iron deficiency and/or anemia and found 53 of 107 patients (49.5%) who were screened received a diagnosis, and 19 of 27 patients (70.3%) who were diagnosed with a bleeding disorder also had iron deficiency and/or anemia.
“In adolescents who are already known to have a bleeding disorder, consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding,” Dr. O’Brien and her colleagues wrote.
Potential limitations in the study include the refractory nature of referrals at a tertiary care center potentially overestimating the prevalence of HMB in this population as well as the study’s retrospective design when investigating and measuring heavy menstrual bleeding, but researchers noted patients were reviewed and classified by a specialist pediatric hematologist.
The authors reported no relevant conflicts of interest.
SOURCE: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22. doi: 10.1016/j.jpag.2018.11.005.
Over one-third of adolescents presenting with heavy menstrual bleeding were diagnosed with a bleeding disorder after screening, according to results of a retrospective study.
The high incidence of bleeding disorders detected argues for routine screening of adolescents with heavy menstrual bleeding (HMB), Brooke O’Brien, MD, of the University of Queensland, Brisbane, Australia, and her colleagues wrote in the Journal of Pediatric & Adolescent Gynecology.
“These findings support comprehensive and systematic hemostatic evaluation in adolescents with HMB,” Dr. O’Brien and her colleagues wrote. “A higher level of awareness of bleeding disorders as a cause for HMB in adolescence, especially [von Willebrand disease] and platelet function disorders, is needed and close multidisciplinary collaboration between the pediatric and adolescent gynecologist and hematologist in a specialized tertiary center should be established in the management of these patients.”
In their study, Dr. O’Brien and her colleagues retrospectively evaluated 124 adolescents with HMB at a pediatric and adolescent gynecology tertiary care center between July 2007 and July 2017. Of these, 77 patients (62.1%) underwent screening for blood disorders.
The researchers found 27 adolescents overall were diagnosed with a blood disorder, which consisted of 35.0% of patients screened and 21.7% of all patients studied. Specifically, 14 of 27 patients (51.6%) screened were diagnosed with von Willebrand disease, 9 of 27 patients (33.3%) screened were found to have inherited platelet function disorders, 3 of 27 patients (11.1%) had inherited or acquired thrombocytopenia, and 1 of 27 patients (3.7%) had factor IX deficiency. The researchers also screened for iron deficiency and/or anemia and found 53 of 107 patients (49.5%) who were screened received a diagnosis, and 19 of 27 patients (70.3%) who were diagnosed with a bleeding disorder also had iron deficiency and/or anemia.
“In adolescents who are already known to have a bleeding disorder, consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding,” Dr. O’Brien and her colleagues wrote.
Potential limitations in the study include the refractory nature of referrals at a tertiary care center potentially overestimating the prevalence of HMB in this population as well as the study’s retrospective design when investigating and measuring heavy menstrual bleeding, but researchers noted patients were reviewed and classified by a specialist pediatric hematologist.
The authors reported no relevant conflicts of interest.
SOURCE: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22. doi: 10.1016/j.jpag.2018.11.005.
Over one-third of adolescents presenting with heavy menstrual bleeding were diagnosed with a bleeding disorder after screening, according to results of a retrospective study.
The high incidence of bleeding disorders detected argues for routine screening of adolescents with heavy menstrual bleeding (HMB), Brooke O’Brien, MD, of the University of Queensland, Brisbane, Australia, and her colleagues wrote in the Journal of Pediatric & Adolescent Gynecology.
“These findings support comprehensive and systematic hemostatic evaluation in adolescents with HMB,” Dr. O’Brien and her colleagues wrote. “A higher level of awareness of bleeding disorders as a cause for HMB in adolescence, especially [von Willebrand disease] and platelet function disorders, is needed and close multidisciplinary collaboration between the pediatric and adolescent gynecologist and hematologist in a specialized tertiary center should be established in the management of these patients.”
In their study, Dr. O’Brien and her colleagues retrospectively evaluated 124 adolescents with HMB at a pediatric and adolescent gynecology tertiary care center between July 2007 and July 2017. Of these, 77 patients (62.1%) underwent screening for blood disorders.
The researchers found 27 adolescents overall were diagnosed with a blood disorder, which consisted of 35.0% of patients screened and 21.7% of all patients studied. Specifically, 14 of 27 patients (51.6%) screened were diagnosed with von Willebrand disease, 9 of 27 patients (33.3%) screened were found to have inherited platelet function disorders, 3 of 27 patients (11.1%) had inherited or acquired thrombocytopenia, and 1 of 27 patients (3.7%) had factor IX deficiency. The researchers also screened for iron deficiency and/or anemia and found 53 of 107 patients (49.5%) who were screened received a diagnosis, and 19 of 27 patients (70.3%) who were diagnosed with a bleeding disorder also had iron deficiency and/or anemia.
“In adolescents who are already known to have a bleeding disorder, consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding,” Dr. O’Brien and her colleagues wrote.
Potential limitations in the study include the refractory nature of referrals at a tertiary care center potentially overestimating the prevalence of HMB in this population as well as the study’s retrospective design when investigating and measuring heavy menstrual bleeding, but researchers noted patients were reviewed and classified by a specialist pediatric hematologist.
The authors reported no relevant conflicts of interest.
SOURCE: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22. doi: 10.1016/j.jpag.2018.11.005.
FROM THE JOURNAL OF PEDIATRIC & ADOLESCENT GYNECOLOGY
Key clinical point: More than one-third of adolescents with heavy menstrual bleeding were diagnosed with a bleeding disorder.
Major finding: After screening, 35% of women with heavy menstrual bleeding had a bleeding disorder; over half of those screened had von Willebrand disease.
Study details: A retrospective study of 124 adolescents at the Queensland Paediatric and Adolescent Gynaecology Service between July 2007 and July 2017.
Disclosures: The authors reported no relevant conflicts of interest.
Source: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22 . doi: 10.1016/j.jpag.2018.11.005.
Your guide to ASH 2018: Abstracts to watch
With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.
Lymphomas
Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.
The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.
Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.
In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).
Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).
Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).
Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.
“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
CAR T-cell therapy
There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).
“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.
The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).
Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.
The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.
The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).
Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
MDS/MPN
Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.
“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.
The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).
Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.
“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.
The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.
“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.
The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
AML
For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.
In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.
“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”
The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).
Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.
“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”
The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).
Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.
The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
Notable posters
Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.
Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.
How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.
You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.
Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.
With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.
Lymphomas
Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.
The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.
Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.
In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).
Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).
Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).
Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.
“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
CAR T-cell therapy
There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).
“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.
The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).
Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.
The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.
The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).
Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
MDS/MPN
Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.
“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.
The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).
Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.
“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.
The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.
“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.
The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
AML
For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.
In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.
“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”
The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).
Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.
“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”
The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).
Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.
The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
Notable posters
Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.
Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.
How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.
You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.
Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.
With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.
Lymphomas
Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.
The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.
Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.
In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).
Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).
Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).
Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.
“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
CAR T-cell therapy
There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).
“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.
The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).
Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.
The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.
The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).
Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
MDS/MPN
Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.
“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.
The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).
Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.
“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.
The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.
“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.
The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
AML
For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.
In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.
“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”
The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).
Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.
“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”
The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).
Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.
The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
Notable posters
Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.
Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.
How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.
You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.
Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.
EC approves product for hemophilia A
The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.
Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.
The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.
The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.
Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
Study design
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated damoctocog alfa pegol for perioperative management.
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
Efficacy
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.
Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.
Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.
The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.
The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.
Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
Study design
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated damoctocog alfa pegol for perioperative management.
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
Efficacy
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.
Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
The European Commission (EC) has approved damoctocog alfa pegol (Jivi®), a recombinant human factor VIII therapy.
Damoctocog alfa pegol (formerly BAY94-9027) is approved for the treatment and prophylaxis of bleeding in previously treated patients age 12 and older who have hemophilia A.
The approval is valid in the European Union, Norway, Iceland, and Liechtenstein.
The EC’s decision to approve damoctocog alfa pegol is supported by the phase 2/3 PROTECT VIII trial.
Some results from this trial were published in the Journal of Thrombosis and Haemostasis in 2016. Additional results are available in the U.S. prescribing information for Jivi.
Study design
PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.
In part A, researchers evaluated different dosing regimens for damoctocog alfa pegol used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A.
In part B, researchers evaluated damoctocog alfa pegol for perioperative management.
In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.
Patients received damoctocog alfa pegol for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.
Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).
Efficacy
The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).
The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).
The median ABR for patients treated on demand was 24.1.
There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were “moderate,” and 3.3% were “poor.”
There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A.
Damoctocog alfa pegol provided “good” or “excellent” hemostatic control during all surgeries.
Safety
Safety data are available for 148 patients age 12 and older.
Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).
A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.
One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.
Canada expands approval for antihemophilic factor
Health Canada has extended the approved indication for Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.
The product is now approved for use in hemophilia A patients under the age of 12 for the control and prevention of bleeding episodes, as prophylaxis to prevent or reduce the frequency of bleeding, and for perioperative management of bleeding.
Adynovate (formerly BAX 855) was first approved in Canada in November 2016. At that time, it was authorized for use in hemophilia A patients age 12 and older as on-demand treatment, as prophylaxis, and for perioperative management.
Adynovate is built on the full-length Advate molecule, but Adynovate leverages pegylation technology designed to extend the amount of FVIII available for use in the body.
The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.
Health Canada’s decision to expand the indication for Adynovate is supported by results from a phase 3 trial of pediatric patients as well as a phase 3 trial of patients undergoing surgery.
Pediatric trial
The pediatric trial enrolled 73 patients, ages 1 to 11, with previously treated hemophilia A.
Sixty-six patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.
The median annualized bleeding rate was 2.0 for all bleeds and 0 for both joint and spontaneous bleeds.
Thirty-eight percent of patients did not have any bleeding episodes, 67% had no spontaneous bleeds, and 73% had no joint bleeds.
One patient developed inhibitors, but there were no other treatment-related adverse events.
Results from this trial were published in Haemophilia in November 2016 and are available in the Canadian product monograph for Adynovate.
Perioperative study
The perioperative study included 15 patients, ages 19 to 52, with severe hemophilia A who were undergoing surgical procedures (11 of them major and four minor).
The patients received Adynovate at varying doses and schedules, depending on each patient’s pharmacokinetic profile for major procedures or Adynovate incremental recovery for minor procedures.
Intraoperative and perioperative hemostatic efficacy of Adynovate was deemed “excellent” for all 15 patients. The “excellent” rating meant that blood loss was less than or equal to that expected for the type of procedure performed in a non-hemophilic population.
Postoperatively (day 1 after the procedure), hemostatic efficacy was rated “good” for one procedure and “excellent” for the rest. The “good” rating meant that postoperative blood loss was up to 50% more than expected for the type of procedure performed in a non-hemophilic population.
There were no treatment-related adverse events or signs of immunogenicity in this trial.
Results were published in Haemophilia in June 2016 and are available in the Canadian product monograph for Adynovate.
Health Canada has extended the approved indication for Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.
The product is now approved for use in hemophilia A patients under the age of 12 for the control and prevention of bleeding episodes, as prophylaxis to prevent or reduce the frequency of bleeding, and for perioperative management of bleeding.
Adynovate (formerly BAX 855) was first approved in Canada in November 2016. At that time, it was authorized for use in hemophilia A patients age 12 and older as on-demand treatment, as prophylaxis, and for perioperative management.
Adynovate is built on the full-length Advate molecule, but Adynovate leverages pegylation technology designed to extend the amount of FVIII available for use in the body.
The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.
Health Canada’s decision to expand the indication for Adynovate is supported by results from a phase 3 trial of pediatric patients as well as a phase 3 trial of patients undergoing surgery.
Pediatric trial
The pediatric trial enrolled 73 patients, ages 1 to 11, with previously treated hemophilia A.
Sixty-six patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.
The median annualized bleeding rate was 2.0 for all bleeds and 0 for both joint and spontaneous bleeds.
Thirty-eight percent of patients did not have any bleeding episodes, 67% had no spontaneous bleeds, and 73% had no joint bleeds.
One patient developed inhibitors, but there were no other treatment-related adverse events.
Results from this trial were published in Haemophilia in November 2016 and are available in the Canadian product monograph for Adynovate.
Perioperative study
The perioperative study included 15 patients, ages 19 to 52, with severe hemophilia A who were undergoing surgical procedures (11 of them major and four minor).
The patients received Adynovate at varying doses and schedules, depending on each patient’s pharmacokinetic profile for major procedures or Adynovate incremental recovery for minor procedures.
Intraoperative and perioperative hemostatic efficacy of Adynovate was deemed “excellent” for all 15 patients. The “excellent” rating meant that blood loss was less than or equal to that expected for the type of procedure performed in a non-hemophilic population.
Postoperatively (day 1 after the procedure), hemostatic efficacy was rated “good” for one procedure and “excellent” for the rest. The “good” rating meant that postoperative blood loss was up to 50% more than expected for the type of procedure performed in a non-hemophilic population.
There were no treatment-related adverse events or signs of immunogenicity in this trial.
Results were published in Haemophilia in June 2016 and are available in the Canadian product monograph for Adynovate.
Health Canada has extended the approved indication for Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.
The product is now approved for use in hemophilia A patients under the age of 12 for the control and prevention of bleeding episodes, as prophylaxis to prevent or reduce the frequency of bleeding, and for perioperative management of bleeding.
Adynovate (formerly BAX 855) was first approved in Canada in November 2016. At that time, it was authorized for use in hemophilia A patients age 12 and older as on-demand treatment, as prophylaxis, and for perioperative management.
Adynovate is built on the full-length Advate molecule, but Adynovate leverages pegylation technology designed to extend the amount of FVIII available for use in the body.
The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.
Health Canada’s decision to expand the indication for Adynovate is supported by results from a phase 3 trial of pediatric patients as well as a phase 3 trial of patients undergoing surgery.
Pediatric trial
The pediatric trial enrolled 73 patients, ages 1 to 11, with previously treated hemophilia A.
Sixty-six patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.
The median annualized bleeding rate was 2.0 for all bleeds and 0 for both joint and spontaneous bleeds.
Thirty-eight percent of patients did not have any bleeding episodes, 67% had no spontaneous bleeds, and 73% had no joint bleeds.
One patient developed inhibitors, but there were no other treatment-related adverse events.
Results from this trial were published in Haemophilia in November 2016 and are available in the Canadian product monograph for Adynovate.
Perioperative study
The perioperative study included 15 patients, ages 19 to 52, with severe hemophilia A who were undergoing surgical procedures (11 of them major and four minor).
The patients received Adynovate at varying doses and schedules, depending on each patient’s pharmacokinetic profile for major procedures or Adynovate incremental recovery for minor procedures.
Intraoperative and perioperative hemostatic efficacy of Adynovate was deemed “excellent” for all 15 patients. The “excellent” rating meant that blood loss was less than or equal to that expected for the type of procedure performed in a non-hemophilic population.
Postoperatively (day 1 after the procedure), hemostatic efficacy was rated “good” for one procedure and “excellent” for the rest. The “good” rating meant that postoperative blood loss was up to 50% more than expected for the type of procedure performed in a non-hemophilic population.
There were no treatment-related adverse events or signs of immunogenicity in this trial.
Results were published in Haemophilia in June 2016 and are available in the Canadian product monograph for Adynovate.
Invasive strategy increased bleeding risk in frail older AMI patients
Frail older patients with acute myocardial infarction (AMI) may be at increased bleeding risk if managed with an invasive strategy, results of a large U.S. registry study suggest.
The increased bleeding risk was seen among frail older AMI patients who underwent cardiac catheterization, but it was not seen in those treated with more conservative medical management, according to study results.
That finding highlights the conundrum with invasive management strategies for frail patients with AMI, wrote John A. Dodson, MD, MPH, of New York University and study coinvestigators.
“Awareness of vulnerability and greater utilization of evidence-based strategies to reduce bleeding, including radial access and properly dose-adjusted anticoagulant therapies, may mitigate some bleeding events,” they wrote in JACC: Cardiovascular Interventions.
Results of this study, the first large U.S. registry analysis evaluating in-hospital bleeding risk in frail older adults with AMI, confirm findings from several previous small cohort studies linking frailty in AMI patients to in-hospital bleeding, investigators reported.
The analysis included a total of 129,330 AMI patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were aged at least 65 years in 2015 or 2016.
About one in six of these older patients were frail, as defined by a composite score based on impaired walking, cognition, and activities of daily living, investigators reported.
The bleeding rate was significantly higher among frail patients undergoing cardiac catheterization, at 9.4% for patients rated as having vulnerable/mild frailty and 9.9% for patients with moderate to severe frailty (P less than.001), compared with fit/well patients, whose rate was 6.5%, investigators wrote. By contrast, there was no significant difference in bleeding rates for frail versus nonfrail patients managed conservatively, they said.
After adjusting for bleeding risk factors, frailty was independently associated with increased risk of bleeding, compared with fit/well status, with odds ratios of 1.33 for vulnerable/mild frailty and 1.40 for moderate to severe frailty. Again, no association was found between frailty and bleeding risk in patients managed conservatively, according to investigators.
Frail patients in the ACTION registry were more often older and female and less likely to undergo cardiac catheterization when compared with fit or well patients, they added in the report.
Like the small cohort studies that preceded it, this large U.S. registry study shows that frailty is an “important additional risk factor” among older adults with AMI who are managed with an invasive strategy, investigators said.
“When applicable, estimation of bleeding risk in frail patients before invasive care may facilitate clinical decision making and the informed consent process,” they wrote.
The ACTION registry, an ongoing quality improvement initiative sponsored by the American College of Cardiology and the American Heart Association, started collecting frailty characteristics among hospitalized AMI patients in 2015, investigators noted.
Dr. Dodson reported support from the National Institutes of Health/National Institute on Aging and from the American Heart Association. Study coauthors provided disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96
SOURCE: Dodson JA et al. JACC Cardiovasc Intv. 2018;11:2287-96.
This analysis is important and has clinical implications beyond those of previous analyses linking frailty to poor outcomes in patients with cardiovascular disease, according to John A. Bittl, MD.
“The present study helps to transform the rote recording of frailty from a mere quality metric in the medical record into an actionable diagnosis,” Dr. Bittl said in an editorial comment on the findings.
Results of the study show an association between invasive cardiac procedures and increased bleeding in frail patients with AMI.
The benefits of an invasive procedure might be outweighed by the incremental risk added by frailty in older AMI patients at low to moderate risk of poor outcomes, Dr. Bittl suggested.
By contrast, frail older AMI patients at high risk for poor outcomes might be better candidates for an invasive procedure if they can undergo a transradial approach, he said, noting that in the study by Dodson and colleagues, only 26% of frail patients received radial access despite randomized trials showing the approach reduces risk of bleeding.
“In this way, diagnosing frailty in a patient with AMI facilitates clinical decision making and helps to personalize an approach to optimize outcomes,” Dr. Bittl concluded.
Dr. Bittl is with the Interventional Cardiology Group, Florida Hospital Ocala (Fla.) He reported no relationships relevant to his editorial comment ( JACC Cardiovasc Interv. 2018 Nov 26;11[2];2297-93 ).
This analysis is important and has clinical implications beyond those of previous analyses linking frailty to poor outcomes in patients with cardiovascular disease, according to John A. Bittl, MD.
“The present study helps to transform the rote recording of frailty from a mere quality metric in the medical record into an actionable diagnosis,” Dr. Bittl said in an editorial comment on the findings.
Results of the study show an association between invasive cardiac procedures and increased bleeding in frail patients with AMI.
The benefits of an invasive procedure might be outweighed by the incremental risk added by frailty in older AMI patients at low to moderate risk of poor outcomes, Dr. Bittl suggested.
By contrast, frail older AMI patients at high risk for poor outcomes might be better candidates for an invasive procedure if they can undergo a transradial approach, he said, noting that in the study by Dodson and colleagues, only 26% of frail patients received radial access despite randomized trials showing the approach reduces risk of bleeding.
“In this way, diagnosing frailty in a patient with AMI facilitates clinical decision making and helps to personalize an approach to optimize outcomes,” Dr. Bittl concluded.
Dr. Bittl is with the Interventional Cardiology Group, Florida Hospital Ocala (Fla.) He reported no relationships relevant to his editorial comment ( JACC Cardiovasc Interv. 2018 Nov 26;11[2];2297-93 ).
This analysis is important and has clinical implications beyond those of previous analyses linking frailty to poor outcomes in patients with cardiovascular disease, according to John A. Bittl, MD.
“The present study helps to transform the rote recording of frailty from a mere quality metric in the medical record into an actionable diagnosis,” Dr. Bittl said in an editorial comment on the findings.
Results of the study show an association between invasive cardiac procedures and increased bleeding in frail patients with AMI.
The benefits of an invasive procedure might be outweighed by the incremental risk added by frailty in older AMI patients at low to moderate risk of poor outcomes, Dr. Bittl suggested.
By contrast, frail older AMI patients at high risk for poor outcomes might be better candidates for an invasive procedure if they can undergo a transradial approach, he said, noting that in the study by Dodson and colleagues, only 26% of frail patients received radial access despite randomized trials showing the approach reduces risk of bleeding.
“In this way, diagnosing frailty in a patient with AMI facilitates clinical decision making and helps to personalize an approach to optimize outcomes,” Dr. Bittl concluded.
Dr. Bittl is with the Interventional Cardiology Group, Florida Hospital Ocala (Fla.) He reported no relationships relevant to his editorial comment ( JACC Cardiovasc Interv. 2018 Nov 26;11[2];2297-93 ).
Frail older patients with acute myocardial infarction (AMI) may be at increased bleeding risk if managed with an invasive strategy, results of a large U.S. registry study suggest.
The increased bleeding risk was seen among frail older AMI patients who underwent cardiac catheterization, but it was not seen in those treated with more conservative medical management, according to study results.
That finding highlights the conundrum with invasive management strategies for frail patients with AMI, wrote John A. Dodson, MD, MPH, of New York University and study coinvestigators.
“Awareness of vulnerability and greater utilization of evidence-based strategies to reduce bleeding, including radial access and properly dose-adjusted anticoagulant therapies, may mitigate some bleeding events,” they wrote in JACC: Cardiovascular Interventions.
Results of this study, the first large U.S. registry analysis evaluating in-hospital bleeding risk in frail older adults with AMI, confirm findings from several previous small cohort studies linking frailty in AMI patients to in-hospital bleeding, investigators reported.
The analysis included a total of 129,330 AMI patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were aged at least 65 years in 2015 or 2016.
About one in six of these older patients were frail, as defined by a composite score based on impaired walking, cognition, and activities of daily living, investigators reported.
The bleeding rate was significantly higher among frail patients undergoing cardiac catheterization, at 9.4% for patients rated as having vulnerable/mild frailty and 9.9% for patients with moderate to severe frailty (P less than.001), compared with fit/well patients, whose rate was 6.5%, investigators wrote. By contrast, there was no significant difference in bleeding rates for frail versus nonfrail patients managed conservatively, they said.
After adjusting for bleeding risk factors, frailty was independently associated with increased risk of bleeding, compared with fit/well status, with odds ratios of 1.33 for vulnerable/mild frailty and 1.40 for moderate to severe frailty. Again, no association was found between frailty and bleeding risk in patients managed conservatively, according to investigators.
Frail patients in the ACTION registry were more often older and female and less likely to undergo cardiac catheterization when compared with fit or well patients, they added in the report.
Like the small cohort studies that preceded it, this large U.S. registry study shows that frailty is an “important additional risk factor” among older adults with AMI who are managed with an invasive strategy, investigators said.
“When applicable, estimation of bleeding risk in frail patients before invasive care may facilitate clinical decision making and the informed consent process,” they wrote.
The ACTION registry, an ongoing quality improvement initiative sponsored by the American College of Cardiology and the American Heart Association, started collecting frailty characteristics among hospitalized AMI patients in 2015, investigators noted.
Dr. Dodson reported support from the National Institutes of Health/National Institute on Aging and from the American Heart Association. Study coauthors provided disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96
SOURCE: Dodson JA et al. JACC Cardiovasc Intv. 2018;11:2287-96.
Frail older patients with acute myocardial infarction (AMI) may be at increased bleeding risk if managed with an invasive strategy, results of a large U.S. registry study suggest.
The increased bleeding risk was seen among frail older AMI patients who underwent cardiac catheterization, but it was not seen in those treated with more conservative medical management, according to study results.
That finding highlights the conundrum with invasive management strategies for frail patients with AMI, wrote John A. Dodson, MD, MPH, of New York University and study coinvestigators.
“Awareness of vulnerability and greater utilization of evidence-based strategies to reduce bleeding, including radial access and properly dose-adjusted anticoagulant therapies, may mitigate some bleeding events,” they wrote in JACC: Cardiovascular Interventions.
Results of this study, the first large U.S. registry analysis evaluating in-hospital bleeding risk in frail older adults with AMI, confirm findings from several previous small cohort studies linking frailty in AMI patients to in-hospital bleeding, investigators reported.
The analysis included a total of 129,330 AMI patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were aged at least 65 years in 2015 or 2016.
About one in six of these older patients were frail, as defined by a composite score based on impaired walking, cognition, and activities of daily living, investigators reported.
The bleeding rate was significantly higher among frail patients undergoing cardiac catheterization, at 9.4% for patients rated as having vulnerable/mild frailty and 9.9% for patients with moderate to severe frailty (P less than.001), compared with fit/well patients, whose rate was 6.5%, investigators wrote. By contrast, there was no significant difference in bleeding rates for frail versus nonfrail patients managed conservatively, they said.
After adjusting for bleeding risk factors, frailty was independently associated with increased risk of bleeding, compared with fit/well status, with odds ratios of 1.33 for vulnerable/mild frailty and 1.40 for moderate to severe frailty. Again, no association was found between frailty and bleeding risk in patients managed conservatively, according to investigators.
Frail patients in the ACTION registry were more often older and female and less likely to undergo cardiac catheterization when compared with fit or well patients, they added in the report.
Like the small cohort studies that preceded it, this large U.S. registry study shows that frailty is an “important additional risk factor” among older adults with AMI who are managed with an invasive strategy, investigators said.
“When applicable, estimation of bleeding risk in frail patients before invasive care may facilitate clinical decision making and the informed consent process,” they wrote.
The ACTION registry, an ongoing quality improvement initiative sponsored by the American College of Cardiology and the American Heart Association, started collecting frailty characteristics among hospitalized AMI patients in 2015, investigators noted.
Dr. Dodson reported support from the National Institutes of Health/National Institute on Aging and from the American Heart Association. Study coauthors provided disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96
SOURCE: Dodson JA et al. JACC Cardiovasc Intv. 2018;11:2287-96.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
Key clinical point: Frail older patients with acute myocardial infarction may be at increased bleeding risk if managed with an invasive strategy.
Major finding: Frailty was associated with increased risk of bleeding, with odds ratios of 1.33 and 1.40, compared with fit or well patients.
Study details: Analysis including 129,330 AMI patients in a U.S. registry who were at least 65 years of age.
Disclosures: Researchers reported support from the National Institutes of Health/National Institute on Aging, as well as other disclosures related to Bayer, Janssen, Abbott Vascular, Jarvik Heart, LifeCuff Technologies, and Ancora Heart.
Source: Dodson JA et al. JACC Cardiovasc Interv. 2018 Nov 26;11:2287-96.
Risk score can predict thrombosis in ITP
Research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score was able to identify all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly, within a matter of days, suggesting they should be reevaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ont., and her colleagues reported their findings in Blood.
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome.
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L.
- Major bleeding (grade 2 bleeding that does not involve the skin) at the time of visit.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests an increased risk of thrombosis, and a negative score suggests an increased risk of bleeding.
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months. During that time, there were 41 encounters between patients and clinicians. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld during 22 encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
Three of the 13 patients continued on anticoagulation during 10 encounters. The patients received additional ITP treatments at 6 of these encounters.
Major bleeding was present at 2 of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
The TH2 score accurately predicted all seven thrombotic events. There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score – suggesting an increased risk of thrombosis – when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be reevaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number patients evaluated. The TH2 score should be validated in additional, larger studies, they advised.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.
SOURCE: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.
Research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score was able to identify all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly, within a matter of days, suggesting they should be reevaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ont., and her colleagues reported their findings in Blood.
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome.
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L.
- Major bleeding (grade 2 bleeding that does not involve the skin) at the time of visit.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests an increased risk of thrombosis, and a negative score suggests an increased risk of bleeding.
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months. During that time, there were 41 encounters between patients and clinicians. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld during 22 encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
Three of the 13 patients continued on anticoagulation during 10 encounters. The patients received additional ITP treatments at 6 of these encounters.
Major bleeding was present at 2 of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
The TH2 score accurately predicted all seven thrombotic events. There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score – suggesting an increased risk of thrombosis – when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be reevaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number patients evaluated. The TH2 score should be validated in additional, larger studies, they advised.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.
SOURCE: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.
Research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score was able to identify all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly, within a matter of days, suggesting they should be reevaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ont., and her colleagues reported their findings in Blood.
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome.
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L.
- Major bleeding (grade 2 bleeding that does not involve the skin) at the time of visit.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests an increased risk of thrombosis, and a negative score suggests an increased risk of bleeding.
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months. During that time, there were 41 encounters between patients and clinicians. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld during 22 encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
Three of the 13 patients continued on anticoagulation during 10 encounters. The patients received additional ITP treatments at 6 of these encounters.
Major bleeding was present at 2 of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
The TH2 score accurately predicted all seven thrombotic events. There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score – suggesting an increased risk of thrombosis – when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be reevaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number patients evaluated. The TH2 score should be validated in additional, larger studies, they advised.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.
SOURCE: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.
FROM BLOOD
Key clinical point:
Major finding: The score predicted all seven thrombotic events in the study.
Study details: Retrospective study of 13 patients with ITP.
Disclosures: One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma.
Source: Balitsky AK et al. Blood. 2018 Nov 8. doi: 10.1182/blood-2018-08-868406.
Score can predict thrombosis in ITP
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
Preop anemia management saves blood, costs
BOSTON – A pilot anemia optimization program resulted in significant increases in day-of-surgery hemoglobin levels and reductions in RBC transfusion rates and costs in one center, but whether patient outcomes also improved is still not known.
By diagnosing anemia at the preanesthesia visit and providing anemic patients with dietary guidance and supplementation prior to cardiac surgery, blood program managers noticed a more than $360 reduction in per-patient blood-product acquisition costs, a more than $1,800 average reduction per patient in transfusion costs, and overall cost savings of more than $100,000 over 18 months, compared with historical data.
The findings were reported by Christine M. Cahill, RN, from Strong Memorial Hospital in Rochester, N.Y., and the University of Rochester (N.Y.), at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
“Anemia has been thought of as a relatively benign thing our patients live with traditionally, but what we have been finding lately is that anemia is actually more serious than we once thought, and is an independent risk factor for hospitalization, readmission, increased patient length of stay, loss of function, and diminished quality of life,” she said.
Anemia also increases the likelihood that a patient will require allogeneic transfusions and is an independent risk factor for morbidity and mortality, she added.
The pilot program, which ran from February 2016 to September 2017, was designed to test the feasibility of diagnosing anemia during a cardiology consult visit and implementing a management plan.
During the study period, 240 patients presenting for elective cardiac surgery were screened for anemia, and 58 were diagnosed as anemic, defined as a hemoglobin level of less than 12 g/dL. These patients were referred for anemia work-ups, which found that 33 patients had iron-deficient anemia and 25 had anemia from other causes. Controls were patients who underwent cardiac surgery from March to July 2015, matched by age, sex, and procedures.
Treatments for iron-deficient patients included oral iron (7 patients), intravenous iron with or without folate (20 patients), or oral folate with or without vitamin B12 (5 patients). One iron-deficient patient could not have surgery delayed for anemia management.
Of the iron-replete patients, one received oral iron and 17 received folate plus or minus vitamin B12. The remaining seven iron-replete patients were not treated for anemia.
One iron-deficient patient had a reaction to the infusion and did not receive a scheduled second dose due to the need for immediate surgery. A second patient scheduled for intravenous iron and folate broke an arm and therefore missed an intravenous infusion appointment. No other complications or reactions occurred.
Intraoperative transfusion units used in the anemia management group totaled 10, compared with 68 for controls. Postoperative transfusion units used were also significantly lower following anemia management at 13 versus 122, respectively.
The rate of RBC transfusions among patients with anemia management was 24%, compared with 60% for controls (P less than .0001). Patients in the management program also had significantly higher day-of-surgery hemoglobin, at 11.01 g/dL versus 10.16 g/dL (P less than .001), and less RBC utilization, at an average 0.40 units per patient versus 2.07 for controls (P less than .0001).
The average per patient savings in acquisition costs was $367.40, the average transfusion cost saving was $1,837, and the total cost savings over the life of the pilot program was $106,546.
The keys to success for similar programs is “to make sure you do your homework,” Ms. Cahill said. Specifically, she recommended feasibility studies, evaluation of the potential impact of infusions on the service, work flow analyses, and cost analyses. It’s also important to get high-level administrative support as well as buy-in from surgeons and patients.
Future studies should include assessment of patient outcomes, safety, and length of ICU and hospital stay, she emphasized.
The study was internally funded. Ms. Cahill reported having no conflicts of interest.
SOURCE: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
BOSTON – A pilot anemia optimization program resulted in significant increases in day-of-surgery hemoglobin levels and reductions in RBC transfusion rates and costs in one center, but whether patient outcomes also improved is still not known.
By diagnosing anemia at the preanesthesia visit and providing anemic patients with dietary guidance and supplementation prior to cardiac surgery, blood program managers noticed a more than $360 reduction in per-patient blood-product acquisition costs, a more than $1,800 average reduction per patient in transfusion costs, and overall cost savings of more than $100,000 over 18 months, compared with historical data.
The findings were reported by Christine M. Cahill, RN, from Strong Memorial Hospital in Rochester, N.Y., and the University of Rochester (N.Y.), at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
“Anemia has been thought of as a relatively benign thing our patients live with traditionally, but what we have been finding lately is that anemia is actually more serious than we once thought, and is an independent risk factor for hospitalization, readmission, increased patient length of stay, loss of function, and diminished quality of life,” she said.
Anemia also increases the likelihood that a patient will require allogeneic transfusions and is an independent risk factor for morbidity and mortality, she added.
The pilot program, which ran from February 2016 to September 2017, was designed to test the feasibility of diagnosing anemia during a cardiology consult visit and implementing a management plan.
During the study period, 240 patients presenting for elective cardiac surgery were screened for anemia, and 58 were diagnosed as anemic, defined as a hemoglobin level of less than 12 g/dL. These patients were referred for anemia work-ups, which found that 33 patients had iron-deficient anemia and 25 had anemia from other causes. Controls were patients who underwent cardiac surgery from March to July 2015, matched by age, sex, and procedures.
Treatments for iron-deficient patients included oral iron (7 patients), intravenous iron with or without folate (20 patients), or oral folate with or without vitamin B12 (5 patients). One iron-deficient patient could not have surgery delayed for anemia management.
Of the iron-replete patients, one received oral iron and 17 received folate plus or minus vitamin B12. The remaining seven iron-replete patients were not treated for anemia.
One iron-deficient patient had a reaction to the infusion and did not receive a scheduled second dose due to the need for immediate surgery. A second patient scheduled for intravenous iron and folate broke an arm and therefore missed an intravenous infusion appointment. No other complications or reactions occurred.
Intraoperative transfusion units used in the anemia management group totaled 10, compared with 68 for controls. Postoperative transfusion units used were also significantly lower following anemia management at 13 versus 122, respectively.
The rate of RBC transfusions among patients with anemia management was 24%, compared with 60% for controls (P less than .0001). Patients in the management program also had significantly higher day-of-surgery hemoglobin, at 11.01 g/dL versus 10.16 g/dL (P less than .001), and less RBC utilization, at an average 0.40 units per patient versus 2.07 for controls (P less than .0001).
The average per patient savings in acquisition costs was $367.40, the average transfusion cost saving was $1,837, and the total cost savings over the life of the pilot program was $106,546.
The keys to success for similar programs is “to make sure you do your homework,” Ms. Cahill said. Specifically, she recommended feasibility studies, evaluation of the potential impact of infusions on the service, work flow analyses, and cost analyses. It’s also important to get high-level administrative support as well as buy-in from surgeons and patients.
Future studies should include assessment of patient outcomes, safety, and length of ICU and hospital stay, she emphasized.
The study was internally funded. Ms. Cahill reported having no conflicts of interest.
SOURCE: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
BOSTON – A pilot anemia optimization program resulted in significant increases in day-of-surgery hemoglobin levels and reductions in RBC transfusion rates and costs in one center, but whether patient outcomes also improved is still not known.
By diagnosing anemia at the preanesthesia visit and providing anemic patients with dietary guidance and supplementation prior to cardiac surgery, blood program managers noticed a more than $360 reduction in per-patient blood-product acquisition costs, a more than $1,800 average reduction per patient in transfusion costs, and overall cost savings of more than $100,000 over 18 months, compared with historical data.
The findings were reported by Christine M. Cahill, RN, from Strong Memorial Hospital in Rochester, N.Y., and the University of Rochester (N.Y.), at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
“Anemia has been thought of as a relatively benign thing our patients live with traditionally, but what we have been finding lately is that anemia is actually more serious than we once thought, and is an independent risk factor for hospitalization, readmission, increased patient length of stay, loss of function, and diminished quality of life,” she said.
Anemia also increases the likelihood that a patient will require allogeneic transfusions and is an independent risk factor for morbidity and mortality, she added.
The pilot program, which ran from February 2016 to September 2017, was designed to test the feasibility of diagnosing anemia during a cardiology consult visit and implementing a management plan.
During the study period, 240 patients presenting for elective cardiac surgery were screened for anemia, and 58 were diagnosed as anemic, defined as a hemoglobin level of less than 12 g/dL. These patients were referred for anemia work-ups, which found that 33 patients had iron-deficient anemia and 25 had anemia from other causes. Controls were patients who underwent cardiac surgery from March to July 2015, matched by age, sex, and procedures.
Treatments for iron-deficient patients included oral iron (7 patients), intravenous iron with or without folate (20 patients), or oral folate with or without vitamin B12 (5 patients). One iron-deficient patient could not have surgery delayed for anemia management.
Of the iron-replete patients, one received oral iron and 17 received folate plus or minus vitamin B12. The remaining seven iron-replete patients were not treated for anemia.
One iron-deficient patient had a reaction to the infusion and did not receive a scheduled second dose due to the need for immediate surgery. A second patient scheduled for intravenous iron and folate broke an arm and therefore missed an intravenous infusion appointment. No other complications or reactions occurred.
Intraoperative transfusion units used in the anemia management group totaled 10, compared with 68 for controls. Postoperative transfusion units used were also significantly lower following anemia management at 13 versus 122, respectively.
The rate of RBC transfusions among patients with anemia management was 24%, compared with 60% for controls (P less than .0001). Patients in the management program also had significantly higher day-of-surgery hemoglobin, at 11.01 g/dL versus 10.16 g/dL (P less than .001), and less RBC utilization, at an average 0.40 units per patient versus 2.07 for controls (P less than .0001).
The average per patient savings in acquisition costs was $367.40, the average transfusion cost saving was $1,837, and the total cost savings over the life of the pilot program was $106,546.
The keys to success for similar programs is “to make sure you do your homework,” Ms. Cahill said. Specifically, she recommended feasibility studies, evaluation of the potential impact of infusions on the service, work flow analyses, and cost analyses. It’s also important to get high-level administrative support as well as buy-in from surgeons and patients.
Future studies should include assessment of patient outcomes, safety, and length of ICU and hospital stay, she emphasized.
The study was internally funded. Ms. Cahill reported having no conflicts of interest.
SOURCE: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
REPORTING FROM AABB 2018
Key clinical point:
Major finding: The total cost savings over the life of a pilot anemia management program was $106,546.
Study details: A case-control study with 58 patients scheduled for elective cardiac surgery and matched historical controls.
Disclosures: The study was internally funded. Ms. Cahill reported having no conflicts of interest.
Source: Cahill CM et al. AABB 2018, Abstract PBM4-ST4-22.
Denosumab effective against osteoporosis in TDT patients
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.
The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).
The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).
Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.
There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.
In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.
The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.
SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.
The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).
The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).
Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.
There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.
In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.
The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.
SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.
The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).
The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).
Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.
There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.
In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.
The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.
SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.
FROM BLOOD ADVANCES
Key clinical point:
Major finding: The mean increase in L1-L4 bone mineral density was 5.92% in patients treated with denosumab, compared with 2.92% in patients who received placebo (P = .043).
Study details: A phase 2b study that included 63 patients.
Disclosures: The research was funded by Amgen. The authors reported having no competing financial interests.
Source: Terpos E et al. Blood Adv. 2018;2:2837-47.
