Hematology

In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering a peek into the much anticipated (and much hyped) clinical and research abstracts that will be presented at the 2018 ASH annual meeting.

Shorter R-CHOP regimen for DLBCL

Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).

Ibrutinib mastery in CLL

Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).

The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.

Anemia support in beta-thalassemia, MDS

In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.

The investigators report that the experimental agent was “generally well tolerated” (abstract 163).

“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.

Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.

“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.

Worth the wait

The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.

Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.

The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).

Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).

“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.

On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).

“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.

Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).

The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6­).

In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering a peek into the much anticipated (and much hyped) clinical and research abstracts that will be presented at the 2018 ASH annual meeting.

Shorter R-CHOP regimen for DLBCL

Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).

Ibrutinib mastery in CLL

Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).

The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.

Anemia support in beta-thalassemia, MDS

In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.

The investigators report that the experimental agent was “generally well tolerated” (abstract 163).

“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.

Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.

“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.

Worth the wait

The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.

Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.

The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).

Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).

“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.

On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).

“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.

Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).

The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6­).

In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering a peek into the much anticipated (and much hyped) clinical and research abstracts that will be presented at the 2018 ASH annual meeting.

Shorter R-CHOP regimen for DLBCL

Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).

Ibrutinib mastery in CLL

Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).

The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.

Anemia support in beta-thalassemia, MDS

In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.

The investigators report that the experimental agent was “generally well tolerated” (abstract 163).

“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.

Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.

“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.

Worth the wait

The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.

Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.

The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).

Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).

“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.

On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).

“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.

Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).

The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6­).

Ibrutinib and checkpoint inhibitors may improve the efficacy of chimeric antigen receptor (CAR) T-cell therapies, according to investigators in two separate studies.

Meanwhile, responses to tisagenlecleucel appear to be even more durable with longer follow-up, according to preliminary results from two more CAR T-cell therapy studies slated for presentation at the annual meeting of the American Society of Hematology.

A fifth study will show that bone marrow transplant may effectively consolidate remission after CAR T-cell therapy, according to Robert A. Brodsky, MD, ASH secretary, who highlighted the studies during a media briefing.

The ibrutinib study (abstract 299) shows that administering this BTK inhibitor starting 2 weeks prior to leukapheresis and continuing until 3 months after JCAR014 could improve responses and may decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Of 16 patients in an ibrutinib cohort and 18 patients in a no-ibrutinib cohort, the proportion of responders was 88% and 56%, respectively, according to preliminary data reported in the abstract. Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients in the no-ibrutinib cohort, and 0 of 17 patients in the ibrutinib cohort.

Those findings are “early and preliminary, but very exciting” for ibrutinib in combination with this CD-19 specific CAR T-cell therapy said Dr. Brodsky, director of the division of hematology at Johns Hopkins University in Baltimore.

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia (ALL).

In data to date, 14 patients with early CAR T-cell loss, partial response, or no response to CAR T-cell therapy received a PD-1 inhibitor.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said. “Sure enough, they were able to see that in roughly half of the patients. So again, very small, preliminary data, but very exciting that it is safe to give checkpoint inhibitors with CAR T-cells and it may be efficacious at getting the immune response back.”

One of the two tisagenlecleucel updates (abstract 895) showed that in the ELIANA trial, which included pediatric and young adults patients with relapsed/refractory ALL, the probability of relapse-free survival at 18 months was 66%.

“These are some very fast-growing tumors and these are refractory resistant patients, so as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

In the other tisagenlecleucel update (abstract 1684), investigators showed sustained disease control in Juliet, the global trial including adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with 40% of patients still in remission at 18 months, according to Dr. Brodsky.

One more report Dr. Brodsky highlighted (abstract 967) will look at long-term follow-up after administration of SCRI-CAR19v1, a CD19-specific CAR T-cell product. Preliminary data suggest a survival advantage when hematopoietic stem cell transplantation is done after CAR T-cell induced remission.

“This study is very small and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Ibrutinib and checkpoint inhibitors may improve the efficacy of chimeric antigen receptor (CAR) T-cell therapies, according to investigators in two separate studies.

Meanwhile, responses to tisagenlecleucel appear to be even more durable with longer follow-up, according to preliminary results from two more CAR T-cell therapy studies slated for presentation at the annual meeting of the American Society of Hematology.

A fifth study will show that bone marrow transplant may effectively consolidate remission after CAR T-cell therapy, according to Robert A. Brodsky, MD, ASH secretary, who highlighted the studies during a media briefing.

The ibrutinib study (abstract 299) shows that administering this BTK inhibitor starting 2 weeks prior to leukapheresis and continuing until 3 months after JCAR014 could improve responses and may decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Of 16 patients in an ibrutinib cohort and 18 patients in a no-ibrutinib cohort, the proportion of responders was 88% and 56%, respectively, according to preliminary data reported in the abstract. Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients in the no-ibrutinib cohort, and 0 of 17 patients in the ibrutinib cohort.

Those findings are “early and preliminary, but very exciting” for ibrutinib in combination with this CD-19 specific CAR T-cell therapy said Dr. Brodsky, director of the division of hematology at Johns Hopkins University in Baltimore.

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia (ALL).

In data to date, 14 patients with early CAR T-cell loss, partial response, or no response to CAR T-cell therapy received a PD-1 inhibitor.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said. “Sure enough, they were able to see that in roughly half of the patients. So again, very small, preliminary data, but very exciting that it is safe to give checkpoint inhibitors with CAR T-cells and it may be efficacious at getting the immune response back.”

One of the two tisagenlecleucel updates (abstract 895) showed that in the ELIANA trial, which included pediatric and young adults patients with relapsed/refractory ALL, the probability of relapse-free survival at 18 months was 66%.

“These are some very fast-growing tumors and these are refractory resistant patients, so as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

In the other tisagenlecleucel update (abstract 1684), investigators showed sustained disease control in Juliet, the global trial including adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with 40% of patients still in remission at 18 months, according to Dr. Brodsky.

One more report Dr. Brodsky highlighted (abstract 967) will look at long-term follow-up after administration of SCRI-CAR19v1, a CD19-specific CAR T-cell product. Preliminary data suggest a survival advantage when hematopoietic stem cell transplantation is done after CAR T-cell induced remission.

“This study is very small and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Ibrutinib and checkpoint inhibitors may improve the efficacy of chimeric antigen receptor (CAR) T-cell therapies, according to investigators in two separate studies.

Meanwhile, responses to tisagenlecleucel appear to be even more durable with longer follow-up, according to preliminary results from two more CAR T-cell therapy studies slated for presentation at the annual meeting of the American Society of Hematology.

A fifth study will show that bone marrow transplant may effectively consolidate remission after CAR T-cell therapy, according to Robert A. Brodsky, MD, ASH secretary, who highlighted the studies during a media briefing.

The ibrutinib study (abstract 299) shows that administering this BTK inhibitor starting 2 weeks prior to leukapheresis and continuing until 3 months after JCAR014 could improve responses and may decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Of 16 patients in an ibrutinib cohort and 18 patients in a no-ibrutinib cohort, the proportion of responders was 88% and 56%, respectively, according to preliminary data reported in the abstract. Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients in the no-ibrutinib cohort, and 0 of 17 patients in the ibrutinib cohort.

Those findings are “early and preliminary, but very exciting” for ibrutinib in combination with this CD-19 specific CAR T-cell therapy said Dr. Brodsky, director of the division of hematology at Johns Hopkins University in Baltimore.

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia (ALL).

In data to date, 14 patients with early CAR T-cell loss, partial response, or no response to CAR T-cell therapy received a PD-1 inhibitor.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said. “Sure enough, they were able to see that in roughly half of the patients. So again, very small, preliminary data, but very exciting that it is safe to give checkpoint inhibitors with CAR T-cells and it may be efficacious at getting the immune response back.”

One of the two tisagenlecleucel updates (abstract 895) showed that in the ELIANA trial, which included pediatric and young adults patients with relapsed/refractory ALL, the probability of relapse-free survival at 18 months was 66%.

“These are some very fast-growing tumors and these are refractory resistant patients, so as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

In the other tisagenlecleucel update (abstract 1684), investigators showed sustained disease control in Juliet, the global trial including adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with 40% of patients still in remission at 18 months, according to Dr. Brodsky.

One more report Dr. Brodsky highlighted (abstract 967) will look at long-term follow-up after administration of SCRI-CAR19v1, a CD19-specific CAR T-cell product. Preliminary data suggest a survival advantage when hematopoietic stem cell transplantation is done after CAR T-cell induced remission.

“This study is very small and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.

Mitchel L. Zoler/MDedge News

The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.

Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.

In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.

Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.

The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.

The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.

Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.

[email protected]

SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.

CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.

Mitchel L. Zoler/MDedge News

The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.

Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.

In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.

Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.

The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.

The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.

Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.

[email protected]

SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.

CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.

Mitchel L. Zoler/MDedge News

The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.

Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.

In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.

Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.

The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.

The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.

Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.

[email protected]

SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.

Recurrence risk is significant among all patients with venous thromboembolism (VTE), though recurrence is most frequent in patients with cancer-related VTE, according to a nationwide Danish study.

Ida Ehlers Albertsen, MD, of Aalborg (Denmark) University Hospital and her coauthors followed 73,993 patients who were diagnosed with incident VTE during January 2000–December 2015. The patients’ VTEs were classified as either cancer-related, unprovoked (occurring in patients without any provoking factors), or provoked (occurring in patients with one or more provoking factors, such as recent major surgery, recent fracture/trauma, obesity, or hormone replacement therapy).

The researchers found similar risks of recurrence among patients with unprovoked and provoked VTE at 6-month follow-up, with rates per 100 person-years of 6.80 and 6.92, respectively. By comparison, the recurrence rate for cancer-related VTE at 6 months was 9.06. The findings were reported in the American Journal of Medicine.

However, at 10-year follow-up the rates were 3.70 for cancer-related VTE, 2.84 for unprovoked VTE, and 2.22 for provoked VTE, which reinforces the belief that “unprovoked venous thromboembolism is associated with long-term higher risk of recurrence than provoked venous thromboembolism.”

Additionally, at 10-year follow-up, the absolute recurrence risk of cancer-related VTE and unprovoked VTE were both at approximately 20%, with recurrence risk of provoked VTE at just above 15%. Compared with the recurrence risk of provoked VTE at 10-year follow-up, the hazard ratios of cancer-related VTE and unprovoked VTE recurrence risk were 1.23 (95% confidence interval, 1.13-1.33) and 1.18 (95% CI, 1.13-1.24), respectively.

The coauthors observed several challenges in comparing their study to previous analyses on recurrent risk, noting that the definition of provoked VTE “varies throughout the literature” and that the majority of VTE studies “provide cumulative incidence proportions and not the actual rates.” They also stated that indefinite or extended therapy for all VTE patients comes with its own potential complications, even with the improved safety of non–vitamin K antagonist oral anticoagulants, writing that “treatment should be given to patients where the benefits outweigh the risks.”

Despite the differences in recurrence rates at 6-month and 10-year follow-up, the coauthors suggested that enough risk was present in all types to warrant additional studies and reconsider how VTE patients are categorized.

“A high recurrence risk in all types of venous thromboembolism indicates that further research is needed to optimize risk stratification for venous thromboembolism patients,” they wrote.

The study was partially funded by a grant from the Obel Family Foundation. Some authors reported financial disclosures related to Janssen, Bayer, Roche, and others.

SOURCE: Albertsen IE et al. Am J Med. 2018 Sep;131(9):1067-74.e4.

Recurrence risk is significant among all patients with venous thromboembolism (VTE), though recurrence is most frequent in patients with cancer-related VTE, according to a nationwide Danish study.

Ida Ehlers Albertsen, MD, of Aalborg (Denmark) University Hospital and her coauthors followed 73,993 patients who were diagnosed with incident VTE during January 2000–December 2015. The patients’ VTEs were classified as either cancer-related, unprovoked (occurring in patients without any provoking factors), or provoked (occurring in patients with one or more provoking factors, such as recent major surgery, recent fracture/trauma, obesity, or hormone replacement therapy).

The researchers found similar risks of recurrence among patients with unprovoked and provoked VTE at 6-month follow-up, with rates per 100 person-years of 6.80 and 6.92, respectively. By comparison, the recurrence rate for cancer-related VTE at 6 months was 9.06. The findings were reported in the American Journal of Medicine.

However, at 10-year follow-up the rates were 3.70 for cancer-related VTE, 2.84 for unprovoked VTE, and 2.22 for provoked VTE, which reinforces the belief that “unprovoked venous thromboembolism is associated with long-term higher risk of recurrence than provoked venous thromboembolism.”

Additionally, at 10-year follow-up, the absolute recurrence risk of cancer-related VTE and unprovoked VTE were both at approximately 20%, with recurrence risk of provoked VTE at just above 15%. Compared with the recurrence risk of provoked VTE at 10-year follow-up, the hazard ratios of cancer-related VTE and unprovoked VTE recurrence risk were 1.23 (95% confidence interval, 1.13-1.33) and 1.18 (95% CI, 1.13-1.24), respectively.

The coauthors observed several challenges in comparing their study to previous analyses on recurrent risk, noting that the definition of provoked VTE “varies throughout the literature” and that the majority of VTE studies “provide cumulative incidence proportions and not the actual rates.” They also stated that indefinite or extended therapy for all VTE patients comes with its own potential complications, even with the improved safety of non–vitamin K antagonist oral anticoagulants, writing that “treatment should be given to patients where the benefits outweigh the risks.”

Despite the differences in recurrence rates at 6-month and 10-year follow-up, the coauthors suggested that enough risk was present in all types to warrant additional studies and reconsider how VTE patients are categorized.

“A high recurrence risk in all types of venous thromboembolism indicates that further research is needed to optimize risk stratification for venous thromboembolism patients,” they wrote.

The study was partially funded by a grant from the Obel Family Foundation. Some authors reported financial disclosures related to Janssen, Bayer, Roche, and others.

SOURCE: Albertsen IE et al. Am J Med. 2018 Sep;131(9):1067-74.e4.

Recurrence risk is significant among all patients with venous thromboembolism (VTE), though recurrence is most frequent in patients with cancer-related VTE, according to a nationwide Danish study.

Ida Ehlers Albertsen, MD, of Aalborg (Denmark) University Hospital and her coauthors followed 73,993 patients who were diagnosed with incident VTE during January 2000–December 2015. The patients’ VTEs were classified as either cancer-related, unprovoked (occurring in patients without any provoking factors), or provoked (occurring in patients with one or more provoking factors, such as recent major surgery, recent fracture/trauma, obesity, or hormone replacement therapy).

The researchers found similar risks of recurrence among patients with unprovoked and provoked VTE at 6-month follow-up, with rates per 100 person-years of 6.80 and 6.92, respectively. By comparison, the recurrence rate for cancer-related VTE at 6 months was 9.06. The findings were reported in the American Journal of Medicine.

However, at 10-year follow-up the rates were 3.70 for cancer-related VTE, 2.84 for unprovoked VTE, and 2.22 for provoked VTE, which reinforces the belief that “unprovoked venous thromboembolism is associated with long-term higher risk of recurrence than provoked venous thromboembolism.”

Additionally, at 10-year follow-up, the absolute recurrence risk of cancer-related VTE and unprovoked VTE were both at approximately 20%, with recurrence risk of provoked VTE at just above 15%. Compared with the recurrence risk of provoked VTE at 10-year follow-up, the hazard ratios of cancer-related VTE and unprovoked VTE recurrence risk were 1.23 (95% confidence interval, 1.13-1.33) and 1.18 (95% CI, 1.13-1.24), respectively.

The coauthors observed several challenges in comparing their study to previous analyses on recurrent risk, noting that the definition of provoked VTE “varies throughout the literature” and that the majority of VTE studies “provide cumulative incidence proportions and not the actual rates.” They also stated that indefinite or extended therapy for all VTE patients comes with its own potential complications, even with the improved safety of non–vitamin K antagonist oral anticoagulants, writing that “treatment should be given to patients where the benefits outweigh the risks.”

Despite the differences in recurrence rates at 6-month and 10-year follow-up, the coauthors suggested that enough risk was present in all types to warrant additional studies and reconsider how VTE patients are categorized.

“A high recurrence risk in all types of venous thromboembolism indicates that further research is needed to optimize risk stratification for venous thromboembolism patients,” they wrote.

The study was partially funded by a grant from the Obel Family Foundation. Some authors reported financial disclosures related to Janssen, Bayer, Roche, and others.

SOURCE: Albertsen IE et al. Am J Med. 2018 Sep;131(9):1067-74.e4.

The Food and Drug Administration has approved emapalumab-lzsg (Gamifant) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

[email protected]

The Food and Drug Administration has approved emapalumab-lzsg (Gamifant) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

[email protected]

The Food and Drug Administration has approved emapalumab-lzsg (Gamifant) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

[email protected]

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.

CHICAGO – Changes in quantitative lung CT scores for scleroderma-related interstitial lung disease independently validate the superiority of hematopoietic stem cell transplantation versus cyclophosphamide for severe systemic sclerosis, according to findings in a subset of patients from the SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial.

Mitchel L. Zoler/MDedge News

The recently published findings from the SCOT trial showed that myeloablation followed by autologous hematopoietic stem cell transplant (HSCT) significantly improved event-free and overall survival of systemic sclerosis patients at 54 months, compared with 12 monthly treatments with intravenous cyclophosphamide (N Engl J Med. 2018;378:35-47).

In a subset of 75 patients from the SCOT trial, the investigators analyzed changes in lung parenchymal abnormalities on high-resolution CT scans between baseline and serial follow-up exams performed yearly for up to 5 years. Follow-up scans at 14, 26, 48, and 54 months in available patients at each time point showed that whole-lung quantitative interstitial lung disease (QILD) scores – a validated measure that combines various CT texture-based characteristics to determine disease extent – decreased significantly by 7% at 54 months in patients who underwent HSCT, compared with no change in those who received cyclophosphamide (CYC; P = .024), Keith M. Sullivan, MD, reported at the annual meeting of the American College of Rheumatology.

Additionally, whole-lung quantitative lung fibrosis (QLF) scores were stable (–1%) in the HSCT patients, but increased 3% in the CYC patients (P = .047), said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.


Dr. Sullivan was the first author on the SCOT trial, and he reported the current study results on behalf of lead investigator Jonathan Goldin, MD, PhD, of the department of radiologic sciences at the University of California, Los Angeles.

“These are really kind of meaningful associations, especially since the worst of the [CYC] treatment group didn’t make it to month 54,” Dr. Sullivan said.

Quantitative scores of scleroderma-related interstitial lung disease were measured using computer-based quantitative image analysis of standardized, noncontrast, volumetric, thin-section, thoracic, high-resolution CT. The same CT machine was used for all time points (except for one subject) with careful attention to breath hold reproducibility and image quality. Baseline characteristics were not different between the HSCT and CYC groups, he noted, stressing the rigorous study design.

CT assessments were also compared for the most severe lobe in each patient and showed similar findings, with both QILD and QLF scores for that lobe improving in the HSCT patients relative to the CYC patients (P = .004 and P = .002, respectively), Dr. Sullivan said, adding that the direction of change in structural measures of QILD and QLF for both whole lung and most severe lobe CTs tracked with physiological pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 second, and diffusing capacity of the lungs for carbon monoxide.

“The FVC improved while QILD decreased, and that’s what you would expect to see,” he said. “So for each of these ways of displaying data, there was an expected and sensible inverse correlation.”

Scleroderma-related interstitial lung disease is a major cause of morbidity and mortality in severe systemic sclerosis. In the wake of the SCOT trial findings, questions remained with respect to correlation between those findings and pulmonary function; if the improvements with HSCT are real and meaningful, they should have meaningful correlation with pulmonary function, and these findings demonstrate those correlates, he said.

“Changes in quantitative lung CT scoring of scleroderma lung disease provide an objective radiologic validation of the long-term benefits of transplant compared to cyclophosphamide in individuals with severe scleroderma and lung involvement. Improvement in imaging after transplant continues for up to 54 months after randomization, giving radiologic confirmation of a durable treatment benefit,” Dr. Sullivan concluded.

The investigators reported having no relevant disclosures.

[email protected]

SOURCE: Goldin J et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 901.

CHICAGO – Changes in quantitative lung CT scores for scleroderma-related interstitial lung disease independently validate the superiority of hematopoietic stem cell transplantation versus cyclophosphamide for severe systemic sclerosis, according to findings in a subset of patients from the SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial.

Mitchel L. Zoler/MDedge News

The recently published findings from the SCOT trial showed that myeloablation followed by autologous hematopoietic stem cell transplant (HSCT) significantly improved event-free and overall survival of systemic sclerosis patients at 54 months, compared with 12 monthly treatments with intravenous cyclophosphamide (N Engl J Med. 2018;378:35-47).

In a subset of 75 patients from the SCOT trial, the investigators analyzed changes in lung parenchymal abnormalities on high-resolution CT scans between baseline and serial follow-up exams performed yearly for up to 5 years. Follow-up scans at 14, 26, 48, and 54 months in available patients at each time point showed that whole-lung quantitative interstitial lung disease (QILD) scores – a validated measure that combines various CT texture-based characteristics to determine disease extent – decreased significantly by 7% at 54 months in patients who underwent HSCT, compared with no change in those who received cyclophosphamide (CYC; P = .024), Keith M. Sullivan, MD, reported at the annual meeting of the American College of Rheumatology.

Additionally, whole-lung quantitative lung fibrosis (QLF) scores were stable (–1%) in the HSCT patients, but increased 3% in the CYC patients (P = .047), said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.


Dr. Sullivan was the first author on the SCOT trial, and he reported the current study results on behalf of lead investigator Jonathan Goldin, MD, PhD, of the department of radiologic sciences at the University of California, Los Angeles.

“These are really kind of meaningful associations, especially since the worst of the [CYC] treatment group didn’t make it to month 54,” Dr. Sullivan said.

Quantitative scores of scleroderma-related interstitial lung disease were measured using computer-based quantitative image analysis of standardized, noncontrast, volumetric, thin-section, thoracic, high-resolution CT. The same CT machine was used for all time points (except for one subject) with careful attention to breath hold reproducibility and image quality. Baseline characteristics were not different between the HSCT and CYC groups, he noted, stressing the rigorous study design.

CT assessments were also compared for the most severe lobe in each patient and showed similar findings, with both QILD and QLF scores for that lobe improving in the HSCT patients relative to the CYC patients (P = .004 and P = .002, respectively), Dr. Sullivan said, adding that the direction of change in structural measures of QILD and QLF for both whole lung and most severe lobe CTs tracked with physiological pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 second, and diffusing capacity of the lungs for carbon monoxide.

“The FVC improved while QILD decreased, and that’s what you would expect to see,” he said. “So for each of these ways of displaying data, there was an expected and sensible inverse correlation.”

Scleroderma-related interstitial lung disease is a major cause of morbidity and mortality in severe systemic sclerosis. In the wake of the SCOT trial findings, questions remained with respect to correlation between those findings and pulmonary function; if the improvements with HSCT are real and meaningful, they should have meaningful correlation with pulmonary function, and these findings demonstrate those correlates, he said.

“Changes in quantitative lung CT scoring of scleroderma lung disease provide an objective radiologic validation of the long-term benefits of transplant compared to cyclophosphamide in individuals with severe scleroderma and lung involvement. Improvement in imaging after transplant continues for up to 54 months after randomization, giving radiologic confirmation of a durable treatment benefit,” Dr. Sullivan concluded.

The investigators reported having no relevant disclosures.

[email protected]

SOURCE: Goldin J et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 901.

CHICAGO – Changes in quantitative lung CT scores for scleroderma-related interstitial lung disease independently validate the superiority of hematopoietic stem cell transplantation versus cyclophosphamide for severe systemic sclerosis, according to findings in a subset of patients from the SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial.

Mitchel L. Zoler/MDedge News

The recently published findings from the SCOT trial showed that myeloablation followed by autologous hematopoietic stem cell transplant (HSCT) significantly improved event-free and overall survival of systemic sclerosis patients at 54 months, compared with 12 monthly treatments with intravenous cyclophosphamide (N Engl J Med. 2018;378:35-47).

In a subset of 75 patients from the SCOT trial, the investigators analyzed changes in lung parenchymal abnormalities on high-resolution CT scans between baseline and serial follow-up exams performed yearly for up to 5 years. Follow-up scans at 14, 26, 48, and 54 months in available patients at each time point showed that whole-lung quantitative interstitial lung disease (QILD) scores – a validated measure that combines various CT texture-based characteristics to determine disease extent – decreased significantly by 7% at 54 months in patients who underwent HSCT, compared with no change in those who received cyclophosphamide (CYC; P = .024), Keith M. Sullivan, MD, reported at the annual meeting of the American College of Rheumatology.

Additionally, whole-lung quantitative lung fibrosis (QLF) scores were stable (–1%) in the HSCT patients, but increased 3% in the CYC patients (P = .047), said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.


Dr. Sullivan was the first author on the SCOT trial, and he reported the current study results on behalf of lead investigator Jonathan Goldin, MD, PhD, of the department of radiologic sciences at the University of California, Los Angeles.

“These are really kind of meaningful associations, especially since the worst of the [CYC] treatment group didn’t make it to month 54,” Dr. Sullivan said.

Quantitative scores of scleroderma-related interstitial lung disease were measured using computer-based quantitative image analysis of standardized, noncontrast, volumetric, thin-section, thoracic, high-resolution CT. The same CT machine was used for all time points (except for one subject) with careful attention to breath hold reproducibility and image quality. Baseline characteristics were not different between the HSCT and CYC groups, he noted, stressing the rigorous study design.

CT assessments were also compared for the most severe lobe in each patient and showed similar findings, with both QILD and QLF scores for that lobe improving in the HSCT patients relative to the CYC patients (P = .004 and P = .002, respectively), Dr. Sullivan said, adding that the direction of change in structural measures of QILD and QLF for both whole lung and most severe lobe CTs tracked with physiological pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 second, and diffusing capacity of the lungs for carbon monoxide.

“The FVC improved while QILD decreased, and that’s what you would expect to see,” he said. “So for each of these ways of displaying data, there was an expected and sensible inverse correlation.”

Scleroderma-related interstitial lung disease is a major cause of morbidity and mortality in severe systemic sclerosis. In the wake of the SCOT trial findings, questions remained with respect to correlation between those findings and pulmonary function; if the improvements with HSCT are real and meaningful, they should have meaningful correlation with pulmonary function, and these findings demonstrate those correlates, he said.

“Changes in quantitative lung CT scoring of scleroderma lung disease provide an objective radiologic validation of the long-term benefits of transplant compared to cyclophosphamide in individuals with severe scleroderma and lung involvement. Improvement in imaging after transplant continues for up to 54 months after randomization, giving radiologic confirmation of a durable treatment benefit,” Dr. Sullivan concluded.

The investigators reported having no relevant disclosures.

[email protected]

SOURCE: Goldin J et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 901.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

In patients with a new diagnosis of advanced cancer, an intervention that combined palliative care with rehabilitation helped improve quality of life, results of a randomized, single-center study suggest.

Patients had a significant improvement in their most pressing quality-of-life issues after participating in the intervention, which included individualized palliative care consultations and a patient/caregiver “school” of lectures, discussion, and physical exercise, investigators said.

These findings suggest that every patient facing an advanced cancer diagnosis should at least have an initial exploratory consultation with a specialized palliative care team, and should be offered not only the usual components of palliative care, but also cancer rehabilitation, said Lise Nottelmann, MD, of the department of oncology at Vejle Hospital in Denmark.

“We should be active as a health care system in approaching these patients and offering them this intervention, or at least a consultation exploring these aspects of quality of life,” Dr. Nottelmann said in an interview at the 2018 Palliative and Supportive Care in Oncology Symposium.

The study by Dr. Nottelmann and her colleagues, presented at the symposium, comprised 301 patients with nonresectable solid tumors, including lung, gastrointestinal, prostate, and others. Those patients were randomly allocated to the palliative rehabilitation intervention or to standard care only.

Every patient participated in two consultations with a specialized palliative care team, and then had the opportunity for individualized contact with the team in a 12-week open contact period. They were also invited to participate in the school sessions, each of which included a 20-minute lecture on topics such as physical activity and good nutrition plus a 40-minute discussion period, followed by an exercise session.

Of the patients randomized to the palliative rehabilitation intervention, 26 participated only in the initial consultations, while 59 participated in the group program, and 47 had individual consultations, Dr. Nottelmann reported.

To measure quality of life, the investigators asked patients to identify a “primary problem” that corresponded to one of 12 scales in the EORTC QLQ-C30 questionnaire related to physical and role functioning, emotional and cognitive functioning, or symptoms.

The primary endpoint of the analysis was improvement in QLQ-C30 scores at 12 weeks. The analysis was done on specific scales in the patients who identified a primary problem, combined with global QLQ-C30 scores for the remaining one-quarter of the patients who did not, Dr. Nottelmann said.

After 12 weeks, the patients in the intervention arm had a significant improvement versus the no-intervention arm as measured by a version of the EORTC QLQ-C30 questionnaire. The absolute between-group difference in scores was 3.0 (95% confidence interval, 0.0-6.0; P less than .047), according to researchers.

Starting palliative care earlier in the course of cancer, as done in this intervention, is an increasingly accepted practice, supported by large studies and recent clinical practice guidelines that recommend early integration of palliative care into the seriously ill patient’s care plan.

What was different about this intervention was the integration of rehabilitation aspects into palliative care, Dr. Nottelmann said in the interview. While not traditionally thought of as a component of palliative care, the concept of palliative rehabilitation is gaining ground, she said.

The goal of rehabilitative palliative care is to help individuals with life-limiting or terminal conditions actively self-manage their conditions so they can “live fully” and enjoy the best quality of life possible, according to Hospice UK, a national charity for hospice care in the United Kingdom.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. Dr. Nottelmann and her colleagues reported research funding from the Danish Cancer Society. Dr. Nottelmann had no disclosures related to the presentation. One coauthor provided disclosures related to Roche, Amgen, Bayer, and Merck Sharp & Dohme.

SOURCE: Nottelmann L et al. PallOnc 2018, Abstract 75.

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

BETHESDA, MD – While there are experimental treatments such as sevuparin and gene therapy in testing for sickle cell disease (SCD), researchers said this field is lagging because of a lack of funding.

Dr_Microbe/Thinkstock

Yogen Saunthararajah, MD, of the Cleveland Clinic, described what he called a “paltry” landscape of new drugs for SCD at Sickle Cell in Focus, a conference held by the National Institutes of Health.

There are only four main approaches taken by drugs now in clinical testing for addressing the root causes of SCD, despite decades’ worth of research of the genetic and mechanistic underpinnings of this disease, he said.

“It’s pretty sad,” Dr. Saunthararajah said, referring to the quantity of efforts, not their quality.

Within days of his presentation at the conference, one of the drugs he highlighted had officially fallen out of contention. An Oct. 26 post on NIH’s Clinicaltrials.gov site said Incyte had terminated its phase 1 study of INCB059872 in SCD “due to a business decision” not to pursue this indication. Incyte confirmed that it dropped development of INCB059872 for SCD but will continue testing it for other indications, including acute myeloid leukemia (AML).

Dr. Saunthararajah said that work on another approach, using decitabine (Dacogen), for which he has done a phase 1 study, is “struggling,” because of the search for funding.

Two other approaches that Dr. Saunthararajah cited in his presentation appear to remain on track. These are gene therapy and the once-daily voxelotor treatment from Global Blood Therapeutics.

In the field of gene therapy, Sangamo Therapeutics and Sanofi’s Bioverativ in May said the Food and Drug Administration had cleared the way for them to start a phase 1/2 clinical trial for the BIVV003 product that they are developing together. This uses zinc finger nuclease (ZFN) gene-editing technology to modifying a short sequence of the BCL11A gene, with the aim of reactivating fetal hemoglobin.

Bluebird Bio’s LentiGlobin gene therapy has advanced as far as phase 3 for transfusion-dependent beta-thalassemia and phase 1/2 for SCD. In October, the European Medicines Agency accepted the company’s application for approval of LentiGlobin gene therapy for the treatment of adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and a non-beta⁰/beta⁰ genotype. The company has not said when it expects to file with the FDA for approval of this treatment.

In the field of oral therapies, Global Blood Therapeutics has said it’s in discussions with the FDA about a potential accelerated approval of voxelotor. The tablet is meant to inhibit the underlying mechanism that causes sickling of red blood cells. In June, the company completed a planned review of early data from its phase 3 trial, known as the HOPE study.

“On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1,500-mg and 900-mg doses after 12 weeks of treatment versus placebo,” Global Blood Therapeutics said in an August regulatory filing with the Securities and Exchange Commission.

The company has said that voxelotor may meet the FDA’s standard for accelerated approval under Subpart H program.

In his presentation at the NIH conference, Tom Williams, MD, PhD, of KEMRI/Wellcome Trust Research Programme highlighted a recent review of experimental SCD treatments by Marilyn Jo Telen, MD, of Duke University, Durham, N.C. (Blood. 2016;127[7]:810-9).

Also among the drugs being tested for SCD is Modus Therapeutics’ sevuparin, which Dr. Williams described as being “a heparin-like molecule without the anticoagulant complications.”

The compound originated as a “passion project” of Mats Wahlgren, MD, PhD, of the Karolinska Institute, Stockholm, who developed it for the treatment of malaria, Dr. Williams said. The company that’s developing sevuparin, Modus Therapeutics, is moving it forward first as a treatment for SCD for commercial reasons, Dr. Williams said.

“They think it’s a better first target,” he said.

An ongoing study of sevuparin for painful crisis is expected to be completed in December, with data then expected to be released in the middle of 2019, Ellen K. Donnelly, PhD, chief executive officer of Modus Therapeutics, said in an interview. She cited a mix of scientific, medical and commercial reasons for her company’s decision to advance sevuparin in SCD.

“First, and most importantly, there is proof of clinical benefit of a similar molecule (the low-molecular-weight heparin called tinzaparin) in patients with sickle cell disease,” Dr. Donnelly said. “Unfortunately, there is a bleeding risk with tinzaparin that limits use of the agent for the treatment of sickle cell disease. Sevuparin does not have the bleeding risk and thus is a strong candidate for SCD.”

Dr. Donnelly also noted the emphasis that the FDA’s Division of Hematology Products has put on development of therapeutics for SCD as a reason for proceeding first with this indication. The agency and the American Society of Hematology in early October held a workshop of experts, physicians, patients, and industry collaborators focused on identifying new endpoints for clinical studies.

Still, she noted that commercial reasons did factor into this decision.

“[I]t is possible for a small company like Modus to take an asset all the way to market when developing a therapeutic for a rare disease given the need for fewer patients and smaller trials,” Dr. Donnelly wrote. “As you can see from www.clinicaltrials.gov, we were able to run our phase 2 study with a small number of sites. In addition, in SCD it is possible to get approval with only one or two confirmatory studies.”
 

Financial interests

Other drugs in testing for SCD include rivipansel from GlycoMimetics, for which Pfizer is leading development. The sponsors expect to complete the so-called RESET trial by 2019, according to the clinicaltrials.gov. In this study, which is intended to enroll 350 participants, patients who have vaso-occlusive crises are randomly selected for treatment with either rivipansel or placebo.

Speaking during a question-and-answer session at the NIH conference, Robert Swift, PhD, said there’s a need for inexpensive oral drugs to treat SCD. Many other options will remain beyond the finances of people living in poor countries, he said.

“We need to focus not only on the root cause, but on something that is oral and inexpensive to solve the greater sickle cell problem,” Dr. Swift said.

Large drugmakers already have hospital-based sales forces, making SCD drugs administered in this setting attractive to them, he said.

“This is partly about where money is. The drug companies are going where the money is. It’s not oral drugs to treat everybody, it’s something else,” Dr. Swift said. “So someone else is going to have to fund the basic research” into treatments that could be more broadly used.

Dr. Swift said in an interview that he has received NIH funding for developing SCD-101, an oral drug, for which a placebo-controlled crossover study is underway.

Presenters at the NIH conference, including Dr. Saunthararajah, expressed frustration about what they see as relatively little work being done on SCD despite decades of knowledge about the root causes. Like Dr. Swift, he criticized the approach taken in selecting which treatments advance in this field.

“It’s not being driven by what is the most cost effective, what the patients need the most,” Dr. Saunthararajah said. “It’s driven by what will make the most money, not just for [the] drug company, but also for the hospital and also for the physicians.”

Dr. Saunthararajah reported having patents and patent applications around decitabine/tetrahydrouridine, 5-azacytidine/tetrahydrouridine, and differentiation therapy for oncology. He has also been a consultant for EpiDestiny, Novo Nordisk, and Takeda Oncology. Dr. Williams reported having no relevant financial disclosures. Dr. Swift is a managing member of Invenux and reported equity in Mast Therapeutics and SCD Development.

This article was updated on 11/9/2018.

BETHESDA, MD – While there are experimental treatments such as sevuparin and gene therapy in testing for sickle cell disease (SCD), researchers said this field is lagging because of a lack of funding.

Dr_Microbe/Thinkstock

Yogen Saunthararajah, MD, of the Cleveland Clinic, described what he called a “paltry” landscape of new drugs for SCD at Sickle Cell in Focus, a conference held by the National Institutes of Health.

There are only four main approaches taken by drugs now in clinical testing for addressing the root causes of SCD, despite decades’ worth of research of the genetic and mechanistic underpinnings of this disease, he said.

“It’s pretty sad,” Dr. Saunthararajah said, referring to the quantity of efforts, not their quality.

Within days of his presentation at the conference, one of the drugs he highlighted had officially fallen out of contention. An Oct. 26 post on NIH’s Clinicaltrials.gov site said Incyte had terminated its phase 1 study of INCB059872 in SCD “due to a business decision” not to pursue this indication. Incyte confirmed that it dropped development of INCB059872 for SCD but will continue testing it for other indications, including acute myeloid leukemia (AML).

Dr. Saunthararajah said that work on another approach, using decitabine (Dacogen), for which he has done a phase 1 study, is “struggling,” because of the search for funding.

Two other approaches that Dr. Saunthararajah cited in his presentation appear to remain on track. These are gene therapy and the once-daily voxelotor treatment from Global Blood Therapeutics.

In the field of gene therapy, Sangamo Therapeutics and Sanofi’s Bioverativ in May said the Food and Drug Administration had cleared the way for them to start a phase 1/2 clinical trial for the BIVV003 product that they are developing together. This uses zinc finger nuclease (ZFN) gene-editing technology to modifying a short sequence of the BCL11A gene, with the aim of reactivating fetal hemoglobin.

Bluebird Bio’s LentiGlobin gene therapy has advanced as far as phase 3 for transfusion-dependent beta-thalassemia and phase 1/2 for SCD. In October, the European Medicines Agency accepted the company’s application for approval of LentiGlobin gene therapy for the treatment of adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and a non-beta⁰/beta⁰ genotype. The company has not said when it expects to file with the FDA for approval of this treatment.

In the field of oral therapies, Global Blood Therapeutics has said it’s in discussions with the FDA about a potential accelerated approval of voxelotor. The tablet is meant to inhibit the underlying mechanism that causes sickling of red blood cells. In June, the company completed a planned review of early data from its phase 3 trial, known as the HOPE study.

“On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1,500-mg and 900-mg doses after 12 weeks of treatment versus placebo,” Global Blood Therapeutics said in an August regulatory filing with the Securities and Exchange Commission.

The company has said that voxelotor may meet the FDA’s standard for accelerated approval under Subpart H program.

In his presentation at the NIH conference, Tom Williams, MD, PhD, of KEMRI/Wellcome Trust Research Programme highlighted a recent review of experimental SCD treatments by Marilyn Jo Telen, MD, of Duke University, Durham, N.C. (Blood. 2016;127[7]:810-9).

Also among the drugs being tested for SCD is Modus Therapeutics’ sevuparin, which Dr. Williams described as being “a heparin-like molecule without the anticoagulant complications.”

The compound originated as a “passion project” of Mats Wahlgren, MD, PhD, of the Karolinska Institute, Stockholm, who developed it for the treatment of malaria, Dr. Williams said. The company that’s developing sevuparin, Modus Therapeutics, is moving it forward first as a treatment for SCD for commercial reasons, Dr. Williams said.

“They think it’s a better first target,” he said.

An ongoing study of sevuparin for painful crisis is expected to be completed in December, with data then expected to be released in the middle of 2019, Ellen K. Donnelly, PhD, chief executive officer of Modus Therapeutics, said in an interview. She cited a mix of scientific, medical and commercial reasons for her company’s decision to advance sevuparin in SCD.

“First, and most importantly, there is proof of clinical benefit of a similar molecule (the low-molecular-weight heparin called tinzaparin) in patients with sickle cell disease,” Dr. Donnelly said. “Unfortunately, there is a bleeding risk with tinzaparin that limits use of the agent for the treatment of sickle cell disease. Sevuparin does not have the bleeding risk and thus is a strong candidate for SCD.”

Dr. Donnelly also noted the emphasis that the FDA’s Division of Hematology Products has put on development of therapeutics for SCD as a reason for proceeding first with this indication. The agency and the American Society of Hematology in early October held a workshop of experts, physicians, patients, and industry collaborators focused on identifying new endpoints for clinical studies.

Still, she noted that commercial reasons did factor into this decision.

“[I]t is possible for a small company like Modus to take an asset all the way to market when developing a therapeutic for a rare disease given the need for fewer patients and smaller trials,” Dr. Donnelly wrote. “As you can see from www.clinicaltrials.gov, we were able to run our phase 2 study with a small number of sites. In addition, in SCD it is possible to get approval with only one or two confirmatory studies.”
 

Financial interests

Other drugs in testing for SCD include rivipansel from GlycoMimetics, for which Pfizer is leading development. The sponsors expect to complete the so-called RESET trial by 2019, according to the clinicaltrials.gov. In this study, which is intended to enroll 350 participants, patients who have vaso-occlusive crises are randomly selected for treatment with either rivipansel or placebo.

Speaking during a question-and-answer session at the NIH conference, Robert Swift, PhD, said there’s a need for inexpensive oral drugs to treat SCD. Many other options will remain beyond the finances of people living in poor countries, he said.

“We need to focus not only on the root cause, but on something that is oral and inexpensive to solve the greater sickle cell problem,” Dr. Swift said.

Large drugmakers already have hospital-based sales forces, making SCD drugs administered in this setting attractive to them, he said.

“This is partly about where money is. The drug companies are going where the money is. It’s not oral drugs to treat everybody, it’s something else,” Dr. Swift said. “So someone else is going to have to fund the basic research” into treatments that could be more broadly used.

Dr. Swift said in an interview that he has received NIH funding for developing SCD-101, an oral drug, for which a placebo-controlled crossover study is underway.

Presenters at the NIH conference, including Dr. Saunthararajah, expressed frustration about what they see as relatively little work being done on SCD despite decades of knowledge about the root causes. Like Dr. Swift, he criticized the approach taken in selecting which treatments advance in this field.

“It’s not being driven by what is the most cost effective, what the patients need the most,” Dr. Saunthararajah said. “It’s driven by what will make the most money, not just for [the] drug company, but also for the hospital and also for the physicians.”

Dr. Saunthararajah reported having patents and patent applications around decitabine/tetrahydrouridine, 5-azacytidine/tetrahydrouridine, and differentiation therapy for oncology. He has also been a consultant for EpiDestiny, Novo Nordisk, and Takeda Oncology. Dr. Williams reported having no relevant financial disclosures. Dr. Swift is a managing member of Invenux and reported equity in Mast Therapeutics and SCD Development.

This article was updated on 11/9/2018.

BETHESDA, MD – While there are experimental treatments such as sevuparin and gene therapy in testing for sickle cell disease (SCD), researchers said this field is lagging because of a lack of funding.

Dr_Microbe/Thinkstock

Yogen Saunthararajah, MD, of the Cleveland Clinic, described what he called a “paltry” landscape of new drugs for SCD at Sickle Cell in Focus, a conference held by the National Institutes of Health.

There are only four main approaches taken by drugs now in clinical testing for addressing the root causes of SCD, despite decades’ worth of research of the genetic and mechanistic underpinnings of this disease, he said.

“It’s pretty sad,” Dr. Saunthararajah said, referring to the quantity of efforts, not their quality.

Within days of his presentation at the conference, one of the drugs he highlighted had officially fallen out of contention. An Oct. 26 post on NIH’s Clinicaltrials.gov site said Incyte had terminated its phase 1 study of INCB059872 in SCD “due to a business decision” not to pursue this indication. Incyte confirmed that it dropped development of INCB059872 for SCD but will continue testing it for other indications, including acute myeloid leukemia (AML).

Dr. Saunthararajah said that work on another approach, using decitabine (Dacogen), for which he has done a phase 1 study, is “struggling,” because of the search for funding.

Two other approaches that Dr. Saunthararajah cited in his presentation appear to remain on track. These are gene therapy and the once-daily voxelotor treatment from Global Blood Therapeutics.

In the field of gene therapy, Sangamo Therapeutics and Sanofi’s Bioverativ in May said the Food and Drug Administration had cleared the way for them to start a phase 1/2 clinical trial for the BIVV003 product that they are developing together. This uses zinc finger nuclease (ZFN) gene-editing technology to modifying a short sequence of the BCL11A gene, with the aim of reactivating fetal hemoglobin.

Bluebird Bio’s LentiGlobin gene therapy has advanced as far as phase 3 for transfusion-dependent beta-thalassemia and phase 1/2 for SCD. In October, the European Medicines Agency accepted the company’s application for approval of LentiGlobin gene therapy for the treatment of adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and a non-beta⁰/beta⁰ genotype. The company has not said when it expects to file with the FDA for approval of this treatment.

In the field of oral therapies, Global Blood Therapeutics has said it’s in discussions with the FDA about a potential accelerated approval of voxelotor. The tablet is meant to inhibit the underlying mechanism that causes sickling of red blood cells. In June, the company completed a planned review of early data from its phase 3 trial, known as the HOPE study.

“On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1,500-mg and 900-mg doses after 12 weeks of treatment versus placebo,” Global Blood Therapeutics said in an August regulatory filing with the Securities and Exchange Commission.

The company has said that voxelotor may meet the FDA’s standard for accelerated approval under Subpart H program.

In his presentation at the NIH conference, Tom Williams, MD, PhD, of KEMRI/Wellcome Trust Research Programme highlighted a recent review of experimental SCD treatments by Marilyn Jo Telen, MD, of Duke University, Durham, N.C. (Blood. 2016;127[7]:810-9).

Also among the drugs being tested for SCD is Modus Therapeutics’ sevuparin, which Dr. Williams described as being “a heparin-like molecule without the anticoagulant complications.”

The compound originated as a “passion project” of Mats Wahlgren, MD, PhD, of the Karolinska Institute, Stockholm, who developed it for the treatment of malaria, Dr. Williams said. The company that’s developing sevuparin, Modus Therapeutics, is moving it forward first as a treatment for SCD for commercial reasons, Dr. Williams said.

“They think it’s a better first target,” he said.

An ongoing study of sevuparin for painful crisis is expected to be completed in December, with data then expected to be released in the middle of 2019, Ellen K. Donnelly, PhD, chief executive officer of Modus Therapeutics, said in an interview. She cited a mix of scientific, medical and commercial reasons for her company’s decision to advance sevuparin in SCD.

“First, and most importantly, there is proof of clinical benefit of a similar molecule (the low-molecular-weight heparin called tinzaparin) in patients with sickle cell disease,” Dr. Donnelly said. “Unfortunately, there is a bleeding risk with tinzaparin that limits use of the agent for the treatment of sickle cell disease. Sevuparin does not have the bleeding risk and thus is a strong candidate for SCD.”

Dr. Donnelly also noted the emphasis that the FDA’s Division of Hematology Products has put on development of therapeutics for SCD as a reason for proceeding first with this indication. The agency and the American Society of Hematology in early October held a workshop of experts, physicians, patients, and industry collaborators focused on identifying new endpoints for clinical studies.

Still, she noted that commercial reasons did factor into this decision.

“[I]t is possible for a small company like Modus to take an asset all the way to market when developing a therapeutic for a rare disease given the need for fewer patients and smaller trials,” Dr. Donnelly wrote. “As you can see from www.clinicaltrials.gov, we were able to run our phase 2 study with a small number of sites. In addition, in SCD it is possible to get approval with only one or two confirmatory studies.”
 

Financial interests

Other drugs in testing for SCD include rivipansel from GlycoMimetics, for which Pfizer is leading development. The sponsors expect to complete the so-called RESET trial by 2019, according to the clinicaltrials.gov. In this study, which is intended to enroll 350 participants, patients who have vaso-occlusive crises are randomly selected for treatment with either rivipansel or placebo.

Speaking during a question-and-answer session at the NIH conference, Robert Swift, PhD, said there’s a need for inexpensive oral drugs to treat SCD. Many other options will remain beyond the finances of people living in poor countries, he said.

“We need to focus not only on the root cause, but on something that is oral and inexpensive to solve the greater sickle cell problem,” Dr. Swift said.

Large drugmakers already have hospital-based sales forces, making SCD drugs administered in this setting attractive to them, he said.

“This is partly about where money is. The drug companies are going where the money is. It’s not oral drugs to treat everybody, it’s something else,” Dr. Swift said. “So someone else is going to have to fund the basic research” into treatments that could be more broadly used.

Dr. Swift said in an interview that he has received NIH funding for developing SCD-101, an oral drug, for which a placebo-controlled crossover study is underway.

Presenters at the NIH conference, including Dr. Saunthararajah, expressed frustration about what they see as relatively little work being done on SCD despite decades of knowledge about the root causes. Like Dr. Swift, he criticized the approach taken in selecting which treatments advance in this field.

“It’s not being driven by what is the most cost effective, what the patients need the most,” Dr. Saunthararajah said. “It’s driven by what will make the most money, not just for [the] drug company, but also for the hospital and also for the physicians.”

Dr. Saunthararajah reported having patents and patent applications around decitabine/tetrahydrouridine, 5-azacytidine/tetrahydrouridine, and differentiation therapy for oncology. He has also been a consultant for EpiDestiny, Novo Nordisk, and Takeda Oncology. Dr. Williams reported having no relevant financial disclosures. Dr. Swift is a managing member of Invenux and reported equity in Mast Therapeutics and SCD Development.

This article was updated on 11/9/2018.