SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.

Andrew D. Bowser/MDedge News

The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.

That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.

“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.

The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.

Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).

The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.

The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.

Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.

No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.

Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.

Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.

“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”

Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.

SOURCE: Larocca A, et al. ASH 2018, Abstract 305.

SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.

Andrew D. Bowser/MDedge News

The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.

That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.

“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.

The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.

Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).

The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.

The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.

Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.

No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.

Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.

Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.

“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”

Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.

SOURCE: Larocca A, et al. ASH 2018, Abstract 305.

SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.

Andrew D. Bowser/MDedge News

The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.

That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.

“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.

The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.

Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).

The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.

The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.

Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.

No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.

Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.

Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.

“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”

Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.

SOURCE: Larocca A, et al. ASH 2018, Abstract 305.

SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the annual meeting of the American Society of Hematology.

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.

The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.

SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the annual meeting of the American Society of Hematology.

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.

The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.

SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the annual meeting of the American Society of Hematology.

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.

The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.

SAN DIEGO – The success or failure of hematopoietic cell transplants may be related to the diversity of species in the gut microbiome, investigators contend.

Neil Osterweil/MDedge News

A study of fecal samples from patients scheduled to undergo hematopoietic cell transplant (HCT) in the United States, Europe, and Japan showed that intestinal microbial diversity was significantly associated with overall survival, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York City.

“Patients with low diversity pretransplant have a poorer overall survival than patients with a higher diversity after transplantation,” he said at the annual meeting of the American Society of Hematology. “The implication is, if we could come up with a way to remediate microbiome injury, there might be time to implement it before the transplant.”

There are about 100 trillion symbiotic microbes in and on the human body, and 95% of them live in the gastrointestinal tract, which has a surface area that if stretched out would equal the size of two tennis courts, Dr. Peled said.

Previous studies by his group and others have shown that the composition of intestinal microbiota is associated with survival, relapses, graft-versus-host disease, and infections in patients in the early weeks after allogeneic HCT.

The international team previously reported that intestinal diversity measured around the time of neutrophil engraftment was predictive of overall survival, and they hypothesized that the same might be true of the pretransplant microbiota composition.

To test this idea, they collected 1,922 stools samples approximately once weekly for 3 weeks pretransplant from 991 adult patients scheduled for allo-HCT for various diagnoses in two U.S. cohorts and one cohort each in Europe and Japan.

They found that on average patients in all four cohorts had microbiota diversity values ranging from 70% to 150% lower than those of healthy volunteers whose samples were sequenced by the investigators, as well as those in a publicly available database.

The investigators also asked whether one or more bacterial species accounted for 30% or more of a microbiome, a phenomenon known as “monodomination.”

“A third, or in some cases 95+%, of bacteria in an individual’s intestine are all the exact same strain,” Dr. Peled said.

They found that the incidence and prevalence of the monodomination phenotype was “strikingly similar” at all four transplant sites.


The patterns of microbiota injury were similar despite differences in antibiotic strategies among the four centers and different dietary patterns of patients in the regions studied.

Studies in animal models suggest that T cells responsible for graft-versus-host disease migrate to the gut as early as 2 or 3 days post transplant, and by that time more than half of transplant patients have a monodomination event in their guts, Dr. Peled said.

Some strategies to remediate or prevent microbiome damage – and potentially improve HCT outcomes – may include the use of over-the-counter or custom-made probiotics, fecal transplants, a “prebiotic” approach in which the patient is asked to follow a specific diet that promotes the growth of beneficial bacteria, or a “postbiotic” approach in which patients receive metabolites of agents or foods thought to have a beneficial effect.

“Finally, we can think about different antibiotic strategies, to use or not use different types of antibiotics at different times in a rational way,” Dr. Peled said.

Dr. Peled reported current or prior financial relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SOURCE: Peled JU et al. ASH 2018, Abstract 811.

SAN DIEGO – The success or failure of hematopoietic cell transplants may be related to the diversity of species in the gut microbiome, investigators contend.

Neil Osterweil/MDedge News

A study of fecal samples from patients scheduled to undergo hematopoietic cell transplant (HCT) in the United States, Europe, and Japan showed that intestinal microbial diversity was significantly associated with overall survival, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York City.

“Patients with low diversity pretransplant have a poorer overall survival than patients with a higher diversity after transplantation,” he said at the annual meeting of the American Society of Hematology. “The implication is, if we could come up with a way to remediate microbiome injury, there might be time to implement it before the transplant.”

There are about 100 trillion symbiotic microbes in and on the human body, and 95% of them live in the gastrointestinal tract, which has a surface area that if stretched out would equal the size of two tennis courts, Dr. Peled said.

Previous studies by his group and others have shown that the composition of intestinal microbiota is associated with survival, relapses, graft-versus-host disease, and infections in patients in the early weeks after allogeneic HCT.

The international team previously reported that intestinal diversity measured around the time of neutrophil engraftment was predictive of overall survival, and they hypothesized that the same might be true of the pretransplant microbiota composition.

To test this idea, they collected 1,922 stools samples approximately once weekly for 3 weeks pretransplant from 991 adult patients scheduled for allo-HCT for various diagnoses in two U.S. cohorts and one cohort each in Europe and Japan.

They found that on average patients in all four cohorts had microbiota diversity values ranging from 70% to 150% lower than those of healthy volunteers whose samples were sequenced by the investigators, as well as those in a publicly available database.

The investigators also asked whether one or more bacterial species accounted for 30% or more of a microbiome, a phenomenon known as “monodomination.”

“A third, or in some cases 95+%, of bacteria in an individual’s intestine are all the exact same strain,” Dr. Peled said.

They found that the incidence and prevalence of the monodomination phenotype was “strikingly similar” at all four transplant sites.


The patterns of microbiota injury were similar despite differences in antibiotic strategies among the four centers and different dietary patterns of patients in the regions studied.

Studies in animal models suggest that T cells responsible for graft-versus-host disease migrate to the gut as early as 2 or 3 days post transplant, and by that time more than half of transplant patients have a monodomination event in their guts, Dr. Peled said.

Some strategies to remediate or prevent microbiome damage – and potentially improve HCT outcomes – may include the use of over-the-counter or custom-made probiotics, fecal transplants, a “prebiotic” approach in which the patient is asked to follow a specific diet that promotes the growth of beneficial bacteria, or a “postbiotic” approach in which patients receive metabolites of agents or foods thought to have a beneficial effect.

“Finally, we can think about different antibiotic strategies, to use or not use different types of antibiotics at different times in a rational way,” Dr. Peled said.

Dr. Peled reported current or prior financial relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SOURCE: Peled JU et al. ASH 2018, Abstract 811.

SAN DIEGO – The success or failure of hematopoietic cell transplants may be related to the diversity of species in the gut microbiome, investigators contend.

Neil Osterweil/MDedge News

A study of fecal samples from patients scheduled to undergo hematopoietic cell transplant (HCT) in the United States, Europe, and Japan showed that intestinal microbial diversity was significantly associated with overall survival, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York City.

“Patients with low diversity pretransplant have a poorer overall survival than patients with a higher diversity after transplantation,” he said at the annual meeting of the American Society of Hematology. “The implication is, if we could come up with a way to remediate microbiome injury, there might be time to implement it before the transplant.”

There are about 100 trillion symbiotic microbes in and on the human body, and 95% of them live in the gastrointestinal tract, which has a surface area that if stretched out would equal the size of two tennis courts, Dr. Peled said.

Previous studies by his group and others have shown that the composition of intestinal microbiota is associated with survival, relapses, graft-versus-host disease, and infections in patients in the early weeks after allogeneic HCT.

The international team previously reported that intestinal diversity measured around the time of neutrophil engraftment was predictive of overall survival, and they hypothesized that the same might be true of the pretransplant microbiota composition.

To test this idea, they collected 1,922 stools samples approximately once weekly for 3 weeks pretransplant from 991 adult patients scheduled for allo-HCT for various diagnoses in two U.S. cohorts and one cohort each in Europe and Japan.

They found that on average patients in all four cohorts had microbiota diversity values ranging from 70% to 150% lower than those of healthy volunteers whose samples were sequenced by the investigators, as well as those in a publicly available database.

The investigators also asked whether one or more bacterial species accounted for 30% or more of a microbiome, a phenomenon known as “monodomination.”

“A third, or in some cases 95+%, of bacteria in an individual’s intestine are all the exact same strain,” Dr. Peled said.

They found that the incidence and prevalence of the monodomination phenotype was “strikingly similar” at all four transplant sites.


The patterns of microbiota injury were similar despite differences in antibiotic strategies among the four centers and different dietary patterns of patients in the regions studied.

Studies in animal models suggest that T cells responsible for graft-versus-host disease migrate to the gut as early as 2 or 3 days post transplant, and by that time more than half of transplant patients have a monodomination event in their guts, Dr. Peled said.

Some strategies to remediate or prevent microbiome damage – and potentially improve HCT outcomes – may include the use of over-the-counter or custom-made probiotics, fecal transplants, a “prebiotic” approach in which the patient is asked to follow a specific diet that promotes the growth of beneficial bacteria, or a “postbiotic” approach in which patients receive metabolites of agents or foods thought to have a beneficial effect.

“Finally, we can think about different antibiotic strategies, to use or not use different types of antibiotics at different times in a rational way,” Dr. Peled said.

Dr. Peled reported current or prior financial relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SOURCE: Peled JU et al. ASH 2018, Abstract 811.

The 38th episode of the Psychcast includes the best of from this year in psychopharmacology. In this episode we go back to the summer for two master classes on ketamine and stimulants, respectively and we drop in on two conversations between Lorenzo Norris, MD on anxiety and comorbid ADHD as well as a conversation on benzodiazapines. The Psychcast will be back with new content in 2019.

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The 38th episode of the Psychcast includes the best of from this year in psychopharmacology. In this episode we go back to the summer for two master classes on ketamine and stimulants, respectively and we drop in on two conversations between Lorenzo Norris, MD on anxiety and comorbid ADHD as well as a conversation on benzodiazapines. The Psychcast will be back with new content in 2019.

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Spotify

The 38th episode of the Psychcast includes the best of from this year in psychopharmacology. In this episode we go back to the summer for two master classes on ketamine and stimulants, respectively and we drop in on two conversations between Lorenzo Norris, MD on anxiety and comorbid ADHD as well as a conversation on benzodiazapines. The Psychcast will be back with new content in 2019.

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In this episode, we revisit the conversation with Lorenzo Norris, MD. The Postcall Podcast will return with all new content in 2019.

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In this episode, we revisit the conversation with Lorenzo Norris, MD. The Postcall Podcast will return with all new content in 2019.

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Spotify
 

In this episode, we revisit the conversation with Lorenzo Norris, MD. The Postcall Podcast will return with all new content in 2019.

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Physicians are on track to more easily distinguish IBD and IBS thanks to shotgun metagenetic sequencing of gut microbiota. Also today, evidence is still scant for weight-loss apps, there could be a ruling on the ACA on New Year’s Eve and the U.S. Surgeon General takes on vaping among America’s Youth with the support of physician groups.

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Physicians are on track to more easily distinguish IBD and IBS thanks to shotgun metagenetic sequencing of gut microbiota. Also today, evidence is still scant for weight-loss apps, there could be a ruling on the ACA on New Year’s Eve and the U.S. Surgeon General takes on vaping among America’s Youth with the support of physician groups.

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Physicians are on track to more easily distinguish IBD and IBS thanks to shotgun metagenetic sequencing of gut microbiota. Also today, evidence is still scant for weight-loss apps, there could be a ruling on the ACA on New Year’s Eve and the U.S. Surgeon General takes on vaping among America’s Youth with the support of physician groups.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

There were lots of lovely books published last year. As usual, I’ve only finished some of the many I purchased. Here are a few I liked that you might also enjoy.

Bellott/Getty Images

“Enlightenment Now: The Case for Reason, Science, Humanism, and Progress,” by Steven Pinker, PhD (New York:Viking, 2018). Think life was better 50 years ago? 100? 500? Steven Pinker would say you’re wrong. Whether or not we feel it, empirically, life is better today than it ever has been. We are living longer, healthier lives, have better access to health care, have fewer war-related deaths and food shortages and higher levels of literacy and equal rights. However, Dr. Pinker acknowledges our shortcomings (e.g., providing a living wage) and potential societal pitfalls (e.g., increasing tribalism), although he could have addressed other crucial issues such as climate change more fully. If you’re looking for an optimistic, science-based outlook on humanity, look no further than this book.

“Aware: The Science and Practice of Presence – The Groundbreaking Meditation Practice,” by Daniel J. Siegel, MD (New York:TarcherPerigee, 2018). A clinical professor of psychiatry and director of the UCLA Mindful Awareness Research Center, Dr. Siegel, in his latest book, constructs a compelling argument for practicing presence that is supported by ample scientific evidence. His “Wheel of Awareness” is a tool to cultivate presence, self-awareness, and compassion. He deftly shows how developing “open awareness” and “kind intention” has not only psychological benefits, but also physical ones, such as improving immune function and increasing neural integration in the brain. As he writes, “The scientific findings are now in: Your mind can change the health of your body and slow aging.” That’s a message both we physicians and our patients could benefit from hearing more often.

“When: The Scientific Secrets of Perfect Timing,” by Daniel H. Pink (New York: Riverhead Books, 2018). In his latest book, Mr. Pink delves into timing, and the evolving science of timing, which draws from fields that include biology, psychology, neuroscience, and economics. Through extensive research (he analyzed over 700 studies) and fascinating real-life examples, the data are clear: We overwhelmingly perform optimally in the morning, suffer a mid-day slump, then rally once more in the evening (of course, there are productive night owls too). These peaks and dips affect both our moods and decision-making abilities, resulting in real-world impact (judges, for example, are more lenient in sentencing following a break). With practical takeaways you can immediately incorporate into your daily routine, you can start to feel more productive, energized, and happy, which is good news for both you and your patients.

“Natural Causes An Epidemic of Wellness, the Certainty of Dying, and Killing Ourselves to Live Longer,” by Barbara Ehrenreich, PhD (New York:Twelve, 2018). Infuriating, tender, disquieting, moving. Barbara Ehrenreich’s latest book is provocative. As a septuagenarian and cancer survivor who has forsworn most future medical measures, including Pap smears and cancer screenings (even though she has medical insurance), Dr. Ehrenreich castigates both the traditional medical and integrative holistic health establishments. Yes, she’s critical of us and nurses and fitness gurus and mindfulness coaches and Silicon Valley. Why should I read this you ask? Because it’s good to understand contrarian views, especially when they are thoughtfully articulated. Because there are many patients who share her beliefs, and understanding opposing perspectives might help us become better clinicians. Because she may cause you to be reflective. Do we order too many tests? Do we overprescribe meds? Are we setting up patients for false hopes of longevity? Is providing more care always the best option? This exercise is beneficial for all types of healers.

“Leadership in Turbulent Times,” by Doris Kearns Goodwin, PhD, (New York:Simon & Schuster, 2018). I’m a presidential biography junkie. As physicians in what some may rightly call a turbulent health care culture, we face challenges each day that require our best intentions, our best diagnostic skills, our best empathic efforts, our best selves. Dr. Goodwin, in her prototypical engaging and informative prose, shows us four American presidents, Abraham Lincoln, Theodore Roosevelt, Franklin D. Roosevelt, and Lyndon B. Johnson, who persevered through devastatingly turbulent times. While we don’t have to make decisions regarding warfare, we do have an unmistakable impact on the lives of thousands of patients, and this book provides insights that can help all of us become better informed, better prepared leaders for our patients, our coworkers, and our communities at large.

“You and I Eat the Same: On the Countless Ways Food and Cooking Connect Us to One Another,” edited by Chris Ying; foreword by René Redzepi (New York:Artisan, 2018). Open a newspaper or turn on the news, and it’s difficult not to feel as if we live in an alarmingly polarized society. We can find many issues that divide us, but as healers, I hope we also strive to find ways to connect us. In 19 engaging and thought-provoking essays, this book explores the various ways that food connects us as humans. Whether it’s an historical deep dive into our love of meat wrapped in flatbread (which we’ve been doing for over 1,000 years) or tackling philosophical questions like, “Is there such a thing as a ‘non-ethnic’ restaurant?” this book will inform, inspire, and delight, and provide delicious topics for a bite of small talk with your patients.

“The Great Alone,” by Kristin Hannah (New York:St. Martin’s Press, 2018). Lured by Alaska’s majestic splendor and remoteness, the Allbright family (former POW, Ernt; abused wife, Cora; and coming-of-age daughter, Leni) are happy with their new life. For a minute. What ensues, namely punishing 16-hour days of darkness punctuated by episodes of oppressive snowfall, paranoia, and domestic violence, is grueling: “Night swept in like nothing Leni had ever seen before, like the winged shadow of a creature too big and predatory to comprehend.” Yet, this book is also a story about the bonds of family, both those we are born into and those we choose, love, sacrifice, and resilience.

If you have any books you read over the last to year to add to this list, please write to me at [email protected].

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter.

There were lots of lovely books published last year. As usual, I’ve only finished some of the many I purchased. Here are a few I liked that you might also enjoy.

Bellott/Getty Images

“Enlightenment Now: The Case for Reason, Science, Humanism, and Progress,” by Steven Pinker, PhD (New York:Viking, 2018). Think life was better 50 years ago? 100? 500? Steven Pinker would say you’re wrong. Whether or not we feel it, empirically, life is better today than it ever has been. We are living longer, healthier lives, have better access to health care, have fewer war-related deaths and food shortages and higher levels of literacy and equal rights. However, Dr. Pinker acknowledges our shortcomings (e.g., providing a living wage) and potential societal pitfalls (e.g., increasing tribalism), although he could have addressed other crucial issues such as climate change more fully. If you’re looking for an optimistic, science-based outlook on humanity, look no further than this book.

“Aware: The Science and Practice of Presence – The Groundbreaking Meditation Practice,” by Daniel J. Siegel, MD (New York:TarcherPerigee, 2018). A clinical professor of psychiatry and director of the UCLA Mindful Awareness Research Center, Dr. Siegel, in his latest book, constructs a compelling argument for practicing presence that is supported by ample scientific evidence. His “Wheel of Awareness” is a tool to cultivate presence, self-awareness, and compassion. He deftly shows how developing “open awareness” and “kind intention” has not only psychological benefits, but also physical ones, such as improving immune function and increasing neural integration in the brain. As he writes, “The scientific findings are now in: Your mind can change the health of your body and slow aging.” That’s a message both we physicians and our patients could benefit from hearing more often.

“When: The Scientific Secrets of Perfect Timing,” by Daniel H. Pink (New York: Riverhead Books, 2018). In his latest book, Mr. Pink delves into timing, and the evolving science of timing, which draws from fields that include biology, psychology, neuroscience, and economics. Through extensive research (he analyzed over 700 studies) and fascinating real-life examples, the data are clear: We overwhelmingly perform optimally in the morning, suffer a mid-day slump, then rally once more in the evening (of course, there are productive night owls too). These peaks and dips affect both our moods and decision-making abilities, resulting in real-world impact (judges, for example, are more lenient in sentencing following a break). With practical takeaways you can immediately incorporate into your daily routine, you can start to feel more productive, energized, and happy, which is good news for both you and your patients.

“Natural Causes An Epidemic of Wellness, the Certainty of Dying, and Killing Ourselves to Live Longer,” by Barbara Ehrenreich, PhD (New York:Twelve, 2018). Infuriating, tender, disquieting, moving. Barbara Ehrenreich’s latest book is provocative. As a septuagenarian and cancer survivor who has forsworn most future medical measures, including Pap smears and cancer screenings (even though she has medical insurance), Dr. Ehrenreich castigates both the traditional medical and integrative holistic health establishments. Yes, she’s critical of us and nurses and fitness gurus and mindfulness coaches and Silicon Valley. Why should I read this you ask? Because it’s good to understand contrarian views, especially when they are thoughtfully articulated. Because there are many patients who share her beliefs, and understanding opposing perspectives might help us become better clinicians. Because she may cause you to be reflective. Do we order too many tests? Do we overprescribe meds? Are we setting up patients for false hopes of longevity? Is providing more care always the best option? This exercise is beneficial for all types of healers.

“Leadership in Turbulent Times,” by Doris Kearns Goodwin, PhD, (New York:Simon & Schuster, 2018). I’m a presidential biography junkie. As physicians in what some may rightly call a turbulent health care culture, we face challenges each day that require our best intentions, our best diagnostic skills, our best empathic efforts, our best selves. Dr. Goodwin, in her prototypical engaging and informative prose, shows us four American presidents, Abraham Lincoln, Theodore Roosevelt, Franklin D. Roosevelt, and Lyndon B. Johnson, who persevered through devastatingly turbulent times. While we don’t have to make decisions regarding warfare, we do have an unmistakable impact on the lives of thousands of patients, and this book provides insights that can help all of us become better informed, better prepared leaders for our patients, our coworkers, and our communities at large.

“You and I Eat the Same: On the Countless Ways Food and Cooking Connect Us to One Another,” edited by Chris Ying; foreword by René Redzepi (New York:Artisan, 2018). Open a newspaper or turn on the news, and it’s difficult not to feel as if we live in an alarmingly polarized society. We can find many issues that divide us, but as healers, I hope we also strive to find ways to connect us. In 19 engaging and thought-provoking essays, this book explores the various ways that food connects us as humans. Whether it’s an historical deep dive into our love of meat wrapped in flatbread (which we’ve been doing for over 1,000 years) or tackling philosophical questions like, “Is there such a thing as a ‘non-ethnic’ restaurant?” this book will inform, inspire, and delight, and provide delicious topics for a bite of small talk with your patients.

“The Great Alone,” by Kristin Hannah (New York:St. Martin’s Press, 2018). Lured by Alaska’s majestic splendor and remoteness, the Allbright family (former POW, Ernt; abused wife, Cora; and coming-of-age daughter, Leni) are happy with their new life. For a minute. What ensues, namely punishing 16-hour days of darkness punctuated by episodes of oppressive snowfall, paranoia, and domestic violence, is grueling: “Night swept in like nothing Leni had ever seen before, like the winged shadow of a creature too big and predatory to comprehend.” Yet, this book is also a story about the bonds of family, both those we are born into and those we choose, love, sacrifice, and resilience.

If you have any books you read over the last to year to add to this list, please write to me at [email protected].

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter.

There were lots of lovely books published last year. As usual, I’ve only finished some of the many I purchased. Here are a few I liked that you might also enjoy.

Bellott/Getty Images

“Enlightenment Now: The Case for Reason, Science, Humanism, and Progress,” by Steven Pinker, PhD (New York:Viking, 2018). Think life was better 50 years ago? 100? 500? Steven Pinker would say you’re wrong. Whether or not we feel it, empirically, life is better today than it ever has been. We are living longer, healthier lives, have better access to health care, have fewer war-related deaths and food shortages and higher levels of literacy and equal rights. However, Dr. Pinker acknowledges our shortcomings (e.g., providing a living wage) and potential societal pitfalls (e.g., increasing tribalism), although he could have addressed other crucial issues such as climate change more fully. If you’re looking for an optimistic, science-based outlook on humanity, look no further than this book.

“Aware: The Science and Practice of Presence – The Groundbreaking Meditation Practice,” by Daniel J. Siegel, MD (New York:TarcherPerigee, 2018). A clinical professor of psychiatry and director of the UCLA Mindful Awareness Research Center, Dr. Siegel, in his latest book, constructs a compelling argument for practicing presence that is supported by ample scientific evidence. His “Wheel of Awareness” is a tool to cultivate presence, self-awareness, and compassion. He deftly shows how developing “open awareness” and “kind intention” has not only psychological benefits, but also physical ones, such as improving immune function and increasing neural integration in the brain. As he writes, “The scientific findings are now in: Your mind can change the health of your body and slow aging.” That’s a message both we physicians and our patients could benefit from hearing more often.

“When: The Scientific Secrets of Perfect Timing,” by Daniel H. Pink (New York: Riverhead Books, 2018). In his latest book, Mr. Pink delves into timing, and the evolving science of timing, which draws from fields that include biology, psychology, neuroscience, and economics. Through extensive research (he analyzed over 700 studies) and fascinating real-life examples, the data are clear: We overwhelmingly perform optimally in the morning, suffer a mid-day slump, then rally once more in the evening (of course, there are productive night owls too). These peaks and dips affect both our moods and decision-making abilities, resulting in real-world impact (judges, for example, are more lenient in sentencing following a break). With practical takeaways you can immediately incorporate into your daily routine, you can start to feel more productive, energized, and happy, which is good news for both you and your patients.

“Natural Causes An Epidemic of Wellness, the Certainty of Dying, and Killing Ourselves to Live Longer,” by Barbara Ehrenreich, PhD (New York:Twelve, 2018). Infuriating, tender, disquieting, moving. Barbara Ehrenreich’s latest book is provocative. As a septuagenarian and cancer survivor who has forsworn most future medical measures, including Pap smears and cancer screenings (even though she has medical insurance), Dr. Ehrenreich castigates both the traditional medical and integrative holistic health establishments. Yes, she’s critical of us and nurses and fitness gurus and mindfulness coaches and Silicon Valley. Why should I read this you ask? Because it’s good to understand contrarian views, especially when they are thoughtfully articulated. Because there are many patients who share her beliefs, and understanding opposing perspectives might help us become better clinicians. Because she may cause you to be reflective. Do we order too many tests? Do we overprescribe meds? Are we setting up patients for false hopes of longevity? Is providing more care always the best option? This exercise is beneficial for all types of healers.

“Leadership in Turbulent Times,” by Doris Kearns Goodwin, PhD, (New York:Simon & Schuster, 2018). I’m a presidential biography junkie. As physicians in what some may rightly call a turbulent health care culture, we face challenges each day that require our best intentions, our best diagnostic skills, our best empathic efforts, our best selves. Dr. Goodwin, in her prototypical engaging and informative prose, shows us four American presidents, Abraham Lincoln, Theodore Roosevelt, Franklin D. Roosevelt, and Lyndon B. Johnson, who persevered through devastatingly turbulent times. While we don’t have to make decisions regarding warfare, we do have an unmistakable impact on the lives of thousands of patients, and this book provides insights that can help all of us become better informed, better prepared leaders for our patients, our coworkers, and our communities at large.

“You and I Eat the Same: On the Countless Ways Food and Cooking Connect Us to One Another,” edited by Chris Ying; foreword by René Redzepi (New York:Artisan, 2018). Open a newspaper or turn on the news, and it’s difficult not to feel as if we live in an alarmingly polarized society. We can find many issues that divide us, but as healers, I hope we also strive to find ways to connect us. In 19 engaging and thought-provoking essays, this book explores the various ways that food connects us as humans. Whether it’s an historical deep dive into our love of meat wrapped in flatbread (which we’ve been doing for over 1,000 years) or tackling philosophical questions like, “Is there such a thing as a ‘non-ethnic’ restaurant?” this book will inform, inspire, and delight, and provide delicious topics for a bite of small talk with your patients.

“The Great Alone,” by Kristin Hannah (New York:St. Martin’s Press, 2018). Lured by Alaska’s majestic splendor and remoteness, the Allbright family (former POW, Ernt; abused wife, Cora; and coming-of-age daughter, Leni) are happy with their new life. For a minute. What ensues, namely punishing 16-hour days of darkness punctuated by episodes of oppressive snowfall, paranoia, and domestic violence, is grueling: “Night swept in like nothing Leni had ever seen before, like the winged shadow of a creature too big and predatory to comprehend.” Yet, this book is also a story about the bonds of family, both those we are born into and those we choose, love, sacrifice, and resilience.

If you have any books you read over the last to year to add to this list, please write to me at [email protected].

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter.

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for treosulfan (Trecondi) as part of conditioning prior to allogeneic hematopoietic stem cell transplant (allo-HSCT).

The full indication is for treosulfan to be used in combination with fludarabine for conditioning prior to allo-HSCT in adults with malignant and non-malignant diseases and in pediatric patients older than 1 month who have malignant diseases.

The CHMP’s recommendation for treosulfan will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of a CHMP recommendation.

The CHMP’s opinion of treosulfan is supported by results from a phase 3 trial (NCT00822393), which were presented at the 2017 ASH Annual Meeting.

In this trial, investigators compared two conditioning regimens, treosulfan-fludarabine and busulfan-fludarabine, in elderly or comorbid patients with acute myeloid leukemia or myelodysplastic syndromes who were undergoing allo-HSCT.

The ASH data included 476 patients from the final analysis.

Investigators said safety results between day -6 and day +28 were similar with the two regimens.

The same was true for trilineage engraftment and the cumulative incidence of relapse/progression at 24 months after allo-HSCT.

However, survival rates were higher in the treosulfan arm.

The event-free survival at 24 months was 64.0% in the treosulfan arm and 50.4% in the busulfan arm (P=0.0000164). The overall survival at 24 months was 72.5% and 56.4%, respectively (P=0.0082).

Transplant-related mortality at 24 months was 11.3% in the treosulfan arm and 28.2% in the busulfan arm (P=0.0201).

This trial was sponsored by medac GmbH.

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for treosulfan (Trecondi) as part of conditioning prior to allogeneic hematopoietic stem cell transplant (allo-HSCT).

The full indication is for treosulfan to be used in combination with fludarabine for conditioning prior to allo-HSCT in adults with malignant and non-malignant diseases and in pediatric patients older than 1 month who have malignant diseases.

The CHMP’s recommendation for treosulfan will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of a CHMP recommendation.

The CHMP’s opinion of treosulfan is supported by results from a phase 3 trial (NCT00822393), which were presented at the 2017 ASH Annual Meeting.

In this trial, investigators compared two conditioning regimens, treosulfan-fludarabine and busulfan-fludarabine, in elderly or comorbid patients with acute myeloid leukemia or myelodysplastic syndromes who were undergoing allo-HSCT.

The ASH data included 476 patients from the final analysis.

Investigators said safety results between day -6 and day +28 were similar with the two regimens.

The same was true for trilineage engraftment and the cumulative incidence of relapse/progression at 24 months after allo-HSCT.

However, survival rates were higher in the treosulfan arm.

The event-free survival at 24 months was 64.0% in the treosulfan arm and 50.4% in the busulfan arm (P=0.0000164). The overall survival at 24 months was 72.5% and 56.4%, respectively (P=0.0082).

Transplant-related mortality at 24 months was 11.3% in the treosulfan arm and 28.2% in the busulfan arm (P=0.0201).

This trial was sponsored by medac GmbH.

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for treosulfan (Trecondi) as part of conditioning prior to allogeneic hematopoietic stem cell transplant (allo-HSCT).

The full indication is for treosulfan to be used in combination with fludarabine for conditioning prior to allo-HSCT in adults with malignant and non-malignant diseases and in pediatric patients older than 1 month who have malignant diseases.

The CHMP’s recommendation for treosulfan will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of a CHMP recommendation.

The CHMP’s opinion of treosulfan is supported by results from a phase 3 trial (NCT00822393), which were presented at the 2017 ASH Annual Meeting.

In this trial, investigators compared two conditioning regimens, treosulfan-fludarabine and busulfan-fludarabine, in elderly or comorbid patients with acute myeloid leukemia or myelodysplastic syndromes who were undergoing allo-HSCT.

The ASH data included 476 patients from the final analysis.

Investigators said safety results between day -6 and day +28 were similar with the two regimens.

The same was true for trilineage engraftment and the cumulative incidence of relapse/progression at 24 months after allo-HSCT.

However, survival rates were higher in the treosulfan arm.

The event-free survival at 24 months was 64.0% in the treosulfan arm and 50.4% in the busulfan arm (P=0.0000164). The overall survival at 24 months was 72.5% and 56.4%, respectively (P=0.0082).

Transplant-related mortality at 24 months was 11.3% in the treosulfan arm and 28.2% in the busulfan arm (P=0.0201).

This trial was sponsored by medac GmbH.

Photo by Piotr Bodzek

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for lusutrombopag to treat severe thrombocytopenia in adults with chronic liver disease who are undergoing invasive procedures.

Lusutrombopag is a thrombopoietin (TPO) receptor agonist that acts on the transmembrane domain of TPO receptors to induce proliferation and differentiation of megakaryocyte progenitor cells, thus leading to thrombocytopoiesis.

Lusutrombopag is intended to reduce the need for platelet transfusions before an invasive procedure and for rescue therapy for bleeding in the 7 days after the procedure.

The CHMP’s recommendation for lusutrombopag will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of a CHMP recommendation.

Lusutrombopag trials

The efficacy of lusutrombopag was evaluated in two phase 3 trials—L-PLUS1 (1304M0631) and L-PLUS2 (1423M0634, NCT02389621).

The trials included 312 patients with chronic liver disease, severe thrombocytopenia (platelet counts below 50,000/μL), and a scheduled invasive procedure. The patients received lusutrombopag or placebo once daily for up to 7 days.

In L-PLUS1, 78% (38/49) of patients receiving lusutrombopag did not require platelet transfusions prior to the primary invasive procedure. The same was true for 13% (6/48) of patients who received placebo (P<0.0001).

In L-PLUS2 , 65% (70/108) of patients who received lusutrombopag did not require platelet transfusions prior to the primary invasive procedure or rescue therapy for bleeding in the 7 days after the procedure. The same was true for 29% (31/107) of patients receiving placebo (P<0.0001).

The safety of lusutrombopag was evaluated in three trials—L‐PLUS 1, L‐PLUS 2, and M0626 (1208M062).

The most common adverse event (AE) in these trials (n=341) was headache, which occurred in 5% of patients on lusutrombopag and 4% of patients on placebo.

Serious AEs occurred in 5% of patients on lusutrombopag and 7% of patients on placebo. The most common serious AE was portal vein thrombosis, which occurred in 1% of patients in both treatment groups.

None of the patients discontinued lusutrombopag due to AEs.

The trials were sponsored by Shionogi & Co., Ltd.

Photo by Piotr Bodzek

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for lusutrombopag to treat severe thrombocytopenia in adults with chronic liver disease who are undergoing invasive procedures.

Lusutrombopag is a thrombopoietin (TPO) receptor agonist that acts on the transmembrane domain of TPO receptors to induce proliferation and differentiation of megakaryocyte progenitor cells, thus leading to thrombocytopoiesis.

Lusutrombopag is intended to reduce the need for platelet transfusions before an invasive procedure and for rescue therapy for bleeding in the 7 days after the procedure.

The CHMP’s recommendation for lusutrombopag will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of a CHMP recommendation.

Lusutrombopag trials

The efficacy of lusutrombopag was evaluated in two phase 3 trials—L-PLUS1 (1304M0631) and L-PLUS2 (1423M0634, NCT02389621).

The trials included 312 patients with chronic liver disease, severe thrombocytopenia (platelet counts below 50,000/μL), and a scheduled invasive procedure. The patients received lusutrombopag or placebo once daily for up to 7 days.

In L-PLUS1, 78% (38/49) of patients receiving lusutrombopag did not require platelet transfusions prior to the primary invasive procedure. The same was true for 13% (6/48) of patients who received placebo (P<0.0001).

In L-PLUS2 , 65% (70/108) of patients who received lusutrombopag did not require platelet transfusions prior to the primary invasive procedure or rescue therapy for bleeding in the 7 days after the procedure. The same was true for 29% (31/107) of patients receiving placebo (P<0.0001).

The safety of lusutrombopag was evaluated in three trials—L‐PLUS 1, L‐PLUS 2, and M0626 (1208M062).

The most common adverse event (AE) in these trials (n=341) was headache, which occurred in 5% of patients on lusutrombopag and 4% of patients on placebo.

Serious AEs occurred in 5% of patients on lusutrombopag and 7% of patients on placebo. The most common serious AE was portal vein thrombosis, which occurred in 1% of patients in both treatment groups.

None of the patients discontinued lusutrombopag due to AEs.

The trials were sponsored by Shionogi & Co., Ltd.

Photo by Piotr Bodzek

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for lusutrombopag to treat severe thrombocytopenia in adults with chronic liver disease who are undergoing invasive procedures.

Lusutrombopag is a thrombopoietin (TPO) receptor agonist that acts on the transmembrane domain of TPO receptors to induce proliferation and differentiation of megakaryocyte progenitor cells, thus leading to thrombocytopoiesis.

Lusutrombopag is intended to reduce the need for platelet transfusions before an invasive procedure and for rescue therapy for bleeding in the 7 days after the procedure.

The CHMP’s recommendation for lusutrombopag will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of a CHMP recommendation.

Lusutrombopag trials

The efficacy of lusutrombopag was evaluated in two phase 3 trials—L-PLUS1 (1304M0631) and L-PLUS2 (1423M0634, NCT02389621).

The trials included 312 patients with chronic liver disease, severe thrombocytopenia (platelet counts below 50,000/μL), and a scheduled invasive procedure. The patients received lusutrombopag or placebo once daily for up to 7 days.

In L-PLUS1, 78% (38/49) of patients receiving lusutrombopag did not require platelet transfusions prior to the primary invasive procedure. The same was true for 13% (6/48) of patients who received placebo (P<0.0001).

In L-PLUS2 , 65% (70/108) of patients who received lusutrombopag did not require platelet transfusions prior to the primary invasive procedure or rescue therapy for bleeding in the 7 days after the procedure. The same was true for 29% (31/107) of patients receiving placebo (P<0.0001).

The safety of lusutrombopag was evaluated in three trials—L‐PLUS 1, L‐PLUS 2, and M0626 (1208M062).

The most common adverse event (AE) in these trials (n=341) was headache, which occurred in 5% of patients on lusutrombopag and 4% of patients on placebo.

Serious AEs occurred in 5% of patients on lusutrombopag and 7% of patients on placebo. The most common serious AE was portal vein thrombosis, which occurred in 1% of patients in both treatment groups.

None of the patients discontinued lusutrombopag due to AEs.

The trials were sponsored by Shionogi & Co., Ltd.

This week, the barbershop may become a key battleground in the fight against hypertension, the American Diabetes Association upgrades newer antihyperglycemics, refreshed appropriate use criteria for peripheral artery disease are released, and body mass index as a measure of cardiometabolic risk gets a boost.

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This week, the barbershop may become a key battleground in the fight against hypertension, the American Diabetes Association upgrades newer antihyperglycemics, refreshed appropriate use criteria for peripheral artery disease are released, and body mass index as a measure of cardiometabolic risk gets a boost.

Subscribe to Cardiocast wherever you get your podcasts.

Amazon Alexa

Apple Podcasts

This week, the barbershop may become a key battleground in the fight against hypertension, the American Diabetes Association upgrades newer antihyperglycemics, refreshed appropriate use criteria for peripheral artery disease are released, and body mass index as a measure of cardiometabolic risk gets a boost.

Subscribe to Cardiocast wherever you get your podcasts.

Amazon Alexa

Apple Podcasts