User login
2018 CMSC Post Meeting Highlights
Observational data can’t answer question of inhibiting ankylosing spondylitis progression
AMSTERDAM – The attempt to determine whether biologics such as tumor necrosis factor inhibitors (TNFi) inhibit progression of ankylosing spondylitis has been pursued with observational studies, but these types of studies will never definitively answer the question, according to Robert B.M. Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.
“The methodology is sensitive to a lot of measurement error, making the results spurious,” Dr. Landewé said in an interview, recapping remarks he made in a presentation at the European Congress of Rheumatology.
This was disappointing to many investigators, including several speaking in the same symposium where Dr. Landewé made his remarks. Randomized, controlled trials that employ serial radiographs to document changes in ankylosing spondylitis are expensive, making observational studies an attractive surrogate, but Dr. Landewé said such studies are associated with an inherent risk of residual confounding.
In addition, he believes the effect size of biologics on progression, if it exists at all, is likely to be subtle. In the observational studies that have concluded that there is protection, complicated statistical analyses have been typically employed to produce a significant finding.
Observational studies do have hypothesis-generating value, according to Dr. Landewé, but he cautioned that they produce “more questions than answers.” He also emphasized that the inflammation-related progression that leads to bone growth in ankylosing spondylitis is different than it is in the destructive inflammatory diseases, such as rheumatoid arthritis, where the issue is bone loss.
It is rational to assume that effective anti-inflammatory therapy would prevent progression of inflammatory diseases, but Dr. Landewé said in his presentation that this is the type of bias that undermines the value of observational studies for reaching objective conclusions. Unlike the results of a registered randomized, controlled trial, which will be known to be consistent or not with the underlying hypothesis, there is a strong risk that data in an observational study will be reworked until they produce the desired result.
AMSTERDAM – The attempt to determine whether biologics such as tumor necrosis factor inhibitors (TNFi) inhibit progression of ankylosing spondylitis has been pursued with observational studies, but these types of studies will never definitively answer the question, according to Robert B.M. Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.
“The methodology is sensitive to a lot of measurement error, making the results spurious,” Dr. Landewé said in an interview, recapping remarks he made in a presentation at the European Congress of Rheumatology.
This was disappointing to many investigators, including several speaking in the same symposium where Dr. Landewé made his remarks. Randomized, controlled trials that employ serial radiographs to document changes in ankylosing spondylitis are expensive, making observational studies an attractive surrogate, but Dr. Landewé said such studies are associated with an inherent risk of residual confounding.
In addition, he believes the effect size of biologics on progression, if it exists at all, is likely to be subtle. In the observational studies that have concluded that there is protection, complicated statistical analyses have been typically employed to produce a significant finding.
Observational studies do have hypothesis-generating value, according to Dr. Landewé, but he cautioned that they produce “more questions than answers.” He also emphasized that the inflammation-related progression that leads to bone growth in ankylosing spondylitis is different than it is in the destructive inflammatory diseases, such as rheumatoid arthritis, where the issue is bone loss.
It is rational to assume that effective anti-inflammatory therapy would prevent progression of inflammatory diseases, but Dr. Landewé said in his presentation that this is the type of bias that undermines the value of observational studies for reaching objective conclusions. Unlike the results of a registered randomized, controlled trial, which will be known to be consistent or not with the underlying hypothesis, there is a strong risk that data in an observational study will be reworked until they produce the desired result.
AMSTERDAM – The attempt to determine whether biologics such as tumor necrosis factor inhibitors (TNFi) inhibit progression of ankylosing spondylitis has been pursued with observational studies, but these types of studies will never definitively answer the question, according to Robert B.M. Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.
“The methodology is sensitive to a lot of measurement error, making the results spurious,” Dr. Landewé said in an interview, recapping remarks he made in a presentation at the European Congress of Rheumatology.
This was disappointing to many investigators, including several speaking in the same symposium where Dr. Landewé made his remarks. Randomized, controlled trials that employ serial radiographs to document changes in ankylosing spondylitis are expensive, making observational studies an attractive surrogate, but Dr. Landewé said such studies are associated with an inherent risk of residual confounding.
In addition, he believes the effect size of biologics on progression, if it exists at all, is likely to be subtle. In the observational studies that have concluded that there is protection, complicated statistical analyses have been typically employed to produce a significant finding.
Observational studies do have hypothesis-generating value, according to Dr. Landewé, but he cautioned that they produce “more questions than answers.” He also emphasized that the inflammation-related progression that leads to bone growth in ankylosing spondylitis is different than it is in the destructive inflammatory diseases, such as rheumatoid arthritis, where the issue is bone loss.
It is rational to assume that effective anti-inflammatory therapy would prevent progression of inflammatory diseases, but Dr. Landewé said in his presentation that this is the type of bias that undermines the value of observational studies for reaching objective conclusions. Unlike the results of a registered randomized, controlled trial, which will be known to be consistent or not with the underlying hypothesis, there is a strong risk that data in an observational study will be reworked until they produce the desired result.
REPORTING FROM THE EULAR 2018 CONGRESS
TNF inhibitor may protect against axSpA sacroiliac joint progression
AMSTERDAM – In patients with axial spondyloarthritis, new evidence presented at the European Congress of Rheumatology associated tumor necrosis factor inhibitor therapy with prevention of sacroiliac joint progression.
“We already know that biologics can decelerate progression in the spine. The goal of this analysis was to determine whether there is also reduced risk of progression in the sacroiliac joints,” reported Valeria Rios-Rodríguez, MD, of Charité University Clinic in Berlin.
The patients were drawn from the ESTHER trial (Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 1), which established the efficacy of the tumor necrosis factor (TNF) inhibitor etanercept over sulfasalazine in patients with early axSpA (Ann Rheum Dis. 2011 Jul;70:590-6). In ESTHER, all patients not in remission after 1 year continued on or were switched to maintenance etanercept. These patients provided the basis for Dr. Rios-Rodriguez and her colleagues’ analysis.
In this study of patients who remained on therapy, two blinded and experienced readers scored the radiographs for sacroiliac joint damage. A standardized modified New York grading system was employed. In addition, blinded readers graded MRI scans with the Berlin MRI Scoring System for inflammatory changes. Only 35% of patients had radiographic axSpA at baseline, reflecting the fact that ESTHER enrolled patients with early-stage axSpA.
A variety of factors were evaluated for their association with progression, including age, symptom duration, treatment duration, and HLA-B27 positivity. Of these factors, elevated C-reactive protein, defined as more than 5 mg/L, and the presence of sacroiliac joint osteitis on MRI emerged as predictive factors on univariate analysis.
“Evaluated with two different analyses, both of these factors were found to be independently associated with radiographic progression,” Dr. Rios-Rodriguez said. However, she reiterated that these factors were meaningful only at year 2 and 4 when progression was seen.
“Our results show a deceleration of progression of structural damage in sacroiliac joints in patients under long-term TNF inhibitor therapy. These findings match the deceleration of spine progression observed in previous studies under similar conditions,” she said, noting that the predictors for structural damage in sacroiliac joints identified in this study are similar to the ones identified for the progression in the spine.
“To our knowledge, our data on sacroiliac joints is unique and will continue to be so in the coming years,” she said.
Pfizer provided funding for the study. Dr. Rios-Rodriguez reported financial relationships with AbbVie and Novartis.
SOURCE: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.
AMSTERDAM – In patients with axial spondyloarthritis, new evidence presented at the European Congress of Rheumatology associated tumor necrosis factor inhibitor therapy with prevention of sacroiliac joint progression.
“We already know that biologics can decelerate progression in the spine. The goal of this analysis was to determine whether there is also reduced risk of progression in the sacroiliac joints,” reported Valeria Rios-Rodríguez, MD, of Charité University Clinic in Berlin.
The patients were drawn from the ESTHER trial (Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 1), which established the efficacy of the tumor necrosis factor (TNF) inhibitor etanercept over sulfasalazine in patients with early axSpA (Ann Rheum Dis. 2011 Jul;70:590-6). In ESTHER, all patients not in remission after 1 year continued on or were switched to maintenance etanercept. These patients provided the basis for Dr. Rios-Rodriguez and her colleagues’ analysis.
In this study of patients who remained on therapy, two blinded and experienced readers scored the radiographs for sacroiliac joint damage. A standardized modified New York grading system was employed. In addition, blinded readers graded MRI scans with the Berlin MRI Scoring System for inflammatory changes. Only 35% of patients had radiographic axSpA at baseline, reflecting the fact that ESTHER enrolled patients with early-stage axSpA.
A variety of factors were evaluated for their association with progression, including age, symptom duration, treatment duration, and HLA-B27 positivity. Of these factors, elevated C-reactive protein, defined as more than 5 mg/L, and the presence of sacroiliac joint osteitis on MRI emerged as predictive factors on univariate analysis.
“Evaluated with two different analyses, both of these factors were found to be independently associated with radiographic progression,” Dr. Rios-Rodriguez said. However, she reiterated that these factors were meaningful only at year 2 and 4 when progression was seen.
“Our results show a deceleration of progression of structural damage in sacroiliac joints in patients under long-term TNF inhibitor therapy. These findings match the deceleration of spine progression observed in previous studies under similar conditions,” she said, noting that the predictors for structural damage in sacroiliac joints identified in this study are similar to the ones identified for the progression in the spine.
“To our knowledge, our data on sacroiliac joints is unique and will continue to be so in the coming years,” she said.
Pfizer provided funding for the study. Dr. Rios-Rodriguez reported financial relationships with AbbVie and Novartis.
SOURCE: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.
AMSTERDAM – In patients with axial spondyloarthritis, new evidence presented at the European Congress of Rheumatology associated tumor necrosis factor inhibitor therapy with prevention of sacroiliac joint progression.
“We already know that biologics can decelerate progression in the spine. The goal of this analysis was to determine whether there is also reduced risk of progression in the sacroiliac joints,” reported Valeria Rios-Rodríguez, MD, of Charité University Clinic in Berlin.
The patients were drawn from the ESTHER trial (Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 1), which established the efficacy of the tumor necrosis factor (TNF) inhibitor etanercept over sulfasalazine in patients with early axSpA (Ann Rheum Dis. 2011 Jul;70:590-6). In ESTHER, all patients not in remission after 1 year continued on or were switched to maintenance etanercept. These patients provided the basis for Dr. Rios-Rodriguez and her colleagues’ analysis.
In this study of patients who remained on therapy, two blinded and experienced readers scored the radiographs for sacroiliac joint damage. A standardized modified New York grading system was employed. In addition, blinded readers graded MRI scans with the Berlin MRI Scoring System for inflammatory changes. Only 35% of patients had radiographic axSpA at baseline, reflecting the fact that ESTHER enrolled patients with early-stage axSpA.
A variety of factors were evaluated for their association with progression, including age, symptom duration, treatment duration, and HLA-B27 positivity. Of these factors, elevated C-reactive protein, defined as more than 5 mg/L, and the presence of sacroiliac joint osteitis on MRI emerged as predictive factors on univariate analysis.
“Evaluated with two different analyses, both of these factors were found to be independently associated with radiographic progression,” Dr. Rios-Rodriguez said. However, she reiterated that these factors were meaningful only at year 2 and 4 when progression was seen.
“Our results show a deceleration of progression of structural damage in sacroiliac joints in patients under long-term TNF inhibitor therapy. These findings match the deceleration of spine progression observed in previous studies under similar conditions,” she said, noting that the predictors for structural damage in sacroiliac joints identified in this study are similar to the ones identified for the progression in the spine.
“To our knowledge, our data on sacroiliac joints is unique and will continue to be so in the coming years,” she said.
Pfizer provided funding for the study. Dr. Rios-Rodriguez reported financial relationships with AbbVie and Novartis.
SOURCE: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point:
Major finding: Sacroiliac joint progression was seen in 18% of patients at year 2, 4.1% at year 4, and 0% at year 6.
Study details: A post hoc analysis of a subset of 42 patients in the randomized ESTHER trial.
Disclosures: Pfizer provided funding for the study. Dr. Rios-Rodriguez reported financial relationships with AbbVie and Novartis.
Source: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.
For some SUD patients, kratom may be a self-treatment tool
SAN DIEGO – New research suggests that some patients with substance use disorder are turning to the herbal supplement kratom in an effort to reduce their use of heroin and prescription pain killers.
“Some, but not all, heroin users are utilizing kratom as an opioidlike drug with less risks, primarily as a drug substitute or to help abstain from IV heroin and prescription opiate use,” lead author Kirsten Elin Smith, a PhD student at the University of Louisville and an associate at the University of Kentucky’s Center on Drug and Alcohol Research, said in an interview. “Kratom appears as less risky due to the fact that it is not readily injectable.”
Kratom, a plant-based herbal product that’s available over the counter, produces an opioidlike effect. When the Food and Drug Administration declared in February 2018 that scientific evidence shows that kratom indeed is an opioid, the agency also warned that the drug could lead to abuse, addiction, and death. Several U.S. states and the District of Columbia have banned it, as have some cities and counties. In addition, the Drug Enforcement Administration has put kratom on its list of Drugs and Chemicals of Concern.
Nevertheless, some substance users view kratom as helpful and are open to using it, Ms. Smith and her colleagues reported in Drug and Alcohol Dependence.
“There seem to be three categories of substance-using individuals with some relationship to kratom: Those who use kratom inconsistently and as needed when there isn’t an alternative, those who tried it once and just didn’t find much benefit in it, and didn’t try it again, and those who have been using it regularly/daily as a long-term replacement for opioids, including IV heroin use,” Ms. Smith said.
For the new research, Ms. Smith and her colleagues surveyed 478 polysubstance users at five residential recovery centers in Kentucky. The average age of subjects was 35, 58% were male, 85% were white, and 48% were employed. About 85% of the participants were referred to programs by correctional facilities. Twenty-one percent reported ever using kratom, and 10% reported use within the last 12 months.
What do the findings mean? Along with anecdotal reports now being documented, they suggest the use of kratom by heroin users as a “possible harm-reduction” aid, Ms. Smith said at the meeting.
“These men and women are not necessarily getting kratom on a Friday night and saying, ‘This is going to be a great time.’ ” In the interview, she added that “this shows that substance-using individuals are, above all else, pragmatic.”
“It is unlikely that the majority of these users are consuming kratom primarily for achieving recreational ‘highs,’ ” Ms. Smith and her colleagues wrote in the article.
She added during her presentation that kratom is inexpensive and primarily legal. “If it were going to catch on as a serious drug of abuse, we would have expected to have a kratom epidemic already – but we do not.”
As for the big picture, Ms. Smith said in the interview that
Going forward, Ms. Smith said, she and a colleague plan to document the lives of regular kratom users in an effort to understand the progression from heroin and other drugs to kratom. They also want to know what the users would do if kratom is banned.
“These will be case studies in Kentucky, New Mexico, and possibly somewhere in the Northeast,” she said. “Since data will be collected locally, I think it would be helpful to try and obtain samples of kratom that the individuals report using so it can be analyzed. There may be variation between kratom purchased online vs. local vendors, which needs to be documented as well.”
Ms. Smith reported funding from the University of Louisville Graduate Student Research Fund, and another author was supported by the National Institute on Drug Abuse. The authors reported no relevant disclosures.
SOURCE: Smith KE et al. CPDD 2018. Drug and Alcohol Depend. 2017 Nov 1. 180:340-8.
SAN DIEGO – New research suggests that some patients with substance use disorder are turning to the herbal supplement kratom in an effort to reduce their use of heroin and prescription pain killers.
“Some, but not all, heroin users are utilizing kratom as an opioidlike drug with less risks, primarily as a drug substitute or to help abstain from IV heroin and prescription opiate use,” lead author Kirsten Elin Smith, a PhD student at the University of Louisville and an associate at the University of Kentucky’s Center on Drug and Alcohol Research, said in an interview. “Kratom appears as less risky due to the fact that it is not readily injectable.”
Kratom, a plant-based herbal product that’s available over the counter, produces an opioidlike effect. When the Food and Drug Administration declared in February 2018 that scientific evidence shows that kratom indeed is an opioid, the agency also warned that the drug could lead to abuse, addiction, and death. Several U.S. states and the District of Columbia have banned it, as have some cities and counties. In addition, the Drug Enforcement Administration has put kratom on its list of Drugs and Chemicals of Concern.
Nevertheless, some substance users view kratom as helpful and are open to using it, Ms. Smith and her colleagues reported in Drug and Alcohol Dependence.
“There seem to be three categories of substance-using individuals with some relationship to kratom: Those who use kratom inconsistently and as needed when there isn’t an alternative, those who tried it once and just didn’t find much benefit in it, and didn’t try it again, and those who have been using it regularly/daily as a long-term replacement for opioids, including IV heroin use,” Ms. Smith said.
For the new research, Ms. Smith and her colleagues surveyed 478 polysubstance users at five residential recovery centers in Kentucky. The average age of subjects was 35, 58% were male, 85% were white, and 48% were employed. About 85% of the participants were referred to programs by correctional facilities. Twenty-one percent reported ever using kratom, and 10% reported use within the last 12 months.
What do the findings mean? Along with anecdotal reports now being documented, they suggest the use of kratom by heroin users as a “possible harm-reduction” aid, Ms. Smith said at the meeting.
“These men and women are not necessarily getting kratom on a Friday night and saying, ‘This is going to be a great time.’ ” In the interview, she added that “this shows that substance-using individuals are, above all else, pragmatic.”
“It is unlikely that the majority of these users are consuming kratom primarily for achieving recreational ‘highs,’ ” Ms. Smith and her colleagues wrote in the article.
She added during her presentation that kratom is inexpensive and primarily legal. “If it were going to catch on as a serious drug of abuse, we would have expected to have a kratom epidemic already – but we do not.”
As for the big picture, Ms. Smith said in the interview that
Going forward, Ms. Smith said, she and a colleague plan to document the lives of regular kratom users in an effort to understand the progression from heroin and other drugs to kratom. They also want to know what the users would do if kratom is banned.
“These will be case studies in Kentucky, New Mexico, and possibly somewhere in the Northeast,” she said. “Since data will be collected locally, I think it would be helpful to try and obtain samples of kratom that the individuals report using so it can be analyzed. There may be variation between kratom purchased online vs. local vendors, which needs to be documented as well.”
Ms. Smith reported funding from the University of Louisville Graduate Student Research Fund, and another author was supported by the National Institute on Drug Abuse. The authors reported no relevant disclosures.
SOURCE: Smith KE et al. CPDD 2018. Drug and Alcohol Depend. 2017 Nov 1. 180:340-8.
SAN DIEGO – New research suggests that some patients with substance use disorder are turning to the herbal supplement kratom in an effort to reduce their use of heroin and prescription pain killers.
“Some, but not all, heroin users are utilizing kratom as an opioidlike drug with less risks, primarily as a drug substitute or to help abstain from IV heroin and prescription opiate use,” lead author Kirsten Elin Smith, a PhD student at the University of Louisville and an associate at the University of Kentucky’s Center on Drug and Alcohol Research, said in an interview. “Kratom appears as less risky due to the fact that it is not readily injectable.”
Kratom, a plant-based herbal product that’s available over the counter, produces an opioidlike effect. When the Food and Drug Administration declared in February 2018 that scientific evidence shows that kratom indeed is an opioid, the agency also warned that the drug could lead to abuse, addiction, and death. Several U.S. states and the District of Columbia have banned it, as have some cities and counties. In addition, the Drug Enforcement Administration has put kratom on its list of Drugs and Chemicals of Concern.
Nevertheless, some substance users view kratom as helpful and are open to using it, Ms. Smith and her colleagues reported in Drug and Alcohol Dependence.
“There seem to be three categories of substance-using individuals with some relationship to kratom: Those who use kratom inconsistently and as needed when there isn’t an alternative, those who tried it once and just didn’t find much benefit in it, and didn’t try it again, and those who have been using it regularly/daily as a long-term replacement for opioids, including IV heroin use,” Ms. Smith said.
For the new research, Ms. Smith and her colleagues surveyed 478 polysubstance users at five residential recovery centers in Kentucky. The average age of subjects was 35, 58% were male, 85% were white, and 48% were employed. About 85% of the participants were referred to programs by correctional facilities. Twenty-one percent reported ever using kratom, and 10% reported use within the last 12 months.
What do the findings mean? Along with anecdotal reports now being documented, they suggest the use of kratom by heroin users as a “possible harm-reduction” aid, Ms. Smith said at the meeting.
“These men and women are not necessarily getting kratom on a Friday night and saying, ‘This is going to be a great time.’ ” In the interview, she added that “this shows that substance-using individuals are, above all else, pragmatic.”
“It is unlikely that the majority of these users are consuming kratom primarily for achieving recreational ‘highs,’ ” Ms. Smith and her colleagues wrote in the article.
She added during her presentation that kratom is inexpensive and primarily legal. “If it were going to catch on as a serious drug of abuse, we would have expected to have a kratom epidemic already – but we do not.”
As for the big picture, Ms. Smith said in the interview that
Going forward, Ms. Smith said, she and a colleague plan to document the lives of regular kratom users in an effort to understand the progression from heroin and other drugs to kratom. They also want to know what the users would do if kratom is banned.
“These will be case studies in Kentucky, New Mexico, and possibly somewhere in the Northeast,” she said. “Since data will be collected locally, I think it would be helpful to try and obtain samples of kratom that the individuals report using so it can be analyzed. There may be variation between kratom purchased online vs. local vendors, which needs to be documented as well.”
Ms. Smith reported funding from the University of Louisville Graduate Student Research Fund, and another author was supported by the National Institute on Drug Abuse. The authors reported no relevant disclosures.
SOURCE: Smith KE et al. CPDD 2018. Drug and Alcohol Depend. 2017 Nov 1. 180:340-8.
REPORTING FROM CPDD 2018
Key clinical point: Some polysubstance users might be taking the herb kratom for harm reduction.
Major finding: Nearly 74% of recent kratom users also reported using the addiction drug buprenorphine on a nonprescription basis, even though few prefer it.
Study details: Survey of 478 polysubstance users at five residential recovery centers in Kentucky.
Disclosures: Ms. Smith reported individual funding from the University of Louisville Graduate Student Research Fund, and another author was supported by the National Institute on Drug Abuse. The authors reported no relevant disclosures.
Source: Smith KE et al. CPDD 2018. Drug And Alcohol Depend. 2017 Nov 1. 180:340-8.
Impact of varicella vaccination on herpes zoster is not what was expected
Also today, in T2D, healthy lifestyle lowers CVD risk and mortality, antipsychotics linked to increased body fat and insulin resistance in children, and maternal use of pot and tobacco may boost birth defect risk.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Also today, in T2D, healthy lifestyle lowers CVD risk and mortality, antipsychotics linked to increased body fat and insulin resistance in children, and maternal use of pot and tobacco may boost birth defect risk.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Also today, in T2D, healthy lifestyle lowers CVD risk and mortality, antipsychotics linked to increased body fat and insulin resistance in children, and maternal use of pot and tobacco may boost birth defect risk.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Combo proves ‘beneficial’ for ‘unfit’ CLL patients
STOCKHOLM—Obinutuzumab plus chlorambucil (G-Clb) is a “valid and beneficial” frontline treatment option for “unfit” patients with chronic lymphocytic leukemia (CLL), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).
Final results from the CLL11 study have revealed additional benefits of G-Clb over rituximab plus chlorambucil (R-Clb) in patients with previously untreated CLL and comorbidities.
Prior results from this study showed that G-Clb produced higher response rates and prolonged progression-fee survival (PFS) compared to R-Clb.
Now, with a median follow-up of 5 years, researchers have found that G-Clb prolongs overall survival (OS) and time to next treatment (TTNT) as well.
Valentin Goede, MD, of the University Hospital Cologne in Germany, presented these results during the Presidential Symposium of the EHA Congress (abstract S151).
The study was sponsored by Hoffmann-La Roche.
CLL11 enrolled patients with previously untreated CLL and coexisting medical conditions. They were randomized to receive six 28-day cycles of Clb alone, G-Clb, or R-Clb.
In stage 1, researchers compared G-Clb (n=238) to Clb alone (n=118) and R-Clb (n=233) to Clb alone (n=118). In stage 2, they compared G-Clb (n=333) and R-Clb (n=330).
“The treatment arms were well-balanced, not just with regard to patient [characteristics] but also with disease characteristics,” Dr Goede said.
Overall, the median age was 73 (range, 39-90), the median Cumulative Illness Rating Scale score was 8, and the median creatinine clearance was 62 mL/min.
Efficacy: G-Clb vs Clb
The median observation time for G-Clb vs Clb was 62.5 months.
The median PFS was 31.1 months in the G-Clb arm and 11.1 months in the Clb arm. The 5-year PFS rates were 25% and 2%, respectively. The hazard ratio (HR) was 0.21 (P<0.0001).
The median OS was not reached in the G-Clb arm and was 66.7 months in the Clb arm. The 5-year OS rates were 66% and 53%, respectively. The HR was 0.68 (P=0.0196).
Thirty-nine percent of the G-Clb arm died, as did 49% of the Clb arm. The main causes of death were adverse events (AEs) and disease progression.
Efficacy: G-Clb vs R-Clb
The median observation time for G-Clb vs R-Clb was 59.4 months.
The median PFS was 28.9 months in the G-Clb arm and 15.7 months in the R-Clb arm. The 5-year PFS rates were 23% and 9%, respectively. The HR was 0.49 (P<0.0001).
“The median PFS was nearly doubled, from approximately 15 months in the rituximab arm to almost 30 months in the obinutuzumab arm,” Dr Goede said. “And this translated into a clinically meaningful prolongation of time to next treatment.”
The median TTNT was 56.4 months in the G-Clb arm and 34.9 months in the R-Clb arm. At 5 years, TTNT rates were 49% and 32%, respectively. The HR was 0.58 (P<0.0001).
“In the rituximab arm, the median time to next treatment was a little greater than 2.5 years, and, in the obinutuzumab arm, it was almost 5 years,” Dr Goede said. “From a clinical perspective, I would consider treatment-free intervals of that duration as highly relevant and beneficial in an elderly population.”
The median OS was not reached in the G-Clb arm and was 73.1 months in the R-Clb arm. The 5-year OS rates were 66% and 57%, respectively. The HR was 0.76 (P=0.0245).
“This difference is clinically meaningful, and it is also remarkable in the context of the long follow-up, given the fact that approximately half of the patients have received at least 1 salvage treatment in the meantime,” Dr Goede said.
In all, 37% of the G-Clb arm died, as did 45% of the R-Clb arm. Again, the main causes of death were AEs and disease progression.
Safety
Dr Goede said no new safety signals or late-onset toxicities were detected.
“Adverse events of any grade, but particularly grade 3-5 and serious adverse events, were more frequent in the obinutuzumab arm compared to the other 2 arms,” he noted. “[This] was mainly driven by more infusion reactions and some greater hematological toxicity.”
“Importantly, the rate of fatal adverse events, during treatment but also during follow-up, was not higher in the obinutuzumab arm. And the most common fatal adverse events were second malignancies.”
G-Clb vs Clb
Ninety-five percent of patients in the G-Clb arm and 83% of those in the Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 74% and 51%, respectively. The rates of serious AEs were 47% and 39%, respectively. The rates of fatal AEs were 8% and 11%, respectively.
Seventeen percent of patients in the G-Clb arm and 11% of those in the Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 3% and 9%, respectively.
Fourteen percent of patients in the G-Clb arm and 7% of those in the Clb arm had second malignancies (starting 6 months after treatment initiation). The most common of these were squamous cell carcinoma (2% vs 0%) and basal cell carcinoma (2% vs <1%).
G-Clb vs R-Clb
Ninety-four percent of patients in the G-Clb arm and 90% of those in the R-Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 72% and 60%, respectively. The rates of serious AEs were 45% and 39%, respectively. The rates of fatal AEs were 7% and 10%, respectively.
Fifteen percent of patients in the G-Clb arm and 12% of those in the R-Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 2% and 4%, respectively.
Eleven percent of patients in the G-Clb arm and 10% of those in the Clb arm had second malignancies. Squamous cell carcinoma occurred in 2% of patients in both arms. Basal cell carcinoma occurred in 2% of G-Clb recipients and 1% of R-Clb recipients.
STOCKHOLM—Obinutuzumab plus chlorambucil (G-Clb) is a “valid and beneficial” frontline treatment option for “unfit” patients with chronic lymphocytic leukemia (CLL), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).
Final results from the CLL11 study have revealed additional benefits of G-Clb over rituximab plus chlorambucil (R-Clb) in patients with previously untreated CLL and comorbidities.
Prior results from this study showed that G-Clb produced higher response rates and prolonged progression-fee survival (PFS) compared to R-Clb.
Now, with a median follow-up of 5 years, researchers have found that G-Clb prolongs overall survival (OS) and time to next treatment (TTNT) as well.
Valentin Goede, MD, of the University Hospital Cologne in Germany, presented these results during the Presidential Symposium of the EHA Congress (abstract S151).
The study was sponsored by Hoffmann-La Roche.
CLL11 enrolled patients with previously untreated CLL and coexisting medical conditions. They were randomized to receive six 28-day cycles of Clb alone, G-Clb, or R-Clb.
In stage 1, researchers compared G-Clb (n=238) to Clb alone (n=118) and R-Clb (n=233) to Clb alone (n=118). In stage 2, they compared G-Clb (n=333) and R-Clb (n=330).
“The treatment arms were well-balanced, not just with regard to patient [characteristics] but also with disease characteristics,” Dr Goede said.
Overall, the median age was 73 (range, 39-90), the median Cumulative Illness Rating Scale score was 8, and the median creatinine clearance was 62 mL/min.
Efficacy: G-Clb vs Clb
The median observation time for G-Clb vs Clb was 62.5 months.
The median PFS was 31.1 months in the G-Clb arm and 11.1 months in the Clb arm. The 5-year PFS rates were 25% and 2%, respectively. The hazard ratio (HR) was 0.21 (P<0.0001).
The median OS was not reached in the G-Clb arm and was 66.7 months in the Clb arm. The 5-year OS rates were 66% and 53%, respectively. The HR was 0.68 (P=0.0196).
Thirty-nine percent of the G-Clb arm died, as did 49% of the Clb arm. The main causes of death were adverse events (AEs) and disease progression.
Efficacy: G-Clb vs R-Clb
The median observation time for G-Clb vs R-Clb was 59.4 months.
The median PFS was 28.9 months in the G-Clb arm and 15.7 months in the R-Clb arm. The 5-year PFS rates were 23% and 9%, respectively. The HR was 0.49 (P<0.0001).
“The median PFS was nearly doubled, from approximately 15 months in the rituximab arm to almost 30 months in the obinutuzumab arm,” Dr Goede said. “And this translated into a clinically meaningful prolongation of time to next treatment.”
The median TTNT was 56.4 months in the G-Clb arm and 34.9 months in the R-Clb arm. At 5 years, TTNT rates were 49% and 32%, respectively. The HR was 0.58 (P<0.0001).
“In the rituximab arm, the median time to next treatment was a little greater than 2.5 years, and, in the obinutuzumab arm, it was almost 5 years,” Dr Goede said. “From a clinical perspective, I would consider treatment-free intervals of that duration as highly relevant and beneficial in an elderly population.”
The median OS was not reached in the G-Clb arm and was 73.1 months in the R-Clb arm. The 5-year OS rates were 66% and 57%, respectively. The HR was 0.76 (P=0.0245).
“This difference is clinically meaningful, and it is also remarkable in the context of the long follow-up, given the fact that approximately half of the patients have received at least 1 salvage treatment in the meantime,” Dr Goede said.
In all, 37% of the G-Clb arm died, as did 45% of the R-Clb arm. Again, the main causes of death were AEs and disease progression.
Safety
Dr Goede said no new safety signals or late-onset toxicities were detected.
“Adverse events of any grade, but particularly grade 3-5 and serious adverse events, were more frequent in the obinutuzumab arm compared to the other 2 arms,” he noted. “[This] was mainly driven by more infusion reactions and some greater hematological toxicity.”
“Importantly, the rate of fatal adverse events, during treatment but also during follow-up, was not higher in the obinutuzumab arm. And the most common fatal adverse events were second malignancies.”
G-Clb vs Clb
Ninety-five percent of patients in the G-Clb arm and 83% of those in the Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 74% and 51%, respectively. The rates of serious AEs were 47% and 39%, respectively. The rates of fatal AEs were 8% and 11%, respectively.
Seventeen percent of patients in the G-Clb arm and 11% of those in the Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 3% and 9%, respectively.
Fourteen percent of patients in the G-Clb arm and 7% of those in the Clb arm had second malignancies (starting 6 months after treatment initiation). The most common of these were squamous cell carcinoma (2% vs 0%) and basal cell carcinoma (2% vs <1%).
G-Clb vs R-Clb
Ninety-four percent of patients in the G-Clb arm and 90% of those in the R-Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 72% and 60%, respectively. The rates of serious AEs were 45% and 39%, respectively. The rates of fatal AEs were 7% and 10%, respectively.
Fifteen percent of patients in the G-Clb arm and 12% of those in the R-Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 2% and 4%, respectively.
Eleven percent of patients in the G-Clb arm and 10% of those in the Clb arm had second malignancies. Squamous cell carcinoma occurred in 2% of patients in both arms. Basal cell carcinoma occurred in 2% of G-Clb recipients and 1% of R-Clb recipients.
STOCKHOLM—Obinutuzumab plus chlorambucil (G-Clb) is a “valid and beneficial” frontline treatment option for “unfit” patients with chronic lymphocytic leukemia (CLL), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).
Final results from the CLL11 study have revealed additional benefits of G-Clb over rituximab plus chlorambucil (R-Clb) in patients with previously untreated CLL and comorbidities.
Prior results from this study showed that G-Clb produced higher response rates and prolonged progression-fee survival (PFS) compared to R-Clb.
Now, with a median follow-up of 5 years, researchers have found that G-Clb prolongs overall survival (OS) and time to next treatment (TTNT) as well.
Valentin Goede, MD, of the University Hospital Cologne in Germany, presented these results during the Presidential Symposium of the EHA Congress (abstract S151).
The study was sponsored by Hoffmann-La Roche.
CLL11 enrolled patients with previously untreated CLL and coexisting medical conditions. They were randomized to receive six 28-day cycles of Clb alone, G-Clb, or R-Clb.
In stage 1, researchers compared G-Clb (n=238) to Clb alone (n=118) and R-Clb (n=233) to Clb alone (n=118). In stage 2, they compared G-Clb (n=333) and R-Clb (n=330).
“The treatment arms were well-balanced, not just with regard to patient [characteristics] but also with disease characteristics,” Dr Goede said.
Overall, the median age was 73 (range, 39-90), the median Cumulative Illness Rating Scale score was 8, and the median creatinine clearance was 62 mL/min.
Efficacy: G-Clb vs Clb
The median observation time for G-Clb vs Clb was 62.5 months.
The median PFS was 31.1 months in the G-Clb arm and 11.1 months in the Clb arm. The 5-year PFS rates were 25% and 2%, respectively. The hazard ratio (HR) was 0.21 (P<0.0001).
The median OS was not reached in the G-Clb arm and was 66.7 months in the Clb arm. The 5-year OS rates were 66% and 53%, respectively. The HR was 0.68 (P=0.0196).
Thirty-nine percent of the G-Clb arm died, as did 49% of the Clb arm. The main causes of death were adverse events (AEs) and disease progression.
Efficacy: G-Clb vs R-Clb
The median observation time for G-Clb vs R-Clb was 59.4 months.
The median PFS was 28.9 months in the G-Clb arm and 15.7 months in the R-Clb arm. The 5-year PFS rates were 23% and 9%, respectively. The HR was 0.49 (P<0.0001).
“The median PFS was nearly doubled, from approximately 15 months in the rituximab arm to almost 30 months in the obinutuzumab arm,” Dr Goede said. “And this translated into a clinically meaningful prolongation of time to next treatment.”
The median TTNT was 56.4 months in the G-Clb arm and 34.9 months in the R-Clb arm. At 5 years, TTNT rates were 49% and 32%, respectively. The HR was 0.58 (P<0.0001).
“In the rituximab arm, the median time to next treatment was a little greater than 2.5 years, and, in the obinutuzumab arm, it was almost 5 years,” Dr Goede said. “From a clinical perspective, I would consider treatment-free intervals of that duration as highly relevant and beneficial in an elderly population.”
The median OS was not reached in the G-Clb arm and was 73.1 months in the R-Clb arm. The 5-year OS rates were 66% and 57%, respectively. The HR was 0.76 (P=0.0245).
“This difference is clinically meaningful, and it is also remarkable in the context of the long follow-up, given the fact that approximately half of the patients have received at least 1 salvage treatment in the meantime,” Dr Goede said.
In all, 37% of the G-Clb arm died, as did 45% of the R-Clb arm. Again, the main causes of death were AEs and disease progression.
Safety
Dr Goede said no new safety signals or late-onset toxicities were detected.
“Adverse events of any grade, but particularly grade 3-5 and serious adverse events, were more frequent in the obinutuzumab arm compared to the other 2 arms,” he noted. “[This] was mainly driven by more infusion reactions and some greater hematological toxicity.”
“Importantly, the rate of fatal adverse events, during treatment but also during follow-up, was not higher in the obinutuzumab arm. And the most common fatal adverse events were second malignancies.”
G-Clb vs Clb
Ninety-five percent of patients in the G-Clb arm and 83% of those in the Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 74% and 51%, respectively. The rates of serious AEs were 47% and 39%, respectively. The rates of fatal AEs were 8% and 11%, respectively.
Seventeen percent of patients in the G-Clb arm and 11% of those in the Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 3% and 9%, respectively.
Fourteen percent of patients in the G-Clb arm and 7% of those in the Clb arm had second malignancies (starting 6 months after treatment initiation). The most common of these were squamous cell carcinoma (2% vs 0%) and basal cell carcinoma (2% vs <1%).
G-Clb vs R-Clb
Ninety-four percent of patients in the G-Clb arm and 90% of those in the R-Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 72% and 60%, respectively. The rates of serious AEs were 45% and 39%, respectively. The rates of fatal AEs were 7% and 10%, respectively.
Fifteen percent of patients in the G-Clb arm and 12% of those in the R-Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 2% and 4%, respectively.
Eleven percent of patients in the G-Clb arm and 10% of those in the Clb arm had second malignancies. Squamous cell carcinoma occurred in 2% of patients in both arms. Basal cell carcinoma occurred in 2% of G-Clb recipients and 1% of R-Clb recipients.
Autism Spectrum Disorders Are on the Rise
The estimated prevalence of autism spectrum disorder (ASD) is higher than previously recorded, according to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Between 2000- 2014, the prevalence increased from 6.7 to 16.8 per 1,000 children, a jump of about 150%.
Autism and Developmental Disabilities Monitoring is a surveillance system that estimates the prevalence of autism spectrum disorder among children aged 8 years who live within 11 sites (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Autism and Developmental Disabilities Monitoring does not depend on family or practitioner reporting to determine ASD case status. Instead, staff conduct surveillance in a 2-phase process: reviewing children’s evaluation records from data sources in the community (including “developmental assessments completed by a wide range of health and education providers”), and compiling them into a comprehensive record that is then reviewed by ≤ 1 experienced clinicians.
Certain characteristics remained similar in 2014 compared with earlier surveillance years, ADDM researchers say. For instance, the median age of earliest known ASD diagnosis was 52 months in 2014, compared with close to 53 months in previous years.
However, male-to-female prevalence changed slightly, from 4.5:1 to 4:1, driven by a greater relative increase in ASD prevalence among girls since 2012. Autism and Developmental Disabilities Monitoring also points to a trend that begun in 2002 of a decrease in the ratios of white to black children and white to Hispanic children. Historically, ADDM researchers say, estimates have been 20% to 30% higher among white children compared with black children and 50% to 70% higher compared with Hispanic children. In 2014, those numbers dropped to 7% (the lowest difference ever observed by ADDM) and 22%, respectively.
Implementation of the new DSM-5 case definition had little effect on the overall number of children identified with ASD in 2014, ADDM researchers say.
The estimated prevalence of autism spectrum disorder (ASD) is higher than previously recorded, according to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Between 2000- 2014, the prevalence increased from 6.7 to 16.8 per 1,000 children, a jump of about 150%.
Autism and Developmental Disabilities Monitoring is a surveillance system that estimates the prevalence of autism spectrum disorder among children aged 8 years who live within 11 sites (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Autism and Developmental Disabilities Monitoring does not depend on family or practitioner reporting to determine ASD case status. Instead, staff conduct surveillance in a 2-phase process: reviewing children’s evaluation records from data sources in the community (including “developmental assessments completed by a wide range of health and education providers”), and compiling them into a comprehensive record that is then reviewed by ≤ 1 experienced clinicians.
Certain characteristics remained similar in 2014 compared with earlier surveillance years, ADDM researchers say. For instance, the median age of earliest known ASD diagnosis was 52 months in 2014, compared with close to 53 months in previous years.
However, male-to-female prevalence changed slightly, from 4.5:1 to 4:1, driven by a greater relative increase in ASD prevalence among girls since 2012. Autism and Developmental Disabilities Monitoring also points to a trend that begun in 2002 of a decrease in the ratios of white to black children and white to Hispanic children. Historically, ADDM researchers say, estimates have been 20% to 30% higher among white children compared with black children and 50% to 70% higher compared with Hispanic children. In 2014, those numbers dropped to 7% (the lowest difference ever observed by ADDM) and 22%, respectively.
Implementation of the new DSM-5 case definition had little effect on the overall number of children identified with ASD in 2014, ADDM researchers say.
The estimated prevalence of autism spectrum disorder (ASD) is higher than previously recorded, according to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Between 2000- 2014, the prevalence increased from 6.7 to 16.8 per 1,000 children, a jump of about 150%.
Autism and Developmental Disabilities Monitoring is a surveillance system that estimates the prevalence of autism spectrum disorder among children aged 8 years who live within 11 sites (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Autism and Developmental Disabilities Monitoring does not depend on family or practitioner reporting to determine ASD case status. Instead, staff conduct surveillance in a 2-phase process: reviewing children’s evaluation records from data sources in the community (including “developmental assessments completed by a wide range of health and education providers”), and compiling them into a comprehensive record that is then reviewed by ≤ 1 experienced clinicians.
Certain characteristics remained similar in 2014 compared with earlier surveillance years, ADDM researchers say. For instance, the median age of earliest known ASD diagnosis was 52 months in 2014, compared with close to 53 months in previous years.
However, male-to-female prevalence changed slightly, from 4.5:1 to 4:1, driven by a greater relative increase in ASD prevalence among girls since 2012. Autism and Developmental Disabilities Monitoring also points to a trend that begun in 2002 of a decrease in the ratios of white to black children and white to Hispanic children. Historically, ADDM researchers say, estimates have been 20% to 30% higher among white children compared with black children and 50% to 70% higher compared with Hispanic children. In 2014, those numbers dropped to 7% (the lowest difference ever observed by ADDM) and 22%, respectively.
Implementation of the new DSM-5 case definition had little effect on the overall number of children identified with ASD in 2014, ADDM researchers say.
VA Care Matches—or Bests—Non-VA Care
Researchers from RAND Corp. compared performance between each VA facility and 3 corresponding non-VA settings with similar geographic settings, size, and complexity of care, using recent data on patient safety, mortality and readmission, inpatient and outpatient effectiveness, and patient-centered care.
VA hospitals performed on average the same as or significantly better than the non-VA hospitals on all 6 measures of inpatient safety, all 3 inpatient mortality measures, and 12 inpatient effectiveness measures. VA facilities also performed significantly better than commercial HMOs and Medicaid HMOs for all 16 outpatient effectiveness measures. Compared with Medicare HMOs, the VA did significantly better on 14 measures and did not differ on 2.
However, the VA performance was worse than the non-VA hospitals on 3 readmission measures and 2 effectiveness measures. For example, VA inpatient performance was significantly lower on the patient experience measure for pain management.
The researchers saw “high variation” across VA facilities in performance on some quality measures, although they note that variation was even greater among non-VA hospitals. “The variation among VA health facilities shows that veterans in some areas are not receiving the same high-quality care that other VA facilities are able to provide,” said Carrie Farmer, a co-author of the study.
Researchers from RAND Corp. compared performance between each VA facility and 3 corresponding non-VA settings with similar geographic settings, size, and complexity of care, using recent data on patient safety, mortality and readmission, inpatient and outpatient effectiveness, and patient-centered care.
VA hospitals performed on average the same as or significantly better than the non-VA hospitals on all 6 measures of inpatient safety, all 3 inpatient mortality measures, and 12 inpatient effectiveness measures. VA facilities also performed significantly better than commercial HMOs and Medicaid HMOs for all 16 outpatient effectiveness measures. Compared with Medicare HMOs, the VA did significantly better on 14 measures and did not differ on 2.
However, the VA performance was worse than the non-VA hospitals on 3 readmission measures and 2 effectiveness measures. For example, VA inpatient performance was significantly lower on the patient experience measure for pain management.
The researchers saw “high variation” across VA facilities in performance on some quality measures, although they note that variation was even greater among non-VA hospitals. “The variation among VA health facilities shows that veterans in some areas are not receiving the same high-quality care that other VA facilities are able to provide,” said Carrie Farmer, a co-author of the study.
Researchers from RAND Corp. compared performance between each VA facility and 3 corresponding non-VA settings with similar geographic settings, size, and complexity of care, using recent data on patient safety, mortality and readmission, inpatient and outpatient effectiveness, and patient-centered care.
VA hospitals performed on average the same as or significantly better than the non-VA hospitals on all 6 measures of inpatient safety, all 3 inpatient mortality measures, and 12 inpatient effectiveness measures. VA facilities also performed significantly better than commercial HMOs and Medicaid HMOs for all 16 outpatient effectiveness measures. Compared with Medicare HMOs, the VA did significantly better on 14 measures and did not differ on 2.
However, the VA performance was worse than the non-VA hospitals on 3 readmission measures and 2 effectiveness measures. For example, VA inpatient performance was significantly lower on the patient experience measure for pain management.
The researchers saw “high variation” across VA facilities in performance on some quality measures, although they note that variation was even greater among non-VA hospitals. “The variation among VA health facilities shows that veterans in some areas are not receiving the same high-quality care that other VA facilities are able to provide,” said Carrie Farmer, a co-author of the study.
Umbralisib can revitalize ruxolitinib in MF
STOCKHOLM—The PI3K delta inhibitor umbralisib can “augment or resurrect” responses to ruxolitinib in patients with myelofibrosis (MF), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).
Results of a phase 1 study showed that adding umbralisib to treatment with ruxolitinib could induce responses in MF patients who had a suboptimal or lost response to ruxolitinib.
Of the 23 patients who received the combination, 2 achieved a complete remission (CR), 11 had clinical improvement, and 8 had stable disease.
In addition, umbralisib plus ruxolitinib was considered well-tolerated. The most common adverse event (AE) was anemia.
Tamara K. Moyo, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee, presented these results at the EHA Congress as abstract S133. The research was sponsored by TG Therapeutics.
Patients
Dr Moyo reported results in 23 MF patients who had a suboptimal response, lost a response, or had no response while on a stable dose of ruxolitinib for at least 8 weeks. Their median age was 67 (range, 49-83), and 61% were male.
Patients had primary MF (30%), post-essential thrombocythemia (ET) MF (43%), or post-polycythemia vera (PV) MF (26%). Forty-three percent of patients had JAK2 V617F, 30% had CALR mutations, 17% had MPL mutations, and 13% were triple-negative. One patient had co-occurring CALR and MPL mutations.
Most patients had an ECOG performance score of 0 (39%) or 1 (52%). All had intermediate-1 (35%), intermediate-2 (35%), or high-risk disease (30%) according to DIPSS Plus.
Sixty-one percent of patients had splenomegaly.
Treatment
In stage 1, the patients received stable ruxolitinib and escalating umbralisib. In stage 2, patients received escalating ruxolitinib and umbralisib at the maximum tolerated dose (MTD) established from stage 1.
Patients could then proceed to expansion cohorts in which they would receive any dose of ruxolitinib and umbralisib at the MTD. The expansion cohorts include patients with treatment-naïve MF, PV, chronic myelomonocytic leukemia, and myelodysplastic syndromes/myeloproliferative neoplasms.
However, Dr Moyo reported only on the 23 ruxolitinib-experienced MF patients.
Safety
There were 2 dose-limiting toxicities of asymptomatic, grade 3 amylase/lipase elevations. One occurred in a patient receiving 800 mg of umbralisib daily and 10 mg of ruxolitinib twice daily. The other occurred in a patient receiving 800 mg of umbralisib daily and 15 mg of ruxolitinib twice daily.
Therefore, 600 mg daily was deemed the MTD of umbralisib.
Seventeen patients had at least 1 AE. There were 17 grade 3 or higher AEs in 13 patients.
AEs of any grade included anemia (n=10), neutrophil decrease (n=2), platelet decrease (n=5), AST increase (n=6), ALT increase (n=3), amylase increase (n=3), lipase increase (n=3), diarrhea (n=2), colitis (n=1), dyspnea (n=1), upper respiratory infection (n=2), pneumonia (n=4), other infections (n=6), and sepsis (n=1).
Grade 3 AEs included anemia (n=3), neutrophil decrease (n=2), amylase increase (n=2), lipase increase (n=2), diarrhea (n=2), colitis (n=1), dyspnea (n=1), pneumonia (n=1), and other infections (n=2). The case of sepsis was the only grade 4 AE.
Dr Moyo noted that anemia—the most common AE—was commonly attributed to disease rather than study treatment.
The case of colitis, which was grade 3, was deemed possibly related to treatment, so the patient was removed from the study.
Thirteen patients had discontinued study treatment at the time of analysis. Aside from the patient who discontinued due to colitis, 2 patients went off study due to dose-limiting toxicities, 3 due to progressive disease, 6 due to physician or patient decision, and 1 due to transplant.
Efficacy
Two patients could not be assessed for efficacy, and 8 had stable disease on umbralisib and ruxolitinib.
The combination produced clinical improvement—reduction in spleen volume, increase in hemoglobin, and improvement in MF-related symptoms—in 11 patients (48%).
And 2 patients (9%) achieved a CR. Dr Moyo said there were “few commonalities” between these 2 patients.
Both had intermediate-1-risk disease as well as persistent or progressive MF-related symptoms and thrombocytosis at baseline. However, 1 patient had post-ET MF, and 1 had post-PV MF.
The post-ET MF patient had an MPL driver mutation. She received ruxolitinib at 20 mg twice daily and umbralisib at 400 mg daily. The patient achieved a CR at cycle 15 and remained on study 2 years before proceeding to transplant. The patient is now about 1 year from her transplant with no evidence of disease.
The post-PV patient had a JAK2 V617F driver mutation. She received ruxolitinib at 15 mg twice daily and umbralisib at 600 mg daily. The patient achieved a CR at cycle 5 and remains on study, currently receiving cycle 12 of treatment.
Dr Moyo said these results suggest “the addition of umbralisib to ruxolitinib can augment or resurrect a response in MF patients who have had suboptimal or lost response to ruxolitinib alone, and this treatment combination warrants further investigation.”
STOCKHOLM—The PI3K delta inhibitor umbralisib can “augment or resurrect” responses to ruxolitinib in patients with myelofibrosis (MF), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).
Results of a phase 1 study showed that adding umbralisib to treatment with ruxolitinib could induce responses in MF patients who had a suboptimal or lost response to ruxolitinib.
Of the 23 patients who received the combination, 2 achieved a complete remission (CR), 11 had clinical improvement, and 8 had stable disease.
In addition, umbralisib plus ruxolitinib was considered well-tolerated. The most common adverse event (AE) was anemia.
Tamara K. Moyo, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee, presented these results at the EHA Congress as abstract S133. The research was sponsored by TG Therapeutics.
Patients
Dr Moyo reported results in 23 MF patients who had a suboptimal response, lost a response, or had no response while on a stable dose of ruxolitinib for at least 8 weeks. Their median age was 67 (range, 49-83), and 61% were male.
Patients had primary MF (30%), post-essential thrombocythemia (ET) MF (43%), or post-polycythemia vera (PV) MF (26%). Forty-three percent of patients had JAK2 V617F, 30% had CALR mutations, 17% had MPL mutations, and 13% were triple-negative. One patient had co-occurring CALR and MPL mutations.
Most patients had an ECOG performance score of 0 (39%) or 1 (52%). All had intermediate-1 (35%), intermediate-2 (35%), or high-risk disease (30%) according to DIPSS Plus.
Sixty-one percent of patients had splenomegaly.
Treatment
In stage 1, the patients received stable ruxolitinib and escalating umbralisib. In stage 2, patients received escalating ruxolitinib and umbralisib at the maximum tolerated dose (MTD) established from stage 1.
Patients could then proceed to expansion cohorts in which they would receive any dose of ruxolitinib and umbralisib at the MTD. The expansion cohorts include patients with treatment-naïve MF, PV, chronic myelomonocytic leukemia, and myelodysplastic syndromes/myeloproliferative neoplasms.
However, Dr Moyo reported only on the 23 ruxolitinib-experienced MF patients.
Safety
There were 2 dose-limiting toxicities of asymptomatic, grade 3 amylase/lipase elevations. One occurred in a patient receiving 800 mg of umbralisib daily and 10 mg of ruxolitinib twice daily. The other occurred in a patient receiving 800 mg of umbralisib daily and 15 mg of ruxolitinib twice daily.
Therefore, 600 mg daily was deemed the MTD of umbralisib.
Seventeen patients had at least 1 AE. There were 17 grade 3 or higher AEs in 13 patients.
AEs of any grade included anemia (n=10), neutrophil decrease (n=2), platelet decrease (n=5), AST increase (n=6), ALT increase (n=3), amylase increase (n=3), lipase increase (n=3), diarrhea (n=2), colitis (n=1), dyspnea (n=1), upper respiratory infection (n=2), pneumonia (n=4), other infections (n=6), and sepsis (n=1).
Grade 3 AEs included anemia (n=3), neutrophil decrease (n=2), amylase increase (n=2), lipase increase (n=2), diarrhea (n=2), colitis (n=1), dyspnea (n=1), pneumonia (n=1), and other infections (n=2). The case of sepsis was the only grade 4 AE.
Dr Moyo noted that anemia—the most common AE—was commonly attributed to disease rather than study treatment.
The case of colitis, which was grade 3, was deemed possibly related to treatment, so the patient was removed from the study.
Thirteen patients had discontinued study treatment at the time of analysis. Aside from the patient who discontinued due to colitis, 2 patients went off study due to dose-limiting toxicities, 3 due to progressive disease, 6 due to physician or patient decision, and 1 due to transplant.
Efficacy
Two patients could not be assessed for efficacy, and 8 had stable disease on umbralisib and ruxolitinib.
The combination produced clinical improvement—reduction in spleen volume, increase in hemoglobin, and improvement in MF-related symptoms—in 11 patients (48%).
And 2 patients (9%) achieved a CR. Dr Moyo said there were “few commonalities” between these 2 patients.
Both had intermediate-1-risk disease as well as persistent or progressive MF-related symptoms and thrombocytosis at baseline. However, 1 patient had post-ET MF, and 1 had post-PV MF.
The post-ET MF patient had an MPL driver mutation. She received ruxolitinib at 20 mg twice daily and umbralisib at 400 mg daily. The patient achieved a CR at cycle 15 and remained on study 2 years before proceeding to transplant. The patient is now about 1 year from her transplant with no evidence of disease.
The post-PV patient had a JAK2 V617F driver mutation. She received ruxolitinib at 15 mg twice daily and umbralisib at 600 mg daily. The patient achieved a CR at cycle 5 and remains on study, currently receiving cycle 12 of treatment.
Dr Moyo said these results suggest “the addition of umbralisib to ruxolitinib can augment or resurrect a response in MF patients who have had suboptimal or lost response to ruxolitinib alone, and this treatment combination warrants further investigation.”
STOCKHOLM—The PI3K delta inhibitor umbralisib can “augment or resurrect” responses to ruxolitinib in patients with myelofibrosis (MF), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).
Results of a phase 1 study showed that adding umbralisib to treatment with ruxolitinib could induce responses in MF patients who had a suboptimal or lost response to ruxolitinib.
Of the 23 patients who received the combination, 2 achieved a complete remission (CR), 11 had clinical improvement, and 8 had stable disease.
In addition, umbralisib plus ruxolitinib was considered well-tolerated. The most common adverse event (AE) was anemia.
Tamara K. Moyo, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee, presented these results at the EHA Congress as abstract S133. The research was sponsored by TG Therapeutics.
Patients
Dr Moyo reported results in 23 MF patients who had a suboptimal response, lost a response, or had no response while on a stable dose of ruxolitinib for at least 8 weeks. Their median age was 67 (range, 49-83), and 61% were male.
Patients had primary MF (30%), post-essential thrombocythemia (ET) MF (43%), or post-polycythemia vera (PV) MF (26%). Forty-three percent of patients had JAK2 V617F, 30% had CALR mutations, 17% had MPL mutations, and 13% were triple-negative. One patient had co-occurring CALR and MPL mutations.
Most patients had an ECOG performance score of 0 (39%) or 1 (52%). All had intermediate-1 (35%), intermediate-2 (35%), or high-risk disease (30%) according to DIPSS Plus.
Sixty-one percent of patients had splenomegaly.
Treatment
In stage 1, the patients received stable ruxolitinib and escalating umbralisib. In stage 2, patients received escalating ruxolitinib and umbralisib at the maximum tolerated dose (MTD) established from stage 1.
Patients could then proceed to expansion cohorts in which they would receive any dose of ruxolitinib and umbralisib at the MTD. The expansion cohorts include patients with treatment-naïve MF, PV, chronic myelomonocytic leukemia, and myelodysplastic syndromes/myeloproliferative neoplasms.
However, Dr Moyo reported only on the 23 ruxolitinib-experienced MF patients.
Safety
There were 2 dose-limiting toxicities of asymptomatic, grade 3 amylase/lipase elevations. One occurred in a patient receiving 800 mg of umbralisib daily and 10 mg of ruxolitinib twice daily. The other occurred in a patient receiving 800 mg of umbralisib daily and 15 mg of ruxolitinib twice daily.
Therefore, 600 mg daily was deemed the MTD of umbralisib.
Seventeen patients had at least 1 AE. There were 17 grade 3 or higher AEs in 13 patients.
AEs of any grade included anemia (n=10), neutrophil decrease (n=2), platelet decrease (n=5), AST increase (n=6), ALT increase (n=3), amylase increase (n=3), lipase increase (n=3), diarrhea (n=2), colitis (n=1), dyspnea (n=1), upper respiratory infection (n=2), pneumonia (n=4), other infections (n=6), and sepsis (n=1).
Grade 3 AEs included anemia (n=3), neutrophil decrease (n=2), amylase increase (n=2), lipase increase (n=2), diarrhea (n=2), colitis (n=1), dyspnea (n=1), pneumonia (n=1), and other infections (n=2). The case of sepsis was the only grade 4 AE.
Dr Moyo noted that anemia—the most common AE—was commonly attributed to disease rather than study treatment.
The case of colitis, which was grade 3, was deemed possibly related to treatment, so the patient was removed from the study.
Thirteen patients had discontinued study treatment at the time of analysis. Aside from the patient who discontinued due to colitis, 2 patients went off study due to dose-limiting toxicities, 3 due to progressive disease, 6 due to physician or patient decision, and 1 due to transplant.
Efficacy
Two patients could not be assessed for efficacy, and 8 had stable disease on umbralisib and ruxolitinib.
The combination produced clinical improvement—reduction in spleen volume, increase in hemoglobin, and improvement in MF-related symptoms—in 11 patients (48%).
And 2 patients (9%) achieved a CR. Dr Moyo said there were “few commonalities” between these 2 patients.
Both had intermediate-1-risk disease as well as persistent or progressive MF-related symptoms and thrombocytosis at baseline. However, 1 patient had post-ET MF, and 1 had post-PV MF.
The post-ET MF patient had an MPL driver mutation. She received ruxolitinib at 20 mg twice daily and umbralisib at 400 mg daily. The patient achieved a CR at cycle 15 and remained on study 2 years before proceeding to transplant. The patient is now about 1 year from her transplant with no evidence of disease.
The post-PV patient had a JAK2 V617F driver mutation. She received ruxolitinib at 15 mg twice daily and umbralisib at 600 mg daily. The patient achieved a CR at cycle 5 and remains on study, currently receiving cycle 12 of treatment.
Dr Moyo said these results suggest “the addition of umbralisib to ruxolitinib can augment or resurrect a response in MF patients who have had suboptimal or lost response to ruxolitinib alone, and this treatment combination warrants further investigation.”
Quality improvement initiative reduced unnecessary GAS pharyngitis testing, report says
Unnecessary testing for group A streptococcal (GAS) pharyngitis was less common in one ambulatory pediatrics practice after a collaborative interprofessional quality improvement (QI) initiative, results of a study found.
The average monthly frequency of unnecessary testing in that practice fell from 64% before the intervention to 41% afterward. Although the initiative did not appear to improve appropriate antibiotic use for GAS pharyngitis, most of the providers (88%) perceived an improvement in their ability to communicate with families about appropriate antibiotic use and the need for testing, Laura E. Norton, MD, of the University of Minnesota, Minneapolis, and her associates wrote.
The QI project was implemented at a pediatrics practice with two locations in Kansas City, Mo., with 12 board-certified pediatricians, 19 nurses, and 4 certified nurse practitioners who provide care for more than 40,000 children annually. Interventions that were part of this project included education for providers, patients, and families; office procedure modifications;and discussions with providers about communicating with families, along with periodic feedback to providers on improvement in outcomes measures.
Dr. Norton and her colleagues defined unnecessary GAS pharyngitis testing as testing in a patient with two or more viral symptoms (conjunctivitis, coryza, cough, diarrhea, hoarse voice, and viral exanthema), aged less than 3 years with no documentation of a household contact with GAS pharyngitis, absence of sore throat, or absence of examination findings expected in GAS pharyngitis cases.
The investigators illustrated a reduction in frequency of unnecessary testing from the monthly average of 64% to 41% using a P-chart, a type of graph used in statistical quality control to illustrate the proportion of defective or nonconforming values. They reported a significant reduction in unnecessary testing in children younger than 3 years from the pre- to postintervention period (P = .017).
Dr. Norton and her coauthors said they were aiming for a larger magnitude of improvement, which may have been in part because of cognitive bias. “Some providers reported fear of complications that could result from missed GAS pharyngitis diagnosis as a driver of their decision to perform GAS pharyngitis testing.”
There was no significant improvement in appropriate use of antibiotics for GAS pharyngitis from pre- to postintervention period, which Dr. Norton and her associates said points to a need for further research in other pediatric practices. “Adherence to guideline-based, first-line antibiotic selection was higher in this practice than reported in published national data, leaving little room for improvement.”
Dr. Norton and her coauthors had no relevant financial disclosures.
SOURCE: Norton LE, et al. Pediatrics. 2018;142(1):e20172033.
Unnecessary testing for group A streptococcal (GAS) pharyngitis was less common in one ambulatory pediatrics practice after a collaborative interprofessional quality improvement (QI) initiative, results of a study found.
The average monthly frequency of unnecessary testing in that practice fell from 64% before the intervention to 41% afterward. Although the initiative did not appear to improve appropriate antibiotic use for GAS pharyngitis, most of the providers (88%) perceived an improvement in their ability to communicate with families about appropriate antibiotic use and the need for testing, Laura E. Norton, MD, of the University of Minnesota, Minneapolis, and her associates wrote.
The QI project was implemented at a pediatrics practice with two locations in Kansas City, Mo., with 12 board-certified pediatricians, 19 nurses, and 4 certified nurse practitioners who provide care for more than 40,000 children annually. Interventions that were part of this project included education for providers, patients, and families; office procedure modifications;and discussions with providers about communicating with families, along with periodic feedback to providers on improvement in outcomes measures.
Dr. Norton and her colleagues defined unnecessary GAS pharyngitis testing as testing in a patient with two or more viral symptoms (conjunctivitis, coryza, cough, diarrhea, hoarse voice, and viral exanthema), aged less than 3 years with no documentation of a household contact with GAS pharyngitis, absence of sore throat, or absence of examination findings expected in GAS pharyngitis cases.
The investigators illustrated a reduction in frequency of unnecessary testing from the monthly average of 64% to 41% using a P-chart, a type of graph used in statistical quality control to illustrate the proportion of defective or nonconforming values. They reported a significant reduction in unnecessary testing in children younger than 3 years from the pre- to postintervention period (P = .017).
Dr. Norton and her coauthors said they were aiming for a larger magnitude of improvement, which may have been in part because of cognitive bias. “Some providers reported fear of complications that could result from missed GAS pharyngitis diagnosis as a driver of their decision to perform GAS pharyngitis testing.”
There was no significant improvement in appropriate use of antibiotics for GAS pharyngitis from pre- to postintervention period, which Dr. Norton and her associates said points to a need for further research in other pediatric practices. “Adherence to guideline-based, first-line antibiotic selection was higher in this practice than reported in published national data, leaving little room for improvement.”
Dr. Norton and her coauthors had no relevant financial disclosures.
SOURCE: Norton LE, et al. Pediatrics. 2018;142(1):e20172033.
Unnecessary testing for group A streptococcal (GAS) pharyngitis was less common in one ambulatory pediatrics practice after a collaborative interprofessional quality improvement (QI) initiative, results of a study found.
The average monthly frequency of unnecessary testing in that practice fell from 64% before the intervention to 41% afterward. Although the initiative did not appear to improve appropriate antibiotic use for GAS pharyngitis, most of the providers (88%) perceived an improvement in their ability to communicate with families about appropriate antibiotic use and the need for testing, Laura E. Norton, MD, of the University of Minnesota, Minneapolis, and her associates wrote.
The QI project was implemented at a pediatrics practice with two locations in Kansas City, Mo., with 12 board-certified pediatricians, 19 nurses, and 4 certified nurse practitioners who provide care for more than 40,000 children annually. Interventions that were part of this project included education for providers, patients, and families; office procedure modifications;and discussions with providers about communicating with families, along with periodic feedback to providers on improvement in outcomes measures.
Dr. Norton and her colleagues defined unnecessary GAS pharyngitis testing as testing in a patient with two or more viral symptoms (conjunctivitis, coryza, cough, diarrhea, hoarse voice, and viral exanthema), aged less than 3 years with no documentation of a household contact with GAS pharyngitis, absence of sore throat, or absence of examination findings expected in GAS pharyngitis cases.
The investigators illustrated a reduction in frequency of unnecessary testing from the monthly average of 64% to 41% using a P-chart, a type of graph used in statistical quality control to illustrate the proportion of defective or nonconforming values. They reported a significant reduction in unnecessary testing in children younger than 3 years from the pre- to postintervention period (P = .017).
Dr. Norton and her coauthors said they were aiming for a larger magnitude of improvement, which may have been in part because of cognitive bias. “Some providers reported fear of complications that could result from missed GAS pharyngitis diagnosis as a driver of their decision to perform GAS pharyngitis testing.”
There was no significant improvement in appropriate use of antibiotics for GAS pharyngitis from pre- to postintervention period, which Dr. Norton and her associates said points to a need for further research in other pediatric practices. “Adherence to guideline-based, first-line antibiotic selection was higher in this practice than reported in published national data, leaving little room for improvement.”
Dr. Norton and her coauthors had no relevant financial disclosures.
SOURCE: Norton LE, et al. Pediatrics. 2018;142(1):e20172033.
FROM PEDIATRICS
Key clinical point: An interprofessional collaboration using quality improvement methods may improve adherence to guideline-based GAS pharyngitis testing.
Major finding:
Study details: A quality improvement initiative implemented at one two-location pediatrics practice providing care for more than 40,000 children annually.
Disclosures: The authors had no financial disclosures or potential conflicts of interest.
Source: Norton LE et al. Pediatrics. 2018;142(1):e20172033.