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VIDEO: With new therapies available, it’s the ‘decade of eczema,’ researcher says
SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.
And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.
In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.
SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.
And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.
In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.
SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.
And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.
In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.
REPORTING FROM AAD 18
For women with alcohol SUD, try gender-specific treatment
TAMPA – The distinct features of substance use disorders (SUDs) in women argue for gender-specific treatment, according to a comprehensive update presented at the annual meeting of the American College of Psychiatrists.
“There is a shorter time between landmarks of SUD progression, and these landmarks are reached at lower doses of alcohol consumed less frequently,” reported Shelly F. Greenfield, MD, chief academic officer at McLean Hospital in Boston.
“For each ounce of alcohol consumed, the blood alcohol concentration is higher with a greater potential for adverse physical consequences,” Dr. Greenfield said. These physiologic differences may account for the more rapid progression of SUD severity in women, a phenomenon that Dr. Greenfield referred to as “telescoping.” She said the same type of telescoping, defined as “an accelerated progression from the initiation of substance use to the onset of dependence and first admission to treatment” (Psychiatr Clin North Am. 2011 Jun 28;33[2]:339-55), also has been seen among women for opioids and stimulants (Drug Alcohol Depend. 2004 Jun 11;74[3]:265-72). These greater risks are reflected in a higher SUD-associated mortality in females, compared with SUD-associated mortality in males.
Relative rates of alcohol SUD among women have been climbing steadily for more than 30 years. In the 1980s, for example, a population survey estimated the male-to-female prevalence ratio of alcohol SUD as 5:1. Citing subsequent surveys, Dr. Greenfield traced a rapid narrowing of the gender gap. In one of the most recent surveys, the rate had fallen below 2:1. Rates of heaving drinking and binge drinking are now about 1.4:1 in individuals aged 18-25 years.
“Each time we look at this gap, it has narrowed further,” Dr. Greenfield said. In another survey she cited, illicit drug use among adolescents between ages 12 and 17 years was higher in boys, but alcohol use in males and females was essentially the same.
Several facts suggest that treatment specific to women will improve outcomes. For one, For another, women are more likely to have co-occurring psychiatric disorders. In one study, anxiety (60.7% vs. 35.8%) and mood disorders (53.5% vs. 28.1%) were nearly twice as common in women with SUDs than in their male counterparts. This is relevant to interventions tailored for females because of evidence showing that treatment for SUDs and co-occurring psychiatric disorders should be integrated rather than addressed independently, according to Dr. Greenfield.
Importantly, “there is evidence of improved treatment outcome in women-focused programs,” Dr. Greenfield said. She suggested that successful programs for alcohol SUD in women not only address gender-specific features but that success can be enhanced further with adjunctive services that address the barriers to treatment, such as child care challenges and stigma – which Dr. Greenfield said is greater in women than in men.
A study called the Women’s Recovery Group (WRG), funded by the National Institute on Drug Abuse and led by Dr. Greenfield, is among those that have reinforced the value of female-specific therapy for SUD (Drug Alcohol Depend. 2014 Sep 1;142:245-53). A manual developed from the study and published in a book she wrote called “Treating Women With Substance Use Disorders: The Women’s Recovery Group Manual” (New York: The Guilford Press, 2016), outlines the principles. Dr. Greenfield said the structured 12-session group therapy for relapse prevention has been effective and well received by women. Some of those women have commented on the reinforcing value of shared experiences.
Up until now, women with alcohol SUD have been commonly treated alongside men, but Dr. Greenfield contended that treatment outcomes with alcohol SUD or other forms of SUDs “can be enhanced by programs that provide services specific to women’s needs.” She believes strategies aimed at addressing the more common histories of sexual or physical trauma and psychiatric comorbidities along with gender-related barriers to treatment have the potential to increase treatment success.
In addition to writing “Treating Women With Substance Use Disorders,” Dr. Greenfield is a coeditor of “Women and Addiction: A Comprehensive Handbook” (New York: Guilford, 2009). She reported no conflicts of interest.
TAMPA – The distinct features of substance use disorders (SUDs) in women argue for gender-specific treatment, according to a comprehensive update presented at the annual meeting of the American College of Psychiatrists.
“There is a shorter time between landmarks of SUD progression, and these landmarks are reached at lower doses of alcohol consumed less frequently,” reported Shelly F. Greenfield, MD, chief academic officer at McLean Hospital in Boston.
“For each ounce of alcohol consumed, the blood alcohol concentration is higher with a greater potential for adverse physical consequences,” Dr. Greenfield said. These physiologic differences may account for the more rapid progression of SUD severity in women, a phenomenon that Dr. Greenfield referred to as “telescoping.” She said the same type of telescoping, defined as “an accelerated progression from the initiation of substance use to the onset of dependence and first admission to treatment” (Psychiatr Clin North Am. 2011 Jun 28;33[2]:339-55), also has been seen among women for opioids and stimulants (Drug Alcohol Depend. 2004 Jun 11;74[3]:265-72). These greater risks are reflected in a higher SUD-associated mortality in females, compared with SUD-associated mortality in males.
Relative rates of alcohol SUD among women have been climbing steadily for more than 30 years. In the 1980s, for example, a population survey estimated the male-to-female prevalence ratio of alcohol SUD as 5:1. Citing subsequent surveys, Dr. Greenfield traced a rapid narrowing of the gender gap. In one of the most recent surveys, the rate had fallen below 2:1. Rates of heaving drinking and binge drinking are now about 1.4:1 in individuals aged 18-25 years.
“Each time we look at this gap, it has narrowed further,” Dr. Greenfield said. In another survey she cited, illicit drug use among adolescents between ages 12 and 17 years was higher in boys, but alcohol use in males and females was essentially the same.
Several facts suggest that treatment specific to women will improve outcomes. For one, For another, women are more likely to have co-occurring psychiatric disorders. In one study, anxiety (60.7% vs. 35.8%) and mood disorders (53.5% vs. 28.1%) were nearly twice as common in women with SUDs than in their male counterparts. This is relevant to interventions tailored for females because of evidence showing that treatment for SUDs and co-occurring psychiatric disorders should be integrated rather than addressed independently, according to Dr. Greenfield.
Importantly, “there is evidence of improved treatment outcome in women-focused programs,” Dr. Greenfield said. She suggested that successful programs for alcohol SUD in women not only address gender-specific features but that success can be enhanced further with adjunctive services that address the barriers to treatment, such as child care challenges and stigma – which Dr. Greenfield said is greater in women than in men.
A study called the Women’s Recovery Group (WRG), funded by the National Institute on Drug Abuse and led by Dr. Greenfield, is among those that have reinforced the value of female-specific therapy for SUD (Drug Alcohol Depend. 2014 Sep 1;142:245-53). A manual developed from the study and published in a book she wrote called “Treating Women With Substance Use Disorders: The Women’s Recovery Group Manual” (New York: The Guilford Press, 2016), outlines the principles. Dr. Greenfield said the structured 12-session group therapy for relapse prevention has been effective and well received by women. Some of those women have commented on the reinforcing value of shared experiences.
Up until now, women with alcohol SUD have been commonly treated alongside men, but Dr. Greenfield contended that treatment outcomes with alcohol SUD or other forms of SUDs “can be enhanced by programs that provide services specific to women’s needs.” She believes strategies aimed at addressing the more common histories of sexual or physical trauma and psychiatric comorbidities along with gender-related barriers to treatment have the potential to increase treatment success.
In addition to writing “Treating Women With Substance Use Disorders,” Dr. Greenfield is a coeditor of “Women and Addiction: A Comprehensive Handbook” (New York: Guilford, 2009). She reported no conflicts of interest.
TAMPA – The distinct features of substance use disorders (SUDs) in women argue for gender-specific treatment, according to a comprehensive update presented at the annual meeting of the American College of Psychiatrists.
“There is a shorter time between landmarks of SUD progression, and these landmarks are reached at lower doses of alcohol consumed less frequently,” reported Shelly F. Greenfield, MD, chief academic officer at McLean Hospital in Boston.
“For each ounce of alcohol consumed, the blood alcohol concentration is higher with a greater potential for adverse physical consequences,” Dr. Greenfield said. These physiologic differences may account for the more rapid progression of SUD severity in women, a phenomenon that Dr. Greenfield referred to as “telescoping.” She said the same type of telescoping, defined as “an accelerated progression from the initiation of substance use to the onset of dependence and first admission to treatment” (Psychiatr Clin North Am. 2011 Jun 28;33[2]:339-55), also has been seen among women for opioids and stimulants (Drug Alcohol Depend. 2004 Jun 11;74[3]:265-72). These greater risks are reflected in a higher SUD-associated mortality in females, compared with SUD-associated mortality in males.
Relative rates of alcohol SUD among women have been climbing steadily for more than 30 years. In the 1980s, for example, a population survey estimated the male-to-female prevalence ratio of alcohol SUD as 5:1. Citing subsequent surveys, Dr. Greenfield traced a rapid narrowing of the gender gap. In one of the most recent surveys, the rate had fallen below 2:1. Rates of heaving drinking and binge drinking are now about 1.4:1 in individuals aged 18-25 years.
“Each time we look at this gap, it has narrowed further,” Dr. Greenfield said. In another survey she cited, illicit drug use among adolescents between ages 12 and 17 years was higher in boys, but alcohol use in males and females was essentially the same.
Several facts suggest that treatment specific to women will improve outcomes. For one, For another, women are more likely to have co-occurring psychiatric disorders. In one study, anxiety (60.7% vs. 35.8%) and mood disorders (53.5% vs. 28.1%) were nearly twice as common in women with SUDs than in their male counterparts. This is relevant to interventions tailored for females because of evidence showing that treatment for SUDs and co-occurring psychiatric disorders should be integrated rather than addressed independently, according to Dr. Greenfield.
Importantly, “there is evidence of improved treatment outcome in women-focused programs,” Dr. Greenfield said. She suggested that successful programs for alcohol SUD in women not only address gender-specific features but that success can be enhanced further with adjunctive services that address the barriers to treatment, such as child care challenges and stigma – which Dr. Greenfield said is greater in women than in men.
A study called the Women’s Recovery Group (WRG), funded by the National Institute on Drug Abuse and led by Dr. Greenfield, is among those that have reinforced the value of female-specific therapy for SUD (Drug Alcohol Depend. 2014 Sep 1;142:245-53). A manual developed from the study and published in a book she wrote called “Treating Women With Substance Use Disorders: The Women’s Recovery Group Manual” (New York: The Guilford Press, 2016), outlines the principles. Dr. Greenfield said the structured 12-session group therapy for relapse prevention has been effective and well received by women. Some of those women have commented on the reinforcing value of shared experiences.
Up until now, women with alcohol SUD have been commonly treated alongside men, but Dr. Greenfield contended that treatment outcomes with alcohol SUD or other forms of SUDs “can be enhanced by programs that provide services specific to women’s needs.” She believes strategies aimed at addressing the more common histories of sexual or physical trauma and psychiatric comorbidities along with gender-related barriers to treatment have the potential to increase treatment success.
In addition to writing “Treating Women With Substance Use Disorders,” Dr. Greenfield is a coeditor of “Women and Addiction: A Comprehensive Handbook” (New York: Guilford, 2009). She reported no conflicts of interest.
REPORTING FROM THE COLLEGE 2018
VIDEO: U.S. melanoma incidence hits all-time high
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
SAN DIEGO –
“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.
The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.
Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.
During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.
A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.
REPORTING FROM AAD 18
MDedge Daily News: Is SPF 100 really better?
Is 100 really greater than 50 when it comes to sunscreen? A new hepatitis B vaccine gets the nod, a new JAK inhibitor takes aim at atopic dermatitis, and why house cleaning does women’s lungs no favors.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Is 100 really greater than 50 when it comes to sunscreen? A new hepatitis B vaccine gets the nod, a new JAK inhibitor takes aim at atopic dermatitis, and why house cleaning does women’s lungs no favors.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Is 100 really greater than 50 when it comes to sunscreen? A new hepatitis B vaccine gets the nod, a new JAK inhibitor takes aim at atopic dermatitis, and why house cleaning does women’s lungs no favors.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Regimen deemed ‘safe and feasible’ in MM
SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.
Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.
The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.
The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.
Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.
Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.
“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.
She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.
Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).
The patients had a median of 174 days since diagnosis (range, 98-393).
All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.
Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.
Treatment
Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.
They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.
Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.
Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.
Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.
Safety
“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”
One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.
One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.
Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.
Efficacy
At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).
At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.
“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”
At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.
So the 1-year progression-free survival rate was 86% (13/15).
“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”
*Information in the abstract differs from the presentation.
SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.
Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.
The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.
The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.
Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.
Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.
“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.
She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.
Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).
The patients had a median of 174 days since diagnosis (range, 98-393).
All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.
Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.
Treatment
Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.
They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.
Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.
Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.
Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.
Safety
“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”
One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.
One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.
Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.
Efficacy
At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).
At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.
“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”
At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.
So the 1-year progression-free survival rate was 86% (13/15).
“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”
*Information in the abstract differs from the presentation.
SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.
Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.
The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.
The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.
Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.
Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.
“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.
She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.
Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).
The patients had a median of 174 days since diagnosis (range, 98-393).
All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.
Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.
Treatment
Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.
They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.
Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.
Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.
Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.
Safety
“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”
One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.
One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.
Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.
Efficacy
At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).
At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.
“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”
At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.
So the 1-year progression-free survival rate was 86% (13/15).
“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”
*Information in the abstract differs from the presentation.
Abstract: Impact of the Commercialization of Three Generic Angiotensin II Receptor Blockers on Adverse Events in Quebec, Canada
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017
BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.
METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.
RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).
CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references (paul.poirier@criucpq.ulaval.ca – no reprints)
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017
BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.
METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.
RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).
CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references (paul.poirier@criucpq.ulaval.ca – no reprints)
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017
BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.
METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.
RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).
CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references (paul.poirier@criucpq.ulaval.ca – no reprints)
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Extended-interval dosing of natalizumab linked to lower risk of PML
SAN DIEGO – A large industry-funded study of the multiple sclerosis drug natalizumab suggests that physicians can dramatically lower the likelihood of progressive multifocal leukoencephalopathy in patients at higher risk of the condition by increasing the interval between doses.
Previous research has suggested that natalizumab (Tysabri) doesn’t lose efficacy when given less frequently.
Dr. Zhovtis Ryerson presented the study findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
As a 2014 report explains, natalizumab is a “highly effective disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis,” but the risk of progressive multifocal leukoencephalopathy (PML) “has largely contributed to it being relegated to a second-line position” (Ther Adv Chronic Dis. 2014 Mar;5[2]:62-8).
Patients previously exposed to John Cunningham (JC) virus are at higher risk of PML, a rare viral brain disease that can be severely disabling or deadly. A 2017 report estimated the combined cumulative PML probability at 2.7% (with previous immunosuppressant use) and 1.7% (no previous immunosuppressant use) over 6 years in patients with signs of exposure to the JC virus (Lancet Neurol. 2017 Nov;16[11]:925-33). According to Dr. Zhovtis Ryerson, natalizumab manufacturer Biogen reported in December 2017 that it has confirmed 756 cases of PML in natalizumab-treated patients, all except for 3 in MS patients.
Doctors are wary in the at-risk patient population. “In general,” she said, “clinicians treating patients who are JC virus positive, and therefore have a risk for PML, may not utilize the drug or may take the patient off it after 2 years, which is when the risk goes up.”
Some physicians have experimented with longer intervals between treatments of 300 mg given intravenously, administering it every 5-8 weeks instead of every 4 weeks, with an eye on not extending the interval for too long “because MS disease activity returns after 12 weeks of withholding therapy,” Dr. Zhovtis Ryerson said.
In 2016, Dr. Zhovtis Ryerson and colleagues reported in a retrospective analysis that natalizumab dosing intervals of up to 8 weeks, 5 days didn’t affect the drug’s efficacy (J Neurol Neurosurg Psychiatry. 2016 Aug;87[8]:885-9).
For the primary analyses in the new study – whether dosing history in the last 18 months of natalizumab treatment affects PML – researchers tracked 1,988 patients who took the drug via an extended interval schedule and 13,132 who took it via a standard interval. The patients were tracked in the mandated TOUCH Prescribing Program; all participants showed signs of exposure to the JC virus.
The two groups were similar at about 68% female, an average age at first infusion of about 43, and a median number of about 48 natalizumab infusions.
For patients without previous immunosuppressant use who had received 49-60 doses, the researchers estimated the incidence of PML per 1,000 patients as 1.23 in the extended-interval group and 3.96 in the standard-interval group. The numbers were slightly higher for those who received 61-72 doses. At 48 or fewer doses, there were no PML cases in patients on extended-interval dosing.
“The data showed highly significant risk reductions of up to 94%,” Dr. Zhovtis Ryerson said.
Moving forward, “in collaboration with Biogen, we have more sensitivity analysis to be done to assure that our conclusions on this are correct,” she said. “Furthermore, more evidence of efficacy of extended-interval dosing natalizumab is needed, and we hope to move forward with a prospective, randomized, controlled trial to give clinicians the highest level of evidence we can.”
The study was funded by Biogen. Dr. Zhovtis Ryerson reported personal compensation from Teva, speaker/advisory board activities for Biogen, and research support from Biogen. Seven other authors reported being Biogen employees. Other authors reported no disclosures or various disclosures, including connections to Biogen.
SOURCE: Zhovtis R et al. ACTRIMS Forum 2018 Abstract LB250.
SAN DIEGO – A large industry-funded study of the multiple sclerosis drug natalizumab suggests that physicians can dramatically lower the likelihood of progressive multifocal leukoencephalopathy in patients at higher risk of the condition by increasing the interval between doses.
Previous research has suggested that natalizumab (Tysabri) doesn’t lose efficacy when given less frequently.
Dr. Zhovtis Ryerson presented the study findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
As a 2014 report explains, natalizumab is a “highly effective disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis,” but the risk of progressive multifocal leukoencephalopathy (PML) “has largely contributed to it being relegated to a second-line position” (Ther Adv Chronic Dis. 2014 Mar;5[2]:62-8).
Patients previously exposed to John Cunningham (JC) virus are at higher risk of PML, a rare viral brain disease that can be severely disabling or deadly. A 2017 report estimated the combined cumulative PML probability at 2.7% (with previous immunosuppressant use) and 1.7% (no previous immunosuppressant use) over 6 years in patients with signs of exposure to the JC virus (Lancet Neurol. 2017 Nov;16[11]:925-33). According to Dr. Zhovtis Ryerson, natalizumab manufacturer Biogen reported in December 2017 that it has confirmed 756 cases of PML in natalizumab-treated patients, all except for 3 in MS patients.
Doctors are wary in the at-risk patient population. “In general,” she said, “clinicians treating patients who are JC virus positive, and therefore have a risk for PML, may not utilize the drug or may take the patient off it after 2 years, which is when the risk goes up.”
Some physicians have experimented with longer intervals between treatments of 300 mg given intravenously, administering it every 5-8 weeks instead of every 4 weeks, with an eye on not extending the interval for too long “because MS disease activity returns after 12 weeks of withholding therapy,” Dr. Zhovtis Ryerson said.
In 2016, Dr. Zhovtis Ryerson and colleagues reported in a retrospective analysis that natalizumab dosing intervals of up to 8 weeks, 5 days didn’t affect the drug’s efficacy (J Neurol Neurosurg Psychiatry. 2016 Aug;87[8]:885-9).
For the primary analyses in the new study – whether dosing history in the last 18 months of natalizumab treatment affects PML – researchers tracked 1,988 patients who took the drug via an extended interval schedule and 13,132 who took it via a standard interval. The patients were tracked in the mandated TOUCH Prescribing Program; all participants showed signs of exposure to the JC virus.
The two groups were similar at about 68% female, an average age at first infusion of about 43, and a median number of about 48 natalizumab infusions.
For patients without previous immunosuppressant use who had received 49-60 doses, the researchers estimated the incidence of PML per 1,000 patients as 1.23 in the extended-interval group and 3.96 in the standard-interval group. The numbers were slightly higher for those who received 61-72 doses. At 48 or fewer doses, there were no PML cases in patients on extended-interval dosing.
“The data showed highly significant risk reductions of up to 94%,” Dr. Zhovtis Ryerson said.
Moving forward, “in collaboration with Biogen, we have more sensitivity analysis to be done to assure that our conclusions on this are correct,” she said. “Furthermore, more evidence of efficacy of extended-interval dosing natalizumab is needed, and we hope to move forward with a prospective, randomized, controlled trial to give clinicians the highest level of evidence we can.”
The study was funded by Biogen. Dr. Zhovtis Ryerson reported personal compensation from Teva, speaker/advisory board activities for Biogen, and research support from Biogen. Seven other authors reported being Biogen employees. Other authors reported no disclosures or various disclosures, including connections to Biogen.
SOURCE: Zhovtis R et al. ACTRIMS Forum 2018 Abstract LB250.
SAN DIEGO – A large industry-funded study of the multiple sclerosis drug natalizumab suggests that physicians can dramatically lower the likelihood of progressive multifocal leukoencephalopathy in patients at higher risk of the condition by increasing the interval between doses.
Previous research has suggested that natalizumab (Tysabri) doesn’t lose efficacy when given less frequently.
Dr. Zhovtis Ryerson presented the study findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
As a 2014 report explains, natalizumab is a “highly effective disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis,” but the risk of progressive multifocal leukoencephalopathy (PML) “has largely contributed to it being relegated to a second-line position” (Ther Adv Chronic Dis. 2014 Mar;5[2]:62-8).
Patients previously exposed to John Cunningham (JC) virus are at higher risk of PML, a rare viral brain disease that can be severely disabling or deadly. A 2017 report estimated the combined cumulative PML probability at 2.7% (with previous immunosuppressant use) and 1.7% (no previous immunosuppressant use) over 6 years in patients with signs of exposure to the JC virus (Lancet Neurol. 2017 Nov;16[11]:925-33). According to Dr. Zhovtis Ryerson, natalizumab manufacturer Biogen reported in December 2017 that it has confirmed 756 cases of PML in natalizumab-treated patients, all except for 3 in MS patients.
Doctors are wary in the at-risk patient population. “In general,” she said, “clinicians treating patients who are JC virus positive, and therefore have a risk for PML, may not utilize the drug or may take the patient off it after 2 years, which is when the risk goes up.”
Some physicians have experimented with longer intervals between treatments of 300 mg given intravenously, administering it every 5-8 weeks instead of every 4 weeks, with an eye on not extending the interval for too long “because MS disease activity returns after 12 weeks of withholding therapy,” Dr. Zhovtis Ryerson said.
In 2016, Dr. Zhovtis Ryerson and colleagues reported in a retrospective analysis that natalizumab dosing intervals of up to 8 weeks, 5 days didn’t affect the drug’s efficacy (J Neurol Neurosurg Psychiatry. 2016 Aug;87[8]:885-9).
For the primary analyses in the new study – whether dosing history in the last 18 months of natalizumab treatment affects PML – researchers tracked 1,988 patients who took the drug via an extended interval schedule and 13,132 who took it via a standard interval. The patients were tracked in the mandated TOUCH Prescribing Program; all participants showed signs of exposure to the JC virus.
The two groups were similar at about 68% female, an average age at first infusion of about 43, and a median number of about 48 natalizumab infusions.
For patients without previous immunosuppressant use who had received 49-60 doses, the researchers estimated the incidence of PML per 1,000 patients as 1.23 in the extended-interval group and 3.96 in the standard-interval group. The numbers were slightly higher for those who received 61-72 doses. At 48 or fewer doses, there were no PML cases in patients on extended-interval dosing.
“The data showed highly significant risk reductions of up to 94%,” Dr. Zhovtis Ryerson said.
Moving forward, “in collaboration with Biogen, we have more sensitivity analysis to be done to assure that our conclusions on this are correct,” she said. “Furthermore, more evidence of efficacy of extended-interval dosing natalizumab is needed, and we hope to move forward with a prospective, randomized, controlled trial to give clinicians the highest level of evidence we can.”
The study was funded by Biogen. Dr. Zhovtis Ryerson reported personal compensation from Teva, speaker/advisory board activities for Biogen, and research support from Biogen. Seven other authors reported being Biogen employees. Other authors reported no disclosures or various disclosures, including connections to Biogen.
SOURCE: Zhovtis R et al. ACTRIMS Forum 2018 Abstract LB250.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: , compared with standard-interval dosing in patients who showed signs of exposure to the JC virus.
Major finding: Estimated incidence of PML per 1,000 patients was 1.23 in an extended-interval group and 3.96 in a standard-interval group among those who had received 49-60 natalizumab doses.
Study details: 18-month analysis of multiple sclerosis patients on natalizumab who showed signs of exposure to the JC virus: 1,988 on extended-interval dosing and 13,132 on standard-interval dosing.
Disclosures: The study was funded by Biogen, and multiple study authors report being employees of Biogen or having other relationships to the company.
Source: Zhovtis R et al. ACTRIMS Forum 2018, Abstract LB250.
‘Remarkable’ survival seen with pretransplant JAK inhibitor
SALT LAKE CITY – The use of Janus kinase (JAK) inhibitor therapy prior to hematopoietic stem cell transplantation is safe and may improve posttransplant survival in patients with myelofibrosis, according to findings from an ongoing prospective phase 2 study.
The 1-year overall survival rate among the 28 initial patients in the single-center study of JAK inhibitor therapy followed by myeloablative or reduced-intensity hematopoietic cell transplantation (HCT) was 93%. The 2-year survival rate was 89%, compared with 54% in a closely matched historical cohort of intermediate-2–risk patients who did not receive pre-HCT JAK inhibitor therapy, Rachel B. Salit, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
“So this is pretty exciting for us,” she added, explaining that allogeneic HCT, which is currently indicated only for patients with intermediate-2– or high-risk disease on the Dynamic International Prognostic Scoring System (DIPSS), remains the only curative treatment option for patients with myelofibrosis.
“Transplant outcomes have been associated with DIPSS and DIPSS+ risk scores,” she said, adding that a study demonstrating that association showed a 54% survival rate at 3 years in patients with intermediate-2–risk disease. “Then JAK-2 inhibitors came down the pipe, and they are also indicated for patients with DIPSS intermediate-2– and high-risk disease. They’ve been shown to decrease spleen size, increase quality of life scores, decrease cytokine levels, and improve constitutional symptoms.”
Posttransplant benefits of pre-HCT JAK inhibitor therapy could include improved graft function because of decreased spleen size and cytokines, potentially decreased severe graft-versus-host disease (GVHD), and decreased nonrelapse mortality.
“Our hypothesis was that the use of JAK inhibitors before transplant in patients with myelofibrosis – by decreasing inflammation, improving constitutional symptoms, and reducing splenomegaly – would result in a decreased DIPSS score” and improved posttransplant survival, Dr. Salit said.
Study participants were patients aged 18 years and older (median of 53 years) with primary or secondary myelofibrosis (14 each). About two-thirds of the study participants were men. Prior to JAK inhibitor therapy, 2 patients were low risk, 10 patients were intermediate-1 risk, and 16 patients were intermediate-2 risk according to the DIPSS.
They were given ruxolitinib (Jakafi) for at least 8 weeks prior to HCT (median of 7 months, but up to 3 years), and the treatment was tapered over 1-2 weeks through day 2 or 3 of conditioning chemotherapy, depending on the conditioning regimen. Conditioning regimens were determined by the physician based on donor type.
“After the ruxolitinib, we had 6 patients who were intermediate-1 and 21 who were intermediate-2, so in that way they failed to meet that hypothesis,” Dr. Salit said. This happened because the patients became anemic, so they gained points on their DIPSS scores for declining constitutional symptoms.
Of the 28 participants, 23 received myeloablative HCT, and 5 received reduced-intensity HCT.
“We had a mixture of related, unrelated, and cord blood recipients,” she noted.
At a median follow-up of just over 1 year, and at up to 3 years in some patients, no cases of cytokine release syndrome have occurred with the overlap of ruxolitinib and conditioning chemotherapy, and there have been no graft failures. All patients, including cord blood recipients, engrafted. The median time to engraftment was 19 days, but the range went as high as 35 days. “The 35 was one of our cord blood recipients,” she noted.
Median time to platelet engraftment was 20 days, and median CD3 and CD33 chimerism at day 80 were 88% and 100%, respectively.
Acute grades II-IV GVHD occurred in 70% of patients, but just 15% of these cases were grades III or IV, she said.
Chronic GVHD occurred in 35% of patients, including two severe cases. Two patients relapsed, including one at 6 months with marrow blast and one at 2 years with myeloid sarcoma. Two treatment-related deaths occurred, including one each at days 54 and 81.
The strategy of overlapping a JAK inhibitor with conditioning chemotherapy was safe, and “better in that we haven’t seen any cytokine release syndrome,” she concluded, adding that no graft failures occurred and grades III-IV acute and severe chronic GVHD were encouragingly infrequent.
Future studies should look at the optimal amount of time for JAK inhibitor therapy prior to transplant and whether it’s safe to continue JAK inhibitors through transplant, she said.
“Some of the work in Germany has shown that JAK inhibitors are safe to include up to day 28 through transplant, and that’s something that we’re looking to explore,” she noted.
Dr. Salit reported having no financial disclosures. This study was sponsored by the Fred Hutchinson Cancer Research Center.
sworcester@frontlinemedcom.com
SOURCE: Salit R et al. BMT Tandem Meetings, Abstract 17.
SALT LAKE CITY – The use of Janus kinase (JAK) inhibitor therapy prior to hematopoietic stem cell transplantation is safe and may improve posttransplant survival in patients with myelofibrosis, according to findings from an ongoing prospective phase 2 study.
The 1-year overall survival rate among the 28 initial patients in the single-center study of JAK inhibitor therapy followed by myeloablative or reduced-intensity hematopoietic cell transplantation (HCT) was 93%. The 2-year survival rate was 89%, compared with 54% in a closely matched historical cohort of intermediate-2–risk patients who did not receive pre-HCT JAK inhibitor therapy, Rachel B. Salit, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
“So this is pretty exciting for us,” she added, explaining that allogeneic HCT, which is currently indicated only for patients with intermediate-2– or high-risk disease on the Dynamic International Prognostic Scoring System (DIPSS), remains the only curative treatment option for patients with myelofibrosis.
“Transplant outcomes have been associated with DIPSS and DIPSS+ risk scores,” she said, adding that a study demonstrating that association showed a 54% survival rate at 3 years in patients with intermediate-2–risk disease. “Then JAK-2 inhibitors came down the pipe, and they are also indicated for patients with DIPSS intermediate-2– and high-risk disease. They’ve been shown to decrease spleen size, increase quality of life scores, decrease cytokine levels, and improve constitutional symptoms.”
Posttransplant benefits of pre-HCT JAK inhibitor therapy could include improved graft function because of decreased spleen size and cytokines, potentially decreased severe graft-versus-host disease (GVHD), and decreased nonrelapse mortality.
“Our hypothesis was that the use of JAK inhibitors before transplant in patients with myelofibrosis – by decreasing inflammation, improving constitutional symptoms, and reducing splenomegaly – would result in a decreased DIPSS score” and improved posttransplant survival, Dr. Salit said.
Study participants were patients aged 18 years and older (median of 53 years) with primary or secondary myelofibrosis (14 each). About two-thirds of the study participants were men. Prior to JAK inhibitor therapy, 2 patients were low risk, 10 patients were intermediate-1 risk, and 16 patients were intermediate-2 risk according to the DIPSS.
They were given ruxolitinib (Jakafi) for at least 8 weeks prior to HCT (median of 7 months, but up to 3 years), and the treatment was tapered over 1-2 weeks through day 2 or 3 of conditioning chemotherapy, depending on the conditioning regimen. Conditioning regimens were determined by the physician based on donor type.
“After the ruxolitinib, we had 6 patients who were intermediate-1 and 21 who were intermediate-2, so in that way they failed to meet that hypothesis,” Dr. Salit said. This happened because the patients became anemic, so they gained points on their DIPSS scores for declining constitutional symptoms.
Of the 28 participants, 23 received myeloablative HCT, and 5 received reduced-intensity HCT.
“We had a mixture of related, unrelated, and cord blood recipients,” she noted.
At a median follow-up of just over 1 year, and at up to 3 years in some patients, no cases of cytokine release syndrome have occurred with the overlap of ruxolitinib and conditioning chemotherapy, and there have been no graft failures. All patients, including cord blood recipients, engrafted. The median time to engraftment was 19 days, but the range went as high as 35 days. “The 35 was one of our cord blood recipients,” she noted.
Median time to platelet engraftment was 20 days, and median CD3 and CD33 chimerism at day 80 were 88% and 100%, respectively.
Acute grades II-IV GVHD occurred in 70% of patients, but just 15% of these cases were grades III or IV, she said.
Chronic GVHD occurred in 35% of patients, including two severe cases. Two patients relapsed, including one at 6 months with marrow blast and one at 2 years with myeloid sarcoma. Two treatment-related deaths occurred, including one each at days 54 and 81.
The strategy of overlapping a JAK inhibitor with conditioning chemotherapy was safe, and “better in that we haven’t seen any cytokine release syndrome,” she concluded, adding that no graft failures occurred and grades III-IV acute and severe chronic GVHD were encouragingly infrequent.
Future studies should look at the optimal amount of time for JAK inhibitor therapy prior to transplant and whether it’s safe to continue JAK inhibitors through transplant, she said.
“Some of the work in Germany has shown that JAK inhibitors are safe to include up to day 28 through transplant, and that’s something that we’re looking to explore,” she noted.
Dr. Salit reported having no financial disclosures. This study was sponsored by the Fred Hutchinson Cancer Research Center.
sworcester@frontlinemedcom.com
SOURCE: Salit R et al. BMT Tandem Meetings, Abstract 17.
SALT LAKE CITY – The use of Janus kinase (JAK) inhibitor therapy prior to hematopoietic stem cell transplantation is safe and may improve posttransplant survival in patients with myelofibrosis, according to findings from an ongoing prospective phase 2 study.
The 1-year overall survival rate among the 28 initial patients in the single-center study of JAK inhibitor therapy followed by myeloablative or reduced-intensity hematopoietic cell transplantation (HCT) was 93%. The 2-year survival rate was 89%, compared with 54% in a closely matched historical cohort of intermediate-2–risk patients who did not receive pre-HCT JAK inhibitor therapy, Rachel B. Salit, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
“So this is pretty exciting for us,” she added, explaining that allogeneic HCT, which is currently indicated only for patients with intermediate-2– or high-risk disease on the Dynamic International Prognostic Scoring System (DIPSS), remains the only curative treatment option for patients with myelofibrosis.
“Transplant outcomes have been associated with DIPSS and DIPSS+ risk scores,” she said, adding that a study demonstrating that association showed a 54% survival rate at 3 years in patients with intermediate-2–risk disease. “Then JAK-2 inhibitors came down the pipe, and they are also indicated for patients with DIPSS intermediate-2– and high-risk disease. They’ve been shown to decrease spleen size, increase quality of life scores, decrease cytokine levels, and improve constitutional symptoms.”
Posttransplant benefits of pre-HCT JAK inhibitor therapy could include improved graft function because of decreased spleen size and cytokines, potentially decreased severe graft-versus-host disease (GVHD), and decreased nonrelapse mortality.
“Our hypothesis was that the use of JAK inhibitors before transplant in patients with myelofibrosis – by decreasing inflammation, improving constitutional symptoms, and reducing splenomegaly – would result in a decreased DIPSS score” and improved posttransplant survival, Dr. Salit said.
Study participants were patients aged 18 years and older (median of 53 years) with primary or secondary myelofibrosis (14 each). About two-thirds of the study participants were men. Prior to JAK inhibitor therapy, 2 patients were low risk, 10 patients were intermediate-1 risk, and 16 patients were intermediate-2 risk according to the DIPSS.
They were given ruxolitinib (Jakafi) for at least 8 weeks prior to HCT (median of 7 months, but up to 3 years), and the treatment was tapered over 1-2 weeks through day 2 or 3 of conditioning chemotherapy, depending on the conditioning regimen. Conditioning regimens were determined by the physician based on donor type.
“After the ruxolitinib, we had 6 patients who were intermediate-1 and 21 who were intermediate-2, so in that way they failed to meet that hypothesis,” Dr. Salit said. This happened because the patients became anemic, so they gained points on their DIPSS scores for declining constitutional symptoms.
Of the 28 participants, 23 received myeloablative HCT, and 5 received reduced-intensity HCT.
“We had a mixture of related, unrelated, and cord blood recipients,” she noted.
At a median follow-up of just over 1 year, and at up to 3 years in some patients, no cases of cytokine release syndrome have occurred with the overlap of ruxolitinib and conditioning chemotherapy, and there have been no graft failures. All patients, including cord blood recipients, engrafted. The median time to engraftment was 19 days, but the range went as high as 35 days. “The 35 was one of our cord blood recipients,” she noted.
Median time to platelet engraftment was 20 days, and median CD3 and CD33 chimerism at day 80 were 88% and 100%, respectively.
Acute grades II-IV GVHD occurred in 70% of patients, but just 15% of these cases were grades III or IV, she said.
Chronic GVHD occurred in 35% of patients, including two severe cases. Two patients relapsed, including one at 6 months with marrow blast and one at 2 years with myeloid sarcoma. Two treatment-related deaths occurred, including one each at days 54 and 81.
The strategy of overlapping a JAK inhibitor with conditioning chemotherapy was safe, and “better in that we haven’t seen any cytokine release syndrome,” she concluded, adding that no graft failures occurred and grades III-IV acute and severe chronic GVHD were encouragingly infrequent.
Future studies should look at the optimal amount of time for JAK inhibitor therapy prior to transplant and whether it’s safe to continue JAK inhibitors through transplant, she said.
“Some of the work in Germany has shown that JAK inhibitors are safe to include up to day 28 through transplant, and that’s something that we’re looking to explore,” she noted.
Dr. Salit reported having no financial disclosures. This study was sponsored by the Fred Hutchinson Cancer Research Center.
sworcester@frontlinemedcom.com
SOURCE: Salit R et al. BMT Tandem Meetings, Abstract 17.
REPORTING FROM THE 2018 BMT TANDEM MEETINGS
Key clinical point:
Major finding: The 2-year overall survival rate was 89%.
Study details: Findings in 28 patients from an ongoing prospective phase 2 study.
Disclosures: Dr. Salit reported having no financial disclosures. The study was sponsored by the Fred Hutchinson Cancer Research Center in Seattle.
Source: Salit R et al. BMT Tandem Meetings, Abstract 17.
Poor sleep, suicide risk linked in college students
Suicidal behaviors are associated with poor sleep in college students, even after controlling for depression, a cross-sectional analysis shows. Specifically, students were 6.54 times as likely to be classified with suicide risk if they were depressed and 2.70 times as likely if they had poor quality of sleep.
“Our findings add to a growing body of literature pointing to sleep as an important component to include in screening and intervention efforts to prevent suicidal ideation and attempts on college campuses,” wrote Stephen P. Becker, PhD, a pediatric psychologist affiliated with Cincinnati Children’s Hospital Medical Center, and his colleagues.
Of the 1,700 college students included in this study (J Psychiatr Res. 2018 Jan 12:99:122-8), 82.7% of those classified with suicide risk had poor sleep quality, but only 31.3% of those with poor sleep quality were classified with suicide risk.
Most previous studies had looked only at insomnia or bad dreams rather than other aspects of poor sleep quality, and because this study used the Pittsburgh Sleep Quality Index, it was able to evaluate additional well-validated components of sleep. so that screening and intervention based on sleep quality can be more effective. This is important, because suicide is one of the leading causes of death among young adults.
The researchers declared no conflicts of interest.
Read more about this study in the Journal of Psychiatric Research.
Suicidal behaviors are associated with poor sleep in college students, even after controlling for depression, a cross-sectional analysis shows. Specifically, students were 6.54 times as likely to be classified with suicide risk if they were depressed and 2.70 times as likely if they had poor quality of sleep.
“Our findings add to a growing body of literature pointing to sleep as an important component to include in screening and intervention efforts to prevent suicidal ideation and attempts on college campuses,” wrote Stephen P. Becker, PhD, a pediatric psychologist affiliated with Cincinnati Children’s Hospital Medical Center, and his colleagues.
Of the 1,700 college students included in this study (J Psychiatr Res. 2018 Jan 12:99:122-8), 82.7% of those classified with suicide risk had poor sleep quality, but only 31.3% of those with poor sleep quality were classified with suicide risk.
Most previous studies had looked only at insomnia or bad dreams rather than other aspects of poor sleep quality, and because this study used the Pittsburgh Sleep Quality Index, it was able to evaluate additional well-validated components of sleep. so that screening and intervention based on sleep quality can be more effective. This is important, because suicide is one of the leading causes of death among young adults.
The researchers declared no conflicts of interest.
Read more about this study in the Journal of Psychiatric Research.
Suicidal behaviors are associated with poor sleep in college students, even after controlling for depression, a cross-sectional analysis shows. Specifically, students were 6.54 times as likely to be classified with suicide risk if they were depressed and 2.70 times as likely if they had poor quality of sleep.
“Our findings add to a growing body of literature pointing to sleep as an important component to include in screening and intervention efforts to prevent suicidal ideation and attempts on college campuses,” wrote Stephen P. Becker, PhD, a pediatric psychologist affiliated with Cincinnati Children’s Hospital Medical Center, and his colleagues.
Of the 1,700 college students included in this study (J Psychiatr Res. 2018 Jan 12:99:122-8), 82.7% of those classified with suicide risk had poor sleep quality, but only 31.3% of those with poor sleep quality were classified with suicide risk.
Most previous studies had looked only at insomnia or bad dreams rather than other aspects of poor sleep quality, and because this study used the Pittsburgh Sleep Quality Index, it was able to evaluate additional well-validated components of sleep. so that screening and intervention based on sleep quality can be more effective. This is important, because suicide is one of the leading causes of death among young adults.
The researchers declared no conflicts of interest.
Read more about this study in the Journal of Psychiatric Research.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
Will Indiana Medicaid work requirements pass legal muster?
The recent federal waiver allowing work requirements for Indiana’s Medicaid program has sparked controversy from all sides and led to a debate that analysts say is likely to end in court.
Indiana’s waiver, green-lighted by the U.S. Department of Health & Human Services in February, requires certain Medicaid recipients to work an average of 20 hours a week, be enrolled in school, or participate in a job search/training program in order to qualify for assistance. Proponents say the requirements are a practical approach to improving self-sufficiency for able-bodied Medicaid patients by incentivizing work and community engagement. Critics argue the requirements are burdensome for the state’s most vulnerable populations and jeopardize medical care for some 30,000 recipients. But will the requirements pass legal muster in a court of law?
Typically, when arguments arise over state Medicaid program provisions, they center on whether the requirements help or hinder the program, Mr. Salo said in an interview.
“There isn’t really a clear-cut, black-and-white definition of the purposes of Medicaid written down in the statute,” he said. “Practically speaking, it’s a fairly subjective term. Clearly, the Obama administration said, ‘We don’t think [work requirement] policies further the objectives of the Medicaid program.’ I don’t think there’s anything that would preclude a new administration from saying, ‘We have a slightly different opinion of what the purposes of the Medicaid program are.’ ”
However, Leonardo Cuello, director of health policy for the National Health Law Program, says Indiana’s new requirements are illegal and clearly run contrary to the purpose of the Medicaid program. While the program’s work requirements are taking the spotlight, he notes that the new provisions also include lockout periods if paperwork is late and removes transportation assistance for medical care.
The National Health Law Program is a coplaintiff in a lawsuit challenging similar Medicaid requirements in Kentucky. Like Indiana’s waiver, Kentucky’s approved plan includes lockout provisions for failing to pay premiums on time and has work requirements for able-bodied adult enrollees. Mr. Cuello said his organization is looking closely at taking legal action against Indiana’s waiver as well.
In a statement, HHS Secretary Alex Azar said the approval of Indiana’s expanded Medicaid program is in line with a Trump administration policy to support state efforts to “improve Medicaid enrollee health outcomes and promote independence by incentivizing community engagement among able-bodied, working-age Medicaid beneficiaries.” The policy responds to numerous state requests to test programs through Medicaid demonstration projects under which work and other types of community engagement would be a condition of Medicaid coverage, according to the announcement.
“We look forward to collaborating with Indiana on this next evolution of [the Healthy Indiana Plan], which serves as another example of the Trump administration’s support of state-led efforts and innovative reforms to make our HHS programs really work for Americans,” Mr. Azar said in the statement.
Another legal question that may arise against Indiana’s work requirements for Medicaid is whether the provisions are part of a true “experiment.”
“These waivers are at the broad discretion of the government,” Mr. Blumstein said in an interview. “I think [Indiana’s plan] is compatible with an overall welfare strategy that’s designed to cut costs, to get folks jobs, and then ultimately, into private sector health insurance. In principal, these things are good to try.”
Mr. Blumstein said that he believes HHS has a strong legal position in defending Indiana’s waiver program, but that doesn’t mean a judge will agree, he said.
“Will a court somewhere find against the government? Against Indiana? I can’t say,” he said. “There’s a lot of hostility to change, and some judges share that hostility to change. But based on my TennCare experience, courts should bend over backward to give flexibility to the states to experiment in this way, if they’re approved by the federal government.”
Mr. Cuello of the National Health Law Program said the Indiana and Kentucky waivers both fail to demonstrate any experimental value. Studies show that when such requirements are enforced, patients drop out of Medicaid or forgo medical care.
“These waivers fail a legality test because they’re not part of any experiment,” he said. “An experiment would be: Here’s an innovative way we have for how to provide health care. These are not experiments.”
At press time, eight states had pending waiver requests at the Centers for Medicare & Medicaid Services that would require work as a condition of eligibility for expansion adults and/or traditional populations.
The recent federal waiver allowing work requirements for Indiana’s Medicaid program has sparked controversy from all sides and led to a debate that analysts say is likely to end in court.
Indiana’s waiver, green-lighted by the U.S. Department of Health & Human Services in February, requires certain Medicaid recipients to work an average of 20 hours a week, be enrolled in school, or participate in a job search/training program in order to qualify for assistance. Proponents say the requirements are a practical approach to improving self-sufficiency for able-bodied Medicaid patients by incentivizing work and community engagement. Critics argue the requirements are burdensome for the state’s most vulnerable populations and jeopardize medical care for some 30,000 recipients. But will the requirements pass legal muster in a court of law?
Typically, when arguments arise over state Medicaid program provisions, they center on whether the requirements help or hinder the program, Mr. Salo said in an interview.
“There isn’t really a clear-cut, black-and-white definition of the purposes of Medicaid written down in the statute,” he said. “Practically speaking, it’s a fairly subjective term. Clearly, the Obama administration said, ‘We don’t think [work requirement] policies further the objectives of the Medicaid program.’ I don’t think there’s anything that would preclude a new administration from saying, ‘We have a slightly different opinion of what the purposes of the Medicaid program are.’ ”
However, Leonardo Cuello, director of health policy for the National Health Law Program, says Indiana’s new requirements are illegal and clearly run contrary to the purpose of the Medicaid program. While the program’s work requirements are taking the spotlight, he notes that the new provisions also include lockout periods if paperwork is late and removes transportation assistance for medical care.
The National Health Law Program is a coplaintiff in a lawsuit challenging similar Medicaid requirements in Kentucky. Like Indiana’s waiver, Kentucky’s approved plan includes lockout provisions for failing to pay premiums on time and has work requirements for able-bodied adult enrollees. Mr. Cuello said his organization is looking closely at taking legal action against Indiana’s waiver as well.
In a statement, HHS Secretary Alex Azar said the approval of Indiana’s expanded Medicaid program is in line with a Trump administration policy to support state efforts to “improve Medicaid enrollee health outcomes and promote independence by incentivizing community engagement among able-bodied, working-age Medicaid beneficiaries.” The policy responds to numerous state requests to test programs through Medicaid demonstration projects under which work and other types of community engagement would be a condition of Medicaid coverage, according to the announcement.
“We look forward to collaborating with Indiana on this next evolution of [the Healthy Indiana Plan], which serves as another example of the Trump administration’s support of state-led efforts and innovative reforms to make our HHS programs really work for Americans,” Mr. Azar said in the statement.
Another legal question that may arise against Indiana’s work requirements for Medicaid is whether the provisions are part of a true “experiment.”
“These waivers are at the broad discretion of the government,” Mr. Blumstein said in an interview. “I think [Indiana’s plan] is compatible with an overall welfare strategy that’s designed to cut costs, to get folks jobs, and then ultimately, into private sector health insurance. In principal, these things are good to try.”
Mr. Blumstein said that he believes HHS has a strong legal position in defending Indiana’s waiver program, but that doesn’t mean a judge will agree, he said.
“Will a court somewhere find against the government? Against Indiana? I can’t say,” he said. “There’s a lot of hostility to change, and some judges share that hostility to change. But based on my TennCare experience, courts should bend over backward to give flexibility to the states to experiment in this way, if they’re approved by the federal government.”
Mr. Cuello of the National Health Law Program said the Indiana and Kentucky waivers both fail to demonstrate any experimental value. Studies show that when such requirements are enforced, patients drop out of Medicaid or forgo medical care.
“These waivers fail a legality test because they’re not part of any experiment,” he said. “An experiment would be: Here’s an innovative way we have for how to provide health care. These are not experiments.”
At press time, eight states had pending waiver requests at the Centers for Medicare & Medicaid Services that would require work as a condition of eligibility for expansion adults and/or traditional populations.
The recent federal waiver allowing work requirements for Indiana’s Medicaid program has sparked controversy from all sides and led to a debate that analysts say is likely to end in court.
Indiana’s waiver, green-lighted by the U.S. Department of Health & Human Services in February, requires certain Medicaid recipients to work an average of 20 hours a week, be enrolled in school, or participate in a job search/training program in order to qualify for assistance. Proponents say the requirements are a practical approach to improving self-sufficiency for able-bodied Medicaid patients by incentivizing work and community engagement. Critics argue the requirements are burdensome for the state’s most vulnerable populations and jeopardize medical care for some 30,000 recipients. But will the requirements pass legal muster in a court of law?
Typically, when arguments arise over state Medicaid program provisions, they center on whether the requirements help or hinder the program, Mr. Salo said in an interview.
“There isn’t really a clear-cut, black-and-white definition of the purposes of Medicaid written down in the statute,” he said. “Practically speaking, it’s a fairly subjective term. Clearly, the Obama administration said, ‘We don’t think [work requirement] policies further the objectives of the Medicaid program.’ I don’t think there’s anything that would preclude a new administration from saying, ‘We have a slightly different opinion of what the purposes of the Medicaid program are.’ ”
However, Leonardo Cuello, director of health policy for the National Health Law Program, says Indiana’s new requirements are illegal and clearly run contrary to the purpose of the Medicaid program. While the program’s work requirements are taking the spotlight, he notes that the new provisions also include lockout periods if paperwork is late and removes transportation assistance for medical care.
The National Health Law Program is a coplaintiff in a lawsuit challenging similar Medicaid requirements in Kentucky. Like Indiana’s waiver, Kentucky’s approved plan includes lockout provisions for failing to pay premiums on time and has work requirements for able-bodied adult enrollees. Mr. Cuello said his organization is looking closely at taking legal action against Indiana’s waiver as well.
In a statement, HHS Secretary Alex Azar said the approval of Indiana’s expanded Medicaid program is in line with a Trump administration policy to support state efforts to “improve Medicaid enrollee health outcomes and promote independence by incentivizing community engagement among able-bodied, working-age Medicaid beneficiaries.” The policy responds to numerous state requests to test programs through Medicaid demonstration projects under which work and other types of community engagement would be a condition of Medicaid coverage, according to the announcement.
“We look forward to collaborating with Indiana on this next evolution of [the Healthy Indiana Plan], which serves as another example of the Trump administration’s support of state-led efforts and innovative reforms to make our HHS programs really work for Americans,” Mr. Azar said in the statement.
Another legal question that may arise against Indiana’s work requirements for Medicaid is whether the provisions are part of a true “experiment.”
“These waivers are at the broad discretion of the government,” Mr. Blumstein said in an interview. “I think [Indiana’s plan] is compatible with an overall welfare strategy that’s designed to cut costs, to get folks jobs, and then ultimately, into private sector health insurance. In principal, these things are good to try.”
Mr. Blumstein said that he believes HHS has a strong legal position in defending Indiana’s waiver program, but that doesn’t mean a judge will agree, he said.
“Will a court somewhere find against the government? Against Indiana? I can’t say,” he said. “There’s a lot of hostility to change, and some judges share that hostility to change. But based on my TennCare experience, courts should bend over backward to give flexibility to the states to experiment in this way, if they’re approved by the federal government.”
Mr. Cuello of the National Health Law Program said the Indiana and Kentucky waivers both fail to demonstrate any experimental value. Studies show that when such requirements are enforced, patients drop out of Medicaid or forgo medical care.
“These waivers fail a legality test because they’re not part of any experiment,” he said. “An experiment would be: Here’s an innovative way we have for how to provide health care. These are not experiments.”
At press time, eight states had pending waiver requests at the Centers for Medicare & Medicaid Services that would require work as a condition of eligibility for expansion adults and/or traditional populations.