User login
Recent trials advance axial spondyloarthritis therapy
MAUI, HAWAII – Arguably the most exciting therapeutic development in axial spondyloarthritis in the past year was the demonstrated efficacy and safety of the investigational oral selective Janus kinase 1 inhibitor filgotinib in the setting of active ankylosing spondylitis, speakers agreed at the 2019 Rheumatology Winter Clinical Symposium.
“This is big, big news,” commented symposium director Arthur Kavanaugh, MD. “This is going to be a big deal.”
Other recent clinical trials of note in axial spondyloarthritis (SpA) highlighted by Dr. Kavanaugh and Eric Ruderman, MD, professor of medicine at Northwestern University, Chicago, included a positive phase 3 study of certolizumab pegol (Cimzia) in nonradiographic SpA, two positive phase 3 trials of the interleukin-17A antagonist ixekizumab (Taltz) in radiographic SpA, a positive phase 2b trial of the dual IL-17A/F antagonist bimekizumab, and publication of three surprisingly negative phase 3 trials of the IL-12/23 inhibitor ustekinumab (Stelara).
Filgotinib
TORTUGA was a phase 2b, double-blind, multicenter trial of 116 European patients with active ankylosing spondylitis nonresponsive to NSAIDs who were randomized to oral filgotinib at 200 mg once daily or placebo for 12 weeks. Filgotinib reduced the Ankylosing Spondylitis Disease Activity Score (ASDAS) by a mean of 1.47 points from baseline, a significantly better result for the primary outcome than the 0.57-point decrease in controls (Lancet. 2018 Dec 1;392[10162]:2378-87).
Dr. Ruderman was also favorably impressed with the oral Janus kinase 1 (JAK1) inhibitor’s performance on the secondary outcome measures, including a mean 2.41-point reduction from baseline on the Bath Ankylosing Spondylitis Disease Activity Index, compared with a 1.44-point decrease in controls, with the difference being significant from week 8 onward. The filgotinib group also did significantly better on validated measures of physical function, spinal mobility, physical function, quality of life, peripheral arthritis, fatigue, and spinal and sacroiliac joint inflammation as assessed by MRI.
One patient in the filgotinib group, a smoker, developed pneumonia and another experienced deep venous thrombosis.
The study results are an exciting development because SpA treatments with new mechanisms of action are sorely needed. NSAIDs are considered first-line pharmacotherapy at present, with various tumor necrosis factor (TNF) inhibitors as well as the IL-17 inhibitor secukinumab (Cosentyx) the only approved biologic alternatives.
“This is the most impressive data I’ve seen that JAK inhibitors are effective in ankylosing spondyloarthritis,” commented Paul Emery, MD, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
TORTUGA was the first positive phase 2 trial of a selective JAK1 inhibitor in SpA. However, Dr. Kavanaugh noted that while a phase 2 trial of tofacitinib (Xeljanz) failed to meet its “very convoluted” primary endpoint, the JAK1/3 inhibitor was positive for key secondary endpoints, including favorable MRI changes. And a phase 3 trial of tofacitinib in SpA is underway.
A key remaining question pending the outcome of definitive phase 3 trials is whether specificity of JAK enzyme inhibition matters or if a class effect is at work, according to Dr. Kavanaugh, professor of medicine at the University of California, San Diego.
Certolizumab pegol
The TNF inhibitor is already approved for ankylosing spondylitis, among other indications, but it has now demonstrated efficacy and safety in nonradiographic SpA in a phase 3 trial structured with guidance from the Food and Drug Administration.
“It seems likely that UCB will get the indication for this,” according to Dr. Ruderman.
This 317-patient trial was remarkable in that it entailed a full 52 weeks of double-blind therapy with certolizumab at the standard dose of 200 mg every 2 weeks or placebo. The ASDAS Major Improvement rate, defined as at least a 2-point improvement from baseline, was 47% in the active treatment arm, compared with 7% on placebo. The Assessment in Ankylosing Spondylitis International Society 40% (ASAS 40) response rate, a more patient-reported outcome measure, was 57% in the certolizumab group and 16% in controls in this trial, which was recently published (Arthritis Rheumatol. 2019 March 8. doi: 10.1002/art.40866). All participants had to have baseline MRI evidence of sacroiliac joint inflammation and/or an elevated C-reactive protein.
By way of background, Dr. Ruderman explained that the FDA required 52 weeks of double-blind, placebo-controlled therapy because the agency’s advisory committee had formerly expressed reservations about considering an expanded indication for TNF inhibitors in nonradiographic as opposed to radiographic SpA.
“They were very concerned that approval could result in patients with mechanical back pain or fibromyalgia being treated with biologics. And they weren’t sure nonradiographic SpA was a discrete entity. They wondered if it remits on its own,” according to the rheumatologist.
Dr. Ruderman is curious to see how the FDA is going to handle this situation in light of the positive phase 3 certolizumab results. Will the agency require other companies that market TNF inhibitors to mount a similarly rigorous 52-week, double-blind, placebo-controlled trial in order to obtain an expanded indication? That would seem to pose ethical issues now. Or will the companies be able to gain an expanded indication by retrospective analysis of outcomes in patients with nonradiographic SpA in their existing trials databases? Stay tuned.
Ixekizumab
The COAST-V trial was a phase 3, randomized, double-blind, active- and placebo-controlled trial of 341 patients with radiographic SpA who hadn’t previously been treated with a biologic disease-modifying antirheumatic drug. They were assigned to 80 mg of ixekizumab every 2 weeks, 80 mg every 4 weeks, adalimumab (Humira) at 40 mg every 2 weeks, or placebo. The primary endpoint – an ASAS 40 response at week 16 – was achieved in 52% of patients on ixekizumab every 2 weeks, 48% of those who received ixekizumab every 4 weeks, 36% on adalimumab, and 18% on placebo (Lancet. 2018 Dec 8;392[10163]:2441-51).
In contrast, the phase 3 COAST-W trial included 316 patients with radiographic SpA who were inadequate responders or intolerant to one or more prior anti-TNF agents. The 16-week ASAS 40 response rate was 30.6% with ixekizumab every 2 weeks, similar at 25.4% with ixekizumab every 4 weeks, and 12.5% with placebo (Arthritis Rheumatol. 2018 Oct 20. doi: 10.1002/art.40753).
While the COAST-V trial convincingly showed both ixekizumab and adalimumab were more effective than placebo, the patient numbers were way too small to draw any conclusions about the relative efficacy of the two biologics, according to Dr. Ruderman.
“I don’t think these results are surprising,” Dr. Kavanaugh commented. “It would have been surprising if ixekizumab was ineffective, given that secukinumab works. But it’s nice to have the proof.”
Bimekizumab
This investigational dual IL-17A/F inhibitor demonstrated efficacy and safety for SpA in a 297-patient, phase 2b trial presented at the 2018 European Congress of Rheumatology.
“It’s effective, but it doesn’t look like it’s particularly more effective than either of the existing IL-17A inhibitors. We’ll see going forward if there truly is an advantage here to the additional inhibition of IL-17F in this population. I will say that the preclinical and laboratory data on the potential advantages of IL-17F inhibition are mostly in the psoriasis/psoriatic arthritis space. It’s not clear in ankylosing spondyloarthritis specifically whether we should expect to see a difference,” Dr. Ruderman said.
Ustekinumab
The IL-12/23 inhibitor proved no better than placebo in patients with SpA in three separate phase 3, randomized trials recently published as a single summary article (Arthritis Rheumatol. 2019 Feb;71[2]:258-70).
“Ustekinumab was effective in an earlier open study, so I think everybody was surprised by this,” Dr. Kavanaugh said.
He reported serving as a consultant to and/or receiving research funding from a dozen pharmaceutical companies. Dr. Ruderman reported financial relationships with eight companies.
MAUI, HAWAII – Arguably the most exciting therapeutic development in axial spondyloarthritis in the past year was the demonstrated efficacy and safety of the investigational oral selective Janus kinase 1 inhibitor filgotinib in the setting of active ankylosing spondylitis, speakers agreed at the 2019 Rheumatology Winter Clinical Symposium.
“This is big, big news,” commented symposium director Arthur Kavanaugh, MD. “This is going to be a big deal.”
Other recent clinical trials of note in axial spondyloarthritis (SpA) highlighted by Dr. Kavanaugh and Eric Ruderman, MD, professor of medicine at Northwestern University, Chicago, included a positive phase 3 study of certolizumab pegol (Cimzia) in nonradiographic SpA, two positive phase 3 trials of the interleukin-17A antagonist ixekizumab (Taltz) in radiographic SpA, a positive phase 2b trial of the dual IL-17A/F antagonist bimekizumab, and publication of three surprisingly negative phase 3 trials of the IL-12/23 inhibitor ustekinumab (Stelara).
Filgotinib
TORTUGA was a phase 2b, double-blind, multicenter trial of 116 European patients with active ankylosing spondylitis nonresponsive to NSAIDs who were randomized to oral filgotinib at 200 mg once daily or placebo for 12 weeks. Filgotinib reduced the Ankylosing Spondylitis Disease Activity Score (ASDAS) by a mean of 1.47 points from baseline, a significantly better result for the primary outcome than the 0.57-point decrease in controls (Lancet. 2018 Dec 1;392[10162]:2378-87).
Dr. Ruderman was also favorably impressed with the oral Janus kinase 1 (JAK1) inhibitor’s performance on the secondary outcome measures, including a mean 2.41-point reduction from baseline on the Bath Ankylosing Spondylitis Disease Activity Index, compared with a 1.44-point decrease in controls, with the difference being significant from week 8 onward. The filgotinib group also did significantly better on validated measures of physical function, spinal mobility, physical function, quality of life, peripheral arthritis, fatigue, and spinal and sacroiliac joint inflammation as assessed by MRI.
One patient in the filgotinib group, a smoker, developed pneumonia and another experienced deep venous thrombosis.
The study results are an exciting development because SpA treatments with new mechanisms of action are sorely needed. NSAIDs are considered first-line pharmacotherapy at present, with various tumor necrosis factor (TNF) inhibitors as well as the IL-17 inhibitor secukinumab (Cosentyx) the only approved biologic alternatives.
“This is the most impressive data I’ve seen that JAK inhibitors are effective in ankylosing spondyloarthritis,” commented Paul Emery, MD, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
TORTUGA was the first positive phase 2 trial of a selective JAK1 inhibitor in SpA. However, Dr. Kavanaugh noted that while a phase 2 trial of tofacitinib (Xeljanz) failed to meet its “very convoluted” primary endpoint, the JAK1/3 inhibitor was positive for key secondary endpoints, including favorable MRI changes. And a phase 3 trial of tofacitinib in SpA is underway.
A key remaining question pending the outcome of definitive phase 3 trials is whether specificity of JAK enzyme inhibition matters or if a class effect is at work, according to Dr. Kavanaugh, professor of medicine at the University of California, San Diego.
Certolizumab pegol
The TNF inhibitor is already approved for ankylosing spondylitis, among other indications, but it has now demonstrated efficacy and safety in nonradiographic SpA in a phase 3 trial structured with guidance from the Food and Drug Administration.
“It seems likely that UCB will get the indication for this,” according to Dr. Ruderman.
This 317-patient trial was remarkable in that it entailed a full 52 weeks of double-blind therapy with certolizumab at the standard dose of 200 mg every 2 weeks or placebo. The ASDAS Major Improvement rate, defined as at least a 2-point improvement from baseline, was 47% in the active treatment arm, compared with 7% on placebo. The Assessment in Ankylosing Spondylitis International Society 40% (ASAS 40) response rate, a more patient-reported outcome measure, was 57% in the certolizumab group and 16% in controls in this trial, which was recently published (Arthritis Rheumatol. 2019 March 8. doi: 10.1002/art.40866). All participants had to have baseline MRI evidence of sacroiliac joint inflammation and/or an elevated C-reactive protein.
By way of background, Dr. Ruderman explained that the FDA required 52 weeks of double-blind, placebo-controlled therapy because the agency’s advisory committee had formerly expressed reservations about considering an expanded indication for TNF inhibitors in nonradiographic as opposed to radiographic SpA.
“They were very concerned that approval could result in patients with mechanical back pain or fibromyalgia being treated with biologics. And they weren’t sure nonradiographic SpA was a discrete entity. They wondered if it remits on its own,” according to the rheumatologist.
Dr. Ruderman is curious to see how the FDA is going to handle this situation in light of the positive phase 3 certolizumab results. Will the agency require other companies that market TNF inhibitors to mount a similarly rigorous 52-week, double-blind, placebo-controlled trial in order to obtain an expanded indication? That would seem to pose ethical issues now. Or will the companies be able to gain an expanded indication by retrospective analysis of outcomes in patients with nonradiographic SpA in their existing trials databases? Stay tuned.
Ixekizumab
The COAST-V trial was a phase 3, randomized, double-blind, active- and placebo-controlled trial of 341 patients with radiographic SpA who hadn’t previously been treated with a biologic disease-modifying antirheumatic drug. They were assigned to 80 mg of ixekizumab every 2 weeks, 80 mg every 4 weeks, adalimumab (Humira) at 40 mg every 2 weeks, or placebo. The primary endpoint – an ASAS 40 response at week 16 – was achieved in 52% of patients on ixekizumab every 2 weeks, 48% of those who received ixekizumab every 4 weeks, 36% on adalimumab, and 18% on placebo (Lancet. 2018 Dec 8;392[10163]:2441-51).
In contrast, the phase 3 COAST-W trial included 316 patients with radiographic SpA who were inadequate responders or intolerant to one or more prior anti-TNF agents. The 16-week ASAS 40 response rate was 30.6% with ixekizumab every 2 weeks, similar at 25.4% with ixekizumab every 4 weeks, and 12.5% with placebo (Arthritis Rheumatol. 2018 Oct 20. doi: 10.1002/art.40753).
While the COAST-V trial convincingly showed both ixekizumab and adalimumab were more effective than placebo, the patient numbers were way too small to draw any conclusions about the relative efficacy of the two biologics, according to Dr. Ruderman.
“I don’t think these results are surprising,” Dr. Kavanaugh commented. “It would have been surprising if ixekizumab was ineffective, given that secukinumab works. But it’s nice to have the proof.”
Bimekizumab
This investigational dual IL-17A/F inhibitor demonstrated efficacy and safety for SpA in a 297-patient, phase 2b trial presented at the 2018 European Congress of Rheumatology.
“It’s effective, but it doesn’t look like it’s particularly more effective than either of the existing IL-17A inhibitors. We’ll see going forward if there truly is an advantage here to the additional inhibition of IL-17F in this population. I will say that the preclinical and laboratory data on the potential advantages of IL-17F inhibition are mostly in the psoriasis/psoriatic arthritis space. It’s not clear in ankylosing spondyloarthritis specifically whether we should expect to see a difference,” Dr. Ruderman said.
Ustekinumab
The IL-12/23 inhibitor proved no better than placebo in patients with SpA in three separate phase 3, randomized trials recently published as a single summary article (Arthritis Rheumatol. 2019 Feb;71[2]:258-70).
“Ustekinumab was effective in an earlier open study, so I think everybody was surprised by this,” Dr. Kavanaugh said.
He reported serving as a consultant to and/or receiving research funding from a dozen pharmaceutical companies. Dr. Ruderman reported financial relationships with eight companies.
MAUI, HAWAII – Arguably the most exciting therapeutic development in axial spondyloarthritis in the past year was the demonstrated efficacy and safety of the investigational oral selective Janus kinase 1 inhibitor filgotinib in the setting of active ankylosing spondylitis, speakers agreed at the 2019 Rheumatology Winter Clinical Symposium.
“This is big, big news,” commented symposium director Arthur Kavanaugh, MD. “This is going to be a big deal.”
Other recent clinical trials of note in axial spondyloarthritis (SpA) highlighted by Dr. Kavanaugh and Eric Ruderman, MD, professor of medicine at Northwestern University, Chicago, included a positive phase 3 study of certolizumab pegol (Cimzia) in nonradiographic SpA, two positive phase 3 trials of the interleukin-17A antagonist ixekizumab (Taltz) in radiographic SpA, a positive phase 2b trial of the dual IL-17A/F antagonist bimekizumab, and publication of three surprisingly negative phase 3 trials of the IL-12/23 inhibitor ustekinumab (Stelara).
Filgotinib
TORTUGA was a phase 2b, double-blind, multicenter trial of 116 European patients with active ankylosing spondylitis nonresponsive to NSAIDs who were randomized to oral filgotinib at 200 mg once daily or placebo for 12 weeks. Filgotinib reduced the Ankylosing Spondylitis Disease Activity Score (ASDAS) by a mean of 1.47 points from baseline, a significantly better result for the primary outcome than the 0.57-point decrease in controls (Lancet. 2018 Dec 1;392[10162]:2378-87).
Dr. Ruderman was also favorably impressed with the oral Janus kinase 1 (JAK1) inhibitor’s performance on the secondary outcome measures, including a mean 2.41-point reduction from baseline on the Bath Ankylosing Spondylitis Disease Activity Index, compared with a 1.44-point decrease in controls, with the difference being significant from week 8 onward. The filgotinib group also did significantly better on validated measures of physical function, spinal mobility, physical function, quality of life, peripheral arthritis, fatigue, and spinal and sacroiliac joint inflammation as assessed by MRI.
One patient in the filgotinib group, a smoker, developed pneumonia and another experienced deep venous thrombosis.
The study results are an exciting development because SpA treatments with new mechanisms of action are sorely needed. NSAIDs are considered first-line pharmacotherapy at present, with various tumor necrosis factor (TNF) inhibitors as well as the IL-17 inhibitor secukinumab (Cosentyx) the only approved biologic alternatives.
“This is the most impressive data I’ve seen that JAK inhibitors are effective in ankylosing spondyloarthritis,” commented Paul Emery, MD, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
TORTUGA was the first positive phase 2 trial of a selective JAK1 inhibitor in SpA. However, Dr. Kavanaugh noted that while a phase 2 trial of tofacitinib (Xeljanz) failed to meet its “very convoluted” primary endpoint, the JAK1/3 inhibitor was positive for key secondary endpoints, including favorable MRI changes. And a phase 3 trial of tofacitinib in SpA is underway.
A key remaining question pending the outcome of definitive phase 3 trials is whether specificity of JAK enzyme inhibition matters or if a class effect is at work, according to Dr. Kavanaugh, professor of medicine at the University of California, San Diego.
Certolizumab pegol
The TNF inhibitor is already approved for ankylosing spondylitis, among other indications, but it has now demonstrated efficacy and safety in nonradiographic SpA in a phase 3 trial structured with guidance from the Food and Drug Administration.
“It seems likely that UCB will get the indication for this,” according to Dr. Ruderman.
This 317-patient trial was remarkable in that it entailed a full 52 weeks of double-blind therapy with certolizumab at the standard dose of 200 mg every 2 weeks or placebo. The ASDAS Major Improvement rate, defined as at least a 2-point improvement from baseline, was 47% in the active treatment arm, compared with 7% on placebo. The Assessment in Ankylosing Spondylitis International Society 40% (ASAS 40) response rate, a more patient-reported outcome measure, was 57% in the certolizumab group and 16% in controls in this trial, which was recently published (Arthritis Rheumatol. 2019 March 8. doi: 10.1002/art.40866). All participants had to have baseline MRI evidence of sacroiliac joint inflammation and/or an elevated C-reactive protein.
By way of background, Dr. Ruderman explained that the FDA required 52 weeks of double-blind, placebo-controlled therapy because the agency’s advisory committee had formerly expressed reservations about considering an expanded indication for TNF inhibitors in nonradiographic as opposed to radiographic SpA.
“They were very concerned that approval could result in patients with mechanical back pain or fibromyalgia being treated with biologics. And they weren’t sure nonradiographic SpA was a discrete entity. They wondered if it remits on its own,” according to the rheumatologist.
Dr. Ruderman is curious to see how the FDA is going to handle this situation in light of the positive phase 3 certolizumab results. Will the agency require other companies that market TNF inhibitors to mount a similarly rigorous 52-week, double-blind, placebo-controlled trial in order to obtain an expanded indication? That would seem to pose ethical issues now. Or will the companies be able to gain an expanded indication by retrospective analysis of outcomes in patients with nonradiographic SpA in their existing trials databases? Stay tuned.
Ixekizumab
The COAST-V trial was a phase 3, randomized, double-blind, active- and placebo-controlled trial of 341 patients with radiographic SpA who hadn’t previously been treated with a biologic disease-modifying antirheumatic drug. They were assigned to 80 mg of ixekizumab every 2 weeks, 80 mg every 4 weeks, adalimumab (Humira) at 40 mg every 2 weeks, or placebo. The primary endpoint – an ASAS 40 response at week 16 – was achieved in 52% of patients on ixekizumab every 2 weeks, 48% of those who received ixekizumab every 4 weeks, 36% on adalimumab, and 18% on placebo (Lancet. 2018 Dec 8;392[10163]:2441-51).
In contrast, the phase 3 COAST-W trial included 316 patients with radiographic SpA who were inadequate responders or intolerant to one or more prior anti-TNF agents. The 16-week ASAS 40 response rate was 30.6% with ixekizumab every 2 weeks, similar at 25.4% with ixekizumab every 4 weeks, and 12.5% with placebo (Arthritis Rheumatol. 2018 Oct 20. doi: 10.1002/art.40753).
While the COAST-V trial convincingly showed both ixekizumab and adalimumab were more effective than placebo, the patient numbers were way too small to draw any conclusions about the relative efficacy of the two biologics, according to Dr. Ruderman.
“I don’t think these results are surprising,” Dr. Kavanaugh commented. “It would have been surprising if ixekizumab was ineffective, given that secukinumab works. But it’s nice to have the proof.”
Bimekizumab
This investigational dual IL-17A/F inhibitor demonstrated efficacy and safety for SpA in a 297-patient, phase 2b trial presented at the 2018 European Congress of Rheumatology.
“It’s effective, but it doesn’t look like it’s particularly more effective than either of the existing IL-17A inhibitors. We’ll see going forward if there truly is an advantage here to the additional inhibition of IL-17F in this population. I will say that the preclinical and laboratory data on the potential advantages of IL-17F inhibition are mostly in the psoriasis/psoriatic arthritis space. It’s not clear in ankylosing spondyloarthritis specifically whether we should expect to see a difference,” Dr. Ruderman said.
Ustekinumab
The IL-12/23 inhibitor proved no better than placebo in patients with SpA in three separate phase 3, randomized trials recently published as a single summary article (Arthritis Rheumatol. 2019 Feb;71[2]:258-70).
“Ustekinumab was effective in an earlier open study, so I think everybody was surprised by this,” Dr. Kavanaugh said.
He reported serving as a consultant to and/or receiving research funding from a dozen pharmaceutical companies. Dr. Ruderman reported financial relationships with eight companies.
REPORTING FROM RWCS 2019
Supercharge Your On-Call Bag: 4 Must-Have Items for Dermatology Residents
It is no secret that a well-stocked on-call bag is one of the keys to providing inpatient care as a dermatology resident. Beyond the basic items that should never be left at home, there are some lesser-known tools that I have learned about from my book- and street-smart attendings and co-residents in the Department of Dermatology at the State University of New York Downstate Medical Center (referred to here as Downstate). Here are our top 4 items to pack the next time you are on call. (Bonus: you will find them helpful in clinic, too.)
Item 1: WoundSeal Powder
The most valuable player in my on-call bag, WoundSeal Powder (Biolife) is an over-the-counter hemostatic agent that I learned about from Daniel M. Siegel, MD, MS, a Mohs surgeon at Downstate and former president of the American Academy of Dermatology. The powder consists of a hydrophilic polymer and potassium ferrate.1 When poured over a bleeding wound and pressed in place (eg, with a sterile cotton-tipped swab), the hydrophilic polymer absorbs plasma while the iron in potassium ferrate agglomerates blood solids. The result is a scablike seal that is safe to leave in place until the wound has healed.1
Since Dr. Siegel introduced WoundSeal to Downstate about a decade ago, it has become our department’s go-to hemostatic agent for most punch biopsies performed in the inpatient setting. In our experience, achieving hemostasis in the hospital usually is easier, safer, and faster with WoundSeal than suture. Furthermore, using WoundSeal eliminates the need for patients to follow up for suture removal. From a practical perspective, WoundSeal works best when the biopsy defect is positioned parallel to the ground so the powder can be poured directly over and into the defect. From a cosmetic perspective, we have found that WoundSeal and suture have similar outcomes when used for punch biopsies up to 4 mm in size on the trunk and extremities in both adult and pediatric patients. Working with other dermatology attendings such as Sharon A. Glick, MD; Eve Lowenstein, MD, PhD; and Jeannette Jakus, MD, MBA, I also have found WoundSeal helpful when taking care of suture-phobic children or patients with lesions that are less amenable to suture, such as an ulcer or indurated plaque.
Item 2: Purple Surgical Marker
Another tip I have learned from Drs. Siegel and Jakus: If you are ever in a bind for a topical antibacterial or antifungal agent, look no further than a sterile purple surgical marker. These markers are a surprising source of gentian violet, the same purple dye that is the basis of Gram staining and sold as an over-the-counter antiseptic in 1% to 2% concentrations. Purple surgical markers, on the other hand, are 2.5% to 10% gentian violet.2
Gentian violet has been shown to have antibacterial, antifungal, antiviral, antihelminthic, and antitrypanosomal properties, but its efficacy has been mostly demonstrated against Streptococcus, methicillin-sensitive and methicillin-resistant Staphylococcus aureus, and Candida.3 Given the dermatologic relevance of these organisms, gentian violet is a favorite among attendings at my residency program; it is not uncommon to remove a patient’s dressing and uncover an iatrogenically purple wound. Best of all, pediatric patients are invariably amused when they see someone drawing on their skin with a purple marker.
When using a sterile surgical marker to apply gentian violet to the skin, we use either the marker tip or the ink core, which Dr. Siegel taught me can be easily accessed by snapping most plastic markers in half.
Item 3: Handheld Blacklight
The Wood lamp is a useful tool in the diagnosis of various infectious diseases and pigmentary disorders,4 but it is not always practical to use when on call, as standard ones are relatively large and corded, so they must be plugged into an electric outlet to work. You can therefore imagine the gratitude I have for my co-residents Miriam Lieberman, MD; Jaime Alexander, MD; Nicole Weiler, MD; and Alessandra Haskin, MD, for introducing me to the most convenient Wood lamp: the handheld blacklight. For less than $10, this gadget combines the diagnostic power of UV light with the portability of a pocket-sized, battery-powered flashlight. You will never want to use another Wood lamp again.
Item 4: Normal Saline Flush
Normal saline can be used for more than storing specimens for frozen section or tissue culture; it also can substitute for Michel solution when storing specimens for direct immunofluorescence (DIF) studies. I learned this tip from Edward Heilman, MD, a dermatopathologist at Downstate. For the last 20 years, Dr. Heilman has been successfully storing DIF specimens in refrigerated normal saline for up to 24 hours when Michel solution is unavailable, after which the specimen is processed or transferred to Michel solution for further storage while being transported to an immunofluorescence laboratory.
In 2004, Vodegel et al5 formally studied this technique in 25 patients with autoimmune skin diseases such as pemphigus and pemphigoid. (Thanks to Dr. Lieberman for telling me about this study.) The experiment involved taking 4 punch biopsies from each patient and placing them in either normal saline at −80°C for 24 or 48 hours, room temperature Michel solution for 48 hours, or liquid nitrogen for up to 2 weeks before being processed for DIF and analyzed by a blinded interpreter. Interestingly, specimens stored in normal saline for 24 hours were the most diagnostic, with a conclusive diagnosis reached in 21 of 25 specimens (84%). This result was attributed to the statistically significant reduction (P<.01) in background fluorescence with normal saline compared to Michel solution and liquid nitrogen, which in turn allowed for easier detection of diagnostic immunoreactants. Similar to Dr. Heilman, the authors cautioned against placing DIF specimens in normal saline for more than 24 hours; in their experience, the risk for an artefactual split developing at the dermoepidermal junction increases with this practice.5
- Biolife. How WoundSeal works. WoundSeal website. http://woundseal.com/how-it-works. Accessed March 7, 2019.
- Viscot Medical, LLC. Safety data sheet. http://www.viscot.com/download/MSDS%20Gentian%20Violet%20Ink.pdf. Published September 11, 2014. Accessed March 7, 2019.
- Maley AM, Arbiser JL. Gentian violet: a 19th century drug re-emerges in the 21st century. Exp Dermatol. 2013;22:775-780.
- Klatte JL, van der Beek N, Kemperman PM. 100 years of Wood’s lamp revised. J Eur Acad Dermatol Venereol. 2015;29:842-847.
- Vodegel RM, de Jong MC, Meijer HJ, et al. Enhanced diagnostic immunofluorescence using biopsies transported in saline. BMC Dermatol. 2004;4:10.
It is no secret that a well-stocked on-call bag is one of the keys to providing inpatient care as a dermatology resident. Beyond the basic items that should never be left at home, there are some lesser-known tools that I have learned about from my book- and street-smart attendings and co-residents in the Department of Dermatology at the State University of New York Downstate Medical Center (referred to here as Downstate). Here are our top 4 items to pack the next time you are on call. (Bonus: you will find them helpful in clinic, too.)
Item 1: WoundSeal Powder
The most valuable player in my on-call bag, WoundSeal Powder (Biolife) is an over-the-counter hemostatic agent that I learned about from Daniel M. Siegel, MD, MS, a Mohs surgeon at Downstate and former president of the American Academy of Dermatology. The powder consists of a hydrophilic polymer and potassium ferrate.1 When poured over a bleeding wound and pressed in place (eg, with a sterile cotton-tipped swab), the hydrophilic polymer absorbs plasma while the iron in potassium ferrate agglomerates blood solids. The result is a scablike seal that is safe to leave in place until the wound has healed.1
Since Dr. Siegel introduced WoundSeal to Downstate about a decade ago, it has become our department’s go-to hemostatic agent for most punch biopsies performed in the inpatient setting. In our experience, achieving hemostasis in the hospital usually is easier, safer, and faster with WoundSeal than suture. Furthermore, using WoundSeal eliminates the need for patients to follow up for suture removal. From a practical perspective, WoundSeal works best when the biopsy defect is positioned parallel to the ground so the powder can be poured directly over and into the defect. From a cosmetic perspective, we have found that WoundSeal and suture have similar outcomes when used for punch biopsies up to 4 mm in size on the trunk and extremities in both adult and pediatric patients. Working with other dermatology attendings such as Sharon A. Glick, MD; Eve Lowenstein, MD, PhD; and Jeannette Jakus, MD, MBA, I also have found WoundSeal helpful when taking care of suture-phobic children or patients with lesions that are less amenable to suture, such as an ulcer or indurated plaque.
Item 2: Purple Surgical Marker
Another tip I have learned from Drs. Siegel and Jakus: If you are ever in a bind for a topical antibacterial or antifungal agent, look no further than a sterile purple surgical marker. These markers are a surprising source of gentian violet, the same purple dye that is the basis of Gram staining and sold as an over-the-counter antiseptic in 1% to 2% concentrations. Purple surgical markers, on the other hand, are 2.5% to 10% gentian violet.2
Gentian violet has been shown to have antibacterial, antifungal, antiviral, antihelminthic, and antitrypanosomal properties, but its efficacy has been mostly demonstrated against Streptococcus, methicillin-sensitive and methicillin-resistant Staphylococcus aureus, and Candida.3 Given the dermatologic relevance of these organisms, gentian violet is a favorite among attendings at my residency program; it is not uncommon to remove a patient’s dressing and uncover an iatrogenically purple wound. Best of all, pediatric patients are invariably amused when they see someone drawing on their skin with a purple marker.
When using a sterile surgical marker to apply gentian violet to the skin, we use either the marker tip or the ink core, which Dr. Siegel taught me can be easily accessed by snapping most plastic markers in half.
Item 3: Handheld Blacklight
The Wood lamp is a useful tool in the diagnosis of various infectious diseases and pigmentary disorders,4 but it is not always practical to use when on call, as standard ones are relatively large and corded, so they must be plugged into an electric outlet to work. You can therefore imagine the gratitude I have for my co-residents Miriam Lieberman, MD; Jaime Alexander, MD; Nicole Weiler, MD; and Alessandra Haskin, MD, for introducing me to the most convenient Wood lamp: the handheld blacklight. For less than $10, this gadget combines the diagnostic power of UV light with the portability of a pocket-sized, battery-powered flashlight. You will never want to use another Wood lamp again.
Item 4: Normal Saline Flush
Normal saline can be used for more than storing specimens for frozen section or tissue culture; it also can substitute for Michel solution when storing specimens for direct immunofluorescence (DIF) studies. I learned this tip from Edward Heilman, MD, a dermatopathologist at Downstate. For the last 20 years, Dr. Heilman has been successfully storing DIF specimens in refrigerated normal saline for up to 24 hours when Michel solution is unavailable, after which the specimen is processed or transferred to Michel solution for further storage while being transported to an immunofluorescence laboratory.
In 2004, Vodegel et al5 formally studied this technique in 25 patients with autoimmune skin diseases such as pemphigus and pemphigoid. (Thanks to Dr. Lieberman for telling me about this study.) The experiment involved taking 4 punch biopsies from each patient and placing them in either normal saline at −80°C for 24 or 48 hours, room temperature Michel solution for 48 hours, or liquid nitrogen for up to 2 weeks before being processed for DIF and analyzed by a blinded interpreter. Interestingly, specimens stored in normal saline for 24 hours were the most diagnostic, with a conclusive diagnosis reached in 21 of 25 specimens (84%). This result was attributed to the statistically significant reduction (P<.01) in background fluorescence with normal saline compared to Michel solution and liquid nitrogen, which in turn allowed for easier detection of diagnostic immunoreactants. Similar to Dr. Heilman, the authors cautioned against placing DIF specimens in normal saline for more than 24 hours; in their experience, the risk for an artefactual split developing at the dermoepidermal junction increases with this practice.5
It is no secret that a well-stocked on-call bag is one of the keys to providing inpatient care as a dermatology resident. Beyond the basic items that should never be left at home, there are some lesser-known tools that I have learned about from my book- and street-smart attendings and co-residents in the Department of Dermatology at the State University of New York Downstate Medical Center (referred to here as Downstate). Here are our top 4 items to pack the next time you are on call. (Bonus: you will find them helpful in clinic, too.)
Item 1: WoundSeal Powder
The most valuable player in my on-call bag, WoundSeal Powder (Biolife) is an over-the-counter hemostatic agent that I learned about from Daniel M. Siegel, MD, MS, a Mohs surgeon at Downstate and former president of the American Academy of Dermatology. The powder consists of a hydrophilic polymer and potassium ferrate.1 When poured over a bleeding wound and pressed in place (eg, with a sterile cotton-tipped swab), the hydrophilic polymer absorbs plasma while the iron in potassium ferrate agglomerates blood solids. The result is a scablike seal that is safe to leave in place until the wound has healed.1
Since Dr. Siegel introduced WoundSeal to Downstate about a decade ago, it has become our department’s go-to hemostatic agent for most punch biopsies performed in the inpatient setting. In our experience, achieving hemostasis in the hospital usually is easier, safer, and faster with WoundSeal than suture. Furthermore, using WoundSeal eliminates the need for patients to follow up for suture removal. From a practical perspective, WoundSeal works best when the biopsy defect is positioned parallel to the ground so the powder can be poured directly over and into the defect. From a cosmetic perspective, we have found that WoundSeal and suture have similar outcomes when used for punch biopsies up to 4 mm in size on the trunk and extremities in both adult and pediatric patients. Working with other dermatology attendings such as Sharon A. Glick, MD; Eve Lowenstein, MD, PhD; and Jeannette Jakus, MD, MBA, I also have found WoundSeal helpful when taking care of suture-phobic children or patients with lesions that are less amenable to suture, such as an ulcer or indurated plaque.
Item 2: Purple Surgical Marker
Another tip I have learned from Drs. Siegel and Jakus: If you are ever in a bind for a topical antibacterial or antifungal agent, look no further than a sterile purple surgical marker. These markers are a surprising source of gentian violet, the same purple dye that is the basis of Gram staining and sold as an over-the-counter antiseptic in 1% to 2% concentrations. Purple surgical markers, on the other hand, are 2.5% to 10% gentian violet.2
Gentian violet has been shown to have antibacterial, antifungal, antiviral, antihelminthic, and antitrypanosomal properties, but its efficacy has been mostly demonstrated against Streptococcus, methicillin-sensitive and methicillin-resistant Staphylococcus aureus, and Candida.3 Given the dermatologic relevance of these organisms, gentian violet is a favorite among attendings at my residency program; it is not uncommon to remove a patient’s dressing and uncover an iatrogenically purple wound. Best of all, pediatric patients are invariably amused when they see someone drawing on their skin with a purple marker.
When using a sterile surgical marker to apply gentian violet to the skin, we use either the marker tip or the ink core, which Dr. Siegel taught me can be easily accessed by snapping most plastic markers in half.
Item 3: Handheld Blacklight
The Wood lamp is a useful tool in the diagnosis of various infectious diseases and pigmentary disorders,4 but it is not always practical to use when on call, as standard ones are relatively large and corded, so they must be plugged into an electric outlet to work. You can therefore imagine the gratitude I have for my co-residents Miriam Lieberman, MD; Jaime Alexander, MD; Nicole Weiler, MD; and Alessandra Haskin, MD, for introducing me to the most convenient Wood lamp: the handheld blacklight. For less than $10, this gadget combines the diagnostic power of UV light with the portability of a pocket-sized, battery-powered flashlight. You will never want to use another Wood lamp again.
Item 4: Normal Saline Flush
Normal saline can be used for more than storing specimens for frozen section or tissue culture; it also can substitute for Michel solution when storing specimens for direct immunofluorescence (DIF) studies. I learned this tip from Edward Heilman, MD, a dermatopathologist at Downstate. For the last 20 years, Dr. Heilman has been successfully storing DIF specimens in refrigerated normal saline for up to 24 hours when Michel solution is unavailable, after which the specimen is processed or transferred to Michel solution for further storage while being transported to an immunofluorescence laboratory.
In 2004, Vodegel et al5 formally studied this technique in 25 patients with autoimmune skin diseases such as pemphigus and pemphigoid. (Thanks to Dr. Lieberman for telling me about this study.) The experiment involved taking 4 punch biopsies from each patient and placing them in either normal saline at −80°C for 24 or 48 hours, room temperature Michel solution for 48 hours, or liquid nitrogen for up to 2 weeks before being processed for DIF and analyzed by a blinded interpreter. Interestingly, specimens stored in normal saline for 24 hours were the most diagnostic, with a conclusive diagnosis reached in 21 of 25 specimens (84%). This result was attributed to the statistically significant reduction (P<.01) in background fluorescence with normal saline compared to Michel solution and liquid nitrogen, which in turn allowed for easier detection of diagnostic immunoreactants. Similar to Dr. Heilman, the authors cautioned against placing DIF specimens in normal saline for more than 24 hours; in their experience, the risk for an artefactual split developing at the dermoepidermal junction increases with this practice.5
- Biolife. How WoundSeal works. WoundSeal website. http://woundseal.com/how-it-works. Accessed March 7, 2019.
- Viscot Medical, LLC. Safety data sheet. http://www.viscot.com/download/MSDS%20Gentian%20Violet%20Ink.pdf. Published September 11, 2014. Accessed March 7, 2019.
- Maley AM, Arbiser JL. Gentian violet: a 19th century drug re-emerges in the 21st century. Exp Dermatol. 2013;22:775-780.
- Klatte JL, van der Beek N, Kemperman PM. 100 years of Wood’s lamp revised. J Eur Acad Dermatol Venereol. 2015;29:842-847.
- Vodegel RM, de Jong MC, Meijer HJ, et al. Enhanced diagnostic immunofluorescence using biopsies transported in saline. BMC Dermatol. 2004;4:10.
- Biolife. How WoundSeal works. WoundSeal website. http://woundseal.com/how-it-works. Accessed March 7, 2019.
- Viscot Medical, LLC. Safety data sheet. http://www.viscot.com/download/MSDS%20Gentian%20Violet%20Ink.pdf. Published September 11, 2014. Accessed March 7, 2019.
- Maley AM, Arbiser JL. Gentian violet: a 19th century drug re-emerges in the 21st century. Exp Dermatol. 2013;22:775-780.
- Klatte JL, van der Beek N, Kemperman PM. 100 years of Wood’s lamp revised. J Eur Acad Dermatol Venereol. 2015;29:842-847.
- Vodegel RM, de Jong MC, Meijer HJ, et al. Enhanced diagnostic immunofluorescence using biopsies transported in saline. BMC Dermatol. 2004;4:10.
Resident Pearl
- The following unconventional items will come in handy the next time you are on call (or in clinic) and need an alternative to a suture, topical antimicrobial, Wood lamp, or Michel solution.
Experts offer HM19 ‘must-see’ tips
There are about as many sessions at HM19 as there are cherry blossoms on the springtime trees in the nation’s capital. Attendees are bound to find something they love – probably too many somethings, in fact.
Fear not. Seasoned experts are here to ease your struggle with suggestions for sessions they consider the best of the best and tips on getting the most out of the conference.
“Download the HM19 At Hand app to plan your conference schedule, rate speakers and sessions, and participate in audience-response systems,” said Dustin Smith, MD, SFHM, the HM19 course director and associate professor of medicine at Emory University, Atlanta. “Read the track descriptions first before reviewing the individual sessions to determine which educational tracks initially pique your interest. Don’t be wedded to one track; pick and choose sessions from the different tracks to curate a schedule that best fits your educational needs.”
SHM staff and Annual Conference committee members will be easily identifiable and eager to help on site, Dr. Smith added.
HM19 was the first Annual Conference for which SHM issued a call for content to members and nonmembers alike. The contributions yielded a few new offerings. A new Clinical Mastery track includes sessions for hospitalists wanting to enhance or refine their skills in an effort to achieve a master clinician designation, Dr. Smith said, while the new Between the Guidelines track explores clinical conundrums and lessons from history that may not be covered in clinical practice guidelines.
There also is a new Palliative Care and Pain Management pre-course and a new course on emergent airway management, Dr. Smith noted. His suggestions for sessions that are new, have a new format, or are particularly timely, are too numerous to list in full but include a fun “Medical Jeopardy” session (Wednesday, 9:10 – 9:50 a.m., Maryland C), sessions on discharge dilemmas (Monday, 11:25 a.m. to 12:05 p.m., Maryland BD/4-6) and LGBTQ health (Wednesday, 10:50 to 11:30 a.m., Maryland BD/4-6) and the workshop “Being Fe(male) in Hospital Medicine Part 2: Diversifying the Discussion” (Tuesday, 2:10 to 3:40 p.m., Potomac 1-3).
The Hospitalist polled its editorial advisory board members for each of their top two suggestions for “must-see” sessions:
Raman Palabindala, MD, SFHM, hospital medicine division chief at the University of Mississippi Medical Center
“A Battle Plan Against Career Inertia: A Blueprint for an Education Series to Retain Hospitalists, Reduce Burnout and Advance Careers” (Monday, 10:35 a.m. – 12:05 p.m., Potomac 1-3)
“I strongly recommend this to all hospitalist leaders – in big or small programs – given the importance of burnout in recent years. [Speaker] Dan Hunt is one of the best,” Dr. Palabindala said.
Special Interest Forums (Monday, 4:30 – 5:25 p.m., Tuesday, 5:30 – 6:25 p.m., multiple rooms)
Dr. Palabindala said these are valuable, small sessions when you have a focused interest in a certain topic – whether IT, academics, policy, or others.
“This is the best place to make contacts with national leaders,” he said. “Be proactive in confirming your spot.”
James Kim, MD, assistant professor of medicine at Emory University
“Delirium and Dementia in the Inpatient Setting” (Tuesday, 11:50 a.m. – 12:30 p.m., Maryland BD/4-6)
“This session is a repeat from previous years, but it is an engaging lecture with a lot of great material,” Dr. Kim said. “It has changed my approach to my practice of inpatients.”
“The Role of Primary Palliative Care in Complex, Chronic Disease Management” (Tuesday, 3:50 – 4:50 p.m., National Harbor 12-13)
“As the population grows older, palliative care’s role in disease management is going to become more important,” he said. “I watched one of Dr. [Aziz] Ansari’s lectures in a previous SHM meeting, and he delivers a dynamic presentation that is both informative and entertaining.”
Hyung (Harry) Cho, MD, SFHM, chief value officer at NYC Health + Hospitals
“Tweet your Way to the Top? Social Media as a Career Development Tool in Hospital Medicine” (Monday, 12:45 – 2:15 p.m., Potomac 1-3)
This includes a team of presenters who are experienced in the use of Twitter in conjunction with the Journal of Hospital Medicine, Dr. Cho said.
“Research Shark Tank” (Monday, 1:35 – 2:35 p.m., Baltimore 3-5)
This session involves judging and critiquing the latest research proposals with “contestants” in a Shark Tank format. Among the judges is Andrew Auerbach, MD, SFHM, past editor of the JHM. It “looks very engaging,” Dr. Cho said.
Lonika Sood, MD, FHM, clinical education director of internal medicine at Washington State University
“Making Your Educational Activities Count Twice: What it Takes These Days to Publish in Medical Education Journals” (Wednesday, 8:40 – 9:40 a.m., Baltimore 3-5)
“This is an important topic for clinician educators who are interested in taking a scholarly approach to their teaching,” Dr. Sood said. “Having some form of a framework to guide us in the direction of publishing our hard work will be very helpful.”“Managing the Hidden Curriculum: Do
You Know What You’re Teaching?” (Monday, 10:35 – 11:35 a.m., Baltimore 3-5)
“This is also an important, yet ‘hidden’ topic for the clinician educator when they are in the clinical environment with learners. Having hospitalists be aware of what is actually being ‘learned’ as opposed to what they think is being ‘taught’ on the wards is a critical part of the teaching process.”
Raj Sehgal, MD, FHM, clinical associate professor at South Texas Veterans Health Care System and UT Health San Antonio
“Call Night: Common Scenarios Encountered and Strategies to Make It Through the Night” (Monday, 10:35 – 11:15 a.m., Annapolis) and “Nocturnal Admissions: Cases That Keep Me Up at Night” (Monday, 2 – 2:40 p.m., Maryland A/1-3)
“I’m glad to see several different sessions about issues hospitalists face when working nights,” Dr. Sehgal said. “After all, most hours of the week are actually ‘off-hours’ (nights and weekends), so it’s important to focus on how care is delivered during these times. Even though we see the same diagnoses regardless of the time of day, our management is often very different because of external forces, such as the availability of tests and consultants.”
Marina Farah, MD, MHA, a national expert on improving clinical quality, cost, and efficiency
"Delivering Population Health as a Hospitalist in a Value-Based Healthcare Era” (Monday, 3:45 – 4:25 p.m., Maryland A/1-3)
“Hospital care is responsible for a third of the U.S. health care spending,” Dr. Farah said. “Hospitalists serve 75% of total hospital patients and have a unique perspective and power to drive national health care outcomes. This session will offer guidance on what hospitalists can do to improve population health, decrease total cost of care, and succeed under value-based reimbursement models.”
“Things We Do for No Reason: The 2019 Clinical Update for Hospitalists” (Tuesday, 11:50 a.m. – 12:30 p.m., Woodrow Wilson)
“Every hospitalist needs to know clinical practices that aren’t evidence-based, costly, and do not improve patient outcomes,” she said.
Amith Skandhan, MD, SFHM, assistant professor and medical director/clinical liaison for clinical documentation improvement at Southeast Health Medical Center
“How To Be a Great Teaching Attending” (Wednesday, 10 – 10:40 a.m., Maryland C)
“Being an academic hospitalist, I look up to great inpatient teachers,” Dr. Skandhan said. “Dr. [Jeffrey] Wiese has an amazing presence when he talks. His book on bedside teaching has been quite a guide for me as I embarked on my journey as a teacher.”
“Amplify Your Impact: Leverage Data to Accelerate Your Efforts in Quality Improvement” (Tuesday, 3:50 – 5:20 p.m., Potomac 1-3)
“Hospital medicine is a fairly new branch of medicine, and we are now the leaders of inpatient quality improvement,” he said. “To understand data and to convert it to useful information that can be utilized in quality improvement strategies would be great.”
Danielle Scheurer, MD, SFHM, physician editor of The Hospitalist and chief quality officer, Medical University of South Carolina
“Top New Guidelines Every Hospitalist Needs to Know in Clinical Practice” (Monday, 10:35 - 11:15 a.m., Woodrow Wilson)
“It’s important to remain up to date on all the new guideline releases.”“
Your Hospital, Your Group and Yourself: Opportunities for Promoting Well Being and Reducing Burnout” (Monday, 1:35 - 2:35 p.m., National Harbor 12-13)
“This session will help you and your teams to garner ideas and tactics for reducing the prevalence of burnout,” she said.
For more information on the HM19 education sessions, check the latest version of the conference schedule at https://shmannualconference.org/interactive-schedule/ .
There are about as many sessions at HM19 as there are cherry blossoms on the springtime trees in the nation’s capital. Attendees are bound to find something they love – probably too many somethings, in fact.
Fear not. Seasoned experts are here to ease your struggle with suggestions for sessions they consider the best of the best and tips on getting the most out of the conference.
“Download the HM19 At Hand app to plan your conference schedule, rate speakers and sessions, and participate in audience-response systems,” said Dustin Smith, MD, SFHM, the HM19 course director and associate professor of medicine at Emory University, Atlanta. “Read the track descriptions first before reviewing the individual sessions to determine which educational tracks initially pique your interest. Don’t be wedded to one track; pick and choose sessions from the different tracks to curate a schedule that best fits your educational needs.”
SHM staff and Annual Conference committee members will be easily identifiable and eager to help on site, Dr. Smith added.
HM19 was the first Annual Conference for which SHM issued a call for content to members and nonmembers alike. The contributions yielded a few new offerings. A new Clinical Mastery track includes sessions for hospitalists wanting to enhance or refine their skills in an effort to achieve a master clinician designation, Dr. Smith said, while the new Between the Guidelines track explores clinical conundrums and lessons from history that may not be covered in clinical practice guidelines.
There also is a new Palliative Care and Pain Management pre-course and a new course on emergent airway management, Dr. Smith noted. His suggestions for sessions that are new, have a new format, or are particularly timely, are too numerous to list in full but include a fun “Medical Jeopardy” session (Wednesday, 9:10 – 9:50 a.m., Maryland C), sessions on discharge dilemmas (Monday, 11:25 a.m. to 12:05 p.m., Maryland BD/4-6) and LGBTQ health (Wednesday, 10:50 to 11:30 a.m., Maryland BD/4-6) and the workshop “Being Fe(male) in Hospital Medicine Part 2: Diversifying the Discussion” (Tuesday, 2:10 to 3:40 p.m., Potomac 1-3).
The Hospitalist polled its editorial advisory board members for each of their top two suggestions for “must-see” sessions:
Raman Palabindala, MD, SFHM, hospital medicine division chief at the University of Mississippi Medical Center
“A Battle Plan Against Career Inertia: A Blueprint for an Education Series to Retain Hospitalists, Reduce Burnout and Advance Careers” (Monday, 10:35 a.m. – 12:05 p.m., Potomac 1-3)
“I strongly recommend this to all hospitalist leaders – in big or small programs – given the importance of burnout in recent years. [Speaker] Dan Hunt is one of the best,” Dr. Palabindala said.
Special Interest Forums (Monday, 4:30 – 5:25 p.m., Tuesday, 5:30 – 6:25 p.m., multiple rooms)
Dr. Palabindala said these are valuable, small sessions when you have a focused interest in a certain topic – whether IT, academics, policy, or others.
“This is the best place to make contacts with national leaders,” he said. “Be proactive in confirming your spot.”
James Kim, MD, assistant professor of medicine at Emory University
“Delirium and Dementia in the Inpatient Setting” (Tuesday, 11:50 a.m. – 12:30 p.m., Maryland BD/4-6)
“This session is a repeat from previous years, but it is an engaging lecture with a lot of great material,” Dr. Kim said. “It has changed my approach to my practice of inpatients.”
“The Role of Primary Palliative Care in Complex, Chronic Disease Management” (Tuesday, 3:50 – 4:50 p.m., National Harbor 12-13)
“As the population grows older, palliative care’s role in disease management is going to become more important,” he said. “I watched one of Dr. [Aziz] Ansari’s lectures in a previous SHM meeting, and he delivers a dynamic presentation that is both informative and entertaining.”
Hyung (Harry) Cho, MD, SFHM, chief value officer at NYC Health + Hospitals
“Tweet your Way to the Top? Social Media as a Career Development Tool in Hospital Medicine” (Monday, 12:45 – 2:15 p.m., Potomac 1-3)
This includes a team of presenters who are experienced in the use of Twitter in conjunction with the Journal of Hospital Medicine, Dr. Cho said.
“Research Shark Tank” (Monday, 1:35 – 2:35 p.m., Baltimore 3-5)
This session involves judging and critiquing the latest research proposals with “contestants” in a Shark Tank format. Among the judges is Andrew Auerbach, MD, SFHM, past editor of the JHM. It “looks very engaging,” Dr. Cho said.
Lonika Sood, MD, FHM, clinical education director of internal medicine at Washington State University
“Making Your Educational Activities Count Twice: What it Takes These Days to Publish in Medical Education Journals” (Wednesday, 8:40 – 9:40 a.m., Baltimore 3-5)
“This is an important topic for clinician educators who are interested in taking a scholarly approach to their teaching,” Dr. Sood said. “Having some form of a framework to guide us in the direction of publishing our hard work will be very helpful.”“Managing the Hidden Curriculum: Do
You Know What You’re Teaching?” (Monday, 10:35 – 11:35 a.m., Baltimore 3-5)
“This is also an important, yet ‘hidden’ topic for the clinician educator when they are in the clinical environment with learners. Having hospitalists be aware of what is actually being ‘learned’ as opposed to what they think is being ‘taught’ on the wards is a critical part of the teaching process.”
Raj Sehgal, MD, FHM, clinical associate professor at South Texas Veterans Health Care System and UT Health San Antonio
“Call Night: Common Scenarios Encountered and Strategies to Make It Through the Night” (Monday, 10:35 – 11:15 a.m., Annapolis) and “Nocturnal Admissions: Cases That Keep Me Up at Night” (Monday, 2 – 2:40 p.m., Maryland A/1-3)
“I’m glad to see several different sessions about issues hospitalists face when working nights,” Dr. Sehgal said. “After all, most hours of the week are actually ‘off-hours’ (nights and weekends), so it’s important to focus on how care is delivered during these times. Even though we see the same diagnoses regardless of the time of day, our management is often very different because of external forces, such as the availability of tests and consultants.”
Marina Farah, MD, MHA, a national expert on improving clinical quality, cost, and efficiency
"Delivering Population Health as a Hospitalist in a Value-Based Healthcare Era” (Monday, 3:45 – 4:25 p.m., Maryland A/1-3)
“Hospital care is responsible for a third of the U.S. health care spending,” Dr. Farah said. “Hospitalists serve 75% of total hospital patients and have a unique perspective and power to drive national health care outcomes. This session will offer guidance on what hospitalists can do to improve population health, decrease total cost of care, and succeed under value-based reimbursement models.”
“Things We Do for No Reason: The 2019 Clinical Update for Hospitalists” (Tuesday, 11:50 a.m. – 12:30 p.m., Woodrow Wilson)
“Every hospitalist needs to know clinical practices that aren’t evidence-based, costly, and do not improve patient outcomes,” she said.
Amith Skandhan, MD, SFHM, assistant professor and medical director/clinical liaison for clinical documentation improvement at Southeast Health Medical Center
“How To Be a Great Teaching Attending” (Wednesday, 10 – 10:40 a.m., Maryland C)
“Being an academic hospitalist, I look up to great inpatient teachers,” Dr. Skandhan said. “Dr. [Jeffrey] Wiese has an amazing presence when he talks. His book on bedside teaching has been quite a guide for me as I embarked on my journey as a teacher.”
“Amplify Your Impact: Leverage Data to Accelerate Your Efforts in Quality Improvement” (Tuesday, 3:50 – 5:20 p.m., Potomac 1-3)
“Hospital medicine is a fairly new branch of medicine, and we are now the leaders of inpatient quality improvement,” he said. “To understand data and to convert it to useful information that can be utilized in quality improvement strategies would be great.”
Danielle Scheurer, MD, SFHM, physician editor of The Hospitalist and chief quality officer, Medical University of South Carolina
“Top New Guidelines Every Hospitalist Needs to Know in Clinical Practice” (Monday, 10:35 - 11:15 a.m., Woodrow Wilson)
“It’s important to remain up to date on all the new guideline releases.”“
Your Hospital, Your Group and Yourself: Opportunities for Promoting Well Being and Reducing Burnout” (Monday, 1:35 - 2:35 p.m., National Harbor 12-13)
“This session will help you and your teams to garner ideas and tactics for reducing the prevalence of burnout,” she said.
For more information on the HM19 education sessions, check the latest version of the conference schedule at https://shmannualconference.org/interactive-schedule/ .
There are about as many sessions at HM19 as there are cherry blossoms on the springtime trees in the nation’s capital. Attendees are bound to find something they love – probably too many somethings, in fact.
Fear not. Seasoned experts are here to ease your struggle with suggestions for sessions they consider the best of the best and tips on getting the most out of the conference.
“Download the HM19 At Hand app to plan your conference schedule, rate speakers and sessions, and participate in audience-response systems,” said Dustin Smith, MD, SFHM, the HM19 course director and associate professor of medicine at Emory University, Atlanta. “Read the track descriptions first before reviewing the individual sessions to determine which educational tracks initially pique your interest. Don’t be wedded to one track; pick and choose sessions from the different tracks to curate a schedule that best fits your educational needs.”
SHM staff and Annual Conference committee members will be easily identifiable and eager to help on site, Dr. Smith added.
HM19 was the first Annual Conference for which SHM issued a call for content to members and nonmembers alike. The contributions yielded a few new offerings. A new Clinical Mastery track includes sessions for hospitalists wanting to enhance or refine their skills in an effort to achieve a master clinician designation, Dr. Smith said, while the new Between the Guidelines track explores clinical conundrums and lessons from history that may not be covered in clinical practice guidelines.
There also is a new Palliative Care and Pain Management pre-course and a new course on emergent airway management, Dr. Smith noted. His suggestions for sessions that are new, have a new format, or are particularly timely, are too numerous to list in full but include a fun “Medical Jeopardy” session (Wednesday, 9:10 – 9:50 a.m., Maryland C), sessions on discharge dilemmas (Monday, 11:25 a.m. to 12:05 p.m., Maryland BD/4-6) and LGBTQ health (Wednesday, 10:50 to 11:30 a.m., Maryland BD/4-6) and the workshop “Being Fe(male) in Hospital Medicine Part 2: Diversifying the Discussion” (Tuesday, 2:10 to 3:40 p.m., Potomac 1-3).
The Hospitalist polled its editorial advisory board members for each of their top two suggestions for “must-see” sessions:
Raman Palabindala, MD, SFHM, hospital medicine division chief at the University of Mississippi Medical Center
“A Battle Plan Against Career Inertia: A Blueprint for an Education Series to Retain Hospitalists, Reduce Burnout and Advance Careers” (Monday, 10:35 a.m. – 12:05 p.m., Potomac 1-3)
“I strongly recommend this to all hospitalist leaders – in big or small programs – given the importance of burnout in recent years. [Speaker] Dan Hunt is one of the best,” Dr. Palabindala said.
Special Interest Forums (Monday, 4:30 – 5:25 p.m., Tuesday, 5:30 – 6:25 p.m., multiple rooms)
Dr. Palabindala said these are valuable, small sessions when you have a focused interest in a certain topic – whether IT, academics, policy, or others.
“This is the best place to make contacts with national leaders,” he said. “Be proactive in confirming your spot.”
James Kim, MD, assistant professor of medicine at Emory University
“Delirium and Dementia in the Inpatient Setting” (Tuesday, 11:50 a.m. – 12:30 p.m., Maryland BD/4-6)
“This session is a repeat from previous years, but it is an engaging lecture with a lot of great material,” Dr. Kim said. “It has changed my approach to my practice of inpatients.”
“The Role of Primary Palliative Care in Complex, Chronic Disease Management” (Tuesday, 3:50 – 4:50 p.m., National Harbor 12-13)
“As the population grows older, palliative care’s role in disease management is going to become more important,” he said. “I watched one of Dr. [Aziz] Ansari’s lectures in a previous SHM meeting, and he delivers a dynamic presentation that is both informative and entertaining.”
Hyung (Harry) Cho, MD, SFHM, chief value officer at NYC Health + Hospitals
“Tweet your Way to the Top? Social Media as a Career Development Tool in Hospital Medicine” (Monday, 12:45 – 2:15 p.m., Potomac 1-3)
This includes a team of presenters who are experienced in the use of Twitter in conjunction with the Journal of Hospital Medicine, Dr. Cho said.
“Research Shark Tank” (Monday, 1:35 – 2:35 p.m., Baltimore 3-5)
This session involves judging and critiquing the latest research proposals with “contestants” in a Shark Tank format. Among the judges is Andrew Auerbach, MD, SFHM, past editor of the JHM. It “looks very engaging,” Dr. Cho said.
Lonika Sood, MD, FHM, clinical education director of internal medicine at Washington State University
“Making Your Educational Activities Count Twice: What it Takes These Days to Publish in Medical Education Journals” (Wednesday, 8:40 – 9:40 a.m., Baltimore 3-5)
“This is an important topic for clinician educators who are interested in taking a scholarly approach to their teaching,” Dr. Sood said. “Having some form of a framework to guide us in the direction of publishing our hard work will be very helpful.”“Managing the Hidden Curriculum: Do
You Know What You’re Teaching?” (Monday, 10:35 – 11:35 a.m., Baltimore 3-5)
“This is also an important, yet ‘hidden’ topic for the clinician educator when they are in the clinical environment with learners. Having hospitalists be aware of what is actually being ‘learned’ as opposed to what they think is being ‘taught’ on the wards is a critical part of the teaching process.”
Raj Sehgal, MD, FHM, clinical associate professor at South Texas Veterans Health Care System and UT Health San Antonio
“Call Night: Common Scenarios Encountered and Strategies to Make It Through the Night” (Monday, 10:35 – 11:15 a.m., Annapolis) and “Nocturnal Admissions: Cases That Keep Me Up at Night” (Monday, 2 – 2:40 p.m., Maryland A/1-3)
“I’m glad to see several different sessions about issues hospitalists face when working nights,” Dr. Sehgal said. “After all, most hours of the week are actually ‘off-hours’ (nights and weekends), so it’s important to focus on how care is delivered during these times. Even though we see the same diagnoses regardless of the time of day, our management is often very different because of external forces, such as the availability of tests and consultants.”
Marina Farah, MD, MHA, a national expert on improving clinical quality, cost, and efficiency
"Delivering Population Health as a Hospitalist in a Value-Based Healthcare Era” (Monday, 3:45 – 4:25 p.m., Maryland A/1-3)
“Hospital care is responsible for a third of the U.S. health care spending,” Dr. Farah said. “Hospitalists serve 75% of total hospital patients and have a unique perspective and power to drive national health care outcomes. This session will offer guidance on what hospitalists can do to improve population health, decrease total cost of care, and succeed under value-based reimbursement models.”
“Things We Do for No Reason: The 2019 Clinical Update for Hospitalists” (Tuesday, 11:50 a.m. – 12:30 p.m., Woodrow Wilson)
“Every hospitalist needs to know clinical practices that aren’t evidence-based, costly, and do not improve patient outcomes,” she said.
Amith Skandhan, MD, SFHM, assistant professor and medical director/clinical liaison for clinical documentation improvement at Southeast Health Medical Center
“How To Be a Great Teaching Attending” (Wednesday, 10 – 10:40 a.m., Maryland C)
“Being an academic hospitalist, I look up to great inpatient teachers,” Dr. Skandhan said. “Dr. [Jeffrey] Wiese has an amazing presence when he talks. His book on bedside teaching has been quite a guide for me as I embarked on my journey as a teacher.”
“Amplify Your Impact: Leverage Data to Accelerate Your Efforts in Quality Improvement” (Tuesday, 3:50 – 5:20 p.m., Potomac 1-3)
“Hospital medicine is a fairly new branch of medicine, and we are now the leaders of inpatient quality improvement,” he said. “To understand data and to convert it to useful information that can be utilized in quality improvement strategies would be great.”
Danielle Scheurer, MD, SFHM, physician editor of The Hospitalist and chief quality officer, Medical University of South Carolina
“Top New Guidelines Every Hospitalist Needs to Know in Clinical Practice” (Monday, 10:35 - 11:15 a.m., Woodrow Wilson)
“It’s important to remain up to date on all the new guideline releases.”“
Your Hospital, Your Group and Yourself: Opportunities for Promoting Well Being and Reducing Burnout” (Monday, 1:35 - 2:35 p.m., National Harbor 12-13)
“This session will help you and your teams to garner ideas and tactics for reducing the prevalence of burnout,” she said.
For more information on the HM19 education sessions, check the latest version of the conference schedule at https://shmannualconference.org/interactive-schedule/ .
Therapeutic dosing of busulfan helps reduce relapse in ASCT
HOUSTON – Compared with weight-based dosing, pharmacokinetic-directed therapeutic dose monitoring of busulfan used in combination with cyclophosphamide and etoposide reduced relapse risk in non-Hodgkin lymphoma (NHL) patients undergoing autologous stem cell transplantation (ASCT), according to a review of 336 cases.
This was particularly true in patients with less than a complete response at the time of transplant, Brian T. Hill, MD, PhD, reported at the Transplantation & Cellular Therapy Meetings.
The relapse rate at 24 months after ASCT was 19% in 78 adult NHL patients who underwent ASCT with pharmacokinetic-guided therapeutic dose monitoring (PK-TDM), compared with 38% in 258 patients who received weight-based-dosing (WBD) of busulfan with cyclophosphamide and etoposide.
Progression-free survival (PFS) improved with PK-TDM vs. WBD (69% vs. 55%) but overall survival (OS) did not differ between the groups, most likely because of subsequent therapy given at the time of relapse, said Dr. Hill, director of the lymphoid malignancies program and a staff physician at the Cleveland Clinic Taussig Cancer Institute, Ohio.
The findings are from a retrospective comparison of outcomes in patients treated between 2014 and 2017 when PK-TDM was the standard practice, and patients treated between 2007 and 2013 when fixed weight-based dosing was standard, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“In 2013 we began a program of therapeutic dose monitoring at our site,” Dr. Hill said, explaining that with TDM the goal is to eliminate the low and high levels seen with weight-based dosing, and “to get the maximum number of patients into the therapeutic zone.”
TDM became the preferred approach for busulfan dosing because of the drug’s “unpredictable and widely variable pharmacokinetics,” and ASBMT guidelines now call for consideration of TDM with first-line busulfan to minimize the potential complications, he noted.
“But it’s noteworthy that ... there are really no data to show that TDM can reduce the rates of relapse,” he added.
For this study, WBD busulfan dosing was 2.8 mg/kg every 24 hours on day –9 to –6 of ASCT. For PK-TDM, plasma busulfan concentration was serially determined using a previously described and externally validated in-house liquid chromatography–tandem mass spectrometry assay, he said, explaining that busulfan area under the curve (AUC) after first dose was calculated for each patient and used to adjust subsequent doses to target a daily AUC of 4,500 micromol/min.
To account for baseline differences in the two groups, including a higher number of prior chemotherapy regimens in the WBD group and a higher proportion of aggressive B-cell and T-cell lymphoma in the TDM group, two propensity-matched cohorts of 47 patients each were derived via logistic regression analysis.
“In the propensity-matched cohorts we saw a similar pattern, with therapeutic dose monitoring patients having lower relapse and improved progression-free survival, but no change in the nonrelapse mortality or the overall survival,” Dr. Hill said.
Notably, PFS did not differ between the groups when the researchers looked only at those in complete remission at transplant, but a significant improvement in PFS was seen in the TDM vs. WBD cohorts when they looked only at patients with partial remission, stable disease, or progressive disease (collectively considered as those in less than CR at transplant), he said (P = .79 vs. .08, respectively).
On multivariate analysis, less than CR status was associated with an increased risk of relapse after ASCT (hazard ratio, 2.0), and TDM vs. WBD was associated with a decreased risk of relapse (HR, 0.5).
No differences were seen between the groups with respect to changes in pulmonary or liver function from baseline, or in treatment-related mortality rates, Dr. Hill noted.
The findings support the use of PK-TDM for NHL patients undergoing ASCT with busulfan, but further study is needed, he concluded.
Dr. Hill reported having no relevant financial disclosures.
SOURCE: Hill B et al. TCT 2019, Abstract 39.
HOUSTON – Compared with weight-based dosing, pharmacokinetic-directed therapeutic dose monitoring of busulfan used in combination with cyclophosphamide and etoposide reduced relapse risk in non-Hodgkin lymphoma (NHL) patients undergoing autologous stem cell transplantation (ASCT), according to a review of 336 cases.
This was particularly true in patients with less than a complete response at the time of transplant, Brian T. Hill, MD, PhD, reported at the Transplantation & Cellular Therapy Meetings.
The relapse rate at 24 months after ASCT was 19% in 78 adult NHL patients who underwent ASCT with pharmacokinetic-guided therapeutic dose monitoring (PK-TDM), compared with 38% in 258 patients who received weight-based-dosing (WBD) of busulfan with cyclophosphamide and etoposide.
Progression-free survival (PFS) improved with PK-TDM vs. WBD (69% vs. 55%) but overall survival (OS) did not differ between the groups, most likely because of subsequent therapy given at the time of relapse, said Dr. Hill, director of the lymphoid malignancies program and a staff physician at the Cleveland Clinic Taussig Cancer Institute, Ohio.
The findings are from a retrospective comparison of outcomes in patients treated between 2014 and 2017 when PK-TDM was the standard practice, and patients treated between 2007 and 2013 when fixed weight-based dosing was standard, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“In 2013 we began a program of therapeutic dose monitoring at our site,” Dr. Hill said, explaining that with TDM the goal is to eliminate the low and high levels seen with weight-based dosing, and “to get the maximum number of patients into the therapeutic zone.”
TDM became the preferred approach for busulfan dosing because of the drug’s “unpredictable and widely variable pharmacokinetics,” and ASBMT guidelines now call for consideration of TDM with first-line busulfan to minimize the potential complications, he noted.
“But it’s noteworthy that ... there are really no data to show that TDM can reduce the rates of relapse,” he added.
For this study, WBD busulfan dosing was 2.8 mg/kg every 24 hours on day –9 to –6 of ASCT. For PK-TDM, plasma busulfan concentration was serially determined using a previously described and externally validated in-house liquid chromatography–tandem mass spectrometry assay, he said, explaining that busulfan area under the curve (AUC) after first dose was calculated for each patient and used to adjust subsequent doses to target a daily AUC of 4,500 micromol/min.
To account for baseline differences in the two groups, including a higher number of prior chemotherapy regimens in the WBD group and a higher proportion of aggressive B-cell and T-cell lymphoma in the TDM group, two propensity-matched cohorts of 47 patients each were derived via logistic regression analysis.
“In the propensity-matched cohorts we saw a similar pattern, with therapeutic dose monitoring patients having lower relapse and improved progression-free survival, but no change in the nonrelapse mortality or the overall survival,” Dr. Hill said.
Notably, PFS did not differ between the groups when the researchers looked only at those in complete remission at transplant, but a significant improvement in PFS was seen in the TDM vs. WBD cohorts when they looked only at patients with partial remission, stable disease, or progressive disease (collectively considered as those in less than CR at transplant), he said (P = .79 vs. .08, respectively).
On multivariate analysis, less than CR status was associated with an increased risk of relapse after ASCT (hazard ratio, 2.0), and TDM vs. WBD was associated with a decreased risk of relapse (HR, 0.5).
No differences were seen between the groups with respect to changes in pulmonary or liver function from baseline, or in treatment-related mortality rates, Dr. Hill noted.
The findings support the use of PK-TDM for NHL patients undergoing ASCT with busulfan, but further study is needed, he concluded.
Dr. Hill reported having no relevant financial disclosures.
SOURCE: Hill B et al. TCT 2019, Abstract 39.
HOUSTON – Compared with weight-based dosing, pharmacokinetic-directed therapeutic dose monitoring of busulfan used in combination with cyclophosphamide and etoposide reduced relapse risk in non-Hodgkin lymphoma (NHL) patients undergoing autologous stem cell transplantation (ASCT), according to a review of 336 cases.
This was particularly true in patients with less than a complete response at the time of transplant, Brian T. Hill, MD, PhD, reported at the Transplantation & Cellular Therapy Meetings.
The relapse rate at 24 months after ASCT was 19% in 78 adult NHL patients who underwent ASCT with pharmacokinetic-guided therapeutic dose monitoring (PK-TDM), compared with 38% in 258 patients who received weight-based-dosing (WBD) of busulfan with cyclophosphamide and etoposide.
Progression-free survival (PFS) improved with PK-TDM vs. WBD (69% vs. 55%) but overall survival (OS) did not differ between the groups, most likely because of subsequent therapy given at the time of relapse, said Dr. Hill, director of the lymphoid malignancies program and a staff physician at the Cleveland Clinic Taussig Cancer Institute, Ohio.
The findings are from a retrospective comparison of outcomes in patients treated between 2014 and 2017 when PK-TDM was the standard practice, and patients treated between 2007 and 2013 when fixed weight-based dosing was standard, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“In 2013 we began a program of therapeutic dose monitoring at our site,” Dr. Hill said, explaining that with TDM the goal is to eliminate the low and high levels seen with weight-based dosing, and “to get the maximum number of patients into the therapeutic zone.”
TDM became the preferred approach for busulfan dosing because of the drug’s “unpredictable and widely variable pharmacokinetics,” and ASBMT guidelines now call for consideration of TDM with first-line busulfan to minimize the potential complications, he noted.
“But it’s noteworthy that ... there are really no data to show that TDM can reduce the rates of relapse,” he added.
For this study, WBD busulfan dosing was 2.8 mg/kg every 24 hours on day –9 to –6 of ASCT. For PK-TDM, plasma busulfan concentration was serially determined using a previously described and externally validated in-house liquid chromatography–tandem mass spectrometry assay, he said, explaining that busulfan area under the curve (AUC) after first dose was calculated for each patient and used to adjust subsequent doses to target a daily AUC of 4,500 micromol/min.
To account for baseline differences in the two groups, including a higher number of prior chemotherapy regimens in the WBD group and a higher proportion of aggressive B-cell and T-cell lymphoma in the TDM group, two propensity-matched cohorts of 47 patients each were derived via logistic regression analysis.
“In the propensity-matched cohorts we saw a similar pattern, with therapeutic dose monitoring patients having lower relapse and improved progression-free survival, but no change in the nonrelapse mortality or the overall survival,” Dr. Hill said.
Notably, PFS did not differ between the groups when the researchers looked only at those in complete remission at transplant, but a significant improvement in PFS was seen in the TDM vs. WBD cohorts when they looked only at patients with partial remission, stable disease, or progressive disease (collectively considered as those in less than CR at transplant), he said (P = .79 vs. .08, respectively).
On multivariate analysis, less than CR status was associated with an increased risk of relapse after ASCT (hazard ratio, 2.0), and TDM vs. WBD was associated with a decreased risk of relapse (HR, 0.5).
No differences were seen between the groups with respect to changes in pulmonary or liver function from baseline, or in treatment-related mortality rates, Dr. Hill noted.
The findings support the use of PK-TDM for NHL patients undergoing ASCT with busulfan, but further study is needed, he concluded.
Dr. Hill reported having no relevant financial disclosures.
SOURCE: Hill B et al. TCT 2019, Abstract 39.
REPORTING FROM TCT 2019
Anti-CD45 conditioning looks safe, feasible in relapsed AML
HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.
Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.
There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.
SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.
“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”
A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.
Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.
Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.
In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.
Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.
There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.
Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.
“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.
SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.
HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.
Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.
There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.
SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.
“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”
A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.
Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.
Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.
In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.
Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.
There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.
Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.
“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.
SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.
HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.
Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.
There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.
SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.
“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”
A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.
Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.
Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.
In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.
Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.
There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.
Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.
“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.
SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.
REPORTING FROM TCT 2019
Opioid overdose risk greater among HIV patients
SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.
“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.
To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.
There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.
Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).
Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.
Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.
The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.
That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.
“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.
SOURCE: Bosh KA et al. CROI 2019, Abstract 147.
SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.
“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.
To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.
There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.
Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).
Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.
Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.
The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.
That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.
“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.
SOURCE: Bosh KA et al. CROI 2019, Abstract 147.
SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.
“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.
To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.
There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.
Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).
Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.
Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.
The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.
That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.
“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.
SOURCE: Bosh KA et al. CROI 2019, Abstract 147.
REPORTING FROM CROI 2019
HDACi, HMA combo improves survival for older AML patients
For patients older than 65 years with newly diagnosed acute myeloid leukemia (AML) who were ineligible for standard induction therapy, adding the investigational pan-histone deacetylase (pan-HDAC) inhibitor pracinostat to azacitidine resulted in better complete remission and overall survival rates than azacitidine alone, results of a multicenter phase 2 trial showed.
Among 50 patients treated with the combination, 26 (52%) achieved the primary endpoint of either a complete remission (CR), CR with incomplete recovery of blood counts (CRi), or morphologic leukemia-free state (MLFS).
The median overall survival (OS) was 19.1 months, which compares favorably with historical data on similar patients treated with single-agent azacitidine, reported Guillermo Garcia-Manero, MD, from the University of Texas MD Anderson Cancer Center in Houston and his colleagues.
“[T]his study shows that pracinostat in combination with azacitidine has the potential to be a safe and effective regimen in the frontline treatment of older patients with AML unfit for [induction chemotherapy],” they wrote in Blood Advances.
Pracinostat is an oral pan-HDAC inhibitor that has been shown to have modest activity against AML as a single agent, but synergistic activity when combined with hypomethylating agent azacitidine, a standard of care for older patients with AML in the trial.
The investigators enrolled 50 patients with a median age of 75 years (range, 66-84 years). The cohort included 33 patients with de novo AML, 12 with AML secondary to myelodysplasia syndrome or myleoproliferative neoplasia, and five with therapy-related AML.
The patients were treated with pracinostat 60 mg daily for 3 days each week for 3 consecutive weeks in addition to azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle.
As noted, 26 patients reached the clinical endpoint, including 21 with a CR, 2 with a CRi, and 3 with MLFS. Additionally, two patients had a partial response (PR) and four had a PR with incomplete recovery of blood counts.
The median OS was 19.1 months, and the median progression-free survival (PFS) was 12.6 months. The 1-year OS rate was 62%. The 60-day mortality rate was 10%.
The authors noted that the survival data were superior to those seen in the phase 3 AZA-AML-001 study, which compared azacitidine therapy with conventional regimens in patients older than 65 years with newly diagnosed AML who were not eligible for stem cell transplants. In that trial, median OS was 10.4 months, the CR rate was 19.5% (vs. 49% in the present study), the 1-year OS rate was 46.5%, and the 60-day mortality rate was 16.2%.
They acknowledged, however, that the validity of the comparison is limited by their study’s small sample size, potential differences between the study populations, and lack of a control group in the present study. The investigators also found that clearance rates of baseline somatic mutations correlated with response to treatment.
Grade 3 or greater treatment-emergent adverse events occurred in 43 of the 50 patients, including infections, thrombocytopenias, and febrile neutropenias.
“On the basis of these encouraging results, a phase 3, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (NCT03151408) is currently ongoing to confirm superiority of the combination in this difficult-to-treat AML population,” the investigators wrote.
The study was supported by research funding from MEI Pharma, which helped develop pracinostat. Dr. Garcia-Manero reported having no disclosures. Multiple coauthors reported financial relationships with MEI and others. One coauthor is an MEI employee.
SOURCE: Garcia-Manero G et al. Blood Adv. 2019 Feb 26;3(4):508-18.
For patients older than 65 years with newly diagnosed acute myeloid leukemia (AML) who were ineligible for standard induction therapy, adding the investigational pan-histone deacetylase (pan-HDAC) inhibitor pracinostat to azacitidine resulted in better complete remission and overall survival rates than azacitidine alone, results of a multicenter phase 2 trial showed.
Among 50 patients treated with the combination, 26 (52%) achieved the primary endpoint of either a complete remission (CR), CR with incomplete recovery of blood counts (CRi), or morphologic leukemia-free state (MLFS).
The median overall survival (OS) was 19.1 months, which compares favorably with historical data on similar patients treated with single-agent azacitidine, reported Guillermo Garcia-Manero, MD, from the University of Texas MD Anderson Cancer Center in Houston and his colleagues.
“[T]his study shows that pracinostat in combination with azacitidine has the potential to be a safe and effective regimen in the frontline treatment of older patients with AML unfit for [induction chemotherapy],” they wrote in Blood Advances.
Pracinostat is an oral pan-HDAC inhibitor that has been shown to have modest activity against AML as a single agent, but synergistic activity when combined with hypomethylating agent azacitidine, a standard of care for older patients with AML in the trial.
The investigators enrolled 50 patients with a median age of 75 years (range, 66-84 years). The cohort included 33 patients with de novo AML, 12 with AML secondary to myelodysplasia syndrome or myleoproliferative neoplasia, and five with therapy-related AML.
The patients were treated with pracinostat 60 mg daily for 3 days each week for 3 consecutive weeks in addition to azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle.
As noted, 26 patients reached the clinical endpoint, including 21 with a CR, 2 with a CRi, and 3 with MLFS. Additionally, two patients had a partial response (PR) and four had a PR with incomplete recovery of blood counts.
The median OS was 19.1 months, and the median progression-free survival (PFS) was 12.6 months. The 1-year OS rate was 62%. The 60-day mortality rate was 10%.
The authors noted that the survival data were superior to those seen in the phase 3 AZA-AML-001 study, which compared azacitidine therapy with conventional regimens in patients older than 65 years with newly diagnosed AML who were not eligible for stem cell transplants. In that trial, median OS was 10.4 months, the CR rate was 19.5% (vs. 49% in the present study), the 1-year OS rate was 46.5%, and the 60-day mortality rate was 16.2%.
They acknowledged, however, that the validity of the comparison is limited by their study’s small sample size, potential differences between the study populations, and lack of a control group in the present study. The investigators also found that clearance rates of baseline somatic mutations correlated with response to treatment.
Grade 3 or greater treatment-emergent adverse events occurred in 43 of the 50 patients, including infections, thrombocytopenias, and febrile neutropenias.
“On the basis of these encouraging results, a phase 3, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (NCT03151408) is currently ongoing to confirm superiority of the combination in this difficult-to-treat AML population,” the investigators wrote.
The study was supported by research funding from MEI Pharma, which helped develop pracinostat. Dr. Garcia-Manero reported having no disclosures. Multiple coauthors reported financial relationships with MEI and others. One coauthor is an MEI employee.
SOURCE: Garcia-Manero G et al. Blood Adv. 2019 Feb 26;3(4):508-18.
For patients older than 65 years with newly diagnosed acute myeloid leukemia (AML) who were ineligible for standard induction therapy, adding the investigational pan-histone deacetylase (pan-HDAC) inhibitor pracinostat to azacitidine resulted in better complete remission and overall survival rates than azacitidine alone, results of a multicenter phase 2 trial showed.
Among 50 patients treated with the combination, 26 (52%) achieved the primary endpoint of either a complete remission (CR), CR with incomplete recovery of blood counts (CRi), or morphologic leukemia-free state (MLFS).
The median overall survival (OS) was 19.1 months, which compares favorably with historical data on similar patients treated with single-agent azacitidine, reported Guillermo Garcia-Manero, MD, from the University of Texas MD Anderson Cancer Center in Houston and his colleagues.
“[T]his study shows that pracinostat in combination with azacitidine has the potential to be a safe and effective regimen in the frontline treatment of older patients with AML unfit for [induction chemotherapy],” they wrote in Blood Advances.
Pracinostat is an oral pan-HDAC inhibitor that has been shown to have modest activity against AML as a single agent, but synergistic activity when combined with hypomethylating agent azacitidine, a standard of care for older patients with AML in the trial.
The investigators enrolled 50 patients with a median age of 75 years (range, 66-84 years). The cohort included 33 patients with de novo AML, 12 with AML secondary to myelodysplasia syndrome or myleoproliferative neoplasia, and five with therapy-related AML.
The patients were treated with pracinostat 60 mg daily for 3 days each week for 3 consecutive weeks in addition to azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle.
As noted, 26 patients reached the clinical endpoint, including 21 with a CR, 2 with a CRi, and 3 with MLFS. Additionally, two patients had a partial response (PR) and four had a PR with incomplete recovery of blood counts.
The median OS was 19.1 months, and the median progression-free survival (PFS) was 12.6 months. The 1-year OS rate was 62%. The 60-day mortality rate was 10%.
The authors noted that the survival data were superior to those seen in the phase 3 AZA-AML-001 study, which compared azacitidine therapy with conventional regimens in patients older than 65 years with newly diagnosed AML who were not eligible for stem cell transplants. In that trial, median OS was 10.4 months, the CR rate was 19.5% (vs. 49% in the present study), the 1-year OS rate was 46.5%, and the 60-day mortality rate was 16.2%.
They acknowledged, however, that the validity of the comparison is limited by their study’s small sample size, potential differences between the study populations, and lack of a control group in the present study. The investigators also found that clearance rates of baseline somatic mutations correlated with response to treatment.
Grade 3 or greater treatment-emergent adverse events occurred in 43 of the 50 patients, including infections, thrombocytopenias, and febrile neutropenias.
“On the basis of these encouraging results, a phase 3, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (NCT03151408) is currently ongoing to confirm superiority of the combination in this difficult-to-treat AML population,” the investigators wrote.
The study was supported by research funding from MEI Pharma, which helped develop pracinostat. Dr. Garcia-Manero reported having no disclosures. Multiple coauthors reported financial relationships with MEI and others. One coauthor is an MEI employee.
SOURCE: Garcia-Manero G et al. Blood Adv. 2019 Feb 26;3(4):508-18.
FROM BLOOD ADVANCES
Alzheimer’s update: George Grossberg
Dr. Grossberg is the Samuel W. Fordyce professor and director of geriatric psychiatry at Saint Louis University.
And later, Dr. RK talks MDQ.
You can find more from Dr. Grossberg, including videos and articles, by clicking here.
Amazon
Apple Podcasts
Google Podcasts
Spotify
Dr. Grossberg is the Samuel W. Fordyce professor and director of geriatric psychiatry at Saint Louis University.
And later, Dr. RK talks MDQ.
You can find more from Dr. Grossberg, including videos and articles, by clicking here.
Amazon
Apple Podcasts
Google Podcasts
Spotify
Dr. Grossberg is the Samuel W. Fordyce professor and director of geriatric psychiatry at Saint Louis University.
And later, Dr. RK talks MDQ.
You can find more from Dr. Grossberg, including videos and articles, by clicking here.
Amazon
Apple Podcasts
Google Podcasts
Spotify
Aspirin and lower risk of COPD flare-up
Also today, how to handle patients who won’t believe negative drug-allergy results, which complications to watch for in black patients who undergo bariatric surgery, and the measles outbreak now affects a dozen U.S. states.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, how to handle patients who won’t believe negative drug-allergy results, which complications to watch for in black patients who undergo bariatric surgery, and the measles outbreak now affects a dozen U.S. states.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, how to handle patients who won’t believe negative drug-allergy results, which complications to watch for in black patients who undergo bariatric surgery, and the measles outbreak now affects a dozen U.S. states.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Funduscopy: Critical to the Right Diagnosis
It is always good to look the patient in the eye, say researchers from Texas Tech University in Odessa, Texas, and Centro Policlinico Valencia in Venezuela. They report on the case of a patient with atheroembolism, a “rare but feared complication of arteriography.” Most commonly, it affects small-diameter vessels in the skin and kidneys.
The patient, a 69-year-old man, had a history of hypertension, type 2 diabetes, and unstable angina; he had a drug-eluting stent placed in the left anterior descending coronary artery 10 days before he was admitted to the hospital. He arrived at the emergency department with intense abdominal pain, nausea, vomiting, oliguria, and pain in his legs and feet.
Physical examination revealed livedo reticularis (which is caused by small blood clots) in his left foot, and a tender abdomen. His creatinine and blood urea nitrogen levels were increased. Funduscopy showed a Hollenhorst crystal in the right inferotemporal quadrant.
He was treated with methylprednisolone, which improved the abdominal symptoms, renal function, and skin findings; then prednisone. His initial symptoms resolved over the next year.
The clinicians say the usual treatment for atheroembolism is supportive and depends on the affected organ. To their knowledge, they say, no formal studies have evaluated the use of anti-inflammatory therapies for this complication.
Funduscopy was an essential part of their examination, the researchers note, and spared the patient from invasive diagnostic studies such as biopsies. They also say that contrast-induced renal failure might have been the cause of the majority of his symptoms, but the combination of physical exam and differential diagnosis led them to the appropriate cause, as well as allowing for opportune treatment.
It is always good to look the patient in the eye, say researchers from Texas Tech University in Odessa, Texas, and Centro Policlinico Valencia in Venezuela. They report on the case of a patient with atheroembolism, a “rare but feared complication of arteriography.” Most commonly, it affects small-diameter vessels in the skin and kidneys.
The patient, a 69-year-old man, had a history of hypertension, type 2 diabetes, and unstable angina; he had a drug-eluting stent placed in the left anterior descending coronary artery 10 days before he was admitted to the hospital. He arrived at the emergency department with intense abdominal pain, nausea, vomiting, oliguria, and pain in his legs and feet.
Physical examination revealed livedo reticularis (which is caused by small blood clots) in his left foot, and a tender abdomen. His creatinine and blood urea nitrogen levels were increased. Funduscopy showed a Hollenhorst crystal in the right inferotemporal quadrant.
He was treated with methylprednisolone, which improved the abdominal symptoms, renal function, and skin findings; then prednisone. His initial symptoms resolved over the next year.
The clinicians say the usual treatment for atheroembolism is supportive and depends on the affected organ. To their knowledge, they say, no formal studies have evaluated the use of anti-inflammatory therapies for this complication.
Funduscopy was an essential part of their examination, the researchers note, and spared the patient from invasive diagnostic studies such as biopsies. They also say that contrast-induced renal failure might have been the cause of the majority of his symptoms, but the combination of physical exam and differential diagnosis led them to the appropriate cause, as well as allowing for opportune treatment.
It is always good to look the patient in the eye, say researchers from Texas Tech University in Odessa, Texas, and Centro Policlinico Valencia in Venezuela. They report on the case of a patient with atheroembolism, a “rare but feared complication of arteriography.” Most commonly, it affects small-diameter vessels in the skin and kidneys.
The patient, a 69-year-old man, had a history of hypertension, type 2 diabetes, and unstable angina; he had a drug-eluting stent placed in the left anterior descending coronary artery 10 days before he was admitted to the hospital. He arrived at the emergency department with intense abdominal pain, nausea, vomiting, oliguria, and pain in his legs and feet.
Physical examination revealed livedo reticularis (which is caused by small blood clots) in his left foot, and a tender abdomen. His creatinine and blood urea nitrogen levels were increased. Funduscopy showed a Hollenhorst crystal in the right inferotemporal quadrant.
He was treated with methylprednisolone, which improved the abdominal symptoms, renal function, and skin findings; then prednisone. His initial symptoms resolved over the next year.
The clinicians say the usual treatment for atheroembolism is supportive and depends on the affected organ. To their knowledge, they say, no formal studies have evaluated the use of anti-inflammatory therapies for this complication.
Funduscopy was an essential part of their examination, the researchers note, and spared the patient from invasive diagnostic studies such as biopsies. They also say that contrast-induced renal failure might have been the cause of the majority of his symptoms, but the combination of physical exam and differential diagnosis led them to the appropriate cause, as well as allowing for opportune treatment.