To the Editor:

A 63-year-old man presented with a prior diagnosis of severe psoriasis affecting the extremities, neck, face, and scalp of 1 year’s duration. He reported pain, itching, and swelling in the affected areas. He felt the rash was worst on the hands and feet, and pain made performing activities of daily living difficult. His treatment regimen at presentation included triamcinolone cream 0.1% and azathioprine 150 mg daily as prescribed by an outside dermatologist without any response. Physical examination revealed diffuse erythema with lichenification and thick, white, flaking scale on the arms and legs (Figure 1A), face, neck, palms, and soles with islands of sparing. Multiple salmon-colored, follicular-based papules topped with central hyperkeratosis were scattered on these same areas. The palms and soles had severe confluent keratoderma (Figure 2A). Histologic examination of a follicular-based papule showed foci of parakeratosis and hypergranulosis consistent with the patient’s clinical picture of pityriasis rubra pilaris (PRP).

Baseline laboratory tests at the time of PRP diagnosis revealed 20.8% eosinophils (reference range, 0%–7%) and an absolute eosinophil count of 2.17×10⁹/L (reference range, 0–0.7×10⁹/L). Laboratory test results from an outside dermatologist conducted 10 to 12 months prior to the current presentation showed 12% eosinophils with a white blood cell count of 8.9×10⁹/L (reference range, 4.5–11.0×10⁹/L) around the time of rash onset and before treatment with azathioprine, making a drug reaction an unlikely cause of the eosinophilia.

After consulting with the hematology department, a hypereosinophilia workup including erythrocyte sedimentation rate, lactate dehydrogenase, serum protein electrophoresis, urine protein electrophoresis, tryptase, double-stranded DNA antibody, human T-lymphotrophic virus I/II, stool ova, and parasites, as well as a Strongyloides antibody titer, were performed; all were within reference range. His antinuclear antibody level was mildly elevated at 1:160, but the patient had no clinical manifestations of lupus. Given this negative workup, the most likely explanation for the hypereosinophilia was a reactive process secondary to the extreme inflammatory state.

The patient was started on isotretinoin 40 mg daily in addition to urea cream 40% mixed with clobetasol ointment at least once daily to the extremities. Hydrocortisone ointment 2.5% and petrolatum-based ointment were applied to the face, and hydroxyzine was used as needed for pruritus. One month after initiating isotretinoin, erythema had decreased and a repeat complete blood cell count with differential showed a decrease of eosinophils to 14.7% and an absolute eosinophil count of 1.56×10⁹/L. After 2 months of therapy, the patient showed remarkable improvement. After 3.5 months of therapy, the keratoderma on the palms and soles was almost completely resolved, the follicular-based papules disappeared, and the patient had no areas of lichenification (Figures 1B and 2B). After 5 months of therapy, the patient experienced resolution of the PRP, except for residual facial erythema. His eosinophil count continued to trend downward during these 5 months, reaching 7.6% with an absolute eosinophil count of 0.93×10⁹/L. Three years after the initial onset of the rash and 2 years after completing isotretinoin, his eosinophil level was normal at 5.3% with an absolute eosinophil count of 0.7×10⁹/L.

We present a case of PRP and severe eosinophilia. We initially considered a second disease process to explain the extremely elevated eosinophil count; however, a negative eosinophilia workup and simultaneous resolution of these problems suggest that the eosinophilia was related to the severity of the PRP.

To the Editor:

A 63-year-old man presented with a prior diagnosis of severe psoriasis affecting the extremities, neck, face, and scalp of 1 year’s duration. He reported pain, itching, and swelling in the affected areas. He felt the rash was worst on the hands and feet, and pain made performing activities of daily living difficult. His treatment regimen at presentation included triamcinolone cream 0.1% and azathioprine 150 mg daily as prescribed by an outside dermatologist without any response. Physical examination revealed diffuse erythema with lichenification and thick, white, flaking scale on the arms and legs (Figure 1A), face, neck, palms, and soles with islands of sparing. Multiple salmon-colored, follicular-based papules topped with central hyperkeratosis were scattered on these same areas. The palms and soles had severe confluent keratoderma (Figure 2A). Histologic examination of a follicular-based papule showed foci of parakeratosis and hypergranulosis consistent with the patient’s clinical picture of pityriasis rubra pilaris (PRP).

Baseline laboratory tests at the time of PRP diagnosis revealed 20.8% eosinophils (reference range, 0%–7%) and an absolute eosinophil count of 2.17×10⁹/L (reference range, 0–0.7×10⁹/L). Laboratory test results from an outside dermatologist conducted 10 to 12 months prior to the current presentation showed 12% eosinophils with a white blood cell count of 8.9×10⁹/L (reference range, 4.5–11.0×10⁹/L) around the time of rash onset and before treatment with azathioprine, making a drug reaction an unlikely cause of the eosinophilia.

After consulting with the hematology department, a hypereosinophilia workup including erythrocyte sedimentation rate, lactate dehydrogenase, serum protein electrophoresis, urine protein electrophoresis, tryptase, double-stranded DNA antibody, human T-lymphotrophic virus I/II, stool ova, and parasites, as well as a Strongyloides antibody titer, were performed; all were within reference range. His antinuclear antibody level was mildly elevated at 1:160, but the patient had no clinical manifestations of lupus. Given this negative workup, the most likely explanation for the hypereosinophilia was a reactive process secondary to the extreme inflammatory state.

The patient was started on isotretinoin 40 mg daily in addition to urea cream 40% mixed with clobetasol ointment at least once daily to the extremities. Hydrocortisone ointment 2.5% and petrolatum-based ointment were applied to the face, and hydroxyzine was used as needed for pruritus. One month after initiating isotretinoin, erythema had decreased and a repeat complete blood cell count with differential showed a decrease of eosinophils to 14.7% and an absolute eosinophil count of 1.56×10⁹/L. After 2 months of therapy, the patient showed remarkable improvement. After 3.5 months of therapy, the keratoderma on the palms and soles was almost completely resolved, the follicular-based papules disappeared, and the patient had no areas of lichenification (Figures 1B and 2B). After 5 months of therapy, the patient experienced resolution of the PRP, except for residual facial erythema. His eosinophil count continued to trend downward during these 5 months, reaching 7.6% with an absolute eosinophil count of 0.93×10⁹/L. Three years after the initial onset of the rash and 2 years after completing isotretinoin, his eosinophil level was normal at 5.3% with an absolute eosinophil count of 0.7×10⁹/L.

We present a case of PRP and severe eosinophilia. We initially considered a second disease process to explain the extremely elevated eosinophil count; however, a negative eosinophilia workup and simultaneous resolution of these problems suggest that the eosinophilia was related to the severity of the PRP.

To the Editor:

A 63-year-old man presented with a prior diagnosis of severe psoriasis affecting the extremities, neck, face, and scalp of 1 year’s duration. He reported pain, itching, and swelling in the affected areas. He felt the rash was worst on the hands and feet, and pain made performing activities of daily living difficult. His treatment regimen at presentation included triamcinolone cream 0.1% and azathioprine 150 mg daily as prescribed by an outside dermatologist without any response. Physical examination revealed diffuse erythema with lichenification and thick, white, flaking scale on the arms and legs (Figure 1A), face, neck, palms, and soles with islands of sparing. Multiple salmon-colored, follicular-based papules topped with central hyperkeratosis were scattered on these same areas. The palms and soles had severe confluent keratoderma (Figure 2A). Histologic examination of a follicular-based papule showed foci of parakeratosis and hypergranulosis consistent with the patient’s clinical picture of pityriasis rubra pilaris (PRP).

Baseline laboratory tests at the time of PRP diagnosis revealed 20.8% eosinophils (reference range, 0%–7%) and an absolute eosinophil count of 2.17×10⁹/L (reference range, 0–0.7×10⁹/L). Laboratory test results from an outside dermatologist conducted 10 to 12 months prior to the current presentation showed 12% eosinophils with a white blood cell count of 8.9×10⁹/L (reference range, 4.5–11.0×10⁹/L) around the time of rash onset and before treatment with azathioprine, making a drug reaction an unlikely cause of the eosinophilia.

After consulting with the hematology department, a hypereosinophilia workup including erythrocyte sedimentation rate, lactate dehydrogenase, serum protein electrophoresis, urine protein electrophoresis, tryptase, double-stranded DNA antibody, human T-lymphotrophic virus I/II, stool ova, and parasites, as well as a Strongyloides antibody titer, were performed; all were within reference range. His antinuclear antibody level was mildly elevated at 1:160, but the patient had no clinical manifestations of lupus. Given this negative workup, the most likely explanation for the hypereosinophilia was a reactive process secondary to the extreme inflammatory state.

The patient was started on isotretinoin 40 mg daily in addition to urea cream 40% mixed with clobetasol ointment at least once daily to the extremities. Hydrocortisone ointment 2.5% and petrolatum-based ointment were applied to the face, and hydroxyzine was used as needed for pruritus. One month after initiating isotretinoin, erythema had decreased and a repeat complete blood cell count with differential showed a decrease of eosinophils to 14.7% and an absolute eosinophil count of 1.56×10⁹/L. After 2 months of therapy, the patient showed remarkable improvement. After 3.5 months of therapy, the keratoderma on the palms and soles was almost completely resolved, the follicular-based papules disappeared, and the patient had no areas of lichenification (Figures 1B and 2B). After 5 months of therapy, the patient experienced resolution of the PRP, except for residual facial erythema. His eosinophil count continued to trend downward during these 5 months, reaching 7.6% with an absolute eosinophil count of 0.93×10⁹/L. Three years after the initial onset of the rash and 2 years after completing isotretinoin, his eosinophil level was normal at 5.3% with an absolute eosinophil count of 0.7×10⁹/L.

We present a case of PRP and severe eosinophilia. We initially considered a second disease process to explain the extremely elevated eosinophil count; however, a negative eosinophilia workup and simultaneous resolution of these problems suggest that the eosinophilia was related to the severity of the PRP.

To the Editor:

We present a case of Mycobacterium chelonae-abscessus cutaneous infection in a sporotrichoid pattern, a rare presentation most often found in immunocompromised patients. A 34-year-old man with lupus nephritis who was taking oral prednisone, mycophenolate mofetil, and hydroxychloroquine presented with multiple erythematous fluctuant nodules and plaques on the left volar forearm in a sporotrichoid pattern of 3 months’ duration (Figure, A). He denied recent travel, exposure to fish or fish tanks, and penetrating wounds. Punch biopsy showed granulomatous inflammation and scarring with negative tissue cultures. Repeat biopsies and cultures were obtained when the lesions increased in number over 2 months.

Final biopsy showed upper dermal granulomatous inflammation with karyorrhectic debris, suggesting infection, and acid-fast bacilli. Culture grew M chelonae-abscessus on Löwenstein-Jensen agar at 37°C and blood culture media from which the complex was identified using high-performance liquid chromatography. Empiric therapy with renal dosing based on the Infectious Diseases Society of America statement of susceptibilities¹ was initiated with clarithromycin, doxycycline, and ciprofloxacin for 4 months. Furthermore, the prednisone dose was tapered to 7.5 mg daily. Two months later, the lesions regressed and ciprofloxacin was discontinued (Figure, B).

The sporotrichoid spread of nodules suggests infection with mycobacteria, Sporothrix schenckii, Leishmania, Francisella tularensis, or Nocardia. Most cultures for nontuberculous mycobacteria will grow on Löwenstein-Jensen agar between 28°C and 37°C. Runyon rapidly growing (group IV) mycobacteria are defined by their ubiquitous presence in the environment and ability to develop colonies in 7 days.² Cutaneous infections are increasing in prevalence, as reported in a retrospective study spanning nearly 30 years.³ The presentation is variable but often includes the distal extremities and usually is a nodule, ulcer, or abscess at a single site; a sporotrichoid pattern is more rare. Preceding skin trauma is the major risk factor for immunocompetent hosts, and the infection can spontaneously resolve in 8 to 12 months.¹ In contrast, immunosuppressed patients may have no known source of infection and often have a progressive course with an increasing number of lesions and increased time until clearance.⁴

It is difficult to differentiate M chelonae and M abscessus based on growth characteristics, and they share the same 16S ribosomal RNA sequence commonly used to differentiate other mycobacterial species.²Mycobacterium abscessus can be more difficult to treat, thus distinction via polymerase chain reaction of the heat-shock protein 65 gene, hsp65, can be valuable in cases recalcitrant to initial therapy.¹

The likelihood of M chelonae and M abscessus isolates to be initially sensitive to clarithromycin is 100%,¹ and this antibiotic remains the cornerstone of therapy. A clinical trial of treatments for M chelonae-abscessus found that clarithromycin monotherapy can be successful or complicated by resistance⁵; therefore, multidrug therapy is recommended. The antibiotic regimen for our patient was chosen to limit renal toxicity.

In summary, we report a case of M chelonae-abscessus cutaneous infection in a sporotrichoid pattern in a patient with lupus nephritis on immunosuppressive drugs. As the incidence of rapidly growing mycobacterial cutaneous infections rises, dermatologists must be aware of this pattern of infection.

To the Editor:

We present a case of Mycobacterium chelonae-abscessus cutaneous infection in a sporotrichoid pattern, a rare presentation most often found in immunocompromised patients. A 34-year-old man with lupus nephritis who was taking oral prednisone, mycophenolate mofetil, and hydroxychloroquine presented with multiple erythematous fluctuant nodules and plaques on the left volar forearm in a sporotrichoid pattern of 3 months’ duration (Figure, A). He denied recent travel, exposure to fish or fish tanks, and penetrating wounds. Punch biopsy showed granulomatous inflammation and scarring with negative tissue cultures. Repeat biopsies and cultures were obtained when the lesions increased in number over 2 months.

Final biopsy showed upper dermal granulomatous inflammation with karyorrhectic debris, suggesting infection, and acid-fast bacilli. Culture grew M chelonae-abscessus on Löwenstein-Jensen agar at 37°C and blood culture media from which the complex was identified using high-performance liquid chromatography. Empiric therapy with renal dosing based on the Infectious Diseases Society of America statement of susceptibilities¹ was initiated with clarithromycin, doxycycline, and ciprofloxacin for 4 months. Furthermore, the prednisone dose was tapered to 7.5 mg daily. Two months later, the lesions regressed and ciprofloxacin was discontinued (Figure, B).

The sporotrichoid spread of nodules suggests infection with mycobacteria, Sporothrix schenckii, Leishmania, Francisella tularensis, or Nocardia. Most cultures for nontuberculous mycobacteria will grow on Löwenstein-Jensen agar between 28°C and 37°C. Runyon rapidly growing (group IV) mycobacteria are defined by their ubiquitous presence in the environment and ability to develop colonies in 7 days.² Cutaneous infections are increasing in prevalence, as reported in a retrospective study spanning nearly 30 years.³ The presentation is variable but often includes the distal extremities and usually is a nodule, ulcer, or abscess at a single site; a sporotrichoid pattern is more rare. Preceding skin trauma is the major risk factor for immunocompetent hosts, and the infection can spontaneously resolve in 8 to 12 months.¹ In contrast, immunosuppressed patients may have no known source of infection and often have a progressive course with an increasing number of lesions and increased time until clearance.⁴

It is difficult to differentiate M chelonae and M abscessus based on growth characteristics, and they share the same 16S ribosomal RNA sequence commonly used to differentiate other mycobacterial species.²Mycobacterium abscessus can be more difficult to treat, thus distinction via polymerase chain reaction of the heat-shock protein 65 gene, hsp65, can be valuable in cases recalcitrant to initial therapy.¹

The likelihood of M chelonae and M abscessus isolates to be initially sensitive to clarithromycin is 100%,¹ and this antibiotic remains the cornerstone of therapy. A clinical trial of treatments for M chelonae-abscessus found that clarithromycin monotherapy can be successful or complicated by resistance⁵; therefore, multidrug therapy is recommended. The antibiotic regimen for our patient was chosen to limit renal toxicity.

In summary, we report a case of M chelonae-abscessus cutaneous infection in a sporotrichoid pattern in a patient with lupus nephritis on immunosuppressive drugs. As the incidence of rapidly growing mycobacterial cutaneous infections rises, dermatologists must be aware of this pattern of infection.

To the Editor:

We present a case of Mycobacterium chelonae-abscessus cutaneous infection in a sporotrichoid pattern, a rare presentation most often found in immunocompromised patients. A 34-year-old man with lupus nephritis who was taking oral prednisone, mycophenolate mofetil, and hydroxychloroquine presented with multiple erythematous fluctuant nodules and plaques on the left volar forearm in a sporotrichoid pattern of 3 months’ duration (Figure, A). He denied recent travel, exposure to fish or fish tanks, and penetrating wounds. Punch biopsy showed granulomatous inflammation and scarring with negative tissue cultures. Repeat biopsies and cultures were obtained when the lesions increased in number over 2 months.

Final biopsy showed upper dermal granulomatous inflammation with karyorrhectic debris, suggesting infection, and acid-fast bacilli. Culture grew M chelonae-abscessus on Löwenstein-Jensen agar at 37°C and blood culture media from which the complex was identified using high-performance liquid chromatography. Empiric therapy with renal dosing based on the Infectious Diseases Society of America statement of susceptibilities¹ was initiated with clarithromycin, doxycycline, and ciprofloxacin for 4 months. Furthermore, the prednisone dose was tapered to 7.5 mg daily. Two months later, the lesions regressed and ciprofloxacin was discontinued (Figure, B).

The sporotrichoid spread of nodules suggests infection with mycobacteria, Sporothrix schenckii, Leishmania, Francisella tularensis, or Nocardia. Most cultures for nontuberculous mycobacteria will grow on Löwenstein-Jensen agar between 28°C and 37°C. Runyon rapidly growing (group IV) mycobacteria are defined by their ubiquitous presence in the environment and ability to develop colonies in 7 days.² Cutaneous infections are increasing in prevalence, as reported in a retrospective study spanning nearly 30 years.³ The presentation is variable but often includes the distal extremities and usually is a nodule, ulcer, or abscess at a single site; a sporotrichoid pattern is more rare. Preceding skin trauma is the major risk factor for immunocompetent hosts, and the infection can spontaneously resolve in 8 to 12 months.¹ In contrast, immunosuppressed patients may have no known source of infection and often have a progressive course with an increasing number of lesions and increased time until clearance.⁴

It is difficult to differentiate M chelonae and M abscessus based on growth characteristics, and they share the same 16S ribosomal RNA sequence commonly used to differentiate other mycobacterial species.²Mycobacterium abscessus can be more difficult to treat, thus distinction via polymerase chain reaction of the heat-shock protein 65 gene, hsp65, can be valuable in cases recalcitrant to initial therapy.¹

The likelihood of M chelonae and M abscessus isolates to be initially sensitive to clarithromycin is 100%,¹ and this antibiotic remains the cornerstone of therapy. A clinical trial of treatments for M chelonae-abscessus found that clarithromycin monotherapy can be successful or complicated by resistance⁵; therefore, multidrug therapy is recommended. The antibiotic regimen for our patient was chosen to limit renal toxicity.

In summary, we report a case of M chelonae-abscessus cutaneous infection in a sporotrichoid pattern in a patient with lupus nephritis on immunosuppressive drugs. As the incidence of rapidly growing mycobacterial cutaneous infections rises, dermatologists must be aware of this pattern of infection.

The Food and Drug Administration is changing the way it approves orphan drugs after revelations that drugmakers may be abusing a law intended to help patients with rare diseases.

In a blog post Sept. 12, FDA Commissioner Scott Gottlieb, MD, said he wants to ensure financial incentives are granted “in a way that’s consistent with the manner Congress intended” when the Orphan Drug Act was passed in 1983. That legislation gave drugmakers a package of incentives, including tax credits, user-fee waivers and 7 years of market exclusivity if they developed medicines for rare diseases.

A Kaiser Health News investigation published in January 2017 found many drugs that now have orphan status aren’t entirely new. Of about 450 drugs that have won orphan approval since 1983, more than 70 were drugs first approved by the FDA for mass-market use. Those include rosuvastatin (Crestor), aripiprazole (Abilify), and adalimumab (Humira), the world’s best-selling drug.

Dr. Gottlieb announced plans to close a loophole that allows manufacturers to skip pediatric testing requirements when developing a common-disease drug for orphan use in children. He also signaled that bigger changes are being considered, announcing a public meeting to explore issues raised by scientific advances, such as the increase in precision medicine and biologics.

“We need to make sure our policies take notice of all of these new challenges and opportunities,” he wrote. Dr. Gottlieb, through his agency, declined multiple requests for interviews.

Over the years, drugmakers have fueled a boom in orphan drugs, which often carry six-figure price tags. Nearly half of the new drugs approved by the FDA are now for rare diseases – even though many of them also treat and are marketed for common diseases.

Dr. Gottlieb became commissioner in May, a few months after three key Republican senators called for a federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Office agreed to investigate.

The GAO has yet to begin its investigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs.

Those include:

• Eliminating a backlog in drug applications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also skyrocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drugmakers won orphan status.
• Mandating that drugmakers prove their medicine is clinically superior before getting the market exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically superior to get the incentives.
• Closing the loophole for pediatric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and last month Congress mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pediatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, said Sept. 12 that orphan drugs are “still mostly exempt from pediatric study requirements … children deserve access to safe, effective medications.”

Martin Makary, MD, who wrote a critical 2015 paper on orphan approvals, said the changes at the agency indicate that Dr. Gottlieb seems “concerned about all the right things. The government does a lot of lip service in general. This is not lip service.”

The restructuring has been swift in some ways.

Sandra Heibel, PhD, a senior consultant at Haffner Associates, a firm that helps companies submit orphan drug applications, noted that the approval process for designations definitely sped up over the summer, and “we are absolutely getting responses from the FDA back in 90 days. That has come through.”

Other changes to the agency, though, will evolve slowly. For example, the orphan drug office has begun reaching across the FDA’s divisions for help in reviewing drugs. In May, the FDA’s orphan reviews began to work with the office of pediatric therapeutics to review pediatric applications – ideally increasing the expertise applied when considering a company’s request for orphan drug use in children.

In an interview, FDA confirmed that Dr. Gottlieb’s orphan modernization plan is part of a larger effort to increase competition and decrease drug prices. One focus is on targeted drugs – especially those that affect rare diseases or diseases for which there is no effective therapy, the agency said.

“Such drugs present some of the biggest opportunities in medicine to treat and cure debilitating and very costly diseases,” the agency stated.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

The Food and Drug Administration is changing the way it approves orphan drugs after revelations that drugmakers may be abusing a law intended to help patients with rare diseases.

In a blog post Sept. 12, FDA Commissioner Scott Gottlieb, MD, said he wants to ensure financial incentives are granted “in a way that’s consistent with the manner Congress intended” when the Orphan Drug Act was passed in 1983. That legislation gave drugmakers a package of incentives, including tax credits, user-fee waivers and 7 years of market exclusivity if they developed medicines for rare diseases.

A Kaiser Health News investigation published in January 2017 found many drugs that now have orphan status aren’t entirely new. Of about 450 drugs that have won orphan approval since 1983, more than 70 were drugs first approved by the FDA for mass-market use. Those include rosuvastatin (Crestor), aripiprazole (Abilify), and adalimumab (Humira), the world’s best-selling drug.

Dr. Gottlieb announced plans to close a loophole that allows manufacturers to skip pediatric testing requirements when developing a common-disease drug for orphan use in children. He also signaled that bigger changes are being considered, announcing a public meeting to explore issues raised by scientific advances, such as the increase in precision medicine and biologics.

“We need to make sure our policies take notice of all of these new challenges and opportunities,” he wrote. Dr. Gottlieb, through his agency, declined multiple requests for interviews.

Over the years, drugmakers have fueled a boom in orphan drugs, which often carry six-figure price tags. Nearly half of the new drugs approved by the FDA are now for rare diseases – even though many of them also treat and are marketed for common diseases.

Dr. Gottlieb became commissioner in May, a few months after three key Republican senators called for a federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Office agreed to investigate.

The GAO has yet to begin its investigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs.

Those include:

• Eliminating a backlog in drug applications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also skyrocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drugmakers won orphan status.
• Mandating that drugmakers prove their medicine is clinically superior before getting the market exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically superior to get the incentives.
• Closing the loophole for pediatric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and last month Congress mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pediatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, said Sept. 12 that orphan drugs are “still mostly exempt from pediatric study requirements … children deserve access to safe, effective medications.”

Martin Makary, MD, who wrote a critical 2015 paper on orphan approvals, said the changes at the agency indicate that Dr. Gottlieb seems “concerned about all the right things. The government does a lot of lip service in general. This is not lip service.”

The restructuring has been swift in some ways.

Sandra Heibel, PhD, a senior consultant at Haffner Associates, a firm that helps companies submit orphan drug applications, noted that the approval process for designations definitely sped up over the summer, and “we are absolutely getting responses from the FDA back in 90 days. That has come through.”

Other changes to the agency, though, will evolve slowly. For example, the orphan drug office has begun reaching across the FDA’s divisions for help in reviewing drugs. In May, the FDA’s orphan reviews began to work with the office of pediatric therapeutics to review pediatric applications – ideally increasing the expertise applied when considering a company’s request for orphan drug use in children.

In an interview, FDA confirmed that Dr. Gottlieb’s orphan modernization plan is part of a larger effort to increase competition and decrease drug prices. One focus is on targeted drugs – especially those that affect rare diseases or diseases for which there is no effective therapy, the agency said.

“Such drugs present some of the biggest opportunities in medicine to treat and cure debilitating and very costly diseases,” the agency stated.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

The Food and Drug Administration is changing the way it approves orphan drugs after revelations that drugmakers may be abusing a law intended to help patients with rare diseases.

In a blog post Sept. 12, FDA Commissioner Scott Gottlieb, MD, said he wants to ensure financial incentives are granted “in a way that’s consistent with the manner Congress intended” when the Orphan Drug Act was passed in 1983. That legislation gave drugmakers a package of incentives, including tax credits, user-fee waivers and 7 years of market exclusivity if they developed medicines for rare diseases.

A Kaiser Health News investigation published in January 2017 found many drugs that now have orphan status aren’t entirely new. Of about 450 drugs that have won orphan approval since 1983, more than 70 were drugs first approved by the FDA for mass-market use. Those include rosuvastatin (Crestor), aripiprazole (Abilify), and adalimumab (Humira), the world’s best-selling drug.

Dr. Gottlieb announced plans to close a loophole that allows manufacturers to skip pediatric testing requirements when developing a common-disease drug for orphan use in children. He also signaled that bigger changes are being considered, announcing a public meeting to explore issues raised by scientific advances, such as the increase in precision medicine and biologics.

“We need to make sure our policies take notice of all of these new challenges and opportunities,” he wrote. Dr. Gottlieb, through his agency, declined multiple requests for interviews.

Over the years, drugmakers have fueled a boom in orphan drugs, which often carry six-figure price tags. Nearly half of the new drugs approved by the FDA are now for rare diseases – even though many of them also treat and are marketed for common diseases.

Dr. Gottlieb became commissioner in May, a few months after three key Republican senators called for a federal investigation into potential abuses of the Orphan Drug Act, and the Government Accountability Office agreed to investigate.

The GAO has yet to begin its investigation, saying it doesn’t expect to start work until late this year, when staff is available. Regardless, in late June, Dr. Gottlieb announced what would be the first in a series of updates that shift the way the FDA handles orphan drugs.

Those include:

• Eliminating a backlog in drug applications for orphan designation or status. Getting a designation is a critical first step if a company wants to win orphan incentives once the drug is approved for treatment use. And, much like the rise in approvals, the requests by companies to get drugs designated with orphan status has also skyrocketed. Dr. Gottlieb said in June that he wanted to get rid of the backlog; his blog post noted the effort was complete. About half of the 200 applications from drugmakers won orphan status.
• Mandating that drugmakers prove their medicine is clinically superior before getting the market exclusivity that comes with orphan drug status. The agency had lost a lawsuit in which a company said it was owed the exclusivity period regardless of whether its medicine was better. And two more lawsuits had been filed by Eagle Pharmaceuticals and United Therapeutics. The FDA Reauthorization Act, which passed in August, made it law that a drug has to be clinically superior to get the incentives.
• Closing the loophole for pediatric orphan drugs by requiring all drugs approved for common adult diseases, like inflammatory bowel disease, undergo pediatric testing when getting approval as a pediatric orphan drug. Pediatric testing is not required for orphan drugs, and last month Congress mandated that orphan drugs for cancer be tested for children. Still, the American Academy of Pediatrics celebrated the proposed change but warned it was only a first step. Bridgette Jones, MD, chair of American Academy of Pediatrics Committee on Drugs, said Sept. 12 that orphan drugs are “still mostly exempt from pediatric study requirements … children deserve access to safe, effective medications.”

Martin Makary, MD, who wrote a critical 2015 paper on orphan approvals, said the changes at the agency indicate that Dr. Gottlieb seems “concerned about all the right things. The government does a lot of lip service in general. This is not lip service.”

The restructuring has been swift in some ways.

Sandra Heibel, PhD, a senior consultant at Haffner Associates, a firm that helps companies submit orphan drug applications, noted that the approval process for designations definitely sped up over the summer, and “we are absolutely getting responses from the FDA back in 90 days. That has come through.”

Other changes to the agency, though, will evolve slowly. For example, the orphan drug office has begun reaching across the FDA’s divisions for help in reviewing drugs. In May, the FDA’s orphan reviews began to work with the office of pediatric therapeutics to review pediatric applications – ideally increasing the expertise applied when considering a company’s request for orphan drug use in children.

In an interview, FDA confirmed that Dr. Gottlieb’s orphan modernization plan is part of a larger effort to increase competition and decrease drug prices. One focus is on targeted drugs – especially those that affect rare diseases or diseases for which there is no effective therapy, the agency said.

“Such drugs present some of the biggest opportunities in medicine to treat and cure debilitating and very costly diseases,” the agency stated.
 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Click here to Read Supplement.

Topics include:

• The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) initiative
• Ramifications for future pediatric AED approvals by the FDA
• Future PEACE initiatives

Authors:

O’NEILL D’CRUZ, MD, MBA, FAAN

Pediatric Epileptologist and Neurologist

OD Consulting and Neurological Services, PLLC

Chapel Hill, North Carolina

JOHN B. BODENSTEINER, MD

Consultant in Child and Adolescent Neurology and

Professor of Neurology and Pediatrics

Mayo Clinic and Mayo Medical School

Rochester, Minnesota

Click here to Read Supplement.

Click here to Read Supplement.

Topics include:

• The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) initiative
• Ramifications for future pediatric AED approvals by the FDA
• Future PEACE initiatives

Authors:

O’NEILL D’CRUZ, MD, MBA, FAAN

Pediatric Epileptologist and Neurologist

OD Consulting and Neurological Services, PLLC

Chapel Hill, North Carolina

JOHN B. BODENSTEINER, MD

Consultant in Child and Adolescent Neurology and

Professor of Neurology and Pediatrics

Mayo Clinic and Mayo Medical School

Rochester, Minnesota

Click here to Read Supplement.

Click here to Read Supplement.

Topics include:

• The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) initiative
• Ramifications for future pediatric AED approvals by the FDA
• Future PEACE initiatives

Authors:

O’NEILL D’CRUZ, MD, MBA, FAAN

Pediatric Epileptologist and Neurologist

OD Consulting and Neurological Services, PLLC

Chapel Hill, North Carolina

JOHN B. BODENSTEINER, MD

Consultant in Child and Adolescent Neurology and

Professor of Neurology and Pediatrics

Mayo Clinic and Mayo Medical School

Rochester, Minnesota

Click here to Read Supplement.

This year’s annual Assocaition of VA Hematology and Oncology (AVAHO) conference offers nearly 50 sessions over the course of 3 days that focus on providing evidence-based hematology and oncology practice. According to AVAHO President Mary Thomas, MS, “I am hopeful that people come away from this meeting with a different conception of evidence-based practice and how they might apply it.”

John P.A. Ioannidis, MD, DSc, the C. F. Rehnborg Professor in Disease Prevention in the School of Medicine and Professor of Health Research and Policy (Epidemiology) at Stanford University will offer the opening keynote address on integrating evidence into patient care. According to Ms. Thomas, Dr. Ioannidis is a “provocative speaker” who may challenge conceptions and execution of evidence-based practice. Other keynote addresses will be presented by Steve Harvey, vice president of IBM Watson Health, to discuss the use of artificial intelligence in health care and specifically cancer care and playwright Maggie Edson, winner of a Pulitzer Prize for the play “Wit.” Ms. Edson’s presentation should provide a unique look at the patient experience and a new consideration of patients’ perspectives and values.

 The full agenda can be found here: http://www.avaho.org/2017-annual-meeting.html

This year’s annual Assocaition of VA Hematology and Oncology (AVAHO) conference offers nearly 50 sessions over the course of 3 days that focus on providing evidence-based hematology and oncology practice. According to AVAHO President Mary Thomas, MS, “I am hopeful that people come away from this meeting with a different conception of evidence-based practice and how they might apply it.”

John P.A. Ioannidis, MD, DSc, the C. F. Rehnborg Professor in Disease Prevention in the School of Medicine and Professor of Health Research and Policy (Epidemiology) at Stanford University will offer the opening keynote address on integrating evidence into patient care. According to Ms. Thomas, Dr. Ioannidis is a “provocative speaker” who may challenge conceptions and execution of evidence-based practice. Other keynote addresses will be presented by Steve Harvey, vice president of IBM Watson Health, to discuss the use of artificial intelligence in health care and specifically cancer care and playwright Maggie Edson, winner of a Pulitzer Prize for the play “Wit.” Ms. Edson’s presentation should provide a unique look at the patient experience and a new consideration of patients’ perspectives and values.

 The full agenda can be found here: http://www.avaho.org/2017-annual-meeting.html

This year’s annual Assocaition of VA Hematology and Oncology (AVAHO) conference offers nearly 50 sessions over the course of 3 days that focus on providing evidence-based hematology and oncology practice. According to AVAHO President Mary Thomas, MS, “I am hopeful that people come away from this meeting with a different conception of evidence-based practice and how they might apply it.”

John P.A. Ioannidis, MD, DSc, the C. F. Rehnborg Professor in Disease Prevention in the School of Medicine and Professor of Health Research and Policy (Epidemiology) at Stanford University will offer the opening keynote address on integrating evidence into patient care. According to Ms. Thomas, Dr. Ioannidis is a “provocative speaker” who may challenge conceptions and execution of evidence-based practice. Other keynote addresses will be presented by Steve Harvey, vice president of IBM Watson Health, to discuss the use of artificial intelligence in health care and specifically cancer care and playwright Maggie Edson, winner of a Pulitzer Prize for the play “Wit.” Ms. Edson’s presentation should provide a unique look at the patient experience and a new consideration of patients’ perspectives and values.

 The full agenda can be found here: http://www.avaho.org/2017-annual-meeting.html

From Friday September 15 through Sunday September 17, the Association of VA Hematology and Oncology (AVAHO) will be in Denver, Colorado for their 13^th Annual Meeting. If you are looking for something to do in the Mile High City outside of the convention center, here are 4 ways to get the most of a little time to spare.

1. Know the best way to get around

Transportation in a new city can be a stressor, especially when you’re on a compressed schedule. In Denver, there are multiple modes of public transportation with inexpensive price tags. The Regional Transportation District (RTD) has bus and light rail options that take you around Denver and the surrounding areas. For only $5.20, you can get a 1-day pass that allows you to hop on and off as you please. Activity duty U.S. military members ride for free on all RTD services. If you want a more open air option to see the city, try Denver B-cycle. The city-wide bike rental allows you to rent a bike and drop it off at any of the racks around town. Just buy an Access Pass for $9 and you’re good to go!

For more info on RTD, visit http://www.rtd-denver.com/index.shtml

For info in Denver B-cycle, visit https://www.denverbcycle.com/

2. Immerse yourself in culture

Denver has a rich culture and history worth exploring. All around the city there are public art exhibitions for viewing, from the 40-foot tall Blue Bear at the Colorado Convention Center to vibrant murals like the “Love This City” series in 3 different art districts. Information on walking tours is available here. Every 2 years, a week long arts and culture festival called The Biennial of the Americas is held in Denver. Fortunately, the biennial coincides with the AVAHO meeting and offers the opportunity to experience symposiums and concerts by artists, leaders, innovators, and experts from North, South, and Central America and the Caribbean.

For more about Denver Arts and culture visit https://www.denver.org/things-to-do/denver-arts-culture/

3. Eat well

Sometimes the best way to enjoy a city is by eating your way around it. In Denver you can get a taste of the old west when trying Rocky Mountain oysters (bull, sheep, or pig testicles) and locally brewed beers or experience a “smooth as silk, tough as nails” master sommelier like Bobby Stuckey. There are 4 thriving foodie neighborhoods; RiNo where the hipsters get sushi and live jazz, LoHi that continues to be a haven for group outings, Uptown for a mix of old and new school Americana eats, and LoDo as a drinking and dining hub perfect for lunch or dinner. All are easy to access from the meeting via public transportation, taxi, or a short walk.

For more about eating around Denver visit https://denver.eater.com/2017/8/29/16180854/best-food-denver-restaurants-city-guide or https://www.thrillist.com/eat/denver

4. Enjoy the scenery

If nature and fresh air is where you find solace, Denver has no shortage of places for you to experience and enjoy. The Denver Parks and Recreation was founded in 1868 and has about 20,00 acres of mountain parkland and urban parks to visit and more than 80 miles of trails within the city. Just steps from the meeting there are paths for walking or jogging that wind along the South Platte River and Cherry Creek. The architecture in Denver is also a great way take in the scenery and a little bit of history too. There’s a healthy mix of old styles like Beaux Arts at Union Station and French Gothic at Cathedral Basilica of the Immaculate Conception, with new modern designs in the Denver Art Museum: Frederic C. Hamilton Building and the Boettcher Memorial Tropical Conservatory. Whether marveling at nature or buildings, there’s plenty to see.

For more on Denver Parks and Recreation, visit https://www.denvergov.org/content/denvergov/en/denver-parks-and-recreation.html

From Friday September 15 through Sunday September 17, the Association of VA Hematology and Oncology (AVAHO) will be in Denver, Colorado for their 13^th Annual Meeting. If you are looking for something to do in the Mile High City outside of the convention center, here are 4 ways to get the most of a little time to spare.

1. Know the best way to get around

Transportation in a new city can be a stressor, especially when you’re on a compressed schedule. In Denver, there are multiple modes of public transportation with inexpensive price tags. The Regional Transportation District (RTD) has bus and light rail options that take you around Denver and the surrounding areas. For only $5.20, you can get a 1-day pass that allows you to hop on and off as you please. Activity duty U.S. military members ride for free on all RTD services. If you want a more open air option to see the city, try Denver B-cycle. The city-wide bike rental allows you to rent a bike and drop it off at any of the racks around town. Just buy an Access Pass for $9 and you’re good to go!

For more info on RTD, visit http://www.rtd-denver.com/index.shtml

For info in Denver B-cycle, visit https://www.denverbcycle.com/

2. Immerse yourself in culture

Denver has a rich culture and history worth exploring. All around the city there are public art exhibitions for viewing, from the 40-foot tall Blue Bear at the Colorado Convention Center to vibrant murals like the “Love This City” series in 3 different art districts. Information on walking tours is available here. Every 2 years, a week long arts and culture festival called The Biennial of the Americas is held in Denver. Fortunately, the biennial coincides with the AVAHO meeting and offers the opportunity to experience symposiums and concerts by artists, leaders, innovators, and experts from North, South, and Central America and the Caribbean.

For more about Denver Arts and culture visit https://www.denver.org/things-to-do/denver-arts-culture/

3. Eat well

Sometimes the best way to enjoy a city is by eating your way around it. In Denver you can get a taste of the old west when trying Rocky Mountain oysters (bull, sheep, or pig testicles) and locally brewed beers or experience a “smooth as silk, tough as nails” master sommelier like Bobby Stuckey. There are 4 thriving foodie neighborhoods; RiNo where the hipsters get sushi and live jazz, LoHi that continues to be a haven for group outings, Uptown for a mix of old and new school Americana eats, and LoDo as a drinking and dining hub perfect for lunch or dinner. All are easy to access from the meeting via public transportation, taxi, or a short walk.

For more about eating around Denver visit https://denver.eater.com/2017/8/29/16180854/best-food-denver-restaurants-city-guide or https://www.thrillist.com/eat/denver

4. Enjoy the scenery

If nature and fresh air is where you find solace, Denver has no shortage of places for you to experience and enjoy. The Denver Parks and Recreation was founded in 1868 and has about 20,00 acres of mountain parkland and urban parks to visit and more than 80 miles of trails within the city. Just steps from the meeting there are paths for walking or jogging that wind along the South Platte River and Cherry Creek. The architecture in Denver is also a great way take in the scenery and a little bit of history too. There’s a healthy mix of old styles like Beaux Arts at Union Station and French Gothic at Cathedral Basilica of the Immaculate Conception, with new modern designs in the Denver Art Museum: Frederic C. Hamilton Building and the Boettcher Memorial Tropical Conservatory. Whether marveling at nature or buildings, there’s plenty to see.

For more on Denver Parks and Recreation, visit https://www.denvergov.org/content/denvergov/en/denver-parks-and-recreation.html

From Friday September 15 through Sunday September 17, the Association of VA Hematology and Oncology (AVAHO) will be in Denver, Colorado for their 13^th Annual Meeting. If you are looking for something to do in the Mile High City outside of the convention center, here are 4 ways to get the most of a little time to spare.

1. Know the best way to get around

Transportation in a new city can be a stressor, especially when you’re on a compressed schedule. In Denver, there are multiple modes of public transportation with inexpensive price tags. The Regional Transportation District (RTD) has bus and light rail options that take you around Denver and the surrounding areas. For only $5.20, you can get a 1-day pass that allows you to hop on and off as you please. Activity duty U.S. military members ride for free on all RTD services. If you want a more open air option to see the city, try Denver B-cycle. The city-wide bike rental allows you to rent a bike and drop it off at any of the racks around town. Just buy an Access Pass for $9 and you’re good to go!

For more info on RTD, visit http://www.rtd-denver.com/index.shtml

For info in Denver B-cycle, visit https://www.denverbcycle.com/

2. Immerse yourself in culture

Denver has a rich culture and history worth exploring. All around the city there are public art exhibitions for viewing, from the 40-foot tall Blue Bear at the Colorado Convention Center to vibrant murals like the “Love This City” series in 3 different art districts. Information on walking tours is available here. Every 2 years, a week long arts and culture festival called The Biennial of the Americas is held in Denver. Fortunately, the biennial coincides with the AVAHO meeting and offers the opportunity to experience symposiums and concerts by artists, leaders, innovators, and experts from North, South, and Central America and the Caribbean.

For more about Denver Arts and culture visit https://www.denver.org/things-to-do/denver-arts-culture/

3. Eat well

Sometimes the best way to enjoy a city is by eating your way around it. In Denver you can get a taste of the old west when trying Rocky Mountain oysters (bull, sheep, or pig testicles) and locally brewed beers or experience a “smooth as silk, tough as nails” master sommelier like Bobby Stuckey. There are 4 thriving foodie neighborhoods; RiNo where the hipsters get sushi and live jazz, LoHi that continues to be a haven for group outings, Uptown for a mix of old and new school Americana eats, and LoDo as a drinking and dining hub perfect for lunch or dinner. All are easy to access from the meeting via public transportation, taxi, or a short walk.

For more about eating around Denver visit https://denver.eater.com/2017/8/29/16180854/best-food-denver-restaurants-city-guide or https://www.thrillist.com/eat/denver

4. Enjoy the scenery

If nature and fresh air is where you find solace, Denver has no shortage of places for you to experience and enjoy. The Denver Parks and Recreation was founded in 1868 and has about 20,00 acres of mountain parkland and urban parks to visit and more than 80 miles of trails within the city. Just steps from the meeting there are paths for walking or jogging that wind along the South Platte River and Cherry Creek. The architecture in Denver is also a great way take in the scenery and a little bit of history too. There’s a healthy mix of old styles like Beaux Arts at Union Station and French Gothic at Cathedral Basilica of the Immaculate Conception, with new modern designs in the Denver Art Museum: Frederic C. Hamilton Building and the Boettcher Memorial Tropical Conservatory. Whether marveling at nature or buildings, there’s plenty to see.

For more on Denver Parks and Recreation, visit https://www.denvergov.org/content/denvergov/en/denver-parks-and-recreation.html

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Graham Colm

Previous research has suggested that astronauts develop anemia during space flight, but a new study indicates this is not the case for astronauts on long space missions.

“There is an idea of ‘space anemia’ that is associated with space flight,” said Richard Simpson, PhD, of the University of Houston in Texas.

“However, this is based on blood samples from astronauts collected after flight, which may be influenced by various factors—for example, the stress of landing and re-adaptation to conditions on Earth.”

“For this study . . ., living, whole blood samples were collected during space flight and returned to Earth for analysis. This unique sample allowed us to track hematological parameters—such as concentrations of red blood cells, hemoglobin, or hematocrit—in astronauts on board the International Space Station during flight.”

Dr Simpson and his colleagues reported their findings in BMC Hematology.

The researchers found that, during space flight, concentrations of red blood cells (RBCs), platelets, and hemoglobin were higher compared to pre-flight levels. Hematocrit also increased significantly during space flight.

While previous studies had shown this to be the case during the first few days of flight, this is the first study to show that RBC concentrations and hematocrit remain at higher levels even after astronauts’ bodies have adapted to microgravity.

To find out how the blood of astronauts may change if they spend a long time in space, the researchers collected blood samples from 31 astronauts who spent up to 6 months on the International Space Station (ISS). There were 6 female and 25 male subjects, and their mean age was 52 (range, 38–61).

Samples were collected at 180 days and 45 days before the astronauts flew to the ISS. Blood was also collected while they were in space—during the first 2 weeks (early time point), between 2 and 4 months (mid time point), and about 6 months into the mission (late time point).

Samples were returned to Earth for analysis either in Houston or at Star City, Russia, within 48 hours of collection. Post-flight samples were collected 3 to 8 hours after landing and 30 days after the mission had ended.

Results

The researchers said some of the changes observed in the in-flight blood samples were to be expected due to the 48-hour processing delay between sample collection and analysis.

However, the team found that RBC concentration was significantly elevated at all 3 in-flight time points, when compared to the 180-day pre-mission time point (baseline). And RBC counts returned to baseline levels upon Earth landing.

The mean RBC concentrations (x 10⁶ cells/μL) were:

• 4.4 ± 0.4 (range, 3.5–5.1) at baseline
• 4.8 ± 0.5 (range, 3.9–5.7) at the early time point (P<0.05)
• 4.7 ± 0.4 (range, 3.9–5.4) at the mid time point (P<0.05)
• 4.7 ± 0.4 (range, 4.1–5.6) at the late time point (P<0.05).

Hemoglobin was elevated early in flight but returned to pre-flight levels during the mission and fell below baseline levels on landing day. The mean hemoglobin (g/dL) levels were:

• 14.1 ± 1.4 (range, 11.0–17.8) at baseline
• 15.0 ± 1.9 (range, 10.7–17.5) at the early time point (P<0.05)
• 13.5 ± 1.4 (range, 10.1–15.9) on landing day (P<0.05).

Mean corpuscular hemoglobin (MCH) decreased during the mission and was significantly lower than baseline at the late time point. However, MCH returned to pre-flight values upon landing. The mean MCH (pg) was:

• 31.7 ± 1.6 (range, 28.8–36.4) at baseline
• 31.3 ± 1.9 (range 26.3–34.0) at the late time point (P<0.05).

The researchers said they observed significant increases in mean corpuscular volume (MCV) during space flight. However, these reflect the changes observed following the 48-hour processing delay. So there were no variations in MCV attributable to space flight.

The changes observed in hematocrit during space flight were “striking,” according to the researchers. The mean hematocrit levels were:

• 40.9 ± 3.9 (range, 33.1–48.0) at baseline
• 45.9 ± 4.7 (range 38.2–52.1) at the early time point (P<0.05)
• 45.9 ± 5.5 (range 38.9–58.3) at the mid time point (P<0.05)
• 45.0 ± 2.5 (range 38.9–49.9) at the late time point (P<0.05).

Compared to pre-flight levels, hematocrit increased by 12.2% at early, 12.2% at mid, and 10.0% at late time points. In comparison, there was a 4.7% increase in hematocrit in reference samples from non-astronauts after the 48-hour processing delay.

Finally, the researchers found that platelet concentrations were elevated in flight, at the early and mid time points. However, platelets were not significantly elevated at the late time point, and they were stable upon landing.

For all of the astronauts, all blood parameters returned to pre-flight levels within 30 days of landing on Earth.

The researchers said these results are susceptible to the possible influence of dehydration or plasma volume alterations. However, the findings do suggest the increases observed in the ISS samples are partly due to a true in-flight increase in RBC count.

“Although the data does not indicate that significant anemia is present, it must be interpreted in the context of crew plasma volume during flight,” Dr Simpson said. “Overall plasma volume has been shown to be reduced during space flight, but this has not been assessed during long-duration missions.”

“In order to fully interpret the changes to RBC, hematocrit, and other parameters observed in this study, further research into plasma volume during long space missions is needed. This will be addressed in a separate, ongoing NASA investigation.”

Photo by Graham Colm

Previous research has suggested that astronauts develop anemia during space flight, but a new study indicates this is not the case for astronauts on long space missions.

“There is an idea of ‘space anemia’ that is associated with space flight,” said Richard Simpson, PhD, of the University of Houston in Texas.

“However, this is based on blood samples from astronauts collected after flight, which may be influenced by various factors—for example, the stress of landing and re-adaptation to conditions on Earth.”

“For this study . . ., living, whole blood samples were collected during space flight and returned to Earth for analysis. This unique sample allowed us to track hematological parameters—such as concentrations of red blood cells, hemoglobin, or hematocrit—in astronauts on board the International Space Station during flight.”

Dr Simpson and his colleagues reported their findings in BMC Hematology.

The researchers found that, during space flight, concentrations of red blood cells (RBCs), platelets, and hemoglobin were higher compared to pre-flight levels. Hematocrit also increased significantly during space flight.

While previous studies had shown this to be the case during the first few days of flight, this is the first study to show that RBC concentrations and hematocrit remain at higher levels even after astronauts’ bodies have adapted to microgravity.

To find out how the blood of astronauts may change if they spend a long time in space, the researchers collected blood samples from 31 astronauts who spent up to 6 months on the International Space Station (ISS). There were 6 female and 25 male subjects, and their mean age was 52 (range, 38–61).

Samples were collected at 180 days and 45 days before the astronauts flew to the ISS. Blood was also collected while they were in space—during the first 2 weeks (early time point), between 2 and 4 months (mid time point), and about 6 months into the mission (late time point).

Samples were returned to Earth for analysis either in Houston or at Star City, Russia, within 48 hours of collection. Post-flight samples were collected 3 to 8 hours after landing and 30 days after the mission had ended.

Results

The researchers said some of the changes observed in the in-flight blood samples were to be expected due to the 48-hour processing delay between sample collection and analysis.

However, the team found that RBC concentration was significantly elevated at all 3 in-flight time points, when compared to the 180-day pre-mission time point (baseline). And RBC counts returned to baseline levels upon Earth landing.

The mean RBC concentrations (x 10⁶ cells/μL) were:

• 4.4 ± 0.4 (range, 3.5–5.1) at baseline
• 4.8 ± 0.5 (range, 3.9–5.7) at the early time point (P<0.05)
• 4.7 ± 0.4 (range, 3.9–5.4) at the mid time point (P<0.05)
• 4.7 ± 0.4 (range, 4.1–5.6) at the late time point (P<0.05).

Hemoglobin was elevated early in flight but returned to pre-flight levels during the mission and fell below baseline levels on landing day. The mean hemoglobin (g/dL) levels were:

• 14.1 ± 1.4 (range, 11.0–17.8) at baseline
• 15.0 ± 1.9 (range, 10.7–17.5) at the early time point (P<0.05)
• 13.5 ± 1.4 (range, 10.1–15.9) on landing day (P<0.05).

Mean corpuscular hemoglobin (MCH) decreased during the mission and was significantly lower than baseline at the late time point. However, MCH returned to pre-flight values upon landing. The mean MCH (pg) was:

• 31.7 ± 1.6 (range, 28.8–36.4) at baseline
• 31.3 ± 1.9 (range 26.3–34.0) at the late time point (P<0.05).

The researchers said they observed significant increases in mean corpuscular volume (MCV) during space flight. However, these reflect the changes observed following the 48-hour processing delay. So there were no variations in MCV attributable to space flight.

The changes observed in hematocrit during space flight were “striking,” according to the researchers. The mean hematocrit levels were:

• 40.9 ± 3.9 (range, 33.1–48.0) at baseline
• 45.9 ± 4.7 (range 38.2–52.1) at the early time point (P<0.05)
• 45.9 ± 5.5 (range 38.9–58.3) at the mid time point (P<0.05)
• 45.0 ± 2.5 (range 38.9–49.9) at the late time point (P<0.05).

Compared to pre-flight levels, hematocrit increased by 12.2% at early, 12.2% at mid, and 10.0% at late time points. In comparison, there was a 4.7% increase in hematocrit in reference samples from non-astronauts after the 48-hour processing delay.

Finally, the researchers found that platelet concentrations were elevated in flight, at the early and mid time points. However, platelets were not significantly elevated at the late time point, and they were stable upon landing.

For all of the astronauts, all blood parameters returned to pre-flight levels within 30 days of landing on Earth.

The researchers said these results are susceptible to the possible influence of dehydration or plasma volume alterations. However, the findings do suggest the increases observed in the ISS samples are partly due to a true in-flight increase in RBC count.

“Although the data does not indicate that significant anemia is present, it must be interpreted in the context of crew plasma volume during flight,” Dr Simpson said. “Overall plasma volume has been shown to be reduced during space flight, but this has not been assessed during long-duration missions.”

“In order to fully interpret the changes to RBC, hematocrit, and other parameters observed in this study, further research into plasma volume during long space missions is needed. This will be addressed in a separate, ongoing NASA investigation.”

Photo by Graham Colm

Previous research has suggested that astronauts develop anemia during space flight, but a new study indicates this is not the case for astronauts on long space missions.

“There is an idea of ‘space anemia’ that is associated with space flight,” said Richard Simpson, PhD, of the University of Houston in Texas.

“However, this is based on blood samples from astronauts collected after flight, which may be influenced by various factors—for example, the stress of landing and re-adaptation to conditions on Earth.”

“For this study . . ., living, whole blood samples were collected during space flight and returned to Earth for analysis. This unique sample allowed us to track hematological parameters—such as concentrations of red blood cells, hemoglobin, or hematocrit—in astronauts on board the International Space Station during flight.”

Dr Simpson and his colleagues reported their findings in BMC Hematology.

The researchers found that, during space flight, concentrations of red blood cells (RBCs), platelets, and hemoglobin were higher compared to pre-flight levels. Hematocrit also increased significantly during space flight.

While previous studies had shown this to be the case during the first few days of flight, this is the first study to show that RBC concentrations and hematocrit remain at higher levels even after astronauts’ bodies have adapted to microgravity.

To find out how the blood of astronauts may change if they spend a long time in space, the researchers collected blood samples from 31 astronauts who spent up to 6 months on the International Space Station (ISS). There were 6 female and 25 male subjects, and their mean age was 52 (range, 38–61).

Samples were collected at 180 days and 45 days before the astronauts flew to the ISS. Blood was also collected while they were in space—during the first 2 weeks (early time point), between 2 and 4 months (mid time point), and about 6 months into the mission (late time point).

Samples were returned to Earth for analysis either in Houston or at Star City, Russia, within 48 hours of collection. Post-flight samples were collected 3 to 8 hours after landing and 30 days after the mission had ended.

Results

The researchers said some of the changes observed in the in-flight blood samples were to be expected due to the 48-hour processing delay between sample collection and analysis.

However, the team found that RBC concentration was significantly elevated at all 3 in-flight time points, when compared to the 180-day pre-mission time point (baseline). And RBC counts returned to baseline levels upon Earth landing.

The mean RBC concentrations (x 10⁶ cells/μL) were:

• 4.4 ± 0.4 (range, 3.5–5.1) at baseline
• 4.8 ± 0.5 (range, 3.9–5.7) at the early time point (P<0.05)
• 4.7 ± 0.4 (range, 3.9–5.4) at the mid time point (P<0.05)
• 4.7 ± 0.4 (range, 4.1–5.6) at the late time point (P<0.05).

Hemoglobin was elevated early in flight but returned to pre-flight levels during the mission and fell below baseline levels on landing day. The mean hemoglobin (g/dL) levels were:

• 14.1 ± 1.4 (range, 11.0–17.8) at baseline
• 15.0 ± 1.9 (range, 10.7–17.5) at the early time point (P<0.05)
• 13.5 ± 1.4 (range, 10.1–15.9) on landing day (P<0.05).

Mean corpuscular hemoglobin (MCH) decreased during the mission and was significantly lower than baseline at the late time point. However, MCH returned to pre-flight values upon landing. The mean MCH (pg) was:

• 31.7 ± 1.6 (range, 28.8–36.4) at baseline
• 31.3 ± 1.9 (range 26.3–34.0) at the late time point (P<0.05).

The researchers said they observed significant increases in mean corpuscular volume (MCV) during space flight. However, these reflect the changes observed following the 48-hour processing delay. So there were no variations in MCV attributable to space flight.

The changes observed in hematocrit during space flight were “striking,” according to the researchers. The mean hematocrit levels were:

• 40.9 ± 3.9 (range, 33.1–48.0) at baseline
• 45.9 ± 4.7 (range 38.2–52.1) at the early time point (P<0.05)
• 45.9 ± 5.5 (range 38.9–58.3) at the mid time point (P<0.05)
• 45.0 ± 2.5 (range 38.9–49.9) at the late time point (P<0.05).

Compared to pre-flight levels, hematocrit increased by 12.2% at early, 12.2% at mid, and 10.0% at late time points. In comparison, there was a 4.7% increase in hematocrit in reference samples from non-astronauts after the 48-hour processing delay.

Finally, the researchers found that platelet concentrations were elevated in flight, at the early and mid time points. However, platelets were not significantly elevated at the late time point, and they were stable upon landing.

For all of the astronauts, all blood parameters returned to pre-flight levels within 30 days of landing on Earth.

The researchers said these results are susceptible to the possible influence of dehydration or plasma volume alterations. However, the findings do suggest the increases observed in the ISS samples are partly due to a true in-flight increase in RBC count.

“Although the data does not indicate that significant anemia is present, it must be interpreted in the context of crew plasma volume during flight,” Dr Simpson said. “Overall plasma volume has been shown to be reduced during space flight, but this has not been assessed during long-duration missions.”

“In order to fully interpret the changes to RBC, hematocrit, and other parameters observed in this study, further research into plasma volume during long space missions is needed. This will be addressed in a separate, ongoing NASA investigation.”

Institute of Pathology

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.

With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

For more details, see the full prescribing information.

The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

Phase 3 study results

The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.

The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Institute of Pathology

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.

With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

For more details, see the full prescribing information.

The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

Phase 3 study results

The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.

The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Institute of Pathology

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.

With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

For more details, see the full prescribing information.

The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

Phase 3 study results

The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.

The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

The FP recognized a “Christmas tree” pattern on the patient’s back, which led to a diagnosis of pityriasis rosea. Because there are no lab tests to confirm pityriasis rosea, it is usually a clinical diagnosis.

The Christmas tree pattern that signals pityriasis rosea is caused by the long axis of the plaques following the skin lines of the back. While it is a helpful indicator of pityriasis rosea when present, most cases do not show this pattern. In this case, a collarette scale pattern was also visible. This is seen when scaling is visibly raised on the edge of the plaques, like the collar of a shirt.

Pityriasis rosea can be difficult to distinguish from secondary syphilis, which can also present as a papulosquamous eruption. Therefore, taking a sexual history is important when a diagnosis of pityriasis rosea is being considered. In patients with a history of sexually transmitted diseases or high-risk sexual practices, a rapid plasma reagin test should be ordered.

The FP assured the patient and his mother that the pityriasis rosea rash was not contagious, would not cause scarring, and would resolve in one to 2 months without any treatment. The patient declined any medication for the pruritus. At a subsequent visit for a sports physical, the skin was found to be completely clear with no evidence of scarring.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Henderson D, Usatine R. Pityriasis rosea. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 896-900.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP recognized a “Christmas tree” pattern on the patient’s back, which led to a diagnosis of pityriasis rosea. Because there are no lab tests to confirm pityriasis rosea, it is usually a clinical diagnosis.

The Christmas tree pattern that signals pityriasis rosea is caused by the long axis of the plaques following the skin lines of the back. While it is a helpful indicator of pityriasis rosea when present, most cases do not show this pattern. In this case, a collarette scale pattern was also visible. This is seen when scaling is visibly raised on the edge of the plaques, like the collar of a shirt.

Pityriasis rosea can be difficult to distinguish from secondary syphilis, which can also present as a papulosquamous eruption. Therefore, taking a sexual history is important when a diagnosis of pityriasis rosea is being considered. In patients with a history of sexually transmitted diseases or high-risk sexual practices, a rapid plasma reagin test should be ordered.

The FP assured the patient and his mother that the pityriasis rosea rash was not contagious, would not cause scarring, and would resolve in one to 2 months without any treatment. The patient declined any medication for the pruritus. At a subsequent visit for a sports physical, the skin was found to be completely clear with no evidence of scarring.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Henderson D, Usatine R. Pityriasis rosea. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 896-900.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP recognized a “Christmas tree” pattern on the patient’s back, which led to a diagnosis of pityriasis rosea. Because there are no lab tests to confirm pityriasis rosea, it is usually a clinical diagnosis.

The Christmas tree pattern that signals pityriasis rosea is caused by the long axis of the plaques following the skin lines of the back. While it is a helpful indicator of pityriasis rosea when present, most cases do not show this pattern. In this case, a collarette scale pattern was also visible. This is seen when scaling is visibly raised on the edge of the plaques, like the collar of a shirt.

Pityriasis rosea can be difficult to distinguish from secondary syphilis, which can also present as a papulosquamous eruption. Therefore, taking a sexual history is important when a diagnosis of pityriasis rosea is being considered. In patients with a history of sexually transmitted diseases or high-risk sexual practices, a rapid plasma reagin test should be ordered.

The FP assured the patient and his mother that the pityriasis rosea rash was not contagious, would not cause scarring, and would resolve in one to 2 months without any treatment. The patient declined any medication for the pruritus. At a subsequent visit for a sports physical, the skin was found to be completely clear with no evidence of scarring.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Henderson D, Usatine R. Pityriasis rosea. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 896-900.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com