SAN FRANCISCO – The sequential combination of rituximab followed directly by maintenance belimumab shows considerable promise as a strategy to address the aberrant B-cell immunology present in systemic lupus erythematosus (SLE) – and thereby improve clinical outcomes, Y.K. Onno Teng, MD, PhD, reported at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

Dr. Teng, a nephrologist and clinical trialist at Leiden (the Netherlands) University, and his coworkers were pioneers of this one-two punch, in which a two-dose course of rituximab (Rituxan) is given to deplete CD20-positive B-cells, followed by long-term maintenance belimumab (Benlysta) to inhibit repopulation of specific problematic types of B-cells. The rationale for the use of belimumab here lies in the observation that the initial B-cell depletion induced by rituximab triggers a surge in B lymphocyte stimulator (BLyS), which signals the bone marrow to start making more B-cells. And belimumab famously inhibits BLyS, also known as B-cell activating factor, or BAFF.

Dr. Teng presented the 2-year extended results of Synergistic B-cell Immunomodulation in SLE (SYNBIoSe-1), a phase 2a, open-label, single-arm, proof-of-concept study whose 24-week immunologic results have previously been reported (J Autoimmun. 2018 Jul;91:45-54).

Based in part upon the encouraging SYNBIoSe-1 findings as well as the sound mechanistic rationale for this treatment strategy, the combination of rituximab and belimumab is picking up steam in the research world as a potentially important treatment advance in SLE. Currently underway in patients with nonrenal SLE is the phase 3, GlaxoSmithKline-sponsored, global BLISS-BELIEVE trial, as well as the phase 2 BEAT-LUPUS study, a University College London–based randomized trial of rituximab plus either placebo or belimumab. Also, Dr. Teng and his coworkers are now conducting SYNBIoSe-2, in which patients with lupus nephritis are being randomized to standard therapy with glucocorticoids and mycophenolate or to rituximab, belimumab, and mycophenolate.

SYNBIoSe-2 is a further exploration of the encouraging signal of efficacy for lupus nephritis noted in SYNBIoSe-1. Of the 12 participants in SYNBIoSe-1 who had baseline active lupus nephritis, 8 had a positive renal response to the rituximab/belimumab combo, including 6 patients who achieved a prolonged complete renal response through 104 weeks of follow-up.

SYNBIoSe-1 included 15 patients, all with severe refractory SLE as shown by a median 11-year disease duration and a baseline SLE Disease Activity Index score of 18. Two-thirds of patients achieved sustained low-level disease activity, interrupted in one case by a single major disease flare. Two patients stopped treatment because of a lack of response. Several others left the study because they were doing so well on treatment that they decided the time was right to become pregnant.

Immunologically, patients showed an 84% reduction in B-cell repopulation over the course of 2 years. Particularly striking was the long-term inhibition of double-negative B-cells and IgD-positive naive B-cells, which Dr. Teng described as “very trigger happy” in that they readily become transformed into activated antibody-producing cells.

Sustained specific reductions in anti-double-stranded DNA autoantibodies and other pathogenic antinuclear antibodies were also documented through 104 weeks.
 

SYNBIoSe-1 results at odds with CALIBRATE trial results

The favorable impact of the rituximab/belimumab combo on lupus nephritis seen in SYNBIoSe-1 is at odds with the results of CALIBRATE, a U.S. study in which 43 patients with active lupus nephritis despite conventional treatment were randomized open label to induction therapy with two doses of rituximab on top of standard background therapy, followed by either belimumab and prednisone or prednisone alone. In CALIBRATE, the anti-BLyS biologic didn’t improve clinical outcomes. Dr. Teng said he believes he knows why.

“There was an important difference in background immunosuppression in the two studies. We used mycophenolate in SYNBIoSe-1, while they used cyclophosphamide in CALIBRATE,” he noted. “Other investigators have shown that mycophenolate mostly depletes plasma cells, whereas cyclophosphamide is very much depleting proliferating cells, predominantly the B-cell population and to a lesser extent the plasma cell population. I think this phenomenon might explain why adding BLyS inhibition to patients treated with CellCept [mycophenolate] might be of more added value than adding it to cyclophosphamide therapy.”

Dr. Teng reported having no financial conflicts regarding the SYNBIoSe-1 study, which was funded by research grants from the Dutch Kidney Foundation and the Netherlands Organization for Health Research and Development.

[email protected]

SAN FRANCISCO – The sequential combination of rituximab followed directly by maintenance belimumab shows considerable promise as a strategy to address the aberrant B-cell immunology present in systemic lupus erythematosus (SLE) – and thereby improve clinical outcomes, Y.K. Onno Teng, MD, PhD, reported at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

Dr. Teng, a nephrologist and clinical trialist at Leiden (the Netherlands) University, and his coworkers were pioneers of this one-two punch, in which a two-dose course of rituximab (Rituxan) is given to deplete CD20-positive B-cells, followed by long-term maintenance belimumab (Benlysta) to inhibit repopulation of specific problematic types of B-cells. The rationale for the use of belimumab here lies in the observation that the initial B-cell depletion induced by rituximab triggers a surge in B lymphocyte stimulator (BLyS), which signals the bone marrow to start making more B-cells. And belimumab famously inhibits BLyS, also known as B-cell activating factor, or BAFF.

Dr. Teng presented the 2-year extended results of Synergistic B-cell Immunomodulation in SLE (SYNBIoSe-1), a phase 2a, open-label, single-arm, proof-of-concept study whose 24-week immunologic results have previously been reported (J Autoimmun. 2018 Jul;91:45-54).

Based in part upon the encouraging SYNBIoSe-1 findings as well as the sound mechanistic rationale for this treatment strategy, the combination of rituximab and belimumab is picking up steam in the research world as a potentially important treatment advance in SLE. Currently underway in patients with nonrenal SLE is the phase 3, GlaxoSmithKline-sponsored, global BLISS-BELIEVE trial, as well as the phase 2 BEAT-LUPUS study, a University College London–based randomized trial of rituximab plus either placebo or belimumab. Also, Dr. Teng and his coworkers are now conducting SYNBIoSe-2, in which patients with lupus nephritis are being randomized to standard therapy with glucocorticoids and mycophenolate or to rituximab, belimumab, and mycophenolate.

SYNBIoSe-2 is a further exploration of the encouraging signal of efficacy for lupus nephritis noted in SYNBIoSe-1. Of the 12 participants in SYNBIoSe-1 who had baseline active lupus nephritis, 8 had a positive renal response to the rituximab/belimumab combo, including 6 patients who achieved a prolonged complete renal response through 104 weeks of follow-up.

SYNBIoSe-1 included 15 patients, all with severe refractory SLE as shown by a median 11-year disease duration and a baseline SLE Disease Activity Index score of 18. Two-thirds of patients achieved sustained low-level disease activity, interrupted in one case by a single major disease flare. Two patients stopped treatment because of a lack of response. Several others left the study because they were doing so well on treatment that they decided the time was right to become pregnant.

Immunologically, patients showed an 84% reduction in B-cell repopulation over the course of 2 years. Particularly striking was the long-term inhibition of double-negative B-cells and IgD-positive naive B-cells, which Dr. Teng described as “very trigger happy” in that they readily become transformed into activated antibody-producing cells.

Sustained specific reductions in anti-double-stranded DNA autoantibodies and other pathogenic antinuclear antibodies were also documented through 104 weeks.
 

SYNBIoSe-1 results at odds with CALIBRATE trial results

The favorable impact of the rituximab/belimumab combo on lupus nephritis seen in SYNBIoSe-1 is at odds with the results of CALIBRATE, a U.S. study in which 43 patients with active lupus nephritis despite conventional treatment were randomized open label to induction therapy with two doses of rituximab on top of standard background therapy, followed by either belimumab and prednisone or prednisone alone. In CALIBRATE, the anti-BLyS biologic didn’t improve clinical outcomes. Dr. Teng said he believes he knows why.

“There was an important difference in background immunosuppression in the two studies. We used mycophenolate in SYNBIoSe-1, while they used cyclophosphamide in CALIBRATE,” he noted. “Other investigators have shown that mycophenolate mostly depletes plasma cells, whereas cyclophosphamide is very much depleting proliferating cells, predominantly the B-cell population and to a lesser extent the plasma cell population. I think this phenomenon might explain why adding BLyS inhibition to patients treated with CellCept [mycophenolate] might be of more added value than adding it to cyclophosphamide therapy.”

Dr. Teng reported having no financial conflicts regarding the SYNBIoSe-1 study, which was funded by research grants from the Dutch Kidney Foundation and the Netherlands Organization for Health Research and Development.

[email protected]

SAN FRANCISCO – The sequential combination of rituximab followed directly by maintenance belimumab shows considerable promise as a strategy to address the aberrant B-cell immunology present in systemic lupus erythematosus (SLE) – and thereby improve clinical outcomes, Y.K. Onno Teng, MD, PhD, reported at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

Dr. Teng, a nephrologist and clinical trialist at Leiden (the Netherlands) University, and his coworkers were pioneers of this one-two punch, in which a two-dose course of rituximab (Rituxan) is given to deplete CD20-positive B-cells, followed by long-term maintenance belimumab (Benlysta) to inhibit repopulation of specific problematic types of B-cells. The rationale for the use of belimumab here lies in the observation that the initial B-cell depletion induced by rituximab triggers a surge in B lymphocyte stimulator (BLyS), which signals the bone marrow to start making more B-cells. And belimumab famously inhibits BLyS, also known as B-cell activating factor, or BAFF.

Dr. Teng presented the 2-year extended results of Synergistic B-cell Immunomodulation in SLE (SYNBIoSe-1), a phase 2a, open-label, single-arm, proof-of-concept study whose 24-week immunologic results have previously been reported (J Autoimmun. 2018 Jul;91:45-54).

Based in part upon the encouraging SYNBIoSe-1 findings as well as the sound mechanistic rationale for this treatment strategy, the combination of rituximab and belimumab is picking up steam in the research world as a potentially important treatment advance in SLE. Currently underway in patients with nonrenal SLE is the phase 3, GlaxoSmithKline-sponsored, global BLISS-BELIEVE trial, as well as the phase 2 BEAT-LUPUS study, a University College London–based randomized trial of rituximab plus either placebo or belimumab. Also, Dr. Teng and his coworkers are now conducting SYNBIoSe-2, in which patients with lupus nephritis are being randomized to standard therapy with glucocorticoids and mycophenolate or to rituximab, belimumab, and mycophenolate.

SYNBIoSe-2 is a further exploration of the encouraging signal of efficacy for lupus nephritis noted in SYNBIoSe-1. Of the 12 participants in SYNBIoSe-1 who had baseline active lupus nephritis, 8 had a positive renal response to the rituximab/belimumab combo, including 6 patients who achieved a prolonged complete renal response through 104 weeks of follow-up.

SYNBIoSe-1 included 15 patients, all with severe refractory SLE as shown by a median 11-year disease duration and a baseline SLE Disease Activity Index score of 18. Two-thirds of patients achieved sustained low-level disease activity, interrupted in one case by a single major disease flare. Two patients stopped treatment because of a lack of response. Several others left the study because they were doing so well on treatment that they decided the time was right to become pregnant.

Immunologically, patients showed an 84% reduction in B-cell repopulation over the course of 2 years. Particularly striking was the long-term inhibition of double-negative B-cells and IgD-positive naive B-cells, which Dr. Teng described as “very trigger happy” in that they readily become transformed into activated antibody-producing cells.

Sustained specific reductions in anti-double-stranded DNA autoantibodies and other pathogenic antinuclear antibodies were also documented through 104 weeks.
 

SYNBIoSe-1 results at odds with CALIBRATE trial results

The favorable impact of the rituximab/belimumab combo on lupus nephritis seen in SYNBIoSe-1 is at odds with the results of CALIBRATE, a U.S. study in which 43 patients with active lupus nephritis despite conventional treatment were randomized open label to induction therapy with two doses of rituximab on top of standard background therapy, followed by either belimumab and prednisone or prednisone alone. In CALIBRATE, the anti-BLyS biologic didn’t improve clinical outcomes. Dr. Teng said he believes he knows why.

“There was an important difference in background immunosuppression in the two studies. We used mycophenolate in SYNBIoSe-1, while they used cyclophosphamide in CALIBRATE,” he noted. “Other investigators have shown that mycophenolate mostly depletes plasma cells, whereas cyclophosphamide is very much depleting proliferating cells, predominantly the B-cell population and to a lesser extent the plasma cell population. I think this phenomenon might explain why adding BLyS inhibition to patients treated with CellCept [mycophenolate] might be of more added value than adding it to cyclophosphamide therapy.”

Dr. Teng reported having no financial conflicts regarding the SYNBIoSe-1 study, which was funded by research grants from the Dutch Kidney Foundation and the Netherlands Organization for Health Research and Development.

[email protected]

The Diagnosis: Bimatoprost-Induced Hypertrichosis 

Latanoprost, a prostaglandin analogue, typically is prescribed by ophthalmologists as eye drops to reduce intraocular pressure in open-angle glaucoma.¹ Common adverse reactions of latanoprost drops include blurred vision, ocular irritation, darkening of the eyelid skin, and pigmentation of the iris. 

In 1997, Johnstone² reported hypertrichosis and increased pigmentation of the eyelashes of both eyes and adjacent skin after latanoprost drops were used in glaucoma patients. Subsequently, topical latanoprost and bimatoprost, a similar analogue, are now utilized for the cosmetic purpose of thickening and lengthening the eyelashes due to the hypertrichosis effect. Travoprost, another prostaglandin analogue used to treat glaucoma, also has been associated with periocular hypertrichosis.³ Concomitant poliosis of the eyelashes with hypertrichosis from latanoprost also has been reported.⁴ Our patient specifically purchased the eye drops (marketed as generic bimatoprost) to lengthen her eyelashes and had noticed an increase in length. She denied a family history of increased facial hair in females. 

Along with gingival hyperplasia, systemic cyclosporine may cause generalized hypertrichosis consisting of terminal hair growth, particularly on the face and forearms. However, hypertrichosis from cyclosporine ophthalmic emulsion 0.05% rarely has been reported⁵ but would be more likely to occur in a patient reporting a history of chronic dry eye. Oral acetazolamide, not eye drops, is prescribed for glaucoma and typically is not associated with hypertrichosis. Betamethasone and timolol eye drops may cause burning, stinging, redness, or watering of the eyes, but they do not typically cause hypertrichosis.  

Other systemic medications (eg, zidovudine, phenytoin, minoxidil, danazol, anabolic steroids) may cause hypertrichosis but not typically localized to the periocular area. Phenytoin usually causes hair growth on the limbs but not on the face and trunk. Oral minoxidil causes hypertrichosis, predominately on the face, lower legs, and forearms. 

Systemic conditions such as endocrine abnormalities or porphyria cutanea tarda also may cause hypertrichosis; however, it typically does not present in small focal areas, and other stigmata often are present such as signs of virilization in hirsutism (ie, deepening of voice, pattern alopecia, acne) or liver disease with photosensitive erosions and bullae that leave scars and milia in porphyria cutanea tarda. Acquired hypertrichosis lanuginosa deserves consideration, in part due to its association with lung and colon cancers; however, it consists of softer, downy, nonterminal hairs (malignant down) and is more generalized on the face. Malnutrition from anorexia nervosa may similarly induce hypertrichosis lanuginose.  

The molecular mechanism for latanoprost-induced hypertrichosis is unknown; however, it may promote anagen growth as well as hypertrophic changes in the affected follicles.⁶ Patients should use extreme caution when purchasing unregulated medications due to the risk for impurities, less stable formulation, or inaccurate concentrations. Comparison between brand name and approved generic latanoprost has found notable differences, including variations in active-ingredient concentration, poor stability in warmer temperatures, and higher levels of particulate matter.⁷ Some cosmetic eyelash enhancers sold over-the-counter or online may contain prostaglandin analogues, but they may not be listed as ingredients.⁸ One report noted a bimatoprost product with a concentration level double that of brand-name bimatoprost that was discovered using high-performance liquid chromatography-tandem mass spectrometry.⁹ 

Treatment options for eliminating the excess hairs include discontinuing the prostaglandin analogue or applying it only to the eyelid margin with an appropriate applicator. Waxing, manual extraction, laser hair removal, electrolysis, and depilatory creams are alternative treatments. 

The Diagnosis: Bimatoprost-Induced Hypertrichosis 

Latanoprost, a prostaglandin analogue, typically is prescribed by ophthalmologists as eye drops to reduce intraocular pressure in open-angle glaucoma.¹ Common adverse reactions of latanoprost drops include blurred vision, ocular irritation, darkening of the eyelid skin, and pigmentation of the iris. 

In 1997, Johnstone² reported hypertrichosis and increased pigmentation of the eyelashes of both eyes and adjacent skin after latanoprost drops were used in glaucoma patients. Subsequently, topical latanoprost and bimatoprost, a similar analogue, are now utilized for the cosmetic purpose of thickening and lengthening the eyelashes due to the hypertrichosis effect. Travoprost, another prostaglandin analogue used to treat glaucoma, also has been associated with periocular hypertrichosis.³ Concomitant poliosis of the eyelashes with hypertrichosis from latanoprost also has been reported.⁴ Our patient specifically purchased the eye drops (marketed as generic bimatoprost) to lengthen her eyelashes and had noticed an increase in length. She denied a family history of increased facial hair in females. 

Along with gingival hyperplasia, systemic cyclosporine may cause generalized hypertrichosis consisting of terminal hair growth, particularly on the face and forearms. However, hypertrichosis from cyclosporine ophthalmic emulsion 0.05% rarely has been reported⁵ but would be more likely to occur in a patient reporting a history of chronic dry eye. Oral acetazolamide, not eye drops, is prescribed for glaucoma and typically is not associated with hypertrichosis. Betamethasone and timolol eye drops may cause burning, stinging, redness, or watering of the eyes, but they do not typically cause hypertrichosis.  

Other systemic medications (eg, zidovudine, phenytoin, minoxidil, danazol, anabolic steroids) may cause hypertrichosis but not typically localized to the periocular area. Phenytoin usually causes hair growth on the limbs but not on the face and trunk. Oral minoxidil causes hypertrichosis, predominately on the face, lower legs, and forearms. 

Systemic conditions such as endocrine abnormalities or porphyria cutanea tarda also may cause hypertrichosis; however, it typically does not present in small focal areas, and other stigmata often are present such as signs of virilization in hirsutism (ie, deepening of voice, pattern alopecia, acne) or liver disease with photosensitive erosions and bullae that leave scars and milia in porphyria cutanea tarda. Acquired hypertrichosis lanuginosa deserves consideration, in part due to its association with lung and colon cancers; however, it consists of softer, downy, nonterminal hairs (malignant down) and is more generalized on the face. Malnutrition from anorexia nervosa may similarly induce hypertrichosis lanuginose.  

The molecular mechanism for latanoprost-induced hypertrichosis is unknown; however, it may promote anagen growth as well as hypertrophic changes in the affected follicles.⁶ Patients should use extreme caution when purchasing unregulated medications due to the risk for impurities, less stable formulation, or inaccurate concentrations. Comparison between brand name and approved generic latanoprost has found notable differences, including variations in active-ingredient concentration, poor stability in warmer temperatures, and higher levels of particulate matter.⁷ Some cosmetic eyelash enhancers sold over-the-counter or online may contain prostaglandin analogues, but they may not be listed as ingredients.⁸ One report noted a bimatoprost product with a concentration level double that of brand-name bimatoprost that was discovered using high-performance liquid chromatography-tandem mass spectrometry.⁹ 

Treatment options for eliminating the excess hairs include discontinuing the prostaglandin analogue or applying it only to the eyelid margin with an appropriate applicator. Waxing, manual extraction, laser hair removal, electrolysis, and depilatory creams are alternative treatments. 

The Diagnosis: Bimatoprost-Induced Hypertrichosis 

Latanoprost, a prostaglandin analogue, typically is prescribed by ophthalmologists as eye drops to reduce intraocular pressure in open-angle glaucoma.¹ Common adverse reactions of latanoprost drops include blurred vision, ocular irritation, darkening of the eyelid skin, and pigmentation of the iris. 

In 1997, Johnstone² reported hypertrichosis and increased pigmentation of the eyelashes of both eyes and adjacent skin after latanoprost drops were used in glaucoma patients. Subsequently, topical latanoprost and bimatoprost, a similar analogue, are now utilized for the cosmetic purpose of thickening and lengthening the eyelashes due to the hypertrichosis effect. Travoprost, another prostaglandin analogue used to treat glaucoma, also has been associated with periocular hypertrichosis.³ Concomitant poliosis of the eyelashes with hypertrichosis from latanoprost also has been reported.⁴ Our patient specifically purchased the eye drops (marketed as generic bimatoprost) to lengthen her eyelashes and had noticed an increase in length. She denied a family history of increased facial hair in females. 

Along with gingival hyperplasia, systemic cyclosporine may cause generalized hypertrichosis consisting of terminal hair growth, particularly on the face and forearms. However, hypertrichosis from cyclosporine ophthalmic emulsion 0.05% rarely has been reported⁵ but would be more likely to occur in a patient reporting a history of chronic dry eye. Oral acetazolamide, not eye drops, is prescribed for glaucoma and typically is not associated with hypertrichosis. Betamethasone and timolol eye drops may cause burning, stinging, redness, or watering of the eyes, but they do not typically cause hypertrichosis.  

Other systemic medications (eg, zidovudine, phenytoin, minoxidil, danazol, anabolic steroids) may cause hypertrichosis but not typically localized to the periocular area. Phenytoin usually causes hair growth on the limbs but not on the face and trunk. Oral minoxidil causes hypertrichosis, predominately on the face, lower legs, and forearms. 

Systemic conditions such as endocrine abnormalities or porphyria cutanea tarda also may cause hypertrichosis; however, it typically does not present in small focal areas, and other stigmata often are present such as signs of virilization in hirsutism (ie, deepening of voice, pattern alopecia, acne) or liver disease with photosensitive erosions and bullae that leave scars and milia in porphyria cutanea tarda. Acquired hypertrichosis lanuginosa deserves consideration, in part due to its association with lung and colon cancers; however, it consists of softer, downy, nonterminal hairs (malignant down) and is more generalized on the face. Malnutrition from anorexia nervosa may similarly induce hypertrichosis lanuginose.  

The molecular mechanism for latanoprost-induced hypertrichosis is unknown; however, it may promote anagen growth as well as hypertrophic changes in the affected follicles.⁶ Patients should use extreme caution when purchasing unregulated medications due to the risk for impurities, less stable formulation, or inaccurate concentrations. Comparison between brand name and approved generic latanoprost has found notable differences, including variations in active-ingredient concentration, poor stability in warmer temperatures, and higher levels of particulate matter.⁷ Some cosmetic eyelash enhancers sold over-the-counter or online may contain prostaglandin analogues, but they may not be listed as ingredients.⁸ One report noted a bimatoprost product with a concentration level double that of brand-name bimatoprost that was discovered using high-performance liquid chromatography-tandem mass spectrometry.⁹ 

Treatment options for eliminating the excess hairs include discontinuing the prostaglandin analogue or applying it only to the eyelid margin with an appropriate applicator. Waxing, manual extraction, laser hair removal, electrolysis, and depilatory creams are alternative treatments. 

In the last few months, I’ve received several posters. They’re always delivered by UPS, and come in a solid cardboard box to keep them from being crushed.

The boxes get opened, and once I know what they are, the whole thing gets tossed in the office recycling.

I know they’re presented as helpful patient information, with some bullet lists and glossy graphics showing brains, nerve transmitters, or patients. But the basic reality is that they’re just advertisements. Like infomercials on TV, they come across as professional and interesting, but at their heart and soul are just selling something.

No thanks.

Years ago, a company sent me a poster listing the warning signs of stroke. Although it was still an advertisement, I decided to hang it up in my exam room as a sort of public service announcement. Unfortunately, I soon discovered that any patient left staring at it for more than 1-2 minutes would start to complain of at least two of the symptoms listed. It got taken down after a few days.

I have nothing against advertising. It pays for websites, television shows, sporting events, newspapers, and magazines.

But my exam room isn’t the place for it. Patients are bombarded with direct-to-consumer advertising for many drugs in every media outlet. The doctor’s discussion room shouldn’t be one of the them.

The meeting between me and a patient should be frank, honest assessments about what should be done and what, specifically, is best for their individual case. I don’t need marketing for a drug that may or may not be appropriate, or easily covered by insurance, staring back at them.

It’s a thin line. Obviously, magazines out in my lobby are full of pharmaceutical ads, and that doesn’t bother me. But once a patient crosses the line into my consultation area it should just be between me and them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the last few months, I’ve received several posters. They’re always delivered by UPS, and come in a solid cardboard box to keep them from being crushed.

The boxes get opened, and once I know what they are, the whole thing gets tossed in the office recycling.

I know they’re presented as helpful patient information, with some bullet lists and glossy graphics showing brains, nerve transmitters, or patients. But the basic reality is that they’re just advertisements. Like infomercials on TV, they come across as professional and interesting, but at their heart and soul are just selling something.

No thanks.

Years ago, a company sent me a poster listing the warning signs of stroke. Although it was still an advertisement, I decided to hang it up in my exam room as a sort of public service announcement. Unfortunately, I soon discovered that any patient left staring at it for more than 1-2 minutes would start to complain of at least two of the symptoms listed. It got taken down after a few days.

I have nothing against advertising. It pays for websites, television shows, sporting events, newspapers, and magazines.

But my exam room isn’t the place for it. Patients are bombarded with direct-to-consumer advertising for many drugs in every media outlet. The doctor’s discussion room shouldn’t be one of the them.

The meeting between me and a patient should be frank, honest assessments about what should be done and what, specifically, is best for their individual case. I don’t need marketing for a drug that may or may not be appropriate, or easily covered by insurance, staring back at them.

It’s a thin line. Obviously, magazines out in my lobby are full of pharmaceutical ads, and that doesn’t bother me. But once a patient crosses the line into my consultation area it should just be between me and them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the last few months, I’ve received several posters. They’re always delivered by UPS, and come in a solid cardboard box to keep them from being crushed.

The boxes get opened, and once I know what they are, the whole thing gets tossed in the office recycling.

I know they’re presented as helpful patient information, with some bullet lists and glossy graphics showing brains, nerve transmitters, or patients. But the basic reality is that they’re just advertisements. Like infomercials on TV, they come across as professional and interesting, but at their heart and soul are just selling something.

No thanks.

Years ago, a company sent me a poster listing the warning signs of stroke. Although it was still an advertisement, I decided to hang it up in my exam room as a sort of public service announcement. Unfortunately, I soon discovered that any patient left staring at it for more than 1-2 minutes would start to complain of at least two of the symptoms listed. It got taken down after a few days.

I have nothing against advertising. It pays for websites, television shows, sporting events, newspapers, and magazines.

But my exam room isn’t the place for it. Patients are bombarded with direct-to-consumer advertising for many drugs in every media outlet. The doctor’s discussion room shouldn’t be one of the them.

The meeting between me and a patient should be frank, honest assessments about what should be done and what, specifically, is best for their individual case. I don’t need marketing for a drug that may or may not be appropriate, or easily covered by insurance, staring back at them.

It’s a thin line. Obviously, magazines out in my lobby are full of pharmaceutical ads, and that doesn’t bother me. But once a patient crosses the line into my consultation area it should just be between me and them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

SAN FRANCISCO – Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.

Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.

Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.

In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).

Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).

“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.
 

Why routinely measuring hydroxychloroquine levels matters

Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.

Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.

Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).

It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”

She reported having no financial conflicts regarding her presentation.

[email protected]

SAN FRANCISCO – Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.

Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.

Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.

In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).

Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).

“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.
 

Why routinely measuring hydroxychloroquine levels matters

Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.

Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.

Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).

It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”

She reported having no financial conflicts regarding her presentation.

[email protected]

SAN FRANCISCO – Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.

Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.

Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.

In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).

Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).

“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.
 

Why routinely measuring hydroxychloroquine levels matters

Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.

Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.

Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).

It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”

She reported having no financial conflicts regarding her presentation.

[email protected]

NEWPORT BEACH, CALIF. – A five-drug regimen was deemed safe in patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), and it appeared to be effective regardless of patients’ FLT3 status.

Researchers tested this regimen – sorafenib plus granulocyte colony–stimulating factor (G-CSF), cladribine, high-dose cytarabine, and mitoxantrone (GCLAM) – in a phase 1 trial.

Kelsey-Leigh Garcia, a clinical research coordinator at Seattle Cancer Care Alliance, and her colleagues presented the results at the Acute Leukemia Forum of Hemedicus.

“The background for doing this study was our institutional results of GCLAM [Leukemia. 2018 Nov;32(11):2352-62] that showed a higher minimal residual disease–negative complete response rate than 7+3 [cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days] and an international study by Röllig that showed the addition of sorafenib to 7+3 increased event-free survival versus [7+3 and] placebo [Lancet Oncol. 2015 Dec;16(16):1691-9],” Ms. Garcia said.

“GCLAM is the standard backbone at our institution, and we wanted to ask the question, ‘If we add sorafenib, can this improve upon the results of GCLAM?’ ” said Anna Halpern, MD, a hematologist-oncologist at the University of Washington, Seattle and principal investigator of the phase 1 trial.

The trial (NCT02728050) included 47 patients, 39 with AML and 8 with MDS. Patients were aged 60 years or younger and had a median age of 48. They had a median treatment-related mortality score of 1.76 (range, 0.19-12.26). A total of 11 patients (23%) had FLT3-ITD, and 4 (9%) had FLT3-TKD.

Treatment and toxicity

For induction, patients received G-CSF at 5 mcg/kg on days 0-5, cladribine at 5 mg/m² on days 1-5, and cytarabine at 2 g/m² on days 1-5. Mitoxantrone was given at 10 mg/m², 12 mg/m², 15 mg/m², or 18 mg/m² on days 1-3. Sorafenib was given at 200 mg twice daily, 400 mg in the morning and 200 mg in the afternoon, or 400 mg b.i.d. on days 10-19.

For consolidation, patients could receive up to four cycles of G-CSF, cladribine, and cytarabine plus sorafenib on days 8-27. Patients who did not proceed to transplant could receive 12 months of sorafenib as maintenance therapy.

There were four dose-limiting toxicities.

• Grade 4 intracranial hemorrhage with mitoxantrone at 12 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 prolonged count recovery with mitoxantrone at 15 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 sepsis, Sweet syndrome, and Bell’s palsy with mitoxantrone at 18 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 3 cardiomyopathy and acute pericarditis with mitoxantrone at 18 mg/m² and sorafenib at 400 mg b.i.d.

However, these toxicities did not define the maximum-tolerated dose. Therefore, the recommended phase 2 dose of mitoxantrone is 18 mg/m², and the recommended phase 2 dose of sorafenib is 400 mg b.i.d.

There were no grade 5 treatment-related adverse events. Grade 3 events included febrile neutropenia (90%), maculopapular rash (20%), infections (10%), hand-foot syndrome (2%), and diarrhea (1%). Grade 4 events included sepsis, intracranial hemorrhage, and oral mucositis (all 1%).

Response and survival

Among the 46 evaluable patients, 83% achieved a complete response, 78% had a minimal residual disease–negative complete response, and 4% had a minimal residual disease–negative complete response with incomplete count recovery. A morphological leukemia-free state was achieved by 4% of patients, and 8% had resistant disease.

Fifty-nine percent of patients went on to transplant. The median overall survival had not been reached at a median follow-up of 10 months.

The researchers compared outcomes in this trial with outcomes in a cohort of patients who had received GCLAM alone, and there were no significant differences in overall survival or event-free survival.

“The trial wasn’t powered, necessarily, for efficacy, but we compared these results to our historical cohort of medically matched and age-matched patients treated with GCLAM alone and, so far, found no differences in survival between the two groups,” Dr. Halpern said.

She noted, however, that follow-up was short in the sorafenib trial, and it included patients treated with all dose levels of sorafenib and mitoxantrone.

A phase 2 study of sorafenib plus GCLAM in newly diagnosed AML or high-risk MDS is now underway.

Dr. Halpern and Ms. Garcia reported that they had no conflicts of interest. The phase 1 trial was sponsored by the University of Washington in collaboration with the National Cancer Institute, and funding was provided by Bayer.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – A five-drug regimen was deemed safe in patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), and it appeared to be effective regardless of patients’ FLT3 status.

Researchers tested this regimen – sorafenib plus granulocyte colony–stimulating factor (G-CSF), cladribine, high-dose cytarabine, and mitoxantrone (GCLAM) – in a phase 1 trial.

Kelsey-Leigh Garcia, a clinical research coordinator at Seattle Cancer Care Alliance, and her colleagues presented the results at the Acute Leukemia Forum of Hemedicus.

“The background for doing this study was our institutional results of GCLAM [Leukemia. 2018 Nov;32(11):2352-62] that showed a higher minimal residual disease–negative complete response rate than 7+3 [cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days] and an international study by Röllig that showed the addition of sorafenib to 7+3 increased event-free survival versus [7+3 and] placebo [Lancet Oncol. 2015 Dec;16(16):1691-9],” Ms. Garcia said.

“GCLAM is the standard backbone at our institution, and we wanted to ask the question, ‘If we add sorafenib, can this improve upon the results of GCLAM?’ ” said Anna Halpern, MD, a hematologist-oncologist at the University of Washington, Seattle and principal investigator of the phase 1 trial.

The trial (NCT02728050) included 47 patients, 39 with AML and 8 with MDS. Patients were aged 60 years or younger and had a median age of 48. They had a median treatment-related mortality score of 1.76 (range, 0.19-12.26). A total of 11 patients (23%) had FLT3-ITD, and 4 (9%) had FLT3-TKD.

Treatment and toxicity

For induction, patients received G-CSF at 5 mcg/kg on days 0-5, cladribine at 5 mg/m² on days 1-5, and cytarabine at 2 g/m² on days 1-5. Mitoxantrone was given at 10 mg/m², 12 mg/m², 15 mg/m², or 18 mg/m² on days 1-3. Sorafenib was given at 200 mg twice daily, 400 mg in the morning and 200 mg in the afternoon, or 400 mg b.i.d. on days 10-19.

For consolidation, patients could receive up to four cycles of G-CSF, cladribine, and cytarabine plus sorafenib on days 8-27. Patients who did not proceed to transplant could receive 12 months of sorafenib as maintenance therapy.

There were four dose-limiting toxicities.

• Grade 4 intracranial hemorrhage with mitoxantrone at 12 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 prolonged count recovery with mitoxantrone at 15 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 sepsis, Sweet syndrome, and Bell’s palsy with mitoxantrone at 18 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 3 cardiomyopathy and acute pericarditis with mitoxantrone at 18 mg/m² and sorafenib at 400 mg b.i.d.

However, these toxicities did not define the maximum-tolerated dose. Therefore, the recommended phase 2 dose of mitoxantrone is 18 mg/m², and the recommended phase 2 dose of sorafenib is 400 mg b.i.d.

There were no grade 5 treatment-related adverse events. Grade 3 events included febrile neutropenia (90%), maculopapular rash (20%), infections (10%), hand-foot syndrome (2%), and diarrhea (1%). Grade 4 events included sepsis, intracranial hemorrhage, and oral mucositis (all 1%).

Response and survival

Among the 46 evaluable patients, 83% achieved a complete response, 78% had a minimal residual disease–negative complete response, and 4% had a minimal residual disease–negative complete response with incomplete count recovery. A morphological leukemia-free state was achieved by 4% of patients, and 8% had resistant disease.

Fifty-nine percent of patients went on to transplant. The median overall survival had not been reached at a median follow-up of 10 months.

The researchers compared outcomes in this trial with outcomes in a cohort of patients who had received GCLAM alone, and there were no significant differences in overall survival or event-free survival.

“The trial wasn’t powered, necessarily, for efficacy, but we compared these results to our historical cohort of medically matched and age-matched patients treated with GCLAM alone and, so far, found no differences in survival between the two groups,” Dr. Halpern said.

She noted, however, that follow-up was short in the sorafenib trial, and it included patients treated with all dose levels of sorafenib and mitoxantrone.

A phase 2 study of sorafenib plus GCLAM in newly diagnosed AML or high-risk MDS is now underway.

Dr. Halpern and Ms. Garcia reported that they had no conflicts of interest. The phase 1 trial was sponsored by the University of Washington in collaboration with the National Cancer Institute, and funding was provided by Bayer.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – A five-drug regimen was deemed safe in patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), and it appeared to be effective regardless of patients’ FLT3 status.

Researchers tested this regimen – sorafenib plus granulocyte colony–stimulating factor (G-CSF), cladribine, high-dose cytarabine, and mitoxantrone (GCLAM) – in a phase 1 trial.

Kelsey-Leigh Garcia, a clinical research coordinator at Seattle Cancer Care Alliance, and her colleagues presented the results at the Acute Leukemia Forum of Hemedicus.

“The background for doing this study was our institutional results of GCLAM [Leukemia. 2018 Nov;32(11):2352-62] that showed a higher minimal residual disease–negative complete response rate than 7+3 [cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days] and an international study by Röllig that showed the addition of sorafenib to 7+3 increased event-free survival versus [7+3 and] placebo [Lancet Oncol. 2015 Dec;16(16):1691-9],” Ms. Garcia said.

“GCLAM is the standard backbone at our institution, and we wanted to ask the question, ‘If we add sorafenib, can this improve upon the results of GCLAM?’ ” said Anna Halpern, MD, a hematologist-oncologist at the University of Washington, Seattle and principal investigator of the phase 1 trial.

The trial (NCT02728050) included 47 patients, 39 with AML and 8 with MDS. Patients were aged 60 years or younger and had a median age of 48. They had a median treatment-related mortality score of 1.76 (range, 0.19-12.26). A total of 11 patients (23%) had FLT3-ITD, and 4 (9%) had FLT3-TKD.

Treatment and toxicity

For induction, patients received G-CSF at 5 mcg/kg on days 0-5, cladribine at 5 mg/m² on days 1-5, and cytarabine at 2 g/m² on days 1-5. Mitoxantrone was given at 10 mg/m², 12 mg/m², 15 mg/m², or 18 mg/m² on days 1-3. Sorafenib was given at 200 mg twice daily, 400 mg in the morning and 200 mg in the afternoon, or 400 mg b.i.d. on days 10-19.

For consolidation, patients could receive up to four cycles of G-CSF, cladribine, and cytarabine plus sorafenib on days 8-27. Patients who did not proceed to transplant could receive 12 months of sorafenib as maintenance therapy.

There were four dose-limiting toxicities.

• Grade 4 intracranial hemorrhage with mitoxantrone at 12 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 prolonged count recovery with mitoxantrone at 15 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 sepsis, Sweet syndrome, and Bell’s palsy with mitoxantrone at 18 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 3 cardiomyopathy and acute pericarditis with mitoxantrone at 18 mg/m² and sorafenib at 400 mg b.i.d.

However, these toxicities did not define the maximum-tolerated dose. Therefore, the recommended phase 2 dose of mitoxantrone is 18 mg/m², and the recommended phase 2 dose of sorafenib is 400 mg b.i.d.

There were no grade 5 treatment-related adverse events. Grade 3 events included febrile neutropenia (90%), maculopapular rash (20%), infections (10%), hand-foot syndrome (2%), and diarrhea (1%). Grade 4 events included sepsis, intracranial hemorrhage, and oral mucositis (all 1%).

Response and survival

Among the 46 evaluable patients, 83% achieved a complete response, 78% had a minimal residual disease–negative complete response, and 4% had a minimal residual disease–negative complete response with incomplete count recovery. A morphological leukemia-free state was achieved by 4% of patients, and 8% had resistant disease.

Fifty-nine percent of patients went on to transplant. The median overall survival had not been reached at a median follow-up of 10 months.

The researchers compared outcomes in this trial with outcomes in a cohort of patients who had received GCLAM alone, and there were no significant differences in overall survival or event-free survival.

“The trial wasn’t powered, necessarily, for efficacy, but we compared these results to our historical cohort of medically matched and age-matched patients treated with GCLAM alone and, so far, found no differences in survival between the two groups,” Dr. Halpern said.

She noted, however, that follow-up was short in the sorafenib trial, and it included patients treated with all dose levels of sorafenib and mitoxantrone.

A phase 2 study of sorafenib plus GCLAM in newly diagnosed AML or high-risk MDS is now underway.

Dr. Halpern and Ms. Garcia reported that they had no conflicts of interest. The phase 1 trial was sponsored by the University of Washington in collaboration with the National Cancer Institute, and funding was provided by Bayer.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

SAN FRANCISCO – For almost a year, lupus patients at Duke University in Durham, N.C., have been getting two physician global assessments, the usual one for classic “type I” disease, and a new one for nonspecific “type II” symptoms: fatigue, widespread pain, depression, sleep disturbance, and cognitive dysfunction.

M. Alexander Otto/MDedge News

It’s often the type II problems that affect patients the most, and what they are most concerned about; formally assessing them with the type II physician global assessment (PGA) – a 0- to 3-point visual analog scale – ensures they aren’t overlooked, said Jennifer Rogers, MD, assistant professor of rheumatology at Duke.

It “forces us to address these symptoms,” she said, and the approach seems to be working, according to a study Dr. Rogers presented at an international congress on systemic lupus erythematosus.

In the 5 months leading up to implementation of the PGA II in late spring 2018, type II problems had treatment recommendations in patients’ charts just 53% of the time; the number rose to 89% of the time during the PGA II’s first 5 months (P = .03). Type II PGA scores correlated strongly with patient-reported fibromyalgia and depression symptoms, but did not correlate with PGA scores for type I symptoms, such as nephritis and arthritis.

Type II problems are common in lupus. Patients’ joints might be fine, and their kidney disease in remission, but they can still feel miserable, and will often blame it on a lupus flare. Physicians who disagree end up at odds with their patients, Dr. Rogers explained.

“We decided to rethink how we address these patients, and came up with this new type I, type II categorization.” Now, when paints complain of brain fog, for example, “I say ‘yes, this is your lupus. I believe you,’ but we don’t need to give you more steroids or very expensive immunosuppressives for this. What you need to do is take your Cymbalta, work on your exercise, and maybe see your therapist,” she said.

It validates what people are going through, and builds trust. “Patients like it; they feel heard, and I walk out of the room, and I feel better,” she said.

During its first 5 months, 197 patients had PGAs for type II symptoms, along with type I PGAs. The average age of the patients was 46 years, and 92% were women.

Patients with predominately type II symptoms were more likely than were those with predominately type I disease to be depressed (84% versus 39%), and they reported higher lupus activity, greater symptom severity, and more severe fibromyalgia. The differences were statistically significant.

Type II treatments included medications in 60% of cases, exercise or physical therapy in almost 60% of cases, sleep studies or help with sleep hygiene in about 35%, and psychiatric or psychological referral in almost 20%. Less than 5% of patients were referred to a pain clinic.

There was no external funding for the study, and Dr. Rogers didn’t have any disclosures.

[email protected]

SOURCE: Rogers J et al. Lupus Sci Med. 2019;6[suppl 1]: Abstract 102. doi: 10.1136/lupus-2019-lsm.102

SAN FRANCISCO – For almost a year, lupus patients at Duke University in Durham, N.C., have been getting two physician global assessments, the usual one for classic “type I” disease, and a new one for nonspecific “type II” symptoms: fatigue, widespread pain, depression, sleep disturbance, and cognitive dysfunction.

M. Alexander Otto/MDedge News

It’s often the type II problems that affect patients the most, and what they are most concerned about; formally assessing them with the type II physician global assessment (PGA) – a 0- to 3-point visual analog scale – ensures they aren’t overlooked, said Jennifer Rogers, MD, assistant professor of rheumatology at Duke.

It “forces us to address these symptoms,” she said, and the approach seems to be working, according to a study Dr. Rogers presented at an international congress on systemic lupus erythematosus.

In the 5 months leading up to implementation of the PGA II in late spring 2018, type II problems had treatment recommendations in patients’ charts just 53% of the time; the number rose to 89% of the time during the PGA II’s first 5 months (P = .03). Type II PGA scores correlated strongly with patient-reported fibromyalgia and depression symptoms, but did not correlate with PGA scores for type I symptoms, such as nephritis and arthritis.

Type II problems are common in lupus. Patients’ joints might be fine, and their kidney disease in remission, but they can still feel miserable, and will often blame it on a lupus flare. Physicians who disagree end up at odds with their patients, Dr. Rogers explained.

“We decided to rethink how we address these patients, and came up with this new type I, type II categorization.” Now, when paints complain of brain fog, for example, “I say ‘yes, this is your lupus. I believe you,’ but we don’t need to give you more steroids or very expensive immunosuppressives for this. What you need to do is take your Cymbalta, work on your exercise, and maybe see your therapist,” she said.

It validates what people are going through, and builds trust. “Patients like it; they feel heard, and I walk out of the room, and I feel better,” she said.

During its first 5 months, 197 patients had PGAs for type II symptoms, along with type I PGAs. The average age of the patients was 46 years, and 92% were women.

Patients with predominately type II symptoms were more likely than were those with predominately type I disease to be depressed (84% versus 39%), and they reported higher lupus activity, greater symptom severity, and more severe fibromyalgia. The differences were statistically significant.

Type II treatments included medications in 60% of cases, exercise or physical therapy in almost 60% of cases, sleep studies or help with sleep hygiene in about 35%, and psychiatric or psychological referral in almost 20%. Less than 5% of patients were referred to a pain clinic.

There was no external funding for the study, and Dr. Rogers didn’t have any disclosures.

[email protected]

SOURCE: Rogers J et al. Lupus Sci Med. 2019;6[suppl 1]: Abstract 102. doi: 10.1136/lupus-2019-lsm.102

SAN FRANCISCO – For almost a year, lupus patients at Duke University in Durham, N.C., have been getting two physician global assessments, the usual one for classic “type I” disease, and a new one for nonspecific “type II” symptoms: fatigue, widespread pain, depression, sleep disturbance, and cognitive dysfunction.

M. Alexander Otto/MDedge News

It’s often the type II problems that affect patients the most, and what they are most concerned about; formally assessing them with the type II physician global assessment (PGA) – a 0- to 3-point visual analog scale – ensures they aren’t overlooked, said Jennifer Rogers, MD, assistant professor of rheumatology at Duke.

It “forces us to address these symptoms,” she said, and the approach seems to be working, according to a study Dr. Rogers presented at an international congress on systemic lupus erythematosus.

In the 5 months leading up to implementation of the PGA II in late spring 2018, type II problems had treatment recommendations in patients’ charts just 53% of the time; the number rose to 89% of the time during the PGA II’s first 5 months (P = .03). Type II PGA scores correlated strongly with patient-reported fibromyalgia and depression symptoms, but did not correlate with PGA scores for type I symptoms, such as nephritis and arthritis.

Type II problems are common in lupus. Patients’ joints might be fine, and their kidney disease in remission, but they can still feel miserable, and will often blame it on a lupus flare. Physicians who disagree end up at odds with their patients, Dr. Rogers explained.

“We decided to rethink how we address these patients, and came up with this new type I, type II categorization.” Now, when paints complain of brain fog, for example, “I say ‘yes, this is your lupus. I believe you,’ but we don’t need to give you more steroids or very expensive immunosuppressives for this. What you need to do is take your Cymbalta, work on your exercise, and maybe see your therapist,” she said.

It validates what people are going through, and builds trust. “Patients like it; they feel heard, and I walk out of the room, and I feel better,” she said.

During its first 5 months, 197 patients had PGAs for type II symptoms, along with type I PGAs. The average age of the patients was 46 years, and 92% were women.

Patients with predominately type II symptoms were more likely than were those with predominately type I disease to be depressed (84% versus 39%), and they reported higher lupus activity, greater symptom severity, and more severe fibromyalgia. The differences were statistically significant.

Type II treatments included medications in 60% of cases, exercise or physical therapy in almost 60% of cases, sleep studies or help with sleep hygiene in about 35%, and psychiatric or psychological referral in almost 20%. Less than 5% of patients were referred to a pain clinic.

There was no external funding for the study, and Dr. Rogers didn’t have any disclosures.

[email protected]

SOURCE: Rogers J et al. Lupus Sci Med. 2019;6[suppl 1]: Abstract 102. doi: 10.1136/lupus-2019-lsm.102

First reported in 1895, nevus sebaceus (NS) is a con genital papillomatous hamartoma most commonly found on the scalp and face. ¹ Lesions typically are yellow-orange plaques and often are hairless. Nevus sebaceus is most prominent in the few first months after birth and again at puberty during development of the sebaceous glands. Development of epithelial hyperplasia, cysts, verrucas, and benign or malignant tumors has been reported. ¹ The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma. Cases of malignancy are rare, and basal cell carcinoma is the predominant form (approximately 2% of cases). Squamous cell carcinoma (SCC) and adnexal carcinoma are reported at even lower rates. ¹ Malignant transformation occurring during childhood is extremely uncommon. According to a PubMed search of articles indexed for MEDLINE using the terms nevus sebaceous, malignancy, and squamous cell carcinoma and narrowing the results to children, there have been only 4 prior reports of SCC developing within an NS in a child. ^2-5 We report a case of SCC arising in an NS in a 13-year-old adolescent girl with perineural invasion.

Case Report

A 13-year-old fair-skinned adolescent girl presented with a hairless 2×2.5-cm yellow plaque at the hairline on the anterior central scalp. The plaque had been present since birth and had progressively developed a superiorly located 3×5-mm erythematous verrucous nodule (Figure 1) with an approximate height of 6 mm over the last year. The nodule was subjected to regular trauma and bled with minimal insult. The patient appeared otherwise healthy, with no history of skin cancer or other chronic medical conditions. There was no evidence of lymphadenopathy on examination, and no other skin abnormalities were noted. There was no reported family history of skin cancer or chronic skin conditions suggestive of increased risk for cancer or other pathologic dermatoses. Differential diagnoses for the plaque and nodule complex included verruca, Spitz nevus, or secondary neoplasm within NS.

Excision was conducted under local anesthesia without complication. An elliptical section of skin measuring 0.8×2.5 cm was excised to a depth of 3 mm. The resulting wound was closed using a complex linear repair. The section was placed in formalin specimen transport medium and sent to Walter Reed National Military Medical Center (Bethesda, Maryland). Microscopic examination of the specimen revealed features typical for NS, including mild verrucous epidermal hyperplasia, sebaceous gland hyperplasia, presence of apocrine glands, and hamartomatous follicular proliferations (Figure 2). An even more papillomatous epidermal proliferation that was comprised of atypical squamous cells was present within the lesion. Similar atypical squamous cells infiltrated the superficial dermis in nests, cords, and single cells (Figure 3A). One focus showed perineural invasion with a small superficial nerve fiber surrounded by SCC (Figure 3B). The tumor was completely excised, with negative surgical margins extending approximately 2 mm. Adjuvant radiation therapy and further specialized Mohs micrographic excision were not performed because of the clear histologic appearance of the carcinoma and strong evidence of complete excision.

At 2-week follow-up, the surgical scar on the anterior central forehead was well healed without evidence of SCC recurrence. On physical examination there was neither lymphadenopathy nor signs of neurologic deficit, except for superficial cutaneous hypoesthesia in the immediate area surrounding the healed site. Following discussion with the patient and her parents, it was decided that the patient would obtain baseline laboratory tests, chest radiography, and abdominal ultrasonography, and she would undergo serial follow-up examinations every 3 months for the next 2 years. Annual follow-up was recommended after 2 years, with the caveat to return sooner if recurrence or symptoms were to arise.

Comment

Historically, there has been variability in the histopathologic interpretation of SCC in NS in the literature. Retrospective analysis of the histologic evidence of SCC in the 2 earliest possible cases of pediatric SCC in NS have been questioned due to the lack of clinical data presented and the possibility that the diagnosis of SCC was inaccurate.⁶ Our case was histopathologically interpreted as superficially invasive, well-differentiated SCC arising within an NS; therefore, we classified this case as SCC and took every precaution to ensure the lesion was completely excised, given the potentially invasive nature of SCC.

Our case is unique because it represents SCC in NS with histologic evidence of perineural involvement. Perineural invasion is a major route of tumor spread in SCC and may result in increased occurrence of regional lymph node spread and distant metastases, with path of least resistance or neural cell adhesion as possible spreading methods.^7-9 However, there is a notable amount of prognostic variability based on tumor type, the nerve involved, and degree of involvement.⁹ It is common for cutaneous SCC to occur with invasion of small intradermal nerves, but a poor outcome is less likely in asymptomatic patients who have perineural involvement that was incidentally discovered on histologic examination.¹⁰

In our patient, the entire tumor was completely removed with local excision. Recurrence of the SCC or future symptoms of deep neural invasion were not anticipated given the postoperative evidence of clear margins in the excised skin and subdermal structures as well as the lack of preoperative and postoperative symptoms. Close clinical follow-up was warranted to monitor for early signs of recurrence or neural involvement. We have confidence that the planned follow-up regimen in our patient will reveal any early signs of new occurrence or recurrence.

In the case of recurrence, Mohs micrographic surgery would likely be indicated. We elected not to treat with adjuvant radiotherapy because its benefit in cutaneous SCC with perineural invasion is debatable based on the lack of randomized controlled clinical evidence.^10,11 The patient obtained postoperative baseline complete blood cell count with differential, posterior/anterior and lateral chest radiographs, as well as abdominal ultrasonography. Each returned negative findings of hematologic or distant organ metastases, with subsequent follow-up visits also negative for any new concerning findings.

First reported in 1895, nevus sebaceus (NS) is a con genital papillomatous hamartoma most commonly found on the scalp and face. ¹ Lesions typically are yellow-orange plaques and often are hairless. Nevus sebaceus is most prominent in the few first months after birth and again at puberty during development of the sebaceous glands. Development of epithelial hyperplasia, cysts, verrucas, and benign or malignant tumors has been reported. ¹ The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma. Cases of malignancy are rare, and basal cell carcinoma is the predominant form (approximately 2% of cases). Squamous cell carcinoma (SCC) and adnexal carcinoma are reported at even lower rates. ¹ Malignant transformation occurring during childhood is extremely uncommon. According to a PubMed search of articles indexed for MEDLINE using the terms nevus sebaceous, malignancy, and squamous cell carcinoma and narrowing the results to children, there have been only 4 prior reports of SCC developing within an NS in a child. ^2-5 We report a case of SCC arising in an NS in a 13-year-old adolescent girl with perineural invasion.

Case Report

A 13-year-old fair-skinned adolescent girl presented with a hairless 2×2.5-cm yellow plaque at the hairline on the anterior central scalp. The plaque had been present since birth and had progressively developed a superiorly located 3×5-mm erythematous verrucous nodule (Figure 1) with an approximate height of 6 mm over the last year. The nodule was subjected to regular trauma and bled with minimal insult. The patient appeared otherwise healthy, with no history of skin cancer or other chronic medical conditions. There was no evidence of lymphadenopathy on examination, and no other skin abnormalities were noted. There was no reported family history of skin cancer or chronic skin conditions suggestive of increased risk for cancer or other pathologic dermatoses. Differential diagnoses for the plaque and nodule complex included verruca, Spitz nevus, or secondary neoplasm within NS.

Excision was conducted under local anesthesia without complication. An elliptical section of skin measuring 0.8×2.5 cm was excised to a depth of 3 mm. The resulting wound was closed using a complex linear repair. The section was placed in formalin specimen transport medium and sent to Walter Reed National Military Medical Center (Bethesda, Maryland). Microscopic examination of the specimen revealed features typical for NS, including mild verrucous epidermal hyperplasia, sebaceous gland hyperplasia, presence of apocrine glands, and hamartomatous follicular proliferations (Figure 2). An even more papillomatous epidermal proliferation that was comprised of atypical squamous cells was present within the lesion. Similar atypical squamous cells infiltrated the superficial dermis in nests, cords, and single cells (Figure 3A). One focus showed perineural invasion with a small superficial nerve fiber surrounded by SCC (Figure 3B). The tumor was completely excised, with negative surgical margins extending approximately 2 mm. Adjuvant radiation therapy and further specialized Mohs micrographic excision were not performed because of the clear histologic appearance of the carcinoma and strong evidence of complete excision.

At 2-week follow-up, the surgical scar on the anterior central forehead was well healed without evidence of SCC recurrence. On physical examination there was neither lymphadenopathy nor signs of neurologic deficit, except for superficial cutaneous hypoesthesia in the immediate area surrounding the healed site. Following discussion with the patient and her parents, it was decided that the patient would obtain baseline laboratory tests, chest radiography, and abdominal ultrasonography, and she would undergo serial follow-up examinations every 3 months for the next 2 years. Annual follow-up was recommended after 2 years, with the caveat to return sooner if recurrence or symptoms were to arise.

Comment

Historically, there has been variability in the histopathologic interpretation of SCC in NS in the literature. Retrospective analysis of the histologic evidence of SCC in the 2 earliest possible cases of pediatric SCC in NS have been questioned due to the lack of clinical data presented and the possibility that the diagnosis of SCC was inaccurate.⁶ Our case was histopathologically interpreted as superficially invasive, well-differentiated SCC arising within an NS; therefore, we classified this case as SCC and took every precaution to ensure the lesion was completely excised, given the potentially invasive nature of SCC.

Our case is unique because it represents SCC in NS with histologic evidence of perineural involvement. Perineural invasion is a major route of tumor spread in SCC and may result in increased occurrence of regional lymph node spread and distant metastases, with path of least resistance or neural cell adhesion as possible spreading methods.^7-9 However, there is a notable amount of prognostic variability based on tumor type, the nerve involved, and degree of involvement.⁹ It is common for cutaneous SCC to occur with invasion of small intradermal nerves, but a poor outcome is less likely in asymptomatic patients who have perineural involvement that was incidentally discovered on histologic examination.¹⁰

In our patient, the entire tumor was completely removed with local excision. Recurrence of the SCC or future symptoms of deep neural invasion were not anticipated given the postoperative evidence of clear margins in the excised skin and subdermal structures as well as the lack of preoperative and postoperative symptoms. Close clinical follow-up was warranted to monitor for early signs of recurrence or neural involvement. We have confidence that the planned follow-up regimen in our patient will reveal any early signs of new occurrence or recurrence.

In the case of recurrence, Mohs micrographic surgery would likely be indicated. We elected not to treat with adjuvant radiotherapy because its benefit in cutaneous SCC with perineural invasion is debatable based on the lack of randomized controlled clinical evidence.^10,11 The patient obtained postoperative baseline complete blood cell count with differential, posterior/anterior and lateral chest radiographs, as well as abdominal ultrasonography. Each returned negative findings of hematologic or distant organ metastases, with subsequent follow-up visits also negative for any new concerning findings.

First reported in 1895, nevus sebaceus (NS) is a con genital papillomatous hamartoma most commonly found on the scalp and face. ¹ Lesions typically are yellow-orange plaques and often are hairless. Nevus sebaceus is most prominent in the few first months after birth and again at puberty during development of the sebaceous glands. Development of epithelial hyperplasia, cysts, verrucas, and benign or malignant tumors has been reported. ¹ The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma. Cases of malignancy are rare, and basal cell carcinoma is the predominant form (approximately 2% of cases). Squamous cell carcinoma (SCC) and adnexal carcinoma are reported at even lower rates. ¹ Malignant transformation occurring during childhood is extremely uncommon. According to a PubMed search of articles indexed for MEDLINE using the terms nevus sebaceous, malignancy, and squamous cell carcinoma and narrowing the results to children, there have been only 4 prior reports of SCC developing within an NS in a child. ^2-5 We report a case of SCC arising in an NS in a 13-year-old adolescent girl with perineural invasion.

Case Report

A 13-year-old fair-skinned adolescent girl presented with a hairless 2×2.5-cm yellow plaque at the hairline on the anterior central scalp. The plaque had been present since birth and had progressively developed a superiorly located 3×5-mm erythematous verrucous nodule (Figure 1) with an approximate height of 6 mm over the last year. The nodule was subjected to regular trauma and bled with minimal insult. The patient appeared otherwise healthy, with no history of skin cancer or other chronic medical conditions. There was no evidence of lymphadenopathy on examination, and no other skin abnormalities were noted. There was no reported family history of skin cancer or chronic skin conditions suggestive of increased risk for cancer or other pathologic dermatoses. Differential diagnoses for the plaque and nodule complex included verruca, Spitz nevus, or secondary neoplasm within NS.

Excision was conducted under local anesthesia without complication. An elliptical section of skin measuring 0.8×2.5 cm was excised to a depth of 3 mm. The resulting wound was closed using a complex linear repair. The section was placed in formalin specimen transport medium and sent to Walter Reed National Military Medical Center (Bethesda, Maryland). Microscopic examination of the specimen revealed features typical for NS, including mild verrucous epidermal hyperplasia, sebaceous gland hyperplasia, presence of apocrine glands, and hamartomatous follicular proliferations (Figure 2). An even more papillomatous epidermal proliferation that was comprised of atypical squamous cells was present within the lesion. Similar atypical squamous cells infiltrated the superficial dermis in nests, cords, and single cells (Figure 3A). One focus showed perineural invasion with a small superficial nerve fiber surrounded by SCC (Figure 3B). The tumor was completely excised, with negative surgical margins extending approximately 2 mm. Adjuvant radiation therapy and further specialized Mohs micrographic excision were not performed because of the clear histologic appearance of the carcinoma and strong evidence of complete excision.

At 2-week follow-up, the surgical scar on the anterior central forehead was well healed without evidence of SCC recurrence. On physical examination there was neither lymphadenopathy nor signs of neurologic deficit, except for superficial cutaneous hypoesthesia in the immediate area surrounding the healed site. Following discussion with the patient and her parents, it was decided that the patient would obtain baseline laboratory tests, chest radiography, and abdominal ultrasonography, and she would undergo serial follow-up examinations every 3 months for the next 2 years. Annual follow-up was recommended after 2 years, with the caveat to return sooner if recurrence or symptoms were to arise.

Comment

Historically, there has been variability in the histopathologic interpretation of SCC in NS in the literature. Retrospective analysis of the histologic evidence of SCC in the 2 earliest possible cases of pediatric SCC in NS have been questioned due to the lack of clinical data presented and the possibility that the diagnosis of SCC was inaccurate.⁶ Our case was histopathologically interpreted as superficially invasive, well-differentiated SCC arising within an NS; therefore, we classified this case as SCC and took every precaution to ensure the lesion was completely excised, given the potentially invasive nature of SCC.

Our case is unique because it represents SCC in NS with histologic evidence of perineural involvement. Perineural invasion is a major route of tumor spread in SCC and may result in increased occurrence of regional lymph node spread and distant metastases, with path of least resistance or neural cell adhesion as possible spreading methods.^7-9 However, there is a notable amount of prognostic variability based on tumor type, the nerve involved, and degree of involvement.⁹ It is common for cutaneous SCC to occur with invasion of small intradermal nerves, but a poor outcome is less likely in asymptomatic patients who have perineural involvement that was incidentally discovered on histologic examination.¹⁰

In our patient, the entire tumor was completely removed with local excision. Recurrence of the SCC or future symptoms of deep neural invasion were not anticipated given the postoperative evidence of clear margins in the excised skin and subdermal structures as well as the lack of preoperative and postoperative symptoms. Close clinical follow-up was warranted to monitor for early signs of recurrence or neural involvement. We have confidence that the planned follow-up regimen in our patient will reveal any early signs of new occurrence or recurrence.

In the case of recurrence, Mohs micrographic surgery would likely be indicated. We elected not to treat with adjuvant radiotherapy because its benefit in cutaneous SCC with perineural invasion is debatable based on the lack of randomized controlled clinical evidence.^10,11 The patient obtained postoperative baseline complete blood cell count with differential, posterior/anterior and lateral chest radiographs, as well as abdominal ultrasonography. Each returned negative findings of hematologic or distant organ metastases, with subsequent follow-up visits also negative for any new concerning findings.