Case Report

A 66-year-old man with a history of type 2 diabetes mellitus presented with considerable muscle weakness and infiltrative, flesh-colored plaques on the face, trunk, and arms of 3 months’ duration. The patient required the use of a wheelchair due to muscle weakness. On physical examination he had diffuse, infiltrative, flesh-colored plaques on the entire face (Figure 1A), trunk, and arms. The eyelids and lips were swollen, and the nose was distorted due to the infiltrative plaques (Figure 1B). Additionally, there were hypopigmented macules and patches scattered among the infiltrative plaques on the face, trunk, and arms (Figure 1C).

Punch biopsy specimens were obtained from the left cheek and left upper arm and were submitted for histologic examination with routine hematoxylin and eosin staining (Figure 2). Histopathology showed infiltrating and diffuse monomorphic cells in the dermis with large and hyperchromatic nuclei. Some nuclei were cleaved or folded in configuration. The cells displayed ample surrounding cytoplasm, which was finely granular or vacuolated. The infiltrate was accentuated in the perifollicular adventitial dermis. Immunohistochemistry was positive for CD33 and negative for CD3, CD20, and myeloperoxidase. Additionally, periodic acid–Schiff and Fite stains were negative for microorganisms. These morphologic and immunohistochemical findings were consistent with acute myeloid leukemia (AML). Further testing with complete blood cell count, peripheral blood smear, and bone marrow biopsy confirmed the diagnosis of AML. The patient subsequently died 5 weeks later.

Comment

Presentation of LC
Thirty percent to 40% of leukemia patients present with a variety of nonspecific cutaneous signs, including those related to hemorrhage, infection, and drug eruptions, as well as paraneoplastic lesions.1 Cutaneous signs of leukemia are less commonly due to leukemia cutis (LC), defined as the neoplastic infiltration of the skin or subcutaneous tissue by leukemic cells. The clinical presentation of LC varies, making it difficult to diagnose without immunohistochemistry. It can pre-sent as single or multiple erythematous papules and/or nodules, infiltrated plaques, macules, palpable purpura, ulcers, ecchymoses, and/or vesicles.² Leukemia cutis most often presents on the head, neck, trunk, and sites of current or prior trauma. Gingival hyperplasia is another associated finding in the acute monocytic and myelomonocytic types of AML.³ Additionally, chloromas or granulocytic sarcomas are dermal nodules that can pre-sent in myelogenous leukemia.⁴

LC and AML
Leukemia cutis most commonly is observed in AML compared to the other types of leukemia. The myelomonocytic and monocytic subtypes of AML are most often implicated.^5,6 The majority of patients with LC present with a pre-established (55%–77%) or simultaneous diagnosis of systemic leukemia (23%–38%). Rarely do patients present with LC with lack of systemic involvement and a normal peripheral smear (7%),² which would be diagnosed as aleukemic leukemia.^2,7 Furthermore, LC highly correlates with sites of additional extramedullary involvement; thus, the presence of LC in AML often signifies a poor prognosis.⁸ The 2-year survival rate for AML patients without LC is 30%, but for AML patients with LC it is only 6%.¹

Histopathology
In LC, histology typically reveals a normal epidermis and nodular or diffuse infiltrating cells in the dermis. The cells can appear monomorphic, atypical, or immature, and there is occasional single-filing between collagen bundles. Causative types of neoplasms can be distinguished based on their morphologic, immunophenotypic, and cytogenetic properties.^8-10

Incidence
Of the acute leukemias, AML accounts for the highest prevalence in adults,11 with an annual incidence of 14,590 cases in the United States.¹² The incidence of AML increases with age; the mean age of patients diagnosed with AML is 67 years.¹² Risk is increased with a history of exposure to radiotherapy, chemotherapy, or cigarette smoke; preexisting myeloproliferative or myelodysplastic syndromes and mutations in DNA repair (eg, Fanconi anemia); neutropenia (eg, from elastase mutations); and Down syndrome.¹³

Diagnosis
More than 20% blasts in the bone marrow is required for a diagnosis of AML.¹⁴ Specific to AML is the presence of large immature precursor cells with a granular cytoplasm and, when present, highly diagnostic Auer rods.¹²Acute myeloid leukemia can be distinguished by staining for myeloperoxidase; Sudan Black B; or the antigens CD13, CD33, or c-kit.¹⁵

In our case, CD33 was positive, which is a characteristic finding in AML. Myeloperoxidase also can be positive in AML; however, in our case it was negative, and it can be an insensitive marker in the context of LC. Although most cases of LC present concurrently with bone marrow infiltration, some cases present before systemic involvement; for example, granulocytic sarcomas can occur months earlier than the development of systemic leukemia. Thus, early detection by a dermatologist is essential. Depending on the lesion’s appearance, the differential diagnoses can include lymphoma, drug eruptions, infectious etiologies, sarcoidosis, metastases from other malignancies, and blistering dermatoses.

Management
Systemic therapy should be the cornerstone of therapy. Induction therapy includes the combined use of cytarabine (except in acute promyelocytic leukemia [M3], for which all-trans retinoic acid is indicated) and anthracycline derivatives in a “7+3” regimen to achieve complete remission. Specifically, cytarabine (100–200 mg/m²) typically is continuously administered intravenously for 7 days combined with intravenous administration of either daunorubicin (60–90 mg/m²) or idarubicin (12 mg/m²) on days 1, 2, and 3. Postremission therapy is highly individualized depending on patients’ prognostic factors and is indicated to reduce the likelihood of relapse and to improve patient mortality. High doses of cytarabine and hematopoietic stem cell transplantation commonly are utilized.¹² Resolution of hematologic atypia may result in complete or partial resolution of LC.¹⁰

Conclusion

We diagnosed AML with systemic involvement in our patient based on the cutaneous manifestation of LC. Diagnosis of LC relies on immunohistochemistry and strong clinical suspicion, as cutaneous findings are diverse and nonspecific. Early recognition is essential, as LC in the context of systemic involvement portends a poor prognosis. Our patient died 5 weeks following initial presentation.

Case Report

A 66-year-old man with a history of type 2 diabetes mellitus presented with considerable muscle weakness and infiltrative, flesh-colored plaques on the face, trunk, and arms of 3 months’ duration. The patient required the use of a wheelchair due to muscle weakness. On physical examination he had diffuse, infiltrative, flesh-colored plaques on the entire face (Figure 1A), trunk, and arms. The eyelids and lips were swollen, and the nose was distorted due to the infiltrative plaques (Figure 1B). Additionally, there were hypopigmented macules and patches scattered among the infiltrative plaques on the face, trunk, and arms (Figure 1C).

Punch biopsy specimens were obtained from the left cheek and left upper arm and were submitted for histologic examination with routine hematoxylin and eosin staining (Figure 2). Histopathology showed infiltrating and diffuse monomorphic cells in the dermis with large and hyperchromatic nuclei. Some nuclei were cleaved or folded in configuration. The cells displayed ample surrounding cytoplasm, which was finely granular or vacuolated. The infiltrate was accentuated in the perifollicular adventitial dermis. Immunohistochemistry was positive for CD33 and negative for CD3, CD20, and myeloperoxidase. Additionally, periodic acid–Schiff and Fite stains were negative for microorganisms. These morphologic and immunohistochemical findings were consistent with acute myeloid leukemia (AML). Further testing with complete blood cell count, peripheral blood smear, and bone marrow biopsy confirmed the diagnosis of AML. The patient subsequently died 5 weeks later.

Comment

Presentation of LC
Thirty percent to 40% of leukemia patients present with a variety of nonspecific cutaneous signs, including those related to hemorrhage, infection, and drug eruptions, as well as paraneoplastic lesions.1 Cutaneous signs of leukemia are less commonly due to leukemia cutis (LC), defined as the neoplastic infiltration of the skin or subcutaneous tissue by leukemic cells. The clinical presentation of LC varies, making it difficult to diagnose without immunohistochemistry. It can pre-sent as single or multiple erythematous papules and/or nodules, infiltrated plaques, macules, palpable purpura, ulcers, ecchymoses, and/or vesicles.² Leukemia cutis most often presents on the head, neck, trunk, and sites of current or prior trauma. Gingival hyperplasia is another associated finding in the acute monocytic and myelomonocytic types of AML.³ Additionally, chloromas or granulocytic sarcomas are dermal nodules that can pre-sent in myelogenous leukemia.⁴

LC and AML
Leukemia cutis most commonly is observed in AML compared to the other types of leukemia. The myelomonocytic and monocytic subtypes of AML are most often implicated.^5,6 The majority of patients with LC present with a pre-established (55%–77%) or simultaneous diagnosis of systemic leukemia (23%–38%). Rarely do patients present with LC with lack of systemic involvement and a normal peripheral smear (7%),² which would be diagnosed as aleukemic leukemia.^2,7 Furthermore, LC highly correlates with sites of additional extramedullary involvement; thus, the presence of LC in AML often signifies a poor prognosis.⁸ The 2-year survival rate for AML patients without LC is 30%, but for AML patients with LC it is only 6%.¹

Histopathology
In LC, histology typically reveals a normal epidermis and nodular or diffuse infiltrating cells in the dermis. The cells can appear monomorphic, atypical, or immature, and there is occasional single-filing between collagen bundles. Causative types of neoplasms can be distinguished based on their morphologic, immunophenotypic, and cytogenetic properties.^8-10

Incidence
Of the acute leukemias, AML accounts for the highest prevalence in adults,11 with an annual incidence of 14,590 cases in the United States.¹² The incidence of AML increases with age; the mean age of patients diagnosed with AML is 67 years.¹² Risk is increased with a history of exposure to radiotherapy, chemotherapy, or cigarette smoke; preexisting myeloproliferative or myelodysplastic syndromes and mutations in DNA repair (eg, Fanconi anemia); neutropenia (eg, from elastase mutations); and Down syndrome.¹³

Diagnosis
More than 20% blasts in the bone marrow is required for a diagnosis of AML.¹⁴ Specific to AML is the presence of large immature precursor cells with a granular cytoplasm and, when present, highly diagnostic Auer rods.¹²Acute myeloid leukemia can be distinguished by staining for myeloperoxidase; Sudan Black B; or the antigens CD13, CD33, or c-kit.¹⁵

In our case, CD33 was positive, which is a characteristic finding in AML. Myeloperoxidase also can be positive in AML; however, in our case it was negative, and it can be an insensitive marker in the context of LC. Although most cases of LC present concurrently with bone marrow infiltration, some cases present before systemic involvement; for example, granulocytic sarcomas can occur months earlier than the development of systemic leukemia. Thus, early detection by a dermatologist is essential. Depending on the lesion’s appearance, the differential diagnoses can include lymphoma, drug eruptions, infectious etiologies, sarcoidosis, metastases from other malignancies, and blistering dermatoses.

Management
Systemic therapy should be the cornerstone of therapy. Induction therapy includes the combined use of cytarabine (except in acute promyelocytic leukemia [M3], for which all-trans retinoic acid is indicated) and anthracycline derivatives in a “7+3” regimen to achieve complete remission. Specifically, cytarabine (100–200 mg/m²) typically is continuously administered intravenously for 7 days combined with intravenous administration of either daunorubicin (60–90 mg/m²) or idarubicin (12 mg/m²) on days 1, 2, and 3. Postremission therapy is highly individualized depending on patients’ prognostic factors and is indicated to reduce the likelihood of relapse and to improve patient mortality. High doses of cytarabine and hematopoietic stem cell transplantation commonly are utilized.¹² Resolution of hematologic atypia may result in complete or partial resolution of LC.¹⁰

Conclusion

We diagnosed AML with systemic involvement in our patient based on the cutaneous manifestation of LC. Diagnosis of LC relies on immunohistochemistry and strong clinical suspicion, as cutaneous findings are diverse and nonspecific. Early recognition is essential, as LC in the context of systemic involvement portends a poor prognosis. Our patient died 5 weeks following initial presentation.

Case Report

A 66-year-old man with a history of type 2 diabetes mellitus presented with considerable muscle weakness and infiltrative, flesh-colored plaques on the face, trunk, and arms of 3 months’ duration. The patient required the use of a wheelchair due to muscle weakness. On physical examination he had diffuse, infiltrative, flesh-colored plaques on the entire face (Figure 1A), trunk, and arms. The eyelids and lips were swollen, and the nose was distorted due to the infiltrative plaques (Figure 1B). Additionally, there were hypopigmented macules and patches scattered among the infiltrative plaques on the face, trunk, and arms (Figure 1C).

Punch biopsy specimens were obtained from the left cheek and left upper arm and were submitted for histologic examination with routine hematoxylin and eosin staining (Figure 2). Histopathology showed infiltrating and diffuse monomorphic cells in the dermis with large and hyperchromatic nuclei. Some nuclei were cleaved or folded in configuration. The cells displayed ample surrounding cytoplasm, which was finely granular or vacuolated. The infiltrate was accentuated in the perifollicular adventitial dermis. Immunohistochemistry was positive for CD33 and negative for CD3, CD20, and myeloperoxidase. Additionally, periodic acid–Schiff and Fite stains were negative for microorganisms. These morphologic and immunohistochemical findings were consistent with acute myeloid leukemia (AML). Further testing with complete blood cell count, peripheral blood smear, and bone marrow biopsy confirmed the diagnosis of AML. The patient subsequently died 5 weeks later.

Comment

Presentation of LC
Thirty percent to 40% of leukemia patients present with a variety of nonspecific cutaneous signs, including those related to hemorrhage, infection, and drug eruptions, as well as paraneoplastic lesions.1 Cutaneous signs of leukemia are less commonly due to leukemia cutis (LC), defined as the neoplastic infiltration of the skin or subcutaneous tissue by leukemic cells. The clinical presentation of LC varies, making it difficult to diagnose without immunohistochemistry. It can pre-sent as single or multiple erythematous papules and/or nodules, infiltrated plaques, macules, palpable purpura, ulcers, ecchymoses, and/or vesicles.² Leukemia cutis most often presents on the head, neck, trunk, and sites of current or prior trauma. Gingival hyperplasia is another associated finding in the acute monocytic and myelomonocytic types of AML.³ Additionally, chloromas or granulocytic sarcomas are dermal nodules that can pre-sent in myelogenous leukemia.⁴

LC and AML
Leukemia cutis most commonly is observed in AML compared to the other types of leukemia. The myelomonocytic and monocytic subtypes of AML are most often implicated.^5,6 The majority of patients with LC present with a pre-established (55%–77%) or simultaneous diagnosis of systemic leukemia (23%–38%). Rarely do patients present with LC with lack of systemic involvement and a normal peripheral smear (7%),² which would be diagnosed as aleukemic leukemia.^2,7 Furthermore, LC highly correlates with sites of additional extramedullary involvement; thus, the presence of LC in AML often signifies a poor prognosis.⁸ The 2-year survival rate for AML patients without LC is 30%, but for AML patients with LC it is only 6%.¹

Histopathology
In LC, histology typically reveals a normal epidermis and nodular or diffuse infiltrating cells in the dermis. The cells can appear monomorphic, atypical, or immature, and there is occasional single-filing between collagen bundles. Causative types of neoplasms can be distinguished based on their morphologic, immunophenotypic, and cytogenetic properties.^8-10

Incidence
Of the acute leukemias, AML accounts for the highest prevalence in adults,11 with an annual incidence of 14,590 cases in the United States.¹² The incidence of AML increases with age; the mean age of patients diagnosed with AML is 67 years.¹² Risk is increased with a history of exposure to radiotherapy, chemotherapy, or cigarette smoke; preexisting myeloproliferative or myelodysplastic syndromes and mutations in DNA repair (eg, Fanconi anemia); neutropenia (eg, from elastase mutations); and Down syndrome.¹³

Diagnosis
More than 20% blasts in the bone marrow is required for a diagnosis of AML.¹⁴ Specific to AML is the presence of large immature precursor cells with a granular cytoplasm and, when present, highly diagnostic Auer rods.¹²Acute myeloid leukemia can be distinguished by staining for myeloperoxidase; Sudan Black B; or the antigens CD13, CD33, or c-kit.¹⁵

In our case, CD33 was positive, which is a characteristic finding in AML. Myeloperoxidase also can be positive in AML; however, in our case it was negative, and it can be an insensitive marker in the context of LC. Although most cases of LC present concurrently with bone marrow infiltration, some cases present before systemic involvement; for example, granulocytic sarcomas can occur months earlier than the development of systemic leukemia. Thus, early detection by a dermatologist is essential. Depending on the lesion’s appearance, the differential diagnoses can include lymphoma, drug eruptions, infectious etiologies, sarcoidosis, metastases from other malignancies, and blistering dermatoses.

Management
Systemic therapy should be the cornerstone of therapy. Induction therapy includes the combined use of cytarabine (except in acute promyelocytic leukemia [M3], for which all-trans retinoic acid is indicated) and anthracycline derivatives in a “7+3” regimen to achieve complete remission. Specifically, cytarabine (100–200 mg/m²) typically is continuously administered intravenously for 7 days combined with intravenous administration of either daunorubicin (60–90 mg/m²) or idarubicin (12 mg/m²) on days 1, 2, and 3. Postremission therapy is highly individualized depending on patients’ prognostic factors and is indicated to reduce the likelihood of relapse and to improve patient mortality. High doses of cytarabine and hematopoietic stem cell transplantation commonly are utilized.¹² Resolution of hematologic atypia may result in complete or partial resolution of LC.¹⁰

Conclusion

We diagnosed AML with systemic involvement in our patient based on the cutaneous manifestation of LC. Diagnosis of LC relies on immunohistochemistry and strong clinical suspicion, as cutaneous findings are diverse and nonspecific. Early recognition is essential, as LC in the context of systemic involvement portends a poor prognosis. Our patient died 5 weeks following initial presentation.

NEW YORK – Four-drug combinations are looking promising for the treatment of multiple myeloma, though data from additional randomized trials are needed to define their role in clinical practice, according to Natalie S. Callander, MD, of the University of Wisconsin Carbone Cancer Center, Madison.

“The outlook for myeloma patients is quite good,” Dr. Callander said at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.

“Triplet therapy is the standard, and quad therapy may be in the future.”

The study that set the standard for triplets in myeloma, according to Dr. Callander, is SWOG 0777, an open-label, phase 3 trial that compared bortezomib with lenalidomide and dexamethasone (VRd) to lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma.

Adding bortezomib to lenalidomide and dexamethasone significantly improved both progression-free and overall survival in the 525-patient trial, with a risk-benefit profile that was acceptable (Lancet. 2017 Feb 4;389[10068]:519-27).

The median progression-free survival was 43 months for the triplet, versus 30 months for the two-drug regimen (P = .0018); likewise, median overall survival was significantly improved, at 75 months versus 64 months for triplet versus doublet therapy (P = .025).

“Very convincingly, just receiving that short exposure to bortezomib ended up causing a substantial increase of progression-free and overall survival,” Dr. Callander said.

The efficacy of multiple triplet regimens has been documented, including the combination of carfilzomib, lenalidomide, and dexamethasone (KRd); cyclophosphamide, bortezomib, and dexamethasone (CyBorD); and more recently, ixazomib, lenalidomide, and dexamethasone (IRd). These regimens have “excellent” response rates and survival data, Dr. Callander said.

Data is now emerging on the potential role of four-drug combinations, she added. The combination of elotuzumab plus VRd produced high response rates that were even higher after transplant, with reasonable toxicity, Dr. Callander said of phase 2 trial data presented at the 2017 annual meeting of the American Society of Clinical Oncology.

Similarly, the combination of daratumumab plus KRd had a 100% rate of partial response or better in phase 2 data presented at ASCO in 2017, with rates of very good partial response and complete response that improved with successive cycles of therapy, she said.

Even so, “it remains to be seen whether four drugs will be the new standard,” Dr. Callander told the NCCN attendees.

Four- versus three-drug strategies are being evaluated in ongoing randomized clinical trials, including patients with previously untreated myeloma, she said. Those studies include Cassiopeia, which is evaluating bortezomib, thalidomide, and dexamethasone (with or without daratumumab), and GRIFFIN, which is looking at VRd (with or without daratumumab).

Daratumumab recently received an additional indication in the treatment of myeloma, this time as part of a four-drug regimen, Dr. Callander added in a discussion on treatment options for elderly myeloma patients.

The Food and Drug Administration approved the monoclonal antibody in combination with bortezomib, melphalan, and prednisone (VMP) for treatment of newly diagnosed myeloma patients who are transplant ineligible.

That approval was based on results of the multicenter phase 3 ALCYONE study, showing an 18-month progression-free survival rate of 71.6% for the four-drug combination versus 50.2% for VMP alone (N Engl J Med. 2018;378:518-28).

Dr. Callander reported having no relevant financial disclosures.

NEW YORK – Four-drug combinations are looking promising for the treatment of multiple myeloma, though data from additional randomized trials are needed to define their role in clinical practice, according to Natalie S. Callander, MD, of the University of Wisconsin Carbone Cancer Center, Madison.

“The outlook for myeloma patients is quite good,” Dr. Callander said at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.

“Triplet therapy is the standard, and quad therapy may be in the future.”

The study that set the standard for triplets in myeloma, according to Dr. Callander, is SWOG 0777, an open-label, phase 3 trial that compared bortezomib with lenalidomide and dexamethasone (VRd) to lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma.

Adding bortezomib to lenalidomide and dexamethasone significantly improved both progression-free and overall survival in the 525-patient trial, with a risk-benefit profile that was acceptable (Lancet. 2017 Feb 4;389[10068]:519-27).

The median progression-free survival was 43 months for the triplet, versus 30 months for the two-drug regimen (P = .0018); likewise, median overall survival was significantly improved, at 75 months versus 64 months for triplet versus doublet therapy (P = .025).

“Very convincingly, just receiving that short exposure to bortezomib ended up causing a substantial increase of progression-free and overall survival,” Dr. Callander said.

The efficacy of multiple triplet regimens has been documented, including the combination of carfilzomib, lenalidomide, and dexamethasone (KRd); cyclophosphamide, bortezomib, and dexamethasone (CyBorD); and more recently, ixazomib, lenalidomide, and dexamethasone (IRd). These regimens have “excellent” response rates and survival data, Dr. Callander said.

Data is now emerging on the potential role of four-drug combinations, she added. The combination of elotuzumab plus VRd produced high response rates that were even higher after transplant, with reasonable toxicity, Dr. Callander said of phase 2 trial data presented at the 2017 annual meeting of the American Society of Clinical Oncology.

Similarly, the combination of daratumumab plus KRd had a 100% rate of partial response or better in phase 2 data presented at ASCO in 2017, with rates of very good partial response and complete response that improved with successive cycles of therapy, she said.

Even so, “it remains to be seen whether four drugs will be the new standard,” Dr. Callander told the NCCN attendees.

Four- versus three-drug strategies are being evaluated in ongoing randomized clinical trials, including patients with previously untreated myeloma, she said. Those studies include Cassiopeia, which is evaluating bortezomib, thalidomide, and dexamethasone (with or without daratumumab), and GRIFFIN, which is looking at VRd (with or without daratumumab).

Daratumumab recently received an additional indication in the treatment of myeloma, this time as part of a four-drug regimen, Dr. Callander added in a discussion on treatment options for elderly myeloma patients.

The Food and Drug Administration approved the monoclonal antibody in combination with bortezomib, melphalan, and prednisone (VMP) for treatment of newly diagnosed myeloma patients who are transplant ineligible.

That approval was based on results of the multicenter phase 3 ALCYONE study, showing an 18-month progression-free survival rate of 71.6% for the four-drug combination versus 50.2% for VMP alone (N Engl J Med. 2018;378:518-28).

Dr. Callander reported having no relevant financial disclosures.

NEW YORK – Four-drug combinations are looking promising for the treatment of multiple myeloma, though data from additional randomized trials are needed to define their role in clinical practice, according to Natalie S. Callander, MD, of the University of Wisconsin Carbone Cancer Center, Madison.

“The outlook for myeloma patients is quite good,” Dr. Callander said at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.

“Triplet therapy is the standard, and quad therapy may be in the future.”

The study that set the standard for triplets in myeloma, according to Dr. Callander, is SWOG 0777, an open-label, phase 3 trial that compared bortezomib with lenalidomide and dexamethasone (VRd) to lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma.

Adding bortezomib to lenalidomide and dexamethasone significantly improved both progression-free and overall survival in the 525-patient trial, with a risk-benefit profile that was acceptable (Lancet. 2017 Feb 4;389[10068]:519-27).

The median progression-free survival was 43 months for the triplet, versus 30 months for the two-drug regimen (P = .0018); likewise, median overall survival was significantly improved, at 75 months versus 64 months for triplet versus doublet therapy (P = .025).

“Very convincingly, just receiving that short exposure to bortezomib ended up causing a substantial increase of progression-free and overall survival,” Dr. Callander said.

The efficacy of multiple triplet regimens has been documented, including the combination of carfilzomib, lenalidomide, and dexamethasone (KRd); cyclophosphamide, bortezomib, and dexamethasone (CyBorD); and more recently, ixazomib, lenalidomide, and dexamethasone (IRd). These regimens have “excellent” response rates and survival data, Dr. Callander said.

Data is now emerging on the potential role of four-drug combinations, she added. The combination of elotuzumab plus VRd produced high response rates that were even higher after transplant, with reasonable toxicity, Dr. Callander said of phase 2 trial data presented at the 2017 annual meeting of the American Society of Clinical Oncology.

Similarly, the combination of daratumumab plus KRd had a 100% rate of partial response or better in phase 2 data presented at ASCO in 2017, with rates of very good partial response and complete response that improved with successive cycles of therapy, she said.

Even so, “it remains to be seen whether four drugs will be the new standard,” Dr. Callander told the NCCN attendees.

Four- versus three-drug strategies are being evaluated in ongoing randomized clinical trials, including patients with previously untreated myeloma, she said. Those studies include Cassiopeia, which is evaluating bortezomib, thalidomide, and dexamethasone (with or without daratumumab), and GRIFFIN, which is looking at VRd (with or without daratumumab).

Daratumumab recently received an additional indication in the treatment of myeloma, this time as part of a four-drug regimen, Dr. Callander added in a discussion on treatment options for elderly myeloma patients.

The Food and Drug Administration approved the monoclonal antibody in combination with bortezomib, melphalan, and prednisone (VMP) for treatment of newly diagnosed myeloma patients who are transplant ineligible.

That approval was based on results of the multicenter phase 3 ALCYONE study, showing an 18-month progression-free survival rate of 71.6% for the four-drug combination versus 50.2% for VMP alone (N Engl J Med. 2018;378:518-28).

Dr. Callander reported having no relevant financial disclosures.

Case Report

An 82-year-old woman presented to the clinic with a rash on the face that had been present for a few months. She denied any treatment or prior occurrence. Her medical history was remarkable for non-Hodgkin lymphoma that had been successfully treated with chemotherapy 4 years prior. Additionally, she recently had been diagnosed with stage IV colon cancer. She reported that surgery had been scheduled and she would start adjuvant chemotherapy soon after.

On physical examination she exhibited perioral and perinasal erythematous papules with sparing of the vermilion border. A diagnosis of perioral dermatitis was made, and she was started on topical metronidazole. At 1-month follow-up, her condition had slightly worsened and she was subsequently started on doxycycline. When she returned to the clinic again the following month, physical examination revealed agminated folliculocentric papules with central spicules on the face, nose, ears, upper extremities (Figure 1), and trunk. The differential diagnosis included multiple minute digitate hyperkeratosis, spiculosis of multiple myeloma, and trichodysplasia spinulosa (TS).

Comment

History and Presentation
Trichodysplasia spinulosa was first recognized as hairlike hyperkeratosis.¹ The name by which it is currently known was later championed by Haycox et al.² They reported a case of a 44-year-old man who underwent a combined renal-pancreas transplant and while taking immunosuppressive medication developed erythematous papules with follicular spinous processes and progressive alopecia.² Other synonymous terms used for this condition include pilomatrix dysplasia, cyclosporine-induced folliculodystrophy, virus-associated trichodysplasia,³ and follicular dystrophy of immunosuppression.⁴ Trichodysplasia spinulosa can affect both adult and pediatric immunocompromised patients, including organ transplant recipients on immunosuppressants and cancer patients on chemotherapy.³ The condition also has been reported to precede the recurrence of lymphoma.⁵

Etiology
The connection of TS with a viral etiology was first demonstrated in 1999, and subsequently it was confirmed to be a polyomavirus.² The family name of Polyomaviridae possesses a Greek derivation with poly- meaning many and -oma meaning cancer.³ This name was given after the polyomavirus induced multiple tumors in mice.^3,6 This viral family consists of multiple naked viruses with a surrounding icosahedral capsid containing 3 structural proteins known as VP1, VP2, and VP3. Their life cycle is characterized by early and late phases with respective early and late protein formation.³

Polyomavirus infections maintain an asymptomatic and latent course in immunocompetent patients.⁷ The prevalence and manifestation of these viruses change when the host’s immune system is altered. The first identified JC virus and BK virus of the same family have been found at increased frequencies in blood and lymphoid tissue during host immunosuppression.⁶ Moreover, the Merkel cell polyomavirus detected in Merkel cell carcinoma is well documented in the dermatologic literature.^6,8

A specific polyomavirus has been implicated in the majority of TS cases and has subsequently received the name of TS polyomavirus.⁹ As a polyomavirus, it similarly produces capsid antigens and large/small T antigens. Among the viral protein antigens produced, the large tumor or LT antigen represents one of the most potent viral proteins. It has been postulated to inhibit the retinoblastoma family of proteins, leading to increased inner root sheath cells that allow for further viral replication.^9,10

The disease presents with folliculocentric papules localized mainly on the central face and ears, which grow central keratin spines or spicules that can become 1 to 3 mm in length. Coinciding alopecia and madarosis also may be present.⁹

Diagnosis

Histologic examination reveals abnormal follicular maturation and distension. Additionally, increased proliferation and amount of trichohyalin is seen within the inner root sheath cells. Further testing via viral culture, polymerase chain reaction, electron microscopy, or immunohistochemical stains can confirm the diagnosis. Such testing may not be warranted in all cases given that classic clinical findings coupled with routine histopathology staining can provide enough evidence.^10,11

Management

Currently, a universal successful treatment for TS does not exist. There have been anecdotal successes reported with topical medications such as cidofovir ointment 1%, acyclovir combined with 2-deoxy-D-glucose and epigallocatechin, corticosteroids, topical tacrolimus, topical retinoids, and imiquimod. Additionally, success has been seen with oral minocycline, oral retinoids, valacyclovir, and valganciclovir, with the latter showing the best results. Patients also have shown improvement after modifying their immunosuppressive treatment regimen.^10,12

Conclusion

Given the previously published case of TS preceding the recurrence of lymphoma,⁵ we notified our patient’s oncologist of this potential risk. Her history of lymphoma and immunosuppressive treatment 4 years prior may represent the etiology of the cutaneous presentation; however, the TS with concurrent colon cancer presented prior to starting immunosuppressive therapy, suggesting that it also may have been a paraneoplastic process and not just a sign of immunosuppression. Therefore, we recommend that patients who present with TS should be evaluated for underlying malignancy if not already diagnosed.

Case Report

An 82-year-old woman presented to the clinic with a rash on the face that had been present for a few months. She denied any treatment or prior occurrence. Her medical history was remarkable for non-Hodgkin lymphoma that had been successfully treated with chemotherapy 4 years prior. Additionally, she recently had been diagnosed with stage IV colon cancer. She reported that surgery had been scheduled and she would start adjuvant chemotherapy soon after.

On physical examination she exhibited perioral and perinasal erythematous papules with sparing of the vermilion border. A diagnosis of perioral dermatitis was made, and she was started on topical metronidazole. At 1-month follow-up, her condition had slightly worsened and she was subsequently started on doxycycline. When she returned to the clinic again the following month, physical examination revealed agminated folliculocentric papules with central spicules on the face, nose, ears, upper extremities (Figure 1), and trunk. The differential diagnosis included multiple minute digitate hyperkeratosis, spiculosis of multiple myeloma, and trichodysplasia spinulosa (TS).

Comment

History and Presentation
Trichodysplasia spinulosa was first recognized as hairlike hyperkeratosis.¹ The name by which it is currently known was later championed by Haycox et al.² They reported a case of a 44-year-old man who underwent a combined renal-pancreas transplant and while taking immunosuppressive medication developed erythematous papules with follicular spinous processes and progressive alopecia.² Other synonymous terms used for this condition include pilomatrix dysplasia, cyclosporine-induced folliculodystrophy, virus-associated trichodysplasia,³ and follicular dystrophy of immunosuppression.⁴ Trichodysplasia spinulosa can affect both adult and pediatric immunocompromised patients, including organ transplant recipients on immunosuppressants and cancer patients on chemotherapy.³ The condition also has been reported to precede the recurrence of lymphoma.⁵

Etiology
The connection of TS with a viral etiology was first demonstrated in 1999, and subsequently it was confirmed to be a polyomavirus.² The family name of Polyomaviridae possesses a Greek derivation with poly- meaning many and -oma meaning cancer.³ This name was given after the polyomavirus induced multiple tumors in mice.^3,6 This viral family consists of multiple naked viruses with a surrounding icosahedral capsid containing 3 structural proteins known as VP1, VP2, and VP3. Their life cycle is characterized by early and late phases with respective early and late protein formation.³

Polyomavirus infections maintain an asymptomatic and latent course in immunocompetent patients.⁷ The prevalence and manifestation of these viruses change when the host’s immune system is altered. The first identified JC virus and BK virus of the same family have been found at increased frequencies in blood and lymphoid tissue during host immunosuppression.⁶ Moreover, the Merkel cell polyomavirus detected in Merkel cell carcinoma is well documented in the dermatologic literature.^6,8

A specific polyomavirus has been implicated in the majority of TS cases and has subsequently received the name of TS polyomavirus.⁹ As a polyomavirus, it similarly produces capsid antigens and large/small T antigens. Among the viral protein antigens produced, the large tumor or LT antigen represents one of the most potent viral proteins. It has been postulated to inhibit the retinoblastoma family of proteins, leading to increased inner root sheath cells that allow for further viral replication.^9,10

The disease presents with folliculocentric papules localized mainly on the central face and ears, which grow central keratin spines or spicules that can become 1 to 3 mm in length. Coinciding alopecia and madarosis also may be present.⁹

Diagnosis

Histologic examination reveals abnormal follicular maturation and distension. Additionally, increased proliferation and amount of trichohyalin is seen within the inner root sheath cells. Further testing via viral culture, polymerase chain reaction, electron microscopy, or immunohistochemical stains can confirm the diagnosis. Such testing may not be warranted in all cases given that classic clinical findings coupled with routine histopathology staining can provide enough evidence.^10,11

Management

Currently, a universal successful treatment for TS does not exist. There have been anecdotal successes reported with topical medications such as cidofovir ointment 1%, acyclovir combined with 2-deoxy-D-glucose and epigallocatechin, corticosteroids, topical tacrolimus, topical retinoids, and imiquimod. Additionally, success has been seen with oral minocycline, oral retinoids, valacyclovir, and valganciclovir, with the latter showing the best results. Patients also have shown improvement after modifying their immunosuppressive treatment regimen.^10,12

Conclusion

Given the previously published case of TS preceding the recurrence of lymphoma,⁵ we notified our patient’s oncologist of this potential risk. Her history of lymphoma and immunosuppressive treatment 4 years prior may represent the etiology of the cutaneous presentation; however, the TS with concurrent colon cancer presented prior to starting immunosuppressive therapy, suggesting that it also may have been a paraneoplastic process and not just a sign of immunosuppression. Therefore, we recommend that patients who present with TS should be evaluated for underlying malignancy if not already diagnosed.

Case Report

An 82-year-old woman presented to the clinic with a rash on the face that had been present for a few months. She denied any treatment or prior occurrence. Her medical history was remarkable for non-Hodgkin lymphoma that had been successfully treated with chemotherapy 4 years prior. Additionally, she recently had been diagnosed with stage IV colon cancer. She reported that surgery had been scheduled and she would start adjuvant chemotherapy soon after.

On physical examination she exhibited perioral and perinasal erythematous papules with sparing of the vermilion border. A diagnosis of perioral dermatitis was made, and she was started on topical metronidazole. At 1-month follow-up, her condition had slightly worsened and she was subsequently started on doxycycline. When she returned to the clinic again the following month, physical examination revealed agminated folliculocentric papules with central spicules on the face, nose, ears, upper extremities (Figure 1), and trunk. The differential diagnosis included multiple minute digitate hyperkeratosis, spiculosis of multiple myeloma, and trichodysplasia spinulosa (TS).

Comment

History and Presentation
Trichodysplasia spinulosa was first recognized as hairlike hyperkeratosis.¹ The name by which it is currently known was later championed by Haycox et al.² They reported a case of a 44-year-old man who underwent a combined renal-pancreas transplant and while taking immunosuppressive medication developed erythematous papules with follicular spinous processes and progressive alopecia.² Other synonymous terms used for this condition include pilomatrix dysplasia, cyclosporine-induced folliculodystrophy, virus-associated trichodysplasia,³ and follicular dystrophy of immunosuppression.⁴ Trichodysplasia spinulosa can affect both adult and pediatric immunocompromised patients, including organ transplant recipients on immunosuppressants and cancer patients on chemotherapy.³ The condition also has been reported to precede the recurrence of lymphoma.⁵

Etiology
The connection of TS with a viral etiology was first demonstrated in 1999, and subsequently it was confirmed to be a polyomavirus.² The family name of Polyomaviridae possesses a Greek derivation with poly- meaning many and -oma meaning cancer.³ This name was given after the polyomavirus induced multiple tumors in mice.^3,6 This viral family consists of multiple naked viruses with a surrounding icosahedral capsid containing 3 structural proteins known as VP1, VP2, and VP3. Their life cycle is characterized by early and late phases with respective early and late protein formation.³

Polyomavirus infections maintain an asymptomatic and latent course in immunocompetent patients.⁷ The prevalence and manifestation of these viruses change when the host’s immune system is altered. The first identified JC virus and BK virus of the same family have been found at increased frequencies in blood and lymphoid tissue during host immunosuppression.⁶ Moreover, the Merkel cell polyomavirus detected in Merkel cell carcinoma is well documented in the dermatologic literature.^6,8

A specific polyomavirus has been implicated in the majority of TS cases and has subsequently received the name of TS polyomavirus.⁹ As a polyomavirus, it similarly produces capsid antigens and large/small T antigens. Among the viral protein antigens produced, the large tumor or LT antigen represents one of the most potent viral proteins. It has been postulated to inhibit the retinoblastoma family of proteins, leading to increased inner root sheath cells that allow for further viral replication.^9,10

The disease presents with folliculocentric papules localized mainly on the central face and ears, which grow central keratin spines or spicules that can become 1 to 3 mm in length. Coinciding alopecia and madarosis also may be present.⁹

Diagnosis

Histologic examination reveals abnormal follicular maturation and distension. Additionally, increased proliferation and amount of trichohyalin is seen within the inner root sheath cells. Further testing via viral culture, polymerase chain reaction, electron microscopy, or immunohistochemical stains can confirm the diagnosis. Such testing may not be warranted in all cases given that classic clinical findings coupled with routine histopathology staining can provide enough evidence.^10,11

Management

Currently, a universal successful treatment for TS does not exist. There have been anecdotal successes reported with topical medications such as cidofovir ointment 1%, acyclovir combined with 2-deoxy-D-glucose and epigallocatechin, corticosteroids, topical tacrolimus, topical retinoids, and imiquimod. Additionally, success has been seen with oral minocycline, oral retinoids, valacyclovir, and valganciclovir, with the latter showing the best results. Patients also have shown improvement after modifying their immunosuppressive treatment regimen.^10,12

Conclusion

Given the previously published case of TS preceding the recurrence of lymphoma,⁵ we notified our patient’s oncologist of this potential risk. Her history of lymphoma and immunosuppressive treatment 4 years prior may represent the etiology of the cutaneous presentation; however, the TS with concurrent colon cancer presented prior to starting immunosuppressive therapy, suggesting that it also may have been a paraneoplastic process and not just a sign of immunosuppression. Therefore, we recommend that patients who present with TS should be evaluated for underlying malignancy if not already diagnosed.

NEW YORK – Ibrutinib, and now moxetumomab pasudotox, are two novel therapies that can be tried in patients with previously treated hairy cell leukemia, although data and experience with them are so far limited in this rare disease, experts said during a panel discussion at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.

Since there are so few patients, data on the BTK inhibitor ibrutinib in hairy cell leukemia is largely “anecdotal,” said Andrew D. Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

The anti-CD22 monoclonal antibody moxetumomab pasudotox – approved for hairy cell leukemia in September – isn’t yet on the formulary at Memorial Sloan Kettering, Dr. Zelenetz added in a panel discussion of treatment options for a patient previously treated with purine analogueues and vemurafenib.

Between the two agents, moxetumomab pasudotox has more robust data in this disease, said John N. Allan, MD, of Weill Cornell Medicine, New York.

“I think if you can get access to the drug, that’s probably the best answer,” Dr. Allan said in the case discussion.

Hairy cell leukemia is an indolent B-cell lymphoma that makes up just 2% of all lymphoid leukemias, according to NCCN guidelines.

It is a chronic disease that requires long-term management, according to Dr. Allan.

First-line treatment is usually a purine analogue, either cladribine or pentostatin, and multiple treatments are possible as long as responses of greater than 2 years are achieved, he told attendees at the NCCN conference.

For relapses more than 2 years after first-line treatment, patients can be retreated with the same purine analogue, with or without rituximab, or can be switched to the alternative purine analogue, he said.

Vemurafenib, the BRAF inhibitor, is “surprisingly” effective in 90% of classic hairy cell leukemia patients with the BRAF V600E mutation, Dr. Allan added, though only about 40% of patients achieve complete response.

In discussing therapy options for a hairy cell leukemia patient previously treated with purine analogues and vemurafenib, Dr. Allan noted that the data behind ibrutinib includes case reports and early clinical investigations.

Several phase 1 studies with small numbers of patients show response rates “in the 50% range,” he said.

“This is an option,” he said. “It’s in the guidelines, and it’s something to consider.”

Moxetumomab pasudotox was recently approved for intravenous use in adults with relapsed or refractory hairy cell leukemia who have had at least two previous systemic treatments, including a purine nucleoside analogue. The CD22-directed cytotoxin is the first of its kind for treating patients with hairy cell leukemia, according to the Food and Drug Administration.

In a single-arm, open-label clinical trial including 80 patients with hairy cell leukemia who had previous treatment in line with that indication, 75% had a partial or complete response, of whom 30% had a durable complete response (CR), defined as maintaining hematologic remission for at least 180 days following CR.

Following the FDA’s approval of moxetumomab pasudotox, the NCCN updated its hairy cell leukemia clinical practice guidelines to include the drug as a category 2A recommendation for relapsed/refractory treatment. Other category 2A options in that setting include ibrutinib, vemurafenib with or without rituximab, or a clinical trial.

Along with that, NCCN guideline authors added a full page on special considerations for use of moxetumomab pasudotox. That includes advice on monitoring for capillary leak syndrome and hemolytic uremic syndrome, along with guidance on capillary leak syndrome grading and management by grade.

Dr. Zelenetz reported financial disclosures related to Adaptive Biotechnology, Amgen, AstraZeneca, Celgene, Genentech, Gilead, Hoffman La Roche, MEI Pharma, MorphoSys AG, Novartis, Pfizer, Pharmacyclics, Roche, and Verastem Oncology. Dr. Allan reported disclosures related to AbbVie, Acerta Pharma, Genentech, Pharmacyclics, Sunesis, and Verastem Oncology.

NEW YORK – Ibrutinib, and now moxetumomab pasudotox, are two novel therapies that can be tried in patients with previously treated hairy cell leukemia, although data and experience with them are so far limited in this rare disease, experts said during a panel discussion at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.

Since there are so few patients, data on the BTK inhibitor ibrutinib in hairy cell leukemia is largely “anecdotal,” said Andrew D. Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

The anti-CD22 monoclonal antibody moxetumomab pasudotox – approved for hairy cell leukemia in September – isn’t yet on the formulary at Memorial Sloan Kettering, Dr. Zelenetz added in a panel discussion of treatment options for a patient previously treated with purine analogueues and vemurafenib.

Between the two agents, moxetumomab pasudotox has more robust data in this disease, said John N. Allan, MD, of Weill Cornell Medicine, New York.

“I think if you can get access to the drug, that’s probably the best answer,” Dr. Allan said in the case discussion.

Hairy cell leukemia is an indolent B-cell lymphoma that makes up just 2% of all lymphoid leukemias, according to NCCN guidelines.

It is a chronic disease that requires long-term management, according to Dr. Allan.

First-line treatment is usually a purine analogue, either cladribine or pentostatin, and multiple treatments are possible as long as responses of greater than 2 years are achieved, he told attendees at the NCCN conference.

For relapses more than 2 years after first-line treatment, patients can be retreated with the same purine analogue, with or without rituximab, or can be switched to the alternative purine analogue, he said.

Vemurafenib, the BRAF inhibitor, is “surprisingly” effective in 90% of classic hairy cell leukemia patients with the BRAF V600E mutation, Dr. Allan added, though only about 40% of patients achieve complete response.

In discussing therapy options for a hairy cell leukemia patient previously treated with purine analogues and vemurafenib, Dr. Allan noted that the data behind ibrutinib includes case reports and early clinical investigations.

Several phase 1 studies with small numbers of patients show response rates “in the 50% range,” he said.

“This is an option,” he said. “It’s in the guidelines, and it’s something to consider.”

Moxetumomab pasudotox was recently approved for intravenous use in adults with relapsed or refractory hairy cell leukemia who have had at least two previous systemic treatments, including a purine nucleoside analogue. The CD22-directed cytotoxin is the first of its kind for treating patients with hairy cell leukemia, according to the Food and Drug Administration.

In a single-arm, open-label clinical trial including 80 patients with hairy cell leukemia who had previous treatment in line with that indication, 75% had a partial or complete response, of whom 30% had a durable complete response (CR), defined as maintaining hematologic remission for at least 180 days following CR.

Following the FDA’s approval of moxetumomab pasudotox, the NCCN updated its hairy cell leukemia clinical practice guidelines to include the drug as a category 2A recommendation for relapsed/refractory treatment. Other category 2A options in that setting include ibrutinib, vemurafenib with or without rituximab, or a clinical trial.

Along with that, NCCN guideline authors added a full page on special considerations for use of moxetumomab pasudotox. That includes advice on monitoring for capillary leak syndrome and hemolytic uremic syndrome, along with guidance on capillary leak syndrome grading and management by grade.

Dr. Zelenetz reported financial disclosures related to Adaptive Biotechnology, Amgen, AstraZeneca, Celgene, Genentech, Gilead, Hoffman La Roche, MEI Pharma, MorphoSys AG, Novartis, Pfizer, Pharmacyclics, Roche, and Verastem Oncology. Dr. Allan reported disclosures related to AbbVie, Acerta Pharma, Genentech, Pharmacyclics, Sunesis, and Verastem Oncology.

NEW YORK – Ibrutinib, and now moxetumomab pasudotox, are two novel therapies that can be tried in patients with previously treated hairy cell leukemia, although data and experience with them are so far limited in this rare disease, experts said during a panel discussion at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.

Since there are so few patients, data on the BTK inhibitor ibrutinib in hairy cell leukemia is largely “anecdotal,” said Andrew D. Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

The anti-CD22 monoclonal antibody moxetumomab pasudotox – approved for hairy cell leukemia in September – isn’t yet on the formulary at Memorial Sloan Kettering, Dr. Zelenetz added in a panel discussion of treatment options for a patient previously treated with purine analogueues and vemurafenib.

Between the two agents, moxetumomab pasudotox has more robust data in this disease, said John N. Allan, MD, of Weill Cornell Medicine, New York.

“I think if you can get access to the drug, that’s probably the best answer,” Dr. Allan said in the case discussion.

Hairy cell leukemia is an indolent B-cell lymphoma that makes up just 2% of all lymphoid leukemias, according to NCCN guidelines.

It is a chronic disease that requires long-term management, according to Dr. Allan.

First-line treatment is usually a purine analogue, either cladribine or pentostatin, and multiple treatments are possible as long as responses of greater than 2 years are achieved, he told attendees at the NCCN conference.

For relapses more than 2 years after first-line treatment, patients can be retreated with the same purine analogue, with or without rituximab, or can be switched to the alternative purine analogue, he said.

Vemurafenib, the BRAF inhibitor, is “surprisingly” effective in 90% of classic hairy cell leukemia patients with the BRAF V600E mutation, Dr. Allan added, though only about 40% of patients achieve complete response.

In discussing therapy options for a hairy cell leukemia patient previously treated with purine analogues and vemurafenib, Dr. Allan noted that the data behind ibrutinib includes case reports and early clinical investigations.

Several phase 1 studies with small numbers of patients show response rates “in the 50% range,” he said.

“This is an option,” he said. “It’s in the guidelines, and it’s something to consider.”

Moxetumomab pasudotox was recently approved for intravenous use in adults with relapsed or refractory hairy cell leukemia who have had at least two previous systemic treatments, including a purine nucleoside analogue. The CD22-directed cytotoxin is the first of its kind for treating patients with hairy cell leukemia, according to the Food and Drug Administration.

In a single-arm, open-label clinical trial including 80 patients with hairy cell leukemia who had previous treatment in line with that indication, 75% had a partial or complete response, of whom 30% had a durable complete response (CR), defined as maintaining hematologic remission for at least 180 days following CR.

Following the FDA’s approval of moxetumomab pasudotox, the NCCN updated its hairy cell leukemia clinical practice guidelines to include the drug as a category 2A recommendation for relapsed/refractory treatment. Other category 2A options in that setting include ibrutinib, vemurafenib with or without rituximab, or a clinical trial.

Along with that, NCCN guideline authors added a full page on special considerations for use of moxetumomab pasudotox. That includes advice on monitoring for capillary leak syndrome and hemolytic uremic syndrome, along with guidance on capillary leak syndrome grading and management by grade.

Dr. Zelenetz reported financial disclosures related to Adaptive Biotechnology, Amgen, AstraZeneca, Celgene, Genentech, Gilead, Hoffman La Roche, MEI Pharma, MorphoSys AG, Novartis, Pfizer, Pharmacyclics, Roche, and Verastem Oncology. Dr. Allan reported disclosures related to AbbVie, Acerta Pharma, Genentech, Pharmacyclics, Sunesis, and Verastem Oncology.

Dual-frequency ultrasound (DFU) may be an effective option for patients with treatment-resistant rosacea, according to a new study in Dermatologic Surgery.

In the study, a retrospective medical record analysis of 42 rosacea patients, DFU improved symptoms, including erythema index (EI) and transepithelial water loss (TEWL), and also improved outcomes on the patient self-assessment (PSA), reported Jun Yeong Park, MD, and coauthors, from the department of dermatology, Hallym University Sacred Heart Hospital in Anyang, South Korea.

Of the 42 patients, 26 had erythematotelangiectatic rosacea, 14 had papulopustular rosacea, and 2 had mixed disease; their mean age was 48 years, and they had had rosacea for a mean of 2 years. Patients had started DFU treatment between September 2016 and December 2016, and were not taking oral medication (besides antihistamines), topical ointments, or other laser treatments at the time. Most had been treated with various systemic therapies, topical therapies, or lasers, but had not had adequate improvement of flushing and erythema.

Patients received DFU treatment of the entire face twice per week for the first week, followed by one-week intervals, for a total of 12 weeks. Each treatment session lasted 10 minutes, and included DFU frequencies of 3/4.5 MHz at an ultrasound intensity of 2.0W/cm² for 5 minutes, followed by 4.5 MHz at an intensity of 2.0W/cm². Responses to treatment were based on EI, TEWL values (measured on three different sites on each cheek according to guidelines established by the European Group for Efficacy Measurements on Cosmetics and Other Topical Products), and PSA. PSA was completed on a scale of 0 (absent) to 4 (severe) for erythema, itching sensation, and burning sensation.

At 12 weeks follow-up, the mean EI dropped from 16.3 at baseline to 12.7 at 12 weeks (P less than .01). Mean TEWL values dropped from a baseline of 35.8 g m^–1 h^–1 to 22.8 g m^–1 h^–1 at 12 weeks (P less than .01).

When evaluated by rosacea subtype, a slightly higher reduction in the group with papulopustular rosacea was seen for EI and TEWL, compared with those with the erythematotelangiectatic subtype, but the differences were not statistically significant for either, the authors reported.

Between baseline and 12 weeks, the PSA values for erythema decreased from 2.6 to 1.1. Itching and burning grades also decreased, from 2.4 to 0.4 and from 2.4 to 0.3, respectively.

The findings verify that there were “improvements in the barrier function of patients with refractory rosacea, based on the TEWL level before and after treatment,” the authors noted. “Therefore, DFU may be an additional treatment option for rosacea that is resistant to other treatments.”

This study is the first to evaluate DFU in patients with refractory rosacea “who did not show signs of recovery after undergoing previous therapies,” they noted.

No disclosures were reported.

SOURCE: Park J et al. Dermatol Surg 2018 Sep;44(9):1209-15. doi: 10.1097/DSS.0000000000001552.

Dual-frequency ultrasound (DFU) may be an effective option for patients with treatment-resistant rosacea, according to a new study in Dermatologic Surgery.

In the study, a retrospective medical record analysis of 42 rosacea patients, DFU improved symptoms, including erythema index (EI) and transepithelial water loss (TEWL), and also improved outcomes on the patient self-assessment (PSA), reported Jun Yeong Park, MD, and coauthors, from the department of dermatology, Hallym University Sacred Heart Hospital in Anyang, South Korea.

Of the 42 patients, 26 had erythematotelangiectatic rosacea, 14 had papulopustular rosacea, and 2 had mixed disease; their mean age was 48 years, and they had had rosacea for a mean of 2 years. Patients had started DFU treatment between September 2016 and December 2016, and were not taking oral medication (besides antihistamines), topical ointments, or other laser treatments at the time. Most had been treated with various systemic therapies, topical therapies, or lasers, but had not had adequate improvement of flushing and erythema.

Patients received DFU treatment of the entire face twice per week for the first week, followed by one-week intervals, for a total of 12 weeks. Each treatment session lasted 10 minutes, and included DFU frequencies of 3/4.5 MHz at an ultrasound intensity of 2.0W/cm² for 5 minutes, followed by 4.5 MHz at an intensity of 2.0W/cm². Responses to treatment were based on EI, TEWL values (measured on three different sites on each cheek according to guidelines established by the European Group for Efficacy Measurements on Cosmetics and Other Topical Products), and PSA. PSA was completed on a scale of 0 (absent) to 4 (severe) for erythema, itching sensation, and burning sensation.

At 12 weeks follow-up, the mean EI dropped from 16.3 at baseline to 12.7 at 12 weeks (P less than .01). Mean TEWL values dropped from a baseline of 35.8 g m^–1 h^–1 to 22.8 g m^–1 h^–1 at 12 weeks (P less than .01).

When evaluated by rosacea subtype, a slightly higher reduction in the group with papulopustular rosacea was seen for EI and TEWL, compared with those with the erythematotelangiectatic subtype, but the differences were not statistically significant for either, the authors reported.

Between baseline and 12 weeks, the PSA values for erythema decreased from 2.6 to 1.1. Itching and burning grades also decreased, from 2.4 to 0.4 and from 2.4 to 0.3, respectively.

The findings verify that there were “improvements in the barrier function of patients with refractory rosacea, based on the TEWL level before and after treatment,” the authors noted. “Therefore, DFU may be an additional treatment option for rosacea that is resistant to other treatments.”

This study is the first to evaluate DFU in patients with refractory rosacea “who did not show signs of recovery after undergoing previous therapies,” they noted.

No disclosures were reported.

SOURCE: Park J et al. Dermatol Surg 2018 Sep;44(9):1209-15. doi: 10.1097/DSS.0000000000001552.

Dual-frequency ultrasound (DFU) may be an effective option for patients with treatment-resistant rosacea, according to a new study in Dermatologic Surgery.

In the study, a retrospective medical record analysis of 42 rosacea patients, DFU improved symptoms, including erythema index (EI) and transepithelial water loss (TEWL), and also improved outcomes on the patient self-assessment (PSA), reported Jun Yeong Park, MD, and coauthors, from the department of dermatology, Hallym University Sacred Heart Hospital in Anyang, South Korea.

Of the 42 patients, 26 had erythematotelangiectatic rosacea, 14 had papulopustular rosacea, and 2 had mixed disease; their mean age was 48 years, and they had had rosacea for a mean of 2 years. Patients had started DFU treatment between September 2016 and December 2016, and were not taking oral medication (besides antihistamines), topical ointments, or other laser treatments at the time. Most had been treated with various systemic therapies, topical therapies, or lasers, but had not had adequate improvement of flushing and erythema.

Patients received DFU treatment of the entire face twice per week for the first week, followed by one-week intervals, for a total of 12 weeks. Each treatment session lasted 10 minutes, and included DFU frequencies of 3/4.5 MHz at an ultrasound intensity of 2.0W/cm² for 5 minutes, followed by 4.5 MHz at an intensity of 2.0W/cm². Responses to treatment were based on EI, TEWL values (measured on three different sites on each cheek according to guidelines established by the European Group for Efficacy Measurements on Cosmetics and Other Topical Products), and PSA. PSA was completed on a scale of 0 (absent) to 4 (severe) for erythema, itching sensation, and burning sensation.

At 12 weeks follow-up, the mean EI dropped from 16.3 at baseline to 12.7 at 12 weeks (P less than .01). Mean TEWL values dropped from a baseline of 35.8 g m^–1 h^–1 to 22.8 g m^–1 h^–1 at 12 weeks (P less than .01).

When evaluated by rosacea subtype, a slightly higher reduction in the group with papulopustular rosacea was seen for EI and TEWL, compared with those with the erythematotelangiectatic subtype, but the differences were not statistically significant for either, the authors reported.

Between baseline and 12 weeks, the PSA values for erythema decreased from 2.6 to 1.1. Itching and burning grades also decreased, from 2.4 to 0.4 and from 2.4 to 0.3, respectively.

The findings verify that there were “improvements in the barrier function of patients with refractory rosacea, based on the TEWL level before and after treatment,” the authors noted. “Therefore, DFU may be an additional treatment option for rosacea that is resistant to other treatments.”

This study is the first to evaluate DFU in patients with refractory rosacea “who did not show signs of recovery after undergoing previous therapies,” they noted.

No disclosures were reported.

SOURCE: Park J et al. Dermatol Surg 2018 Sep;44(9):1209-15. doi: 10.1097/DSS.0000000000001552.

NEW YORK – Three novel treatment strategies that target B-cell maturation antigen (BCMA) have shown promise in recent multiple myeloma clinical trials, according to Shaji K. Kumar, MD, of the Mayo Clinic Cancer Center in Rochester, Minn.

Courtesy Wikimedia Commons/KGH/Creative Commons License

These strategies include B-cell maturation antigen (BCMA)–specific chimeric antigen receptor (CAR) T-cell therapies, bispecific T-cell engagers (BiTEs), and a BCMA antibody–drug conjugate, Dr. Kumar said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“Clearly, there are a lot of exciting drugs that are currently in clinical trials, but these three platforms appear to be much more advanced than the others, and hopefully we will see that in the clinic in the near future,” Dr. Kumar said.

The antibody-drug conjugate, GSK2857916, is a humanized IgG1 anti-BCMA antibody conjugated to a microtubule-disrupting agent that has produced an overall response rate in 67% in a group of myeloma patients who had previously received multiple standard-of-care agents.

“Some of the responses were quite durable, lasting several months,” he said.

Now, GSK2857916 is being evaluated in a variety of different combinations, including in a phase 2 study of the antibody-drug conjugate in combination with lenalidomide plus dexamethasone, or bortezomib plus dexamethasone, in patients with relapsed or refractory disease.

Some of the most “exciting” data with anti-BCMA CAR T-cell therapy in myeloma involves bb2121, which showed durable clinical responses in heavily pretreated patients, according to data presented at the 2017 annual meeting of the American Society of Hematology.

“The overall response rate is quite significant,” said Dr. Kumar, who related a 94% rate of overall response that was even higher in patients treated with doses of 150 x 10⁶ CAR+ T cells or more. Many of the response were lasting, he said, with five patients in ongoing response for more than 1 year.

“The results are exciting enough that this is actually moving forward with registration trials,” Dr. Kumar said.

Additionally, promising results have been presented on a novel CAR T-cell product, LCAR-B38M, which principally targets BCMA and led to a significant number of patients who achieved stringent complete response that lasted beyond 1 year.

Multiple BCMA-targeting CAR T-cell products that use different vectors and costimulatory molecules are currently undergoing clinical trials, Dr. Kumar said.

In contrast to CAR T-cell products that must be customized to each patient in a process that takes weeks, BiTEs are a ready-made approach to allow T cells to engage with tumor cells.

“In patients with advanced disease, a lot can change in that short time frame, so having an approach that is off the shelf, which is not patient specific, is quite attractive,” Dr. Kumar said.

BCMA-directed BiTE therapies under investigation include AMG 420 and PF-06863135, he added.

Dr. Kumar reported one disclosure related to Dr. Reddy’s Laboratories.

NEW YORK – Three novel treatment strategies that target B-cell maturation antigen (BCMA) have shown promise in recent multiple myeloma clinical trials, according to Shaji K. Kumar, MD, of the Mayo Clinic Cancer Center in Rochester, Minn.

Courtesy Wikimedia Commons/KGH/Creative Commons License

These strategies include B-cell maturation antigen (BCMA)–specific chimeric antigen receptor (CAR) T-cell therapies, bispecific T-cell engagers (BiTEs), and a BCMA antibody–drug conjugate, Dr. Kumar said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“Clearly, there are a lot of exciting drugs that are currently in clinical trials, but these three platforms appear to be much more advanced than the others, and hopefully we will see that in the clinic in the near future,” Dr. Kumar said.

The antibody-drug conjugate, GSK2857916, is a humanized IgG1 anti-BCMA antibody conjugated to a microtubule-disrupting agent that has produced an overall response rate in 67% in a group of myeloma patients who had previously received multiple standard-of-care agents.

“Some of the responses were quite durable, lasting several months,” he said.

Now, GSK2857916 is being evaluated in a variety of different combinations, including in a phase 2 study of the antibody-drug conjugate in combination with lenalidomide plus dexamethasone, or bortezomib plus dexamethasone, in patients with relapsed or refractory disease.

Some of the most “exciting” data with anti-BCMA CAR T-cell therapy in myeloma involves bb2121, which showed durable clinical responses in heavily pretreated patients, according to data presented at the 2017 annual meeting of the American Society of Hematology.

“The overall response rate is quite significant,” said Dr. Kumar, who related a 94% rate of overall response that was even higher in patients treated with doses of 150 x 10⁶ CAR+ T cells or more. Many of the response were lasting, he said, with five patients in ongoing response for more than 1 year.

“The results are exciting enough that this is actually moving forward with registration trials,” Dr. Kumar said.

Additionally, promising results have been presented on a novel CAR T-cell product, LCAR-B38M, which principally targets BCMA and led to a significant number of patients who achieved stringent complete response that lasted beyond 1 year.

Multiple BCMA-targeting CAR T-cell products that use different vectors and costimulatory molecules are currently undergoing clinical trials, Dr. Kumar said.

In contrast to CAR T-cell products that must be customized to each patient in a process that takes weeks, BiTEs are a ready-made approach to allow T cells to engage with tumor cells.

“In patients with advanced disease, a lot can change in that short time frame, so having an approach that is off the shelf, which is not patient specific, is quite attractive,” Dr. Kumar said.

BCMA-directed BiTE therapies under investigation include AMG 420 and PF-06863135, he added.

Dr. Kumar reported one disclosure related to Dr. Reddy’s Laboratories.

NEW YORK – Three novel treatment strategies that target B-cell maturation antigen (BCMA) have shown promise in recent multiple myeloma clinical trials, according to Shaji K. Kumar, MD, of the Mayo Clinic Cancer Center in Rochester, Minn.

Courtesy Wikimedia Commons/KGH/Creative Commons License

These strategies include B-cell maturation antigen (BCMA)–specific chimeric antigen receptor (CAR) T-cell therapies, bispecific T-cell engagers (BiTEs), and a BCMA antibody–drug conjugate, Dr. Kumar said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“Clearly, there are a lot of exciting drugs that are currently in clinical trials, but these three platforms appear to be much more advanced than the others, and hopefully we will see that in the clinic in the near future,” Dr. Kumar said.

The antibody-drug conjugate, GSK2857916, is a humanized IgG1 anti-BCMA antibody conjugated to a microtubule-disrupting agent that has produced an overall response rate in 67% in a group of myeloma patients who had previously received multiple standard-of-care agents.

“Some of the responses were quite durable, lasting several months,” he said.

Now, GSK2857916 is being evaluated in a variety of different combinations, including in a phase 2 study of the antibody-drug conjugate in combination with lenalidomide plus dexamethasone, or bortezomib plus dexamethasone, in patients with relapsed or refractory disease.

Some of the most “exciting” data with anti-BCMA CAR T-cell therapy in myeloma involves bb2121, which showed durable clinical responses in heavily pretreated patients, according to data presented at the 2017 annual meeting of the American Society of Hematology.

“The overall response rate is quite significant,” said Dr. Kumar, who related a 94% rate of overall response that was even higher in patients treated with doses of 150 x 10⁶ CAR+ T cells or more. Many of the response were lasting, he said, with five patients in ongoing response for more than 1 year.

“The results are exciting enough that this is actually moving forward with registration trials,” Dr. Kumar said.

Additionally, promising results have been presented on a novel CAR T-cell product, LCAR-B38M, which principally targets BCMA and led to a significant number of patients who achieved stringent complete response that lasted beyond 1 year.

Multiple BCMA-targeting CAR T-cell products that use different vectors and costimulatory molecules are currently undergoing clinical trials, Dr. Kumar said.

In contrast to CAR T-cell products that must be customized to each patient in a process that takes weeks, BiTEs are a ready-made approach to allow T cells to engage with tumor cells.

“In patients with advanced disease, a lot can change in that short time frame, so having an approach that is off the shelf, which is not patient specific, is quite attractive,” Dr. Kumar said.

BCMA-directed BiTE therapies under investigation include AMG 420 and PF-06863135, he added.

Dr. Kumar reported one disclosure related to Dr. Reddy’s Laboratories.

The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.

Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.

All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.

The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.

At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.

Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.

Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.

“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”

Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.

SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,

The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.

Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.

All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.

The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.

At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.

Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.

Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.

“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”

Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.

SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,

The oral, multitargeted tyrosine kinase inhibitor pazopanib (Votrient) is active and safe in patients with renal cell carcinoma and other neoplasms caused by von Hippel-Lindau disease, a phase 2 trial has found.

Eric Jonasch, MD, and his coinvestigators at the University of Texas MD Anderson Cancer Center, Houston, conducted the single-arm trial among 31 adult patients with clinical manifestations of von Hippel-Lindau disease, an autosomal dominant disorder that currently has no approved treatment.

All patients were treated with open-label pazopanib (800 mg daily with dose reductions permitted) for 24 weeks, with an option to continue thereafter. Pazopanib derives its antiangiogenic and antineoplastic activity from its selective inhibition of vascular endothelial growth factor receptors (VEGFR)–1, –2, and –3; c-KIT; and platelet-derived growth factor receptor (PDGFR). It is currently approved by the FDA for treatment of advanced renal cell carcinoma and advanced soft-tissue sarcoma.

The trial was stopped before attaining planned enrollment because accrual slowed and it met a prespecified toxicity stopping threshold, according to results reported in Lancet Oncology.

At a median follow-up of 12 months, 42% of patients overall had an objective response to pazopanib. By site, response was seen in 52% of 59 renal cell carcinomas, 53% of 17 pancreatic lesions (mainly serous cystadenomas), and 4% of 49 CNS hemangioblastomas; the median reduction in tumor size was 40.5%, 30.5%, and 13%, respectively.

Slightly more than half of patients, 52%, opted to stay on pazopanib after 24 weeks, with the longest duration being 60 months at data cutoff.

Some 13% of patients withdrew from the study because of grade 3 or 4 transaminitis, and 10% stopped treatment because of general intolerance related to multiple grade 1 and 2 toxicities. There were three treatment-related serious adverse events: one case of appendicitis, one case of gastritis, and one case of fatal CNS bleeding after a fall.

“Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side effect profile consistent with that seen in previous trials,” the investigators concluded. “Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.”

Dr. Jonasch disclosed that he receives research support and honoraria from Novartis. The study was funded by Novartis and by a National Institutes of Health National Cancer Institute core grant.

SOURCE: Jonasch E et al. Lancet Oncol. 2018 Sep 17. doi: 10.1016/S1470-2045(18)30487-X,

As technology continues to advance, so too does its accessibility to the general population. In 2013, 56% of Americans owned a smartphone versus 77% in 2017.¹With the increase in mobile applications (apps) available, it is no surprise that the market has extended into the medical field, with dermatology being no exception.² The majority of dermatology apps can be classified as teledermatology apps, followed by self-surveillance, disease guide, and reference apps. Additional types of dermatology apps include dermoscopy, conference, education, photograph storage and sharing, and journal apps, and others.² In this study, we examined Apple App Store rankings to determine the types of dermatology apps that are most popular among patients and physicians.

METHODS

A popular app rankings analyzer (App Annie) was used to search for dermatology apps along with their App Store rankings.³ Although iOS is not the most popular mobile device operating system, we chose to evaluate app rankings via the App Store because iPhones are the top-selling individual phones of any kind in the United States.⁴

We performed our analysis on a single day (July 14, 2018) given that app rankings can change daily. We incorporated the following keywords, which were commonly used in other dermatology app studies: dermatology, psoriasis, rosacea, acne, skin cancer, melanoma, eczema, and teledermatology. The category ranking was defined as the rank of a free or paid app in the App Store’s top charts for the selected country (United States), market (Apple), and device (iPhone) within their app category (Medical). Inclusion criteria required a ranking in the top 1500 Medical apps and being categorized in the App Store as a Medical app. Exclusion criteria included apps that focused on cosmetics, private practice, direct advertisements, photograph editing, or claims to cure skin disease, as well as non–English-language apps. The App Store descriptions were assessed to determine the type of each app (eg, teledermatology, disease guide) and target audience (patient, physician, or both).

Another search was performed using the same keywords but within the Health and Fitness category to capture potentially more highly ranked apps among patients. We also conducted separate searches within the Medical category using the keywords billing, coding, and ICD (International Classification of Diseases) to evaluate rankings for billing/coding apps, as well as EMR and electronic medical records for electronic medical record (EMR) apps.

RESULTS

The initial search yielded 851 results, which was narrowed down to 29 apps after applying the exclusion criteria. Of note, prior to application of the exclusion criteria, one dermatology app that was considered to be a direct advertisement app claiming to cure acne was ranked fourth of 1500 apps in the Medical category. However, the majority of the search results were excluded because they were not popular enough to be ranked among the top 1500 apps. There were more ranked dermatology apps in the Medical category targeting patients than physicians; 18 of 29 (62%) qualifying apps targeted patients and 11 (38%) targeted physicians (Tables 1 and 2). No apps targeted both groups. The most common type of ranked app targeting patients was self-surveillance (11/18), and the most common type targeting physicians was reference (8/11). The highest ranked app targeting patients was a teledermatology app with a ranking of 184, and the highest ranked app targeting physicians was educational, ranked 353. The least common type of ranked apps targeting patients were “other” (2/18 [11%]; 1 prescription and 1 UV monitor app) and conference (1/18 [6%]). The least common type of ranked apps targeting physicians were education (2/11 [18%]) and dermoscopy (1/11 [9%]).

Our search of the Health and Fitness category yielded 6 apps, all targeting patients; 3 (50%) were self-surveillance apps, and 3 (50%) were classified as other (2 UV monitors and a conferencing app for cancer emotional support)(Table 3).

Our search of the Medical category for billing/coding and EMR apps yielded 232 and 164 apps, respectively; of them, 49 (21%) and 54 (33%) apps were ranked. These apps did not overlap with the dermatology-related search criteria; thus, we were not able to ascertain how many of these apps were used specifically by health care providers in dermatology.

COMMENT

Patient Apps

The most common apps used by patients are fitness and nutrition tracker apps categorized as Health and Fitness^5,6; however, the majority of ranked dermatology apps are categorized as Medical per our findings. In a study of 557 dermatology patients, it was found that among the health-related apps they used, the most common apps after fitness/nutrition were references, followed by patient portals, self-surveillance, and emotional assistance apps.⁶ Our search was consistent with these findings, suggesting that the most desired dermatology apps by patients are those that allow them to be proactive with their health. It is no surprise that the top-ranked app targeting patients was a teledermatology app, followed by multiple self-surveillance apps. The highest ranked self-surveillance app in the Health and Fitness category focused on monitoring the effects of nutrition on symptoms of diseases including skin disorders, while the highest ranked (as well as the majority of) self-surveillance apps in the Medical category encompassed mole monitoring and cancer risk calculators.

Benefits of the ranked dermatology apps in the Medical and Health and Fitness categories targeting patients include more immediate access to health care and education. Despite this popularity among patients, Masud et al⁷ demonstrated that only 20.5% (9/44) of dermatology apps targeting patients may be reliable resources based on a rubric created by the investigators. Overall, there remains a research gap for a standardized scientific approach to evaluating app validity and reliability.

Teledermatology
Teledermatology apps are the most common dermatology apps,² allowing for remote evaluation of patients through either live consultations or transmittance of medical information for later review by board-certified physicians.⁸ Features common to many teledermatology apps include accessibility on Android (Google Inc) and iOS as well as a web version. Security and Health Insurance Portability and Accountability Act compliance is especially important and is enforced through user authentications, data encryption, and automatic logout features. Data is not stored locally and is secured on a private server with backup. Referring providers and consultants often can communicate within the app. Insurance providers also may cover teledermatology services, and if not, the out-of-pocket costs often are affordable.

The highest-ranked patient app (ranked 184 in the Medical category) was a teledermatology app that did not meet the American Telemedicine Association standards for teledermatology apps.⁹ The popularity of this app among patients may have been attributable to multiple ease-of-use and turnaround time features. The user interface was simplistic, and the design was appealing to the eye. The entry field options were minimal to avoid confusion. The turnaround time to receive a diagnosis depended on 1 of 3 options, including a more rapid response for an increased cost. Ease of use was the highlight of this app at the cost of accuracy, as the limited amount of information that users were required to provide physicians compromised diagnostic accuracy in this app.

For comparison, we chose a nonranked (and thus less frequently used) teledermatology app that had previously undergone scientific evaluation using 13 evaluation criteria specific to teledermatology.¹⁰ The app also met the American Telemedicine Association standard for teledermatology apps.⁹ The app was originally a broader telemedicine app but featured a section specific to teledermatology. The user interface was simple but professional, almost resembling an EMR. The input fields included a comprehensive history that permitted a better evaluation of a lesion but might be tedious for users. This app boasted professionalism and accuracy, but from a user standpoint, it may have been too time-consuming.

Striking a balance between ensuring proper care versus appealing to patients is a difficult but important task. Based on this study, it appears that popular patient apps may in fact have less scientific rationale and therefore potentially less accuracy.

Self-surveillance
Although self-surveillance apps did not account for the highest-ranked app, they were the most frequently ranked app type in our study. Most of the ranked self-surveillance apps in the Medical category were for monitoring lesions over time to assess for changes. These apps help users take photographs that are well organized in a single, easy-to-find location. Some apps were risk calculators that assessed the risk for malignancies using a questionnaire. The majority of these self-surveillance apps were specific to skin cancer detection. Of note, one of the ranked self-surveillance apps assessed drug effectiveness by monitoring clinical appearance and symptoms. The lowest ranked self-surveillance app in the top 1500 ranked Medical apps in our search monitored cancer symptoms not specific to dermatology. Although this app had a low ranking (1380/1500), it received a high number of reviews and was well rated at 4.8 out of 5 stars; therefore, it seemed more helpful than the other higher-ranked apps targeting patients, which had higher rankings but minimal to no reviews or ratings. A comparison of the ease-of-use features of all the ranked patient-targeted self-surveillance apps in the Medical category is provided in Table 4.

Physician Apps

After examining the results of apps targeting physicians, we realized that the data may be accurate but may not be as representative of all currently practicing dermatology providers. Given the increased usage of apps among younger age groups,¹¹ our data may be skewed toward medical students and residents, supported by the fact that the top-ranked physician app in our study was an education app and the majority were reference apps. Future studies are needed to reexamine app ranking as this age group transitions from entry-level health care providers in the next 5 to 10 years. These findings also suggest less frequent app use among more veteran health care providers within our specific search parameters. Therefore, we decided to do subsequent searches for available billing/coding and EMR apps, which were many, but as mentioned above, none were specific to dermatology.

General Dermatology References
Most of the dermatology reference apps were formatted as e-books; however, other apps such as the Amazon Kindle app (categorized under Books) providing access to multiple e-books within one app were not included. Some apps included study aid features (eg, flash cards, quizzes), and topics spanned both dermatology and dermatopathology. Apps provide a unique way for on-the-go studying for dermatologists in training, and if the usage continues to grow, there may be a need for increased formal integration in dermatology education in the future.

Journals
Journal apps were not among those listed in the top-ranked apps we evaluated, which we suspect may be because journals were categorized differently from one journal to the next; for example, the Journal of the American Academy of Dermatology was ranked 1168 in the Magazines and Newspapers category. On the other hand, Dermatology World was ranked 1363 in the Reference category. An article’s citation affects the publishing journal’s impact factor, which is one of the most important variables in measuring a journal’s influence. In the future, there may be other variables that could aid in understanding journal impact as it relates to the journal’s accessibility.

Limitations

Our study did not look at Android apps. The top chart apps in the Android and Apple App Stores use undisclosed algorithms likely involving different characteristics such as number of downloads, frequency of updates, number of reviews, ratings, and more. Thus, the rankings across these different markets would not be comparable. Although our choice of keywords stemmed from the majority of prior studies looking at dermatology apps, our search was limited due to the use of these specific keywords. To avoid skewing data by cross-comparison of noncomparable categories, we could not compare apps in the Medical category versus those in other categories.

CONCLUSION

There seems to be a disconnect between the apps that are popular among patients and the scientific validity of the apps. As app usage increases among dermatology providers, whose demographic is shifting younger and younger, apps may become more incorporated in our education, and as such, it will become more critical to develop formal scientific standards. Given these future trends, we may need to increase our current literature and understanding of apps in dermatology with regard to their impact on both patients and health care providers.

As technology continues to advance, so too does its accessibility to the general population. In 2013, 56% of Americans owned a smartphone versus 77% in 2017.¹With the increase in mobile applications (apps) available, it is no surprise that the market has extended into the medical field, with dermatology being no exception.² The majority of dermatology apps can be classified as teledermatology apps, followed by self-surveillance, disease guide, and reference apps. Additional types of dermatology apps include dermoscopy, conference, education, photograph storage and sharing, and journal apps, and others.² In this study, we examined Apple App Store rankings to determine the types of dermatology apps that are most popular among patients and physicians.

METHODS

A popular app rankings analyzer (App Annie) was used to search for dermatology apps along with their App Store rankings.³ Although iOS is not the most popular mobile device operating system, we chose to evaluate app rankings via the App Store because iPhones are the top-selling individual phones of any kind in the United States.⁴

We performed our analysis on a single day (July 14, 2018) given that app rankings can change daily. We incorporated the following keywords, which were commonly used in other dermatology app studies: dermatology, psoriasis, rosacea, acne, skin cancer, melanoma, eczema, and teledermatology. The category ranking was defined as the rank of a free or paid app in the App Store’s top charts for the selected country (United States), market (Apple), and device (iPhone) within their app category (Medical). Inclusion criteria required a ranking in the top 1500 Medical apps and being categorized in the App Store as a Medical app. Exclusion criteria included apps that focused on cosmetics, private practice, direct advertisements, photograph editing, or claims to cure skin disease, as well as non–English-language apps. The App Store descriptions were assessed to determine the type of each app (eg, teledermatology, disease guide) and target audience (patient, physician, or both).

Another search was performed using the same keywords but within the Health and Fitness category to capture potentially more highly ranked apps among patients. We also conducted separate searches within the Medical category using the keywords billing, coding, and ICD (International Classification of Diseases) to evaluate rankings for billing/coding apps, as well as EMR and electronic medical records for electronic medical record (EMR) apps.

RESULTS

The initial search yielded 851 results, which was narrowed down to 29 apps after applying the exclusion criteria. Of note, prior to application of the exclusion criteria, one dermatology app that was considered to be a direct advertisement app claiming to cure acne was ranked fourth of 1500 apps in the Medical category. However, the majority of the search results were excluded because they were not popular enough to be ranked among the top 1500 apps. There were more ranked dermatology apps in the Medical category targeting patients than physicians; 18 of 29 (62%) qualifying apps targeted patients and 11 (38%) targeted physicians (Tables 1 and 2). No apps targeted both groups. The most common type of ranked app targeting patients was self-surveillance (11/18), and the most common type targeting physicians was reference (8/11). The highest ranked app targeting patients was a teledermatology app with a ranking of 184, and the highest ranked app targeting physicians was educational, ranked 353. The least common type of ranked apps targeting patients were “other” (2/18 [11%]; 1 prescription and 1 UV monitor app) and conference (1/18 [6%]). The least common type of ranked apps targeting physicians were education (2/11 [18%]) and dermoscopy (1/11 [9%]).

Our search of the Health and Fitness category yielded 6 apps, all targeting patients; 3 (50%) were self-surveillance apps, and 3 (50%) were classified as other (2 UV monitors and a conferencing app for cancer emotional support)(Table 3).

Our search of the Medical category for billing/coding and EMR apps yielded 232 and 164 apps, respectively; of them, 49 (21%) and 54 (33%) apps were ranked. These apps did not overlap with the dermatology-related search criteria; thus, we were not able to ascertain how many of these apps were used specifically by health care providers in dermatology.

COMMENT

Patient Apps

The most common apps used by patients are fitness and nutrition tracker apps categorized as Health and Fitness^5,6; however, the majority of ranked dermatology apps are categorized as Medical per our findings. In a study of 557 dermatology patients, it was found that among the health-related apps they used, the most common apps after fitness/nutrition were references, followed by patient portals, self-surveillance, and emotional assistance apps.⁶ Our search was consistent with these findings, suggesting that the most desired dermatology apps by patients are those that allow them to be proactive with their health. It is no surprise that the top-ranked app targeting patients was a teledermatology app, followed by multiple self-surveillance apps. The highest ranked self-surveillance app in the Health and Fitness category focused on monitoring the effects of nutrition on symptoms of diseases including skin disorders, while the highest ranked (as well as the majority of) self-surveillance apps in the Medical category encompassed mole monitoring and cancer risk calculators.

Benefits of the ranked dermatology apps in the Medical and Health and Fitness categories targeting patients include more immediate access to health care and education. Despite this popularity among patients, Masud et al⁷ demonstrated that only 20.5% (9/44) of dermatology apps targeting patients may be reliable resources based on a rubric created by the investigators. Overall, there remains a research gap for a standardized scientific approach to evaluating app validity and reliability.

Teledermatology
Teledermatology apps are the most common dermatology apps,² allowing for remote evaluation of patients through either live consultations or transmittance of medical information for later review by board-certified physicians.⁸ Features common to many teledermatology apps include accessibility on Android (Google Inc) and iOS as well as a web version. Security and Health Insurance Portability and Accountability Act compliance is especially important and is enforced through user authentications, data encryption, and automatic logout features. Data is not stored locally and is secured on a private server with backup. Referring providers and consultants often can communicate within the app. Insurance providers also may cover teledermatology services, and if not, the out-of-pocket costs often are affordable.

The highest-ranked patient app (ranked 184 in the Medical category) was a teledermatology app that did not meet the American Telemedicine Association standards for teledermatology apps.⁹ The popularity of this app among patients may have been attributable to multiple ease-of-use and turnaround time features. The user interface was simplistic, and the design was appealing to the eye. The entry field options were minimal to avoid confusion. The turnaround time to receive a diagnosis depended on 1 of 3 options, including a more rapid response for an increased cost. Ease of use was the highlight of this app at the cost of accuracy, as the limited amount of information that users were required to provide physicians compromised diagnostic accuracy in this app.

For comparison, we chose a nonranked (and thus less frequently used) teledermatology app that had previously undergone scientific evaluation using 13 evaluation criteria specific to teledermatology.¹⁰ The app also met the American Telemedicine Association standard for teledermatology apps.⁹ The app was originally a broader telemedicine app but featured a section specific to teledermatology. The user interface was simple but professional, almost resembling an EMR. The input fields included a comprehensive history that permitted a better evaluation of a lesion but might be tedious for users. This app boasted professionalism and accuracy, but from a user standpoint, it may have been too time-consuming.

Striking a balance between ensuring proper care versus appealing to patients is a difficult but important task. Based on this study, it appears that popular patient apps may in fact have less scientific rationale and therefore potentially less accuracy.

Self-surveillance
Although self-surveillance apps did not account for the highest-ranked app, they were the most frequently ranked app type in our study. Most of the ranked self-surveillance apps in the Medical category were for monitoring lesions over time to assess for changes. These apps help users take photographs that are well organized in a single, easy-to-find location. Some apps were risk calculators that assessed the risk for malignancies using a questionnaire. The majority of these self-surveillance apps were specific to skin cancer detection. Of note, one of the ranked self-surveillance apps assessed drug effectiveness by monitoring clinical appearance and symptoms. The lowest ranked self-surveillance app in the top 1500 ranked Medical apps in our search monitored cancer symptoms not specific to dermatology. Although this app had a low ranking (1380/1500), it received a high number of reviews and was well rated at 4.8 out of 5 stars; therefore, it seemed more helpful than the other higher-ranked apps targeting patients, which had higher rankings but minimal to no reviews or ratings. A comparison of the ease-of-use features of all the ranked patient-targeted self-surveillance apps in the Medical category is provided in Table 4.

Physician Apps

After examining the results of apps targeting physicians, we realized that the data may be accurate but may not be as representative of all currently practicing dermatology providers. Given the increased usage of apps among younger age groups,¹¹ our data may be skewed toward medical students and residents, supported by the fact that the top-ranked physician app in our study was an education app and the majority were reference apps. Future studies are needed to reexamine app ranking as this age group transitions from entry-level health care providers in the next 5 to 10 years. These findings also suggest less frequent app use among more veteran health care providers within our specific search parameters. Therefore, we decided to do subsequent searches for available billing/coding and EMR apps, which were many, but as mentioned above, none were specific to dermatology.

General Dermatology References
Most of the dermatology reference apps were formatted as e-books; however, other apps such as the Amazon Kindle app (categorized under Books) providing access to multiple e-books within one app were not included. Some apps included study aid features (eg, flash cards, quizzes), and topics spanned both dermatology and dermatopathology. Apps provide a unique way for on-the-go studying for dermatologists in training, and if the usage continues to grow, there may be a need for increased formal integration in dermatology education in the future.

Journals
Journal apps were not among those listed in the top-ranked apps we evaluated, which we suspect may be because journals were categorized differently from one journal to the next; for example, the Journal of the American Academy of Dermatology was ranked 1168 in the Magazines and Newspapers category. On the other hand, Dermatology World was ranked 1363 in the Reference category. An article’s citation affects the publishing journal’s impact factor, which is one of the most important variables in measuring a journal’s influence. In the future, there may be other variables that could aid in understanding journal impact as it relates to the journal’s accessibility.

Limitations

Our study did not look at Android apps. The top chart apps in the Android and Apple App Stores use undisclosed algorithms likely involving different characteristics such as number of downloads, frequency of updates, number of reviews, ratings, and more. Thus, the rankings across these different markets would not be comparable. Although our choice of keywords stemmed from the majority of prior studies looking at dermatology apps, our search was limited due to the use of these specific keywords. To avoid skewing data by cross-comparison of noncomparable categories, we could not compare apps in the Medical category versus those in other categories.

CONCLUSION

There seems to be a disconnect between the apps that are popular among patients and the scientific validity of the apps. As app usage increases among dermatology providers, whose demographic is shifting younger and younger, apps may become more incorporated in our education, and as such, it will become more critical to develop formal scientific standards. Given these future trends, we may need to increase our current literature and understanding of apps in dermatology with regard to their impact on both patients and health care providers.

As technology continues to advance, so too does its accessibility to the general population. In 2013, 56% of Americans owned a smartphone versus 77% in 2017.¹With the increase in mobile applications (apps) available, it is no surprise that the market has extended into the medical field, with dermatology being no exception.² The majority of dermatology apps can be classified as teledermatology apps, followed by self-surveillance, disease guide, and reference apps. Additional types of dermatology apps include dermoscopy, conference, education, photograph storage and sharing, and journal apps, and others.² In this study, we examined Apple App Store rankings to determine the types of dermatology apps that are most popular among patients and physicians.

METHODS

A popular app rankings analyzer (App Annie) was used to search for dermatology apps along with their App Store rankings.³ Although iOS is not the most popular mobile device operating system, we chose to evaluate app rankings via the App Store because iPhones are the top-selling individual phones of any kind in the United States.⁴

We performed our analysis on a single day (July 14, 2018) given that app rankings can change daily. We incorporated the following keywords, which were commonly used in other dermatology app studies: dermatology, psoriasis, rosacea, acne, skin cancer, melanoma, eczema, and teledermatology. The category ranking was defined as the rank of a free or paid app in the App Store’s top charts for the selected country (United States), market (Apple), and device (iPhone) within their app category (Medical). Inclusion criteria required a ranking in the top 1500 Medical apps and being categorized in the App Store as a Medical app. Exclusion criteria included apps that focused on cosmetics, private practice, direct advertisements, photograph editing, or claims to cure skin disease, as well as non–English-language apps. The App Store descriptions were assessed to determine the type of each app (eg, teledermatology, disease guide) and target audience (patient, physician, or both).

Another search was performed using the same keywords but within the Health and Fitness category to capture potentially more highly ranked apps among patients. We also conducted separate searches within the Medical category using the keywords billing, coding, and ICD (International Classification of Diseases) to evaluate rankings for billing/coding apps, as well as EMR and electronic medical records for electronic medical record (EMR) apps.

RESULTS

The initial search yielded 851 results, which was narrowed down to 29 apps after applying the exclusion criteria. Of note, prior to application of the exclusion criteria, one dermatology app that was considered to be a direct advertisement app claiming to cure acne was ranked fourth of 1500 apps in the Medical category. However, the majority of the search results were excluded because they were not popular enough to be ranked among the top 1500 apps. There were more ranked dermatology apps in the Medical category targeting patients than physicians; 18 of 29 (62%) qualifying apps targeted patients and 11 (38%) targeted physicians (Tables 1 and 2). No apps targeted both groups. The most common type of ranked app targeting patients was self-surveillance (11/18), and the most common type targeting physicians was reference (8/11). The highest ranked app targeting patients was a teledermatology app with a ranking of 184, and the highest ranked app targeting physicians was educational, ranked 353. The least common type of ranked apps targeting patients were “other” (2/18 [11%]; 1 prescription and 1 UV monitor app) and conference (1/18 [6%]). The least common type of ranked apps targeting physicians were education (2/11 [18%]) and dermoscopy (1/11 [9%]).

Our search of the Health and Fitness category yielded 6 apps, all targeting patients; 3 (50%) were self-surveillance apps, and 3 (50%) were classified as other (2 UV monitors and a conferencing app for cancer emotional support)(Table 3).

Our search of the Medical category for billing/coding and EMR apps yielded 232 and 164 apps, respectively; of them, 49 (21%) and 54 (33%) apps were ranked. These apps did not overlap with the dermatology-related search criteria; thus, we were not able to ascertain how many of these apps were used specifically by health care providers in dermatology.

COMMENT

Patient Apps

The most common apps used by patients are fitness and nutrition tracker apps categorized as Health and Fitness^5,6; however, the majority of ranked dermatology apps are categorized as Medical per our findings. In a study of 557 dermatology patients, it was found that among the health-related apps they used, the most common apps after fitness/nutrition were references, followed by patient portals, self-surveillance, and emotional assistance apps.⁶ Our search was consistent with these findings, suggesting that the most desired dermatology apps by patients are those that allow them to be proactive with their health. It is no surprise that the top-ranked app targeting patients was a teledermatology app, followed by multiple self-surveillance apps. The highest ranked self-surveillance app in the Health and Fitness category focused on monitoring the effects of nutrition on symptoms of diseases including skin disorders, while the highest ranked (as well as the majority of) self-surveillance apps in the Medical category encompassed mole monitoring and cancer risk calculators.

Benefits of the ranked dermatology apps in the Medical and Health and Fitness categories targeting patients include more immediate access to health care and education. Despite this popularity among patients, Masud et al⁷ demonstrated that only 20.5% (9/44) of dermatology apps targeting patients may be reliable resources based on a rubric created by the investigators. Overall, there remains a research gap for a standardized scientific approach to evaluating app validity and reliability.

Teledermatology
Teledermatology apps are the most common dermatology apps,² allowing for remote evaluation of patients through either live consultations or transmittance of medical information for later review by board-certified physicians.⁸ Features common to many teledermatology apps include accessibility on Android (Google Inc) and iOS as well as a web version. Security and Health Insurance Portability and Accountability Act compliance is especially important and is enforced through user authentications, data encryption, and automatic logout features. Data is not stored locally and is secured on a private server with backup. Referring providers and consultants often can communicate within the app. Insurance providers also may cover teledermatology services, and if not, the out-of-pocket costs often are affordable.

The highest-ranked patient app (ranked 184 in the Medical category) was a teledermatology app that did not meet the American Telemedicine Association standards for teledermatology apps.⁹ The popularity of this app among patients may have been attributable to multiple ease-of-use and turnaround time features. The user interface was simplistic, and the design was appealing to the eye. The entry field options were minimal to avoid confusion. The turnaround time to receive a diagnosis depended on 1 of 3 options, including a more rapid response for an increased cost. Ease of use was the highlight of this app at the cost of accuracy, as the limited amount of information that users were required to provide physicians compromised diagnostic accuracy in this app.

For comparison, we chose a nonranked (and thus less frequently used) teledermatology app that had previously undergone scientific evaluation using 13 evaluation criteria specific to teledermatology.¹⁰ The app also met the American Telemedicine Association standard for teledermatology apps.⁹ The app was originally a broader telemedicine app but featured a section specific to teledermatology. The user interface was simple but professional, almost resembling an EMR. The input fields included a comprehensive history that permitted a better evaluation of a lesion but might be tedious for users. This app boasted professionalism and accuracy, but from a user standpoint, it may have been too time-consuming.

Striking a balance between ensuring proper care versus appealing to patients is a difficult but important task. Based on this study, it appears that popular patient apps may in fact have less scientific rationale and therefore potentially less accuracy.

Self-surveillance
Although self-surveillance apps did not account for the highest-ranked app, they were the most frequently ranked app type in our study. Most of the ranked self-surveillance apps in the Medical category were for monitoring lesions over time to assess for changes. These apps help users take photographs that are well organized in a single, easy-to-find location. Some apps were risk calculators that assessed the risk for malignancies using a questionnaire. The majority of these self-surveillance apps were specific to skin cancer detection. Of note, one of the ranked self-surveillance apps assessed drug effectiveness by monitoring clinical appearance and symptoms. The lowest ranked self-surveillance app in the top 1500 ranked Medical apps in our search monitored cancer symptoms not specific to dermatology. Although this app had a low ranking (1380/1500), it received a high number of reviews and was well rated at 4.8 out of 5 stars; therefore, it seemed more helpful than the other higher-ranked apps targeting patients, which had higher rankings but minimal to no reviews or ratings. A comparison of the ease-of-use features of all the ranked patient-targeted self-surveillance apps in the Medical category is provided in Table 4.

Physician Apps

After examining the results of apps targeting physicians, we realized that the data may be accurate but may not be as representative of all currently practicing dermatology providers. Given the increased usage of apps among younger age groups,¹¹ our data may be skewed toward medical students and residents, supported by the fact that the top-ranked physician app in our study was an education app and the majority were reference apps. Future studies are needed to reexamine app ranking as this age group transitions from entry-level health care providers in the next 5 to 10 years. These findings also suggest less frequent app use among more veteran health care providers within our specific search parameters. Therefore, we decided to do subsequent searches for available billing/coding and EMR apps, which were many, but as mentioned above, none were specific to dermatology.

General Dermatology References
Most of the dermatology reference apps were formatted as e-books; however, other apps such as the Amazon Kindle app (categorized under Books) providing access to multiple e-books within one app were not included. Some apps included study aid features (eg, flash cards, quizzes), and topics spanned both dermatology and dermatopathology. Apps provide a unique way for on-the-go studying for dermatologists in training, and if the usage continues to grow, there may be a need for increased formal integration in dermatology education in the future.

Journals
Journal apps were not among those listed in the top-ranked apps we evaluated, which we suspect may be because journals were categorized differently from one journal to the next; for example, the Journal of the American Academy of Dermatology was ranked 1168 in the Magazines and Newspapers category. On the other hand, Dermatology World was ranked 1363 in the Reference category. An article’s citation affects the publishing journal’s impact factor, which is one of the most important variables in measuring a journal’s influence. In the future, there may be other variables that could aid in understanding journal impact as it relates to the journal’s accessibility.

Limitations

Our study did not look at Android apps. The top chart apps in the Android and Apple App Stores use undisclosed algorithms likely involving different characteristics such as number of downloads, frequency of updates, number of reviews, ratings, and more. Thus, the rankings across these different markets would not be comparable. Although our choice of keywords stemmed from the majority of prior studies looking at dermatology apps, our search was limited due to the use of these specific keywords. To avoid skewing data by cross-comparison of noncomparable categories, we could not compare apps in the Medical category versus those in other categories.

CONCLUSION

There seems to be a disconnect between the apps that are popular among patients and the scientific validity of the apps. As app usage increases among dermatology providers, whose demographic is shifting younger and younger, apps may become more incorporated in our education, and as such, it will become more critical to develop formal scientific standards. Given these future trends, we may need to increase our current literature and understanding of apps in dermatology with regard to their impact on both patients and health care providers.

CHEST Physician reporting staff will provide on-site coverage of CHEST 2018, the annual meeting of the American College of Chest Physicians, held in San Antonio, Tex., Oct. 6 through Oct. 10. They are planning to report on a wide variety of sessions covering the latest research on treating COPD, sleep medicine, pulmonary hypertension, asthma, and other pulmonary disease. Panels, plenaries, original research presentations, and late-breaking studies will all be covered in depth. Stories will be posted daily during the meeting on the CHEST Physician website. They will also be talking to presenters and discussants about their work, so be sure to watch for video interviews, which also will be published daily.

Among the sessions on the coverage calendar are the following:

The Impact of Obesity on Pulmonary Disorders. Sunday, Oct. 7, 7:30 a.m. to 8:30 a.m., Convention Center 207B

GAMES: Games Augmenting Medical Education. Sunday, Oct. 7, 10:45 a.m. to 11:45 a.m., Convention Center 207B

Current Trends and Controversies in the Practice of Sleep Medicine. Monday, Oct. 8, 7:30 a.m. to 8:30 a.m., Convention Center 214A

Futility? Responding to Nonbeneficial Treatment Requests. Monday, Oct. 8, 11:00 a.m. to 12:00 p.m., Convention Center 212A

Update on Diagnosis and Management of Diffuse Cystic Lung Disease. Tuesday, Oct. 9, 7:30 a.m. to 8:30 a.m., Convention Center 214A

Lung Cancer Screening: News Questions and New Answers. Tuesday, Oct. 9, 8:45 a.m. to 9:45 a.m., Convention Center 207A



Check here on the CHEST Physician website for the latest news from CHEST 2018!

CHEST Physician reporting staff will provide on-site coverage of CHEST 2018, the annual meeting of the American College of Chest Physicians, held in San Antonio, Tex., Oct. 6 through Oct. 10. They are planning to report on a wide variety of sessions covering the latest research on treating COPD, sleep medicine, pulmonary hypertension, asthma, and other pulmonary disease. Panels, plenaries, original research presentations, and late-breaking studies will all be covered in depth. Stories will be posted daily during the meeting on the CHEST Physician website. They will also be talking to presenters and discussants about their work, so be sure to watch for video interviews, which also will be published daily.

Among the sessions on the coverage calendar are the following:

The Impact of Obesity on Pulmonary Disorders. Sunday, Oct. 7, 7:30 a.m. to 8:30 a.m., Convention Center 207B

GAMES: Games Augmenting Medical Education. Sunday, Oct. 7, 10:45 a.m. to 11:45 a.m., Convention Center 207B

Current Trends and Controversies in the Practice of Sleep Medicine. Monday, Oct. 8, 7:30 a.m. to 8:30 a.m., Convention Center 214A

Futility? Responding to Nonbeneficial Treatment Requests. Monday, Oct. 8, 11:00 a.m. to 12:00 p.m., Convention Center 212A

Update on Diagnosis and Management of Diffuse Cystic Lung Disease. Tuesday, Oct. 9, 7:30 a.m. to 8:30 a.m., Convention Center 214A

Lung Cancer Screening: News Questions and New Answers. Tuesday, Oct. 9, 8:45 a.m. to 9:45 a.m., Convention Center 207A



Check here on the CHEST Physician website for the latest news from CHEST 2018!

CHEST Physician reporting staff will provide on-site coverage of CHEST 2018, the annual meeting of the American College of Chest Physicians, held in San Antonio, Tex., Oct. 6 through Oct. 10. They are planning to report on a wide variety of sessions covering the latest research on treating COPD, sleep medicine, pulmonary hypertension, asthma, and other pulmonary disease. Panels, plenaries, original research presentations, and late-breaking studies will all be covered in depth. Stories will be posted daily during the meeting on the CHEST Physician website. They will also be talking to presenters and discussants about their work, so be sure to watch for video interviews, which also will be published daily.

Among the sessions on the coverage calendar are the following:

The Impact of Obesity on Pulmonary Disorders. Sunday, Oct. 7, 7:30 a.m. to 8:30 a.m., Convention Center 207B

GAMES: Games Augmenting Medical Education. Sunday, Oct. 7, 10:45 a.m. to 11:45 a.m., Convention Center 207B

Current Trends and Controversies in the Practice of Sleep Medicine. Monday, Oct. 8, 7:30 a.m. to 8:30 a.m., Convention Center 214A

Futility? Responding to Nonbeneficial Treatment Requests. Monday, Oct. 8, 11:00 a.m. to 12:00 p.m., Convention Center 212A

Update on Diagnosis and Management of Diffuse Cystic Lung Disease. Tuesday, Oct. 9, 7:30 a.m. to 8:30 a.m., Convention Center 214A

Lung Cancer Screening: News Questions and New Answers. Tuesday, Oct. 9, 8:45 a.m. to 9:45 a.m., Convention Center 207A



Check here on the CHEST Physician website for the latest news from CHEST 2018!

TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.

Sharon Worcester/MDedge News

The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”

Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.

Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m²) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.

The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.

The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.

The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”

That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”

Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.

“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”

When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.

“But today, in an all-comer population, this combination has improved survival,” he said.

IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.

SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.

TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.

Sharon Worcester/MDedge News

The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”

Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.

Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m²) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.

The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.

The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.

The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”

That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”

Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.

“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”

When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.

“But today, in an all-comer population, this combination has improved survival,” he said.

IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.

SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.

TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.

Sharon Worcester/MDedge News

The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”

Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.

Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m²) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.

The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.

The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.

The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”

That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”

Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.

“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”

When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.

“But today, in an all-comer population, this combination has improved survival,” he said.

IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.

SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.