To improve patient care and outcomes, leading dermatologists offered their recommendations on scar treatments. Consideration must be given to:

• bioCorneum+

• Mederma Scar Cream Plus SPF 30

• Organic vitamin E oil

• ScarAway Silicone Scar Sheets

• Scar Recovery Gel with Centelline

Cutis invites readers to send us their recommendations. Body scrubs, OTC acne treatments, self-tanners, and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on scar treatments. Consideration must be given to:

• bioCorneum+

• Mederma Scar Cream Plus SPF 30

• Organic vitamin E oil

• ScarAway Silicone Scar Sheets

• Scar Recovery Gel with Centelline

Cutis invites readers to send us their recommendations. Body scrubs, OTC acne treatments, self-tanners, and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on scar treatments. Consideration must be given to:

• bioCorneum+

• Mederma Scar Cream Plus SPF 30

• Organic vitamin E oil

• ScarAway Silicone Scar Sheets

• Scar Recovery Gel with Centelline

Cutis invites readers to send us their recommendations. Body scrubs, OTC acne treatments, self-tanners, and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

A phase 2 study findings suggest that AV7909, a new vaccine for postexposure prophylaxis of anthrax disease, may work faster and require fewer vaccinations with fewer antigens when compared with BioThrax. The authors also speculate that AV7909 might require shorter stints with antimicrobial drugs than the 60-day regimen currently recommended along with the 3-dose series of BioThrax vaccine, which could lead to increased patients adherence.

Related: Clinical Trials Begin for Another Anthrax Vaccine

The drug AV7909 combines BioThrax with CPG7909, a synthetic immunostimulatory oligonucleotide. Earlier trials identified a formulation that enhanced immune response without increasing adverse events (AEs). In a multicenter phase 2 trial that evaluated this formulation, researchers tested 3 vaccine schedules and 2 doses in 168 healthy volunteers. Serum samples were collected before the vaccination and on days 35, 42, 49, 63, and 84. Safety was assessed through Day 84.

Related: Better Anthrax Vaccine on the Horizon

The schedule of 2 full doses of AV7909, given 2 weeks apart, showed a comparable immune response to a 0/14/28-day BioThrax schedule but had a higher and earlier peak. The AV7909 vaccine was safe and well tolerated. Although the AV7909 group reported more AEs (79% for AV7909 vs 65% for BioThrax), no serious AEs were assessed as potentially vaccine related, and none were deemed of potential autoimmune etiology.

Source:Hopkin RJ, Kalsi G, Montalvo-Lugo VM, et al. Vaccine. 2016;34(18):2096-2105.doi: 10.1016/j.vaccine.2016.03.006. 

A phase 2 study findings suggest that AV7909, a new vaccine for postexposure prophylaxis of anthrax disease, may work faster and require fewer vaccinations with fewer antigens when compared with BioThrax. The authors also speculate that AV7909 might require shorter stints with antimicrobial drugs than the 60-day regimen currently recommended along with the 3-dose series of BioThrax vaccine, which could lead to increased patients adherence.

Related: Clinical Trials Begin for Another Anthrax Vaccine

The drug AV7909 combines BioThrax with CPG7909, a synthetic immunostimulatory oligonucleotide. Earlier trials identified a formulation that enhanced immune response without increasing adverse events (AEs). In a multicenter phase 2 trial that evaluated this formulation, researchers tested 3 vaccine schedules and 2 doses in 168 healthy volunteers. Serum samples were collected before the vaccination and on days 35, 42, 49, 63, and 84. Safety was assessed through Day 84.

Related: Better Anthrax Vaccine on the Horizon

The schedule of 2 full doses of AV7909, given 2 weeks apart, showed a comparable immune response to a 0/14/28-day BioThrax schedule but had a higher and earlier peak. The AV7909 vaccine was safe and well tolerated. Although the AV7909 group reported more AEs (79% for AV7909 vs 65% for BioThrax), no serious AEs were assessed as potentially vaccine related, and none were deemed of potential autoimmune etiology.

Source:Hopkin RJ, Kalsi G, Montalvo-Lugo VM, et al. Vaccine. 2016;34(18):2096-2105.doi: 10.1016/j.vaccine.2016.03.006. 

A phase 2 study findings suggest that AV7909, a new vaccine for postexposure prophylaxis of anthrax disease, may work faster and require fewer vaccinations with fewer antigens when compared with BioThrax. The authors also speculate that AV7909 might require shorter stints with antimicrobial drugs than the 60-day regimen currently recommended along with the 3-dose series of BioThrax vaccine, which could lead to increased patients adherence.

Related: Clinical Trials Begin for Another Anthrax Vaccine

The drug AV7909 combines BioThrax with CPG7909, a synthetic immunostimulatory oligonucleotide. Earlier trials identified a formulation that enhanced immune response without increasing adverse events (AEs). In a multicenter phase 2 trial that evaluated this formulation, researchers tested 3 vaccine schedules and 2 doses in 168 healthy volunteers. Serum samples were collected before the vaccination and on days 35, 42, 49, 63, and 84. Safety was assessed through Day 84.

Related: Better Anthrax Vaccine on the Horizon

The schedule of 2 full doses of AV7909, given 2 weeks apart, showed a comparable immune response to a 0/14/28-day BioThrax schedule but had a higher and earlier peak. The AV7909 vaccine was safe and well tolerated. Although the AV7909 group reported more AEs (79% for AV7909 vs 65% for BioThrax), no serious AEs were assessed as potentially vaccine related, and none were deemed of potential autoimmune etiology.

Source:Hopkin RJ, Kalsi G, Montalvo-Lugo VM, et al. Vaccine. 2016;34(18):2096-2105.doi: 10.1016/j.vaccine.2016.03.006. 

Federal officials took the next step in their moonshot to end cancer by announcing on April 4 a blue ribbon panel to guide the effort.

A total of 28 leading researchers, clinicians, and patient advocates have been named to the panel charged with informing the scientific direction and goals of the National Cancer Moonshot Initiative, led by Vice President Joe Biden.

“This Blue Ribbon Panel will ensure that, as [the National Institutes of Health] allocates new resources through the Moonshot, decisions will be grounded in the best science,” Vice President Biden said in a statement. “I look forward to working with this panel and many others involved with the Moonshot to make unprecedented improvements in prevention, diagnosis, and treatment of cancer.”

The key goals of the initiative were set out simultaneously in a perspective from Dr. Francis S. Collins, NIH director, and Dr. Douglas R. Lowy, director of the National Cancer Institute. The editorial was published in the New England Journal of Medicine.

“Fueled by an additional $680 million in the proposed fiscal year 2017 budget for the NIH, plus additional resources for the Food and Drug Administration, the initiative will aim to accelerate progress toward the next generation of interventions that we hope will substantially reduce cancer incidence and dramatically improve patient outcomes,” Dr. Collins and Dr. Lowy wrote. “The NIH’s most compelling opportunities for progress will be set forth by late summer 2016 in a research plan informed by the deliberations of a blue-ribbon panel of experts, which will provide scientific input to the National Cancer Advisory Board. Some possible opportunities include vaccine development, early-detection technology, single-cell genomic analysis, immunotherapy, a focus on pediatric cancer, and enhanced data sharing.”

To read the full editorial, click here.

[email protected]

On Twitter @denisefulton

Federal officials took the next step in their moonshot to end cancer by announcing on April 4 a blue ribbon panel to guide the effort.

A total of 28 leading researchers, clinicians, and patient advocates have been named to the panel charged with informing the scientific direction and goals of the National Cancer Moonshot Initiative, led by Vice President Joe Biden.

“This Blue Ribbon Panel will ensure that, as [the National Institutes of Health] allocates new resources through the Moonshot, decisions will be grounded in the best science,” Vice President Biden said in a statement. “I look forward to working with this panel and many others involved with the Moonshot to make unprecedented improvements in prevention, diagnosis, and treatment of cancer.”

The key goals of the initiative were set out simultaneously in a perspective from Dr. Francis S. Collins, NIH director, and Dr. Douglas R. Lowy, director of the National Cancer Institute. The editorial was published in the New England Journal of Medicine.

“Fueled by an additional $680 million in the proposed fiscal year 2017 budget for the NIH, plus additional resources for the Food and Drug Administration, the initiative will aim to accelerate progress toward the next generation of interventions that we hope will substantially reduce cancer incidence and dramatically improve patient outcomes,” Dr. Collins and Dr. Lowy wrote. “The NIH’s most compelling opportunities for progress will be set forth by late summer 2016 in a research plan informed by the deliberations of a blue-ribbon panel of experts, which will provide scientific input to the National Cancer Advisory Board. Some possible opportunities include vaccine development, early-detection technology, single-cell genomic analysis, immunotherapy, a focus on pediatric cancer, and enhanced data sharing.”

To read the full editorial, click here.

[email protected]

On Twitter @denisefulton

Federal officials took the next step in their moonshot to end cancer by announcing on April 4 a blue ribbon panel to guide the effort.

A total of 28 leading researchers, clinicians, and patient advocates have been named to the panel charged with informing the scientific direction and goals of the National Cancer Moonshot Initiative, led by Vice President Joe Biden.

“This Blue Ribbon Panel will ensure that, as [the National Institutes of Health] allocates new resources through the Moonshot, decisions will be grounded in the best science,” Vice President Biden said in a statement. “I look forward to working with this panel and many others involved with the Moonshot to make unprecedented improvements in prevention, diagnosis, and treatment of cancer.”

The key goals of the initiative were set out simultaneously in a perspective from Dr. Francis S. Collins, NIH director, and Dr. Douglas R. Lowy, director of the National Cancer Institute. The editorial was published in the New England Journal of Medicine.

“Fueled by an additional $680 million in the proposed fiscal year 2017 budget for the NIH, plus additional resources for the Food and Drug Administration, the initiative will aim to accelerate progress toward the next generation of interventions that we hope will substantially reduce cancer incidence and dramatically improve patient outcomes,” Dr. Collins and Dr. Lowy wrote. “The NIH’s most compelling opportunities for progress will be set forth by late summer 2016 in a research plan informed by the deliberations of a blue-ribbon panel of experts, which will provide scientific input to the National Cancer Advisory Board. Some possible opportunities include vaccine development, early-detection technology, single-cell genomic analysis, immunotherapy, a focus on pediatric cancer, and enhanced data sharing.”

To read the full editorial, click here.

[email protected]

On Twitter @denisefulton

Renal status should be evaluated at diagnosis and follow-up in all myeloma patients, according to new guidance from the International Myeloma Working Group published online in the Journal of Clinical Oncology.

Renal impairment (RI) affects up to half of patients with multiple myeloma, and severe RI predicts early death, noted Dr. Meletios Dimopoulos of National and Kapodistrian University of Athens and his associates. Novel therapies have substantially increased survival for myeloma with less severe kidney disease, underscoring the importance of early treatment. To develop the guidelines, the authors reviewed all evidence from randomized trials, systematic reviews, meta-analyses, and prospective and observational studies published through December 2015 (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

Grade A recommendations (evidence obtained from meta-analysis of multiple well-designed, randomized controlled trials) include the following:

Evaluate serum creatinine, estimated glomerular filtration rate, and electrolytes at initial diagnosis and follow-up assessments. Also perform the serum free light chain test, if available, and electrophoresis of a 24-hour urine specimen.

In patients with stabilized serum creatinine, evaluate GFR using the Chronic Kidney Disease Epidemiology Collaboration (preferred) or the Modification of Diet in Renal Disease formulas.

Based on GFR, determine stage of chronic kidney disease (ranging from 1, kidney damage with normal or elevated GFR, to 5, renal failure).

Bortezomib remains the foundational treatment for myeloma-related renal impairment, the authors emphasized. This 26S proteasome inhibitor should be started at the standard dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 3-week cycle.

Another option for patients with creatinine clearance above 15 mL/min is carfilzomib, which needs no dose modification and yields similar results regardless of RI status. However, more data are needed on its renal safety, the authors said.

Patients with creatinine clearance above 30 mL/min can safely receive ixazomib in combination with lenalidomide and dexamethasone.

Those with creatinine clearance above 45 mL/min should receive pomalidomide at a dose of 4 mg/day; it is not yet clear whether the dose should be cut for more severe renal impairment.

Hypercalcemia can be treated with bisphosphonates, but patients with creatinine clearance below 30 mL/min should not receive pamidronate or zoledronic acid.

Avoid nephrotoxic agents, such as as aminoglycosides, furosemide, and contrast agents, in all patients with multiple myeloma and RI.

Dr. Dimopoulos reported receiving honoraria or financial support related to travel, accommodations, or expenses from Amgen, Celgene, Onyx Pharmaceuticals, Janssen-Cilag, Bristol-Myers Squibb, Novartis, and Genesis Pharmaceuticals. Seventeen coauthors also reported financial relationships with a number of pharmaceutical companies. The remaining three coauthors had no disclosures.

Renal status should be evaluated at diagnosis and follow-up in all myeloma patients, according to new guidance from the International Myeloma Working Group published online in the Journal of Clinical Oncology.

Renal impairment (RI) affects up to half of patients with multiple myeloma, and severe RI predicts early death, noted Dr. Meletios Dimopoulos of National and Kapodistrian University of Athens and his associates. Novel therapies have substantially increased survival for myeloma with less severe kidney disease, underscoring the importance of early treatment. To develop the guidelines, the authors reviewed all evidence from randomized trials, systematic reviews, meta-analyses, and prospective and observational studies published through December 2015 (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

Grade A recommendations (evidence obtained from meta-analysis of multiple well-designed, randomized controlled trials) include the following:

Evaluate serum creatinine, estimated glomerular filtration rate, and electrolytes at initial diagnosis and follow-up assessments. Also perform the serum free light chain test, if available, and electrophoresis of a 24-hour urine specimen.

In patients with stabilized serum creatinine, evaluate GFR using the Chronic Kidney Disease Epidemiology Collaboration (preferred) or the Modification of Diet in Renal Disease formulas.

Based on GFR, determine stage of chronic kidney disease (ranging from 1, kidney damage with normal or elevated GFR, to 5, renal failure).

Bortezomib remains the foundational treatment for myeloma-related renal impairment, the authors emphasized. This 26S proteasome inhibitor should be started at the standard dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 3-week cycle.

Another option for patients with creatinine clearance above 15 mL/min is carfilzomib, which needs no dose modification and yields similar results regardless of RI status. However, more data are needed on its renal safety, the authors said.

Patients with creatinine clearance above 30 mL/min can safely receive ixazomib in combination with lenalidomide and dexamethasone.

Those with creatinine clearance above 45 mL/min should receive pomalidomide at a dose of 4 mg/day; it is not yet clear whether the dose should be cut for more severe renal impairment.

Hypercalcemia can be treated with bisphosphonates, but patients with creatinine clearance below 30 mL/min should not receive pamidronate or zoledronic acid.

Avoid nephrotoxic agents, such as as aminoglycosides, furosemide, and contrast agents, in all patients with multiple myeloma and RI.

Dr. Dimopoulos reported receiving honoraria or financial support related to travel, accommodations, or expenses from Amgen, Celgene, Onyx Pharmaceuticals, Janssen-Cilag, Bristol-Myers Squibb, Novartis, and Genesis Pharmaceuticals. Seventeen coauthors also reported financial relationships with a number of pharmaceutical companies. The remaining three coauthors had no disclosures.

Renal status should be evaluated at diagnosis and follow-up in all myeloma patients, according to new guidance from the International Myeloma Working Group published online in the Journal of Clinical Oncology.

Renal impairment (RI) affects up to half of patients with multiple myeloma, and severe RI predicts early death, noted Dr. Meletios Dimopoulos of National and Kapodistrian University of Athens and his associates. Novel therapies have substantially increased survival for myeloma with less severe kidney disease, underscoring the importance of early treatment. To develop the guidelines, the authors reviewed all evidence from randomized trials, systematic reviews, meta-analyses, and prospective and observational studies published through December 2015 (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

Grade A recommendations (evidence obtained from meta-analysis of multiple well-designed, randomized controlled trials) include the following:

Evaluate serum creatinine, estimated glomerular filtration rate, and electrolytes at initial diagnosis and follow-up assessments. Also perform the serum free light chain test, if available, and electrophoresis of a 24-hour urine specimen.

In patients with stabilized serum creatinine, evaluate GFR using the Chronic Kidney Disease Epidemiology Collaboration (preferred) or the Modification of Diet in Renal Disease formulas.

Based on GFR, determine stage of chronic kidney disease (ranging from 1, kidney damage with normal or elevated GFR, to 5, renal failure).

Bortezomib remains the foundational treatment for myeloma-related renal impairment, the authors emphasized. This 26S proteasome inhibitor should be started at the standard dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 3-week cycle.

Another option for patients with creatinine clearance above 15 mL/min is carfilzomib, which needs no dose modification and yields similar results regardless of RI status. However, more data are needed on its renal safety, the authors said.

Patients with creatinine clearance above 30 mL/min can safely receive ixazomib in combination with lenalidomide and dexamethasone.

Those with creatinine clearance above 45 mL/min should receive pomalidomide at a dose of 4 mg/day; it is not yet clear whether the dose should be cut for more severe renal impairment.

Hypercalcemia can be treated with bisphosphonates, but patients with creatinine clearance below 30 mL/min should not receive pamidronate or zoledronic acid.

Avoid nephrotoxic agents, such as as aminoglycosides, furosemide, and contrast agents, in all patients with multiple myeloma and RI.

Dr. Dimopoulos reported receiving honoraria or financial support related to travel, accommodations, or expenses from Amgen, Celgene, Onyx Pharmaceuticals, Janssen-Cilag, Bristol-Myers Squibb, Novartis, and Genesis Pharmaceuticals. Seventeen coauthors also reported financial relationships with a number of pharmaceutical companies. The remaining three coauthors had no disclosures.

WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).

He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.

“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.

He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.

Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.

Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.

The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.

The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).

Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).

He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.

“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.

He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.

Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.

Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.

The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.

The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).

Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).

He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.

“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.

He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.

Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.

Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.

The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.

The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).

Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.

[email protected]

VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).

Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.

None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.

Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.

Patients and treatment

The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.

All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.

A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m²; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m² x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).

Patients then received a CD34⁺ selected graft from a haploidentical donor, containing 11 x 10⁶ CD34⁺ cells/kg (range, 4.7-24.4) and 0.29 x 10⁴ CD3⁺ cells/kg (range, 0-1.8).

The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.

At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 10⁶ CD3⁺ cells/kg.

ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.

Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.

Primary endpoint: TRM

The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.

Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.

The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.

TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.

Relapse and survival

Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.

The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.

Based on Kaplan-Meier estimates, the 1-year OS was 64% in the HSCT + ATIR101 group and 20% in the historical control group (P=0.0026).

GVHD

None of the patients in this trial (0/23) developed grade 3-4 GVHD upon infusion of ATIR101.

However, 3 cases of grade 2 acute GVHD were reported. One case occurred before ATIR101 infusion, and the other 2 cases had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post-ATIR101 infusion).

In the patient who developed GVHD before ATIR101 infusion, GVHD resolved quickly. The patient then received ATIR101 and did not experience any further GVHD.

“With this latest data, we can confirm the safety of ATIR101, without any incidents of grade 3-4 GVHD, significant reduction in transplant-related mortality, low relapse rates, and very good event-free survival, which we believe confirms the efficiency of photodepletion-based elimination of allo-reactive T cells,” Dr Roy said.

“Indeed, the data of patients receiving transplants with a haploidentical donor and an ATIR101 infusion are very similar to those from patients with a matched donor. As a doctor, I am very excited about this development and its potential to change patient fates.”

Dr Roy and his colleagues will continue to follow patients in this trial to collect further long-term outcome data.

Kiadis Pharma is planning to proceed with the development of ATIR101 as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomized phase 3 trial in the second half of 2016.

*Information in the abstract differs from that presented at the meeting.

VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).

Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.

None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.

Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.

Patients and treatment

The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.

All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.

A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m²; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m² x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).

Patients then received a CD34⁺ selected graft from a haploidentical donor, containing 11 x 10⁶ CD34⁺ cells/kg (range, 4.7-24.4) and 0.29 x 10⁴ CD3⁺ cells/kg (range, 0-1.8).

The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.

At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 10⁶ CD3⁺ cells/kg.

ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.

Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.

Primary endpoint: TRM

The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.

Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.

The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.

TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.

Relapse and survival

Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.

The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.

Based on Kaplan-Meier estimates, the 1-year OS was 64% in the HSCT + ATIR101 group and 20% in the historical control group (P=0.0026).

GVHD

None of the patients in this trial (0/23) developed grade 3-4 GVHD upon infusion of ATIR101.

However, 3 cases of grade 2 acute GVHD were reported. One case occurred before ATIR101 infusion, and the other 2 cases had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post-ATIR101 infusion).

In the patient who developed GVHD before ATIR101 infusion, GVHD resolved quickly. The patient then received ATIR101 and did not experience any further GVHD.

“With this latest data, we can confirm the safety of ATIR101, without any incidents of grade 3-4 GVHD, significant reduction in transplant-related mortality, low relapse rates, and very good event-free survival, which we believe confirms the efficiency of photodepletion-based elimination of allo-reactive T cells,” Dr Roy said.

“Indeed, the data of patients receiving transplants with a haploidentical donor and an ATIR101 infusion are very similar to those from patients with a matched donor. As a doctor, I am very excited about this development and its potential to change patient fates.”

Dr Roy and his colleagues will continue to follow patients in this trial to collect further long-term outcome data.

Kiadis Pharma is planning to proceed with the development of ATIR101 as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomized phase 3 trial in the second half of 2016.

*Information in the abstract differs from that presented at the meeting.

VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).

Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.

None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.

Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.

Patients and treatment

The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.

All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.

A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m²; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m² x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).

Patients then received a CD34⁺ selected graft from a haploidentical donor, containing 11 x 10⁶ CD34⁺ cells/kg (range, 4.7-24.4) and 0.29 x 10⁴ CD3⁺ cells/kg (range, 0-1.8).

The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.

At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 10⁶ CD3⁺ cells/kg.

ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.

Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.

Primary endpoint: TRM

The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.

Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.

The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.

TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.

Relapse and survival

Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.

The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.

Based on Kaplan-Meier estimates, the 1-year OS was 64% in the HSCT + ATIR101 group and 20% in the historical control group (P=0.0026).

GVHD

None of the patients in this trial (0/23) developed grade 3-4 GVHD upon infusion of ATIR101.

However, 3 cases of grade 2 acute GVHD were reported. One case occurred before ATIR101 infusion, and the other 2 cases had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post-ATIR101 infusion).

In the patient who developed GVHD before ATIR101 infusion, GVHD resolved quickly. The patient then received ATIR101 and did not experience any further GVHD.

“With this latest data, we can confirm the safety of ATIR101, without any incidents of grade 3-4 GVHD, significant reduction in transplant-related mortality, low relapse rates, and very good event-free survival, which we believe confirms the efficiency of photodepletion-based elimination of allo-reactive T cells,” Dr Roy said.

“Indeed, the data of patients receiving transplants with a haploidentical donor and an ATIR101 infusion are very similar to those from patients with a matched donor. As a doctor, I am very excited about this development and its potential to change patient fates.”

Dr Roy and his colleagues will continue to follow patients in this trial to collect further long-term outcome data.

Kiadis Pharma is planning to proceed with the development of ATIR101 as an adjunctive immuno-therapeutic treatment to a haploidentical HSCT for patients with acute leukemia, initiating a randomized phase 3 trial in the second half of 2016.

*Information in the abstract differs from that presented at the meeting.

Having credible information about how HM groups are structured and operate will benefit the entire healthcare industry and those involved in public policy and research. The survey results will be used by a wide variety of individuals and organizations to make important decisions about practice design and resource allocation.

Visit www.hospitalmedicine.org/survey and complete the notification form to be the first to know when the SOHM report becomes available this fall.

Brett Radler is SHM’s communications coordinator.

Having credible information about how HM groups are structured and operate will benefit the entire healthcare industry and those involved in public policy and research. The survey results will be used by a wide variety of individuals and organizations to make important decisions about practice design and resource allocation.

Visit www.hospitalmedicine.org/survey and complete the notification form to be the first to know when the SOHM report becomes available this fall.

Brett Radler is SHM’s communications coordinator.

Having credible information about how HM groups are structured and operate will benefit the entire healthcare industry and those involved in public policy and research. The survey results will be used by a wide variety of individuals and organizations to make important decisions about practice design and resource allocation.

Visit www.hospitalmedicine.org/survey and complete the notification form to be the first to know when the SOHM report becomes available this fall.

Brett Radler is SHM’s communications coordinator.

Robert Wachter, MD, MHM, chief of the Division of Hospital Medicine at the University of California San Francisco, in his annual address touched on some of the challenges for hospital medicine at the 20-year mark. The Hospitalist asked attendees: How can hospitalists continue to be change leaders and project leaders while also avoiding burnout?

Tamika Smith, MD, hospitalist, Alta Bates Summit Medical Center, Berkeley, Calif.

“I actually consider myself the poster child for work-life balance. I’m a nocturnist. Honestly, I think the secret is to work less. I work 12 to 14 shifts a month; that is how I make it sustainable. … I know that’s my magic number.”

Nisheeth Rai, DO, Aspirus Wausau Hospital, Wausau, Wis.

“I think you have to find a fair balance between your clinical duties. How do you balance the clinical aspect of things? How do you get into more of the management and more projects within the hospital system? We don’t know quite yet, but I think it’s an evolving thing where we’ll just see how the field evolves in the next couple years.”

Nathan Houchens, MD, hospitalist, VA Ann Arbor Healthcare System, Mich.

“It helps to know some of the fundamentals around change behavior. I think it’s also fundamental to recognize that it’s a relationship-based field and that without investment and capital in people it’s very difficult to make change sustainable.”

Janie Mathis, DO, cardiovascular hospitalist, Intermountain Medical Center, Salt Lake City

“I guess have some nonclinical time on the schedule. Schedule off from the nights and swing [shifts], and maybe have that as part of their contract and part of their job description. Have it as part of maybe your bonus, add that into your compensation, so you’re motivated to do it since you’re not going to get time off.”

Robert Wachter, MD, MHM, chief of the Division of Hospital Medicine at the University of California San Francisco, in his annual address touched on some of the challenges for hospital medicine at the 20-year mark. The Hospitalist asked attendees: How can hospitalists continue to be change leaders and project leaders while also avoiding burnout?

Tamika Smith, MD, hospitalist, Alta Bates Summit Medical Center, Berkeley, Calif.

“I actually consider myself the poster child for work-life balance. I’m a nocturnist. Honestly, I think the secret is to work less. I work 12 to 14 shifts a month; that is how I make it sustainable. … I know that’s my magic number.”

Nisheeth Rai, DO, Aspirus Wausau Hospital, Wausau, Wis.

“I think you have to find a fair balance between your clinical duties. How do you balance the clinical aspect of things? How do you get into more of the management and more projects within the hospital system? We don’t know quite yet, but I think it’s an evolving thing where we’ll just see how the field evolves in the next couple years.”

Nathan Houchens, MD, hospitalist, VA Ann Arbor Healthcare System, Mich.

“It helps to know some of the fundamentals around change behavior. I think it’s also fundamental to recognize that it’s a relationship-based field and that without investment and capital in people it’s very difficult to make change sustainable.”

Janie Mathis, DO, cardiovascular hospitalist, Intermountain Medical Center, Salt Lake City

“I guess have some nonclinical time on the schedule. Schedule off from the nights and swing [shifts], and maybe have that as part of their contract and part of their job description. Have it as part of maybe your bonus, add that into your compensation, so you’re motivated to do it since you’re not going to get time off.”

Robert Wachter, MD, MHM, chief of the Division of Hospital Medicine at the University of California San Francisco, in his annual address touched on some of the challenges for hospital medicine at the 20-year mark. The Hospitalist asked attendees: How can hospitalists continue to be change leaders and project leaders while also avoiding burnout?

Tamika Smith, MD, hospitalist, Alta Bates Summit Medical Center, Berkeley, Calif.

“I actually consider myself the poster child for work-life balance. I’m a nocturnist. Honestly, I think the secret is to work less. I work 12 to 14 shifts a month; that is how I make it sustainable. … I know that’s my magic number.”

Nisheeth Rai, DO, Aspirus Wausau Hospital, Wausau, Wis.

“I think you have to find a fair balance between your clinical duties. How do you balance the clinical aspect of things? How do you get into more of the management and more projects within the hospital system? We don’t know quite yet, but I think it’s an evolving thing where we’ll just see how the field evolves in the next couple years.”

Nathan Houchens, MD, hospitalist, VA Ann Arbor Healthcare System, Mich.

“It helps to know some of the fundamentals around change behavior. I think it’s also fundamental to recognize that it’s a relationship-based field and that without investment and capital in people it’s very difficult to make change sustainable.”

Janie Mathis, DO, cardiovascular hospitalist, Intermountain Medical Center, Salt Lake City

“I guess have some nonclinical time on the schedule. Schedule off from the nights and swing [shifts], and maybe have that as part of their contract and part of their job description. Have it as part of maybe your bonus, add that into your compensation, so you’re motivated to do it since you’re not going to get time off.”

Lab mice

Photo by Aaron Logan

Two research teams have found evidence to suggest that mutations in PIK3CA, a gene linked to cancer, may drive venous malformations (VMs) in some patients.

Both groups of researchers showed that PIK3CA mutations give rise to VMs in mice, and PIK3CA mutations are present in humans with VMs.

Subsequent experiments with the mice suggested that PIK3CA inhibitors could be used to treat VMs.

Both groups reported their findings in Science Translational Medicine.

Pau Castel, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues were originally studying the role of PIK3CA in uterine cancer when they noticed that mice harboring PIK3CA mutations developed defective blood vessels that closely resembled VMs.

Sandra Castillo, PhD, of University College London in the UK, and her colleagues generated mice with PIK3CA-activating mutations that also mimicked the human disease, including during mouse embryonic development.

Both teams found the mutations spurred uncontrolled growth of endothelial cells, which formed abnormal clusters and faulty blood vessels.

To verify their mouse models, the researchers analyzed samples from patients with VMs. Dr Castillo and her colleagues looked at samples from 13 children, while Castel and his colleagues evaluated samples from 32 patients (both adults and children).

Dr Castillo and her colleagues found PIK3CA mutations in 25% of patients, and Castel and his colleagues found mutations in PIK3CA and related genes of the PI3K/AKT pathway in about 30% of patients.

Both groups of researchers then tested PI3K inhibitors in their mouse models and found these drugs could stunt blood vessel overgrowth.

“Rapamycin is a drug that blocks a signaling process that happens downstream of PIK3CA, so it stops one of PIK3CA’s effects but does not block it at the source,” Dr Castillo said. “When we gave rapamycin to the mice, it showed clinical benefit, but, in patients, it can have serious side effects and compromise the immune system.”

“Our colleagues at MSK [Memorial Sloan Kettering] then tested drugs on the mice that directly inhibit PIK3CA, developed to treat cancer. These drugs worked well and significantly reduced the size of the malformations, not only when given through the bloodstream but also when applied directly to the skin as a cream.”

Lab mice

Photo by Aaron Logan

Two research teams have found evidence to suggest that mutations in PIK3CA, a gene linked to cancer, may drive venous malformations (VMs) in some patients.

Both groups of researchers showed that PIK3CA mutations give rise to VMs in mice, and PIK3CA mutations are present in humans with VMs.

Subsequent experiments with the mice suggested that PIK3CA inhibitors could be used to treat VMs.

Both groups reported their findings in Science Translational Medicine.

Pau Castel, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues were originally studying the role of PIK3CA in uterine cancer when they noticed that mice harboring PIK3CA mutations developed defective blood vessels that closely resembled VMs.

Sandra Castillo, PhD, of University College London in the UK, and her colleagues generated mice with PIK3CA-activating mutations that also mimicked the human disease, including during mouse embryonic development.

Both teams found the mutations spurred uncontrolled growth of endothelial cells, which formed abnormal clusters and faulty blood vessels.

To verify their mouse models, the researchers analyzed samples from patients with VMs. Dr Castillo and her colleagues looked at samples from 13 children, while Castel and his colleagues evaluated samples from 32 patients (both adults and children).

Dr Castillo and her colleagues found PIK3CA mutations in 25% of patients, and Castel and his colleagues found mutations in PIK3CA and related genes of the PI3K/AKT pathway in about 30% of patients.

Both groups of researchers then tested PI3K inhibitors in their mouse models and found these drugs could stunt blood vessel overgrowth.

“Rapamycin is a drug that blocks a signaling process that happens downstream of PIK3CA, so it stops one of PIK3CA’s effects but does not block it at the source,” Dr Castillo said. “When we gave rapamycin to the mice, it showed clinical benefit, but, in patients, it can have serious side effects and compromise the immune system.”

“Our colleagues at MSK [Memorial Sloan Kettering] then tested drugs on the mice that directly inhibit PIK3CA, developed to treat cancer. These drugs worked well and significantly reduced the size of the malformations, not only when given through the bloodstream but also when applied directly to the skin as a cream.”

Lab mice

Photo by Aaron Logan

Two research teams have found evidence to suggest that mutations in PIK3CA, a gene linked to cancer, may drive venous malformations (VMs) in some patients.

Both groups of researchers showed that PIK3CA mutations give rise to VMs in mice, and PIK3CA mutations are present in humans with VMs.

Subsequent experiments with the mice suggested that PIK3CA inhibitors could be used to treat VMs.

Both groups reported their findings in Science Translational Medicine.

Pau Castel, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues were originally studying the role of PIK3CA in uterine cancer when they noticed that mice harboring PIK3CA mutations developed defective blood vessels that closely resembled VMs.

Sandra Castillo, PhD, of University College London in the UK, and her colleagues generated mice with PIK3CA-activating mutations that also mimicked the human disease, including during mouse embryonic development.

Both teams found the mutations spurred uncontrolled growth of endothelial cells, which formed abnormal clusters and faulty blood vessels.

To verify their mouse models, the researchers analyzed samples from patients with VMs. Dr Castillo and her colleagues looked at samples from 13 children, while Castel and his colleagues evaluated samples from 32 patients (both adults and children).

Dr Castillo and her colleagues found PIK3CA mutations in 25% of patients, and Castel and his colleagues found mutations in PIK3CA and related genes of the PI3K/AKT pathway in about 30% of patients.

Both groups of researchers then tested PI3K inhibitors in their mouse models and found these drugs could stunt blood vessel overgrowth.

“Rapamycin is a drug that blocks a signaling process that happens downstream of PIK3CA, so it stops one of PIK3CA’s effects but does not block it at the source,” Dr Castillo said. “When we gave rapamycin to the mice, it showed clinical benefit, but, in patients, it can have serious side effects and compromise the immune system.”

“Our colleagues at MSK [Memorial Sloan Kettering] then tested drugs on the mice that directly inhibit PIK3CA, developed to treat cancer. These drugs worked well and significantly reduced the size of the malformations, not only when given through the bloodstream but also when applied directly to the skin as a cream.”

 

 

Micrograph showing DLBCL

 

The small-molecule inhibitor CUDC-907 can provide disease control in patients with relapsed or refractory lymphoma and multiple myeloma (MM), according to researchers.

In a phase 1 trial, CUDC-907 produced responses in a small number of patients with diffuse large B-cell lymphoma (DLBCL).

And more than half of patients had stable disease while on CUDC-907, including those with MM, DLBCL, Hodgkin lymphoma (HL), and other lymphomas.

However, a majority of patients in this trial—84%—discontinued treatment due to confirmed progressive disease or signs of progression.

These results were published in The Lancet. The trial was sponsored by Curis, Inc., the company developing CUDC-907, and the Leukemia and Lymphoma Society.

“The data from the phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/refractory DLBCL are very encouraging, and we look forward to data emerging from the current phase 2 trial in patients with MYC-altered DLBCL,” said study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York.

CUDC-907 is an oral, dual inhibitor of class I and II histone deacetylases (HDACs), as well as class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6, and 10 and PI3K-alpha, delta, and beta isoforms.

Between Jan 23, 2013, and July 27, 2015, the phase 1 trial of CUDC-907 enrolled 44 patients who were refractory to or had relapsed after 2 or more previous regimens. The patients’ median age was 63 (range, 22-83), and they had received a median of 5 prior treatments (range, 2-10).

Four patients had MM, 12 had HL, and 12 had DLBCL. The remaining 16 patients had other types of lymphoma, including lymphoplasmacytic lymphoma (n=3), small lymphocytic lymphoma (n=3), mantle cell lymphoma (n=3), follicular lymphoma (n=2), T-cell lymphoma (n=2), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), and gray zone lymphoma (n=1).

Treatment

CUDC-907 was given in a standard 3 + 3 dose-escalation design at 4 different dosing schedules—once daily, twice weekly, 3 times weekly, and daily for 5 days followed by a 2-day break (5/2)—in 21-day cycles.

Patients continued to receive CUDC-907 until disease progression or other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.

Ten patients were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to 3-times-weekly (MTD 150 mg), and 7 to the 5/2 dosing schedule (MTD 60 mg).

Safety

Four dose-limiting toxicities (DLTs) occurred in 3 of 40 DLT-evaluable patients. The DLTs were diarrhea and hyperglycemia in 1 patient on 60 mg once daily, hyperglycemia in 1 patient on 150 mg twice weekly, and diarrhea in 1 patient on 150 mg 3 times weekly. There were no DLTs in patients on the 5/2 schedule.

The incidence of grade 3 or higher adverse events (AEs) was 43% (19/44). The most common of these AEs were thrombocytopenia (20%, n=9), neutropenia (7%, n=3), and hyperglycemia (7%, n=3).

Twenty-five percent of patients (11/44) had serious AEs. Three of these events were considered treatment-related. They were epistaxis and the DLTs of diarrhea and hyperglycemia.

AEs led to dose reductions in 6 patients (14%) and treatment discontinuation in 7 patients (16%).

Efficacy

Thirty-seven patients were evaluable for response, and 5 of these patients responded (14%). All responses—2 complete and 3 partial responses—occurred in patients with DLBCL.

Twenty-one of the response-evaluable patients (57%) had stable disease. This included 1 patient with DLBCL, 2 with MM, 8 with HL, and 10 with the “other” types of lymphoma.

The remaining 11 patients progressed (30%)—3 with DLBCL, 2 with MM, 2 with HL, and 4 with other lymphomas.

Thirty-seven patients (84%) discontinued CUDC-907 because of progressive disease or clinical signs of progressive disease at the data cutoff.

Based on the clinical activity of CUDC-907 in patients with relapsed/refractory DLBCL, particularly those with MYC alterations, Curis has initiated a phase 2 trial of the drug in these patients. The recommended phase 2 dose is 60 mg on the 5/2 dosing schedule.

 

 

Micrograph showing DLBCL

 

The small-molecule inhibitor CUDC-907 can provide disease control in patients with relapsed or refractory lymphoma and multiple myeloma (MM), according to researchers.

In a phase 1 trial, CUDC-907 produced responses in a small number of patients with diffuse large B-cell lymphoma (DLBCL).

And more than half of patients had stable disease while on CUDC-907, including those with MM, DLBCL, Hodgkin lymphoma (HL), and other lymphomas.

However, a majority of patients in this trial—84%—discontinued treatment due to confirmed progressive disease or signs of progression.

These results were published in The Lancet. The trial was sponsored by Curis, Inc., the company developing CUDC-907, and the Leukemia and Lymphoma Society.

“The data from the phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/refractory DLBCL are very encouraging, and we look forward to data emerging from the current phase 2 trial in patients with MYC-altered DLBCL,” said study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York.

CUDC-907 is an oral, dual inhibitor of class I and II histone deacetylases (HDACs), as well as class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6, and 10 and PI3K-alpha, delta, and beta isoforms.

Between Jan 23, 2013, and July 27, 2015, the phase 1 trial of CUDC-907 enrolled 44 patients who were refractory to or had relapsed after 2 or more previous regimens. The patients’ median age was 63 (range, 22-83), and they had received a median of 5 prior treatments (range, 2-10).

Four patients had MM, 12 had HL, and 12 had DLBCL. The remaining 16 patients had other types of lymphoma, including lymphoplasmacytic lymphoma (n=3), small lymphocytic lymphoma (n=3), mantle cell lymphoma (n=3), follicular lymphoma (n=2), T-cell lymphoma (n=2), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), and gray zone lymphoma (n=1).

Treatment

CUDC-907 was given in a standard 3 + 3 dose-escalation design at 4 different dosing schedules—once daily, twice weekly, 3 times weekly, and daily for 5 days followed by a 2-day break (5/2)—in 21-day cycles.

Patients continued to receive CUDC-907 until disease progression or other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.

Ten patients were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to 3-times-weekly (MTD 150 mg), and 7 to the 5/2 dosing schedule (MTD 60 mg).

Safety

Four dose-limiting toxicities (DLTs) occurred in 3 of 40 DLT-evaluable patients. The DLTs were diarrhea and hyperglycemia in 1 patient on 60 mg once daily, hyperglycemia in 1 patient on 150 mg twice weekly, and diarrhea in 1 patient on 150 mg 3 times weekly. There were no DLTs in patients on the 5/2 schedule.

The incidence of grade 3 or higher adverse events (AEs) was 43% (19/44). The most common of these AEs were thrombocytopenia (20%, n=9), neutropenia (7%, n=3), and hyperglycemia (7%, n=3).

Twenty-five percent of patients (11/44) had serious AEs. Three of these events were considered treatment-related. They were epistaxis and the DLTs of diarrhea and hyperglycemia.

AEs led to dose reductions in 6 patients (14%) and treatment discontinuation in 7 patients (16%).

Efficacy

Thirty-seven patients were evaluable for response, and 5 of these patients responded (14%). All responses—2 complete and 3 partial responses—occurred in patients with DLBCL.

Twenty-one of the response-evaluable patients (57%) had stable disease. This included 1 patient with DLBCL, 2 with MM, 8 with HL, and 10 with the “other” types of lymphoma.

The remaining 11 patients progressed (30%)—3 with DLBCL, 2 with MM, 2 with HL, and 4 with other lymphomas.

Thirty-seven patients (84%) discontinued CUDC-907 because of progressive disease or clinical signs of progressive disease at the data cutoff.

Based on the clinical activity of CUDC-907 in patients with relapsed/refractory DLBCL, particularly those with MYC alterations, Curis has initiated a phase 2 trial of the drug in these patients. The recommended phase 2 dose is 60 mg on the 5/2 dosing schedule.

 

 

Micrograph showing DLBCL

 

The small-molecule inhibitor CUDC-907 can provide disease control in patients with relapsed or refractory lymphoma and multiple myeloma (MM), according to researchers.

In a phase 1 trial, CUDC-907 produced responses in a small number of patients with diffuse large B-cell lymphoma (DLBCL).

And more than half of patients had stable disease while on CUDC-907, including those with MM, DLBCL, Hodgkin lymphoma (HL), and other lymphomas.

However, a majority of patients in this trial—84%—discontinued treatment due to confirmed progressive disease or signs of progression.

These results were published in The Lancet. The trial was sponsored by Curis, Inc., the company developing CUDC-907, and the Leukemia and Lymphoma Society.

“The data from the phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/refractory DLBCL are very encouraging, and we look forward to data emerging from the current phase 2 trial in patients with MYC-altered DLBCL,” said study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York.

CUDC-907 is an oral, dual inhibitor of class I and II histone deacetylases (HDACs), as well as class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6, and 10 and PI3K-alpha, delta, and beta isoforms.

Between Jan 23, 2013, and July 27, 2015, the phase 1 trial of CUDC-907 enrolled 44 patients who were refractory to or had relapsed after 2 or more previous regimens. The patients’ median age was 63 (range, 22-83), and they had received a median of 5 prior treatments (range, 2-10).

Four patients had MM, 12 had HL, and 12 had DLBCL. The remaining 16 patients had other types of lymphoma, including lymphoplasmacytic lymphoma (n=3), small lymphocytic lymphoma (n=3), mantle cell lymphoma (n=3), follicular lymphoma (n=2), T-cell lymphoma (n=2), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), and gray zone lymphoma (n=1).

Treatment

CUDC-907 was given in a standard 3 + 3 dose-escalation design at 4 different dosing schedules—once daily, twice weekly, 3 times weekly, and daily for 5 days followed by a 2-day break (5/2)—in 21-day cycles.

Patients continued to receive CUDC-907 until disease progression or other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.

Ten patients were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to 3-times-weekly (MTD 150 mg), and 7 to the 5/2 dosing schedule (MTD 60 mg).

Safety

Four dose-limiting toxicities (DLTs) occurred in 3 of 40 DLT-evaluable patients. The DLTs were diarrhea and hyperglycemia in 1 patient on 60 mg once daily, hyperglycemia in 1 patient on 150 mg twice weekly, and diarrhea in 1 patient on 150 mg 3 times weekly. There were no DLTs in patients on the 5/2 schedule.

The incidence of grade 3 or higher adverse events (AEs) was 43% (19/44). The most common of these AEs were thrombocytopenia (20%, n=9), neutropenia (7%, n=3), and hyperglycemia (7%, n=3).

Twenty-five percent of patients (11/44) had serious AEs. Three of these events were considered treatment-related. They were epistaxis and the DLTs of diarrhea and hyperglycemia.

AEs led to dose reductions in 6 patients (14%) and treatment discontinuation in 7 patients (16%).

Efficacy

Thirty-seven patients were evaluable for response, and 5 of these patients responded (14%). All responses—2 complete and 3 partial responses—occurred in patients with DLBCL.

Twenty-one of the response-evaluable patients (57%) had stable disease. This included 1 patient with DLBCL, 2 with MM, 8 with HL, and 10 with the “other” types of lymphoma.

The remaining 11 patients progressed (30%)—3 with DLBCL, 2 with MM, 2 with HL, and 4 with other lymphomas.

Thirty-seven patients (84%) discontinued CUDC-907 because of progressive disease or clinical signs of progressive disease at the data cutoff.

Based on the clinical activity of CUDC-907 in patients with relapsed/refractory DLBCL, particularly those with MYC alterations, Curis has initiated a phase 2 trial of the drug in these patients. The recommended phase 2 dose is 60 mg on the 5/2 dosing schedule.