VIENNA – Secukinumab proved highly effective specifically for the treatment of moderate to severe scalp psoriasis in a phase IIIb clinical trial, Mark G. Lebwohl, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The scalp is one of the areas most commonly affected by psoriasis, yet few treatment trials have focused on patients with primarily moderate to severe scalp psoriasis. This phase IIIb study was designed to do just that. The 102 participants had psoriasis over a mean of 60% of their scalp for at least 6 months at baseline despite various forms of therapy; 40% had 70% or greater scalp involvement. The study population’s mean baseline Psoriasis Scalp Severity Index score was 34 out of a possible 72, noted Dr. Lebwohl, professor and chairman of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

[email protected]

VIENNA – Secukinumab proved highly effective specifically for the treatment of moderate to severe scalp psoriasis in a phase IIIb clinical trial, Mark G. Lebwohl, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The scalp is one of the areas most commonly affected by psoriasis, yet few treatment trials have focused on patients with primarily moderate to severe scalp psoriasis. This phase IIIb study was designed to do just that. The 102 participants had psoriasis over a mean of 60% of their scalp for at least 6 months at baseline despite various forms of therapy; 40% had 70% or greater scalp involvement. The study population’s mean baseline Psoriasis Scalp Severity Index score was 34 out of a possible 72, noted Dr. Lebwohl, professor and chairman of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

[email protected]

VIENNA – Secukinumab proved highly effective specifically for the treatment of moderate to severe scalp psoriasis in a phase IIIb clinical trial, Mark G. Lebwohl, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The scalp is one of the areas most commonly affected by psoriasis, yet few treatment trials have focused on patients with primarily moderate to severe scalp psoriasis. This phase IIIb study was designed to do just that. The 102 participants had psoriasis over a mean of 60% of their scalp for at least 6 months at baseline despite various forms of therapy; 40% had 70% or greater scalp involvement. The study population’s mean baseline Psoriasis Scalp Severity Index score was 34 out of a possible 72, noted Dr. Lebwohl, professor and chairman of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

[email protected]

The Health Frontiers in Tijuana (HFiT) clinic is a binational partnership between the University of California, San Diego School of Medicine (San Diego, California); the Universidad Autónoma de Baja California School of Medicine (Tijuana, Mexico); and Desayunador Salesiano Padre Chava, a community grassroots organization in Tijuana, Mexico. Health Frontiers in Tijuana provides accessible quality health care for the underserved in Tijuana's Zona Norte.¹ This article is a narrative meant to share my clinical experience as a dermatology resident who worked with HFiT to establish teledermatology services at this clinic.

Teledermatology in Tijuana

The patient population served by the HFiT clinic includes substance users, sex workers, the homeless, deportees, indigent patients, and recently Haitian immigrants.¹ We established teledermatology services under the faculty leadership of Casey Carlos, MD, who was awarded a SkinCare for Developing Countries grant from the American Academy of Dermatology in April 2015 to address the need for teledermatology support for the clinic.²

Over the last 2 years, we have worked closely with 2 medical students from the University of California, San Diego--Nicole Herrick, BS, and Nicole DeMartinis, BA--to apply for the grant and create a system whereby volunteer residents and faculty consultants at the University of California, San Diego, can provide teledermatology services on a weekly basis to support the HFiT staff as they see patients with dermatologic conditions. Initially, we purchased touch screen tablets to use the Africa Teledermatology Project (africa.telederm.org) web-based program. The clinic was already functioning with electronic medical records with volunteers who carried tablets and scribed for the providers as they saw patients. We felt this method would be a great way to incorporate teledermatology into the clinic, and it functioned moderately well for several weeks but was very labor intensive on our part, as we frequently had to travel to Tijuana to retrain rotating clinic volunteers on how to use the program. Often, the Internet connection was slow, which made pulling up the Africa Teledermatology Project website difficult, and photographs also would take too long to upload in the middle of a busy clinic.

We are now exploring how to use a more simple email format to send the teledermatology consultations while still being compliant with the Health Insurance Portability and Accountability Act. We currently use secure university email accounts. Although we are still working out the details, this email-based method seems to work well. It has been a simple solution to accommodate a slow Internet connection and many rotating volunteers without requiring additional training. The email format also allows the photographs to be saved in draft messages, even if the Internet connection times out.

Once the teledermatology consultation is sent, the medical students and I review them and then get an attending physician's input on our proposed working diagnosis and plan. We work to have this process complete within several days to return the answered consultation to the requesting provider.

Final Thoughts

The HFiT providers have shared a lot of positive verbal feedback about this project. One frequent comment is how helpful it is to have access to a dermatologist for challenging cases. We also have heard many times that this project has inspired medical students and volunteers to expand their knowledge of dermatology. We are continuing to form new collaborative relationships with physicians in Tijuana. We will soon have the ability to train primary care providers at HFiT on performing simple skin biopsies and managing basic dermatologic conditions. Through our support of these providers, we are creating a sustainable partnership that is mutually beneficial to the patients in Tijuana as well as the medical students and residents in the United States. It is highly rewarding to all those involved with this project, and I am excited to see what challenges this next year will bring as we welcome many new patients from Haiti into the HFiT patient population.

The Health Frontiers in Tijuana (HFiT) clinic is a binational partnership between the University of California, San Diego School of Medicine (San Diego, California); the Universidad Autónoma de Baja California School of Medicine (Tijuana, Mexico); and Desayunador Salesiano Padre Chava, a community grassroots organization in Tijuana, Mexico. Health Frontiers in Tijuana provides accessible quality health care for the underserved in Tijuana's Zona Norte.¹ This article is a narrative meant to share my clinical experience as a dermatology resident who worked with HFiT to establish teledermatology services at this clinic.

Teledermatology in Tijuana

The patient population served by the HFiT clinic includes substance users, sex workers, the homeless, deportees, indigent patients, and recently Haitian immigrants.¹ We established teledermatology services under the faculty leadership of Casey Carlos, MD, who was awarded a SkinCare for Developing Countries grant from the American Academy of Dermatology in April 2015 to address the need for teledermatology support for the clinic.²

Over the last 2 years, we have worked closely with 2 medical students from the University of California, San Diego--Nicole Herrick, BS, and Nicole DeMartinis, BA--to apply for the grant and create a system whereby volunteer residents and faculty consultants at the University of California, San Diego, can provide teledermatology services on a weekly basis to support the HFiT staff as they see patients with dermatologic conditions. Initially, we purchased touch screen tablets to use the Africa Teledermatology Project (africa.telederm.org) web-based program. The clinic was already functioning with electronic medical records with volunteers who carried tablets and scribed for the providers as they saw patients. We felt this method would be a great way to incorporate teledermatology into the clinic, and it functioned moderately well for several weeks but was very labor intensive on our part, as we frequently had to travel to Tijuana to retrain rotating clinic volunteers on how to use the program. Often, the Internet connection was slow, which made pulling up the Africa Teledermatology Project website difficult, and photographs also would take too long to upload in the middle of a busy clinic.

We are now exploring how to use a more simple email format to send the teledermatology consultations while still being compliant with the Health Insurance Portability and Accountability Act. We currently use secure university email accounts. Although we are still working out the details, this email-based method seems to work well. It has been a simple solution to accommodate a slow Internet connection and many rotating volunteers without requiring additional training. The email format also allows the photographs to be saved in draft messages, even if the Internet connection times out.

Once the teledermatology consultation is sent, the medical students and I review them and then get an attending physician's input on our proposed working diagnosis and plan. We work to have this process complete within several days to return the answered consultation to the requesting provider.

Final Thoughts

The HFiT providers have shared a lot of positive verbal feedback about this project. One frequent comment is how helpful it is to have access to a dermatologist for challenging cases. We also have heard many times that this project has inspired medical students and volunteers to expand their knowledge of dermatology. We are continuing to form new collaborative relationships with physicians in Tijuana. We will soon have the ability to train primary care providers at HFiT on performing simple skin biopsies and managing basic dermatologic conditions. Through our support of these providers, we are creating a sustainable partnership that is mutually beneficial to the patients in Tijuana as well as the medical students and residents in the United States. It is highly rewarding to all those involved with this project, and I am excited to see what challenges this next year will bring as we welcome many new patients from Haiti into the HFiT patient population.

The Health Frontiers in Tijuana (HFiT) clinic is a binational partnership between the University of California, San Diego School of Medicine (San Diego, California); the Universidad Autónoma de Baja California School of Medicine (Tijuana, Mexico); and Desayunador Salesiano Padre Chava, a community grassroots organization in Tijuana, Mexico. Health Frontiers in Tijuana provides accessible quality health care for the underserved in Tijuana's Zona Norte.¹ This article is a narrative meant to share my clinical experience as a dermatology resident who worked with HFiT to establish teledermatology services at this clinic.

Teledermatology in Tijuana

The patient population served by the HFiT clinic includes substance users, sex workers, the homeless, deportees, indigent patients, and recently Haitian immigrants.¹ We established teledermatology services under the faculty leadership of Casey Carlos, MD, who was awarded a SkinCare for Developing Countries grant from the American Academy of Dermatology in April 2015 to address the need for teledermatology support for the clinic.²

Over the last 2 years, we have worked closely with 2 medical students from the University of California, San Diego--Nicole Herrick, BS, and Nicole DeMartinis, BA--to apply for the grant and create a system whereby volunteer residents and faculty consultants at the University of California, San Diego, can provide teledermatology services on a weekly basis to support the HFiT staff as they see patients with dermatologic conditions. Initially, we purchased touch screen tablets to use the Africa Teledermatology Project (africa.telederm.org) web-based program. The clinic was already functioning with electronic medical records with volunteers who carried tablets and scribed for the providers as they saw patients. We felt this method would be a great way to incorporate teledermatology into the clinic, and it functioned moderately well for several weeks but was very labor intensive on our part, as we frequently had to travel to Tijuana to retrain rotating clinic volunteers on how to use the program. Often, the Internet connection was slow, which made pulling up the Africa Teledermatology Project website difficult, and photographs also would take too long to upload in the middle of a busy clinic.

We are now exploring how to use a more simple email format to send the teledermatology consultations while still being compliant with the Health Insurance Portability and Accountability Act. We currently use secure university email accounts. Although we are still working out the details, this email-based method seems to work well. It has been a simple solution to accommodate a slow Internet connection and many rotating volunteers without requiring additional training. The email format also allows the photographs to be saved in draft messages, even if the Internet connection times out.

Once the teledermatology consultation is sent, the medical students and I review them and then get an attending physician's input on our proposed working diagnosis and plan. We work to have this process complete within several days to return the answered consultation to the requesting provider.

Final Thoughts

The HFiT providers have shared a lot of positive verbal feedback about this project. One frequent comment is how helpful it is to have access to a dermatologist for challenging cases. We also have heard many times that this project has inspired medical students and volunteers to expand their knowledge of dermatology. We are continuing to form new collaborative relationships with physicians in Tijuana. We will soon have the ability to train primary care providers at HFiT on performing simple skin biopsies and managing basic dermatologic conditions. Through our support of these providers, we are creating a sustainable partnership that is mutually beneficial to the patients in Tijuana as well as the medical students and residents in the United States. It is highly rewarding to all those involved with this project, and I am excited to see what challenges this next year will bring as we welcome many new patients from Haiti into the HFiT patient population.

VIENNA – Ixekizumab proved markedly more effective than etanercept for treatment of palmoplantar psoriasis in a head-to-head contest in the landmark phase III UNCOVER-3 trial, Alan Menter, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Significant improvement in palmoplantar disease was seen as early as week 2 in patients randomized to ixekizumab (Taltz), a humanized monoclonal antibody directed against interleukin-17A. Moreover, the early improvement was maintained out to week 60 with administration of 80 mg of ixekizumab by subcutaneous injection every 4 weeks in the open-label extension phase of UNCOVER-3. This pivotal trial, including 1,346 patients with moderate to severe psoriasis, helped win regulatory approval for ixekizumab for treatment of chronic plaque psoriasis.

Bruce Jancin/Frontline Medical News

Bruce Jancin/Frontline Medical News

[email protected]

VIENNA – Ixekizumab proved markedly more effective than etanercept for treatment of palmoplantar psoriasis in a head-to-head contest in the landmark phase III UNCOVER-3 trial, Alan Menter, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Significant improvement in palmoplantar disease was seen as early as week 2 in patients randomized to ixekizumab (Taltz), a humanized monoclonal antibody directed against interleukin-17A. Moreover, the early improvement was maintained out to week 60 with administration of 80 mg of ixekizumab by subcutaneous injection every 4 weeks in the open-label extension phase of UNCOVER-3. This pivotal trial, including 1,346 patients with moderate to severe psoriasis, helped win regulatory approval for ixekizumab for treatment of chronic plaque psoriasis.

Bruce Jancin/Frontline Medical News

Bruce Jancin/Frontline Medical News

[email protected]

VIENNA – Ixekizumab proved markedly more effective than etanercept for treatment of palmoplantar psoriasis in a head-to-head contest in the landmark phase III UNCOVER-3 trial, Alan Menter, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Significant improvement in palmoplantar disease was seen as early as week 2 in patients randomized to ixekizumab (Taltz), a humanized monoclonal antibody directed against interleukin-17A. Moreover, the early improvement was maintained out to week 60 with administration of 80 mg of ixekizumab by subcutaneous injection every 4 weeks in the open-label extension phase of UNCOVER-3. This pivotal trial, including 1,346 patients with moderate to severe psoriasis, helped win regulatory approval for ixekizumab for treatment of chronic plaque psoriasis.

Bruce Jancin/Frontline Medical News

Bruce Jancin/Frontline Medical News

[email protected]

In the December podcast for The Journal of Community and Supportive Oncology, Dr David Henry discusses a round-up and review by Linda Bosserman, an Editor on the Journal, of the 2016 oncology landscape – from new therapy approvals, to practice pathways and value-based care, and the implementation of MACRA. Also included are Original Reports on patients’ retrospective assessment of palliative chemotherapy for lung or gastrointestinal cancers, social support needs among patients with advanced breast cancer, and quality of life after surgery for pleural malignant mesothelioma. As always, we focus on cutting edge care for the cancer patient, with two features, one by our regular contributor, Jane de Lartigue, who brings us up to date on new therapies for pancreatic cancer, and a second, practice-oriented article that reports on adopting a team approach for co-managing the clinical and palliative components in caring for our patients. Among the regular offerings, we have Case Reports on paraneoplastic Isaacs syndrome that led to diagnosis of small-cell lung cancer and unicentric Castleman disease that was disguised as a pancreatic neoplasm, and a Community Translations report on the approval of pembrolizumab as the first immune checkpoint inhibitor to receive approval for head and neck cancer.

Listen to the podcast below.

In the December podcast for The Journal of Community and Supportive Oncology, Dr David Henry discusses a round-up and review by Linda Bosserman, an Editor on the Journal, of the 2016 oncology landscape – from new therapy approvals, to practice pathways and value-based care, and the implementation of MACRA. Also included are Original Reports on patients’ retrospective assessment of palliative chemotherapy for lung or gastrointestinal cancers, social support needs among patients with advanced breast cancer, and quality of life after surgery for pleural malignant mesothelioma. As always, we focus on cutting edge care for the cancer patient, with two features, one by our regular contributor, Jane de Lartigue, who brings us up to date on new therapies for pancreatic cancer, and a second, practice-oriented article that reports on adopting a team approach for co-managing the clinical and palliative components in caring for our patients. Among the regular offerings, we have Case Reports on paraneoplastic Isaacs syndrome that led to diagnosis of small-cell lung cancer and unicentric Castleman disease that was disguised as a pancreatic neoplasm, and a Community Translations report on the approval of pembrolizumab as the first immune checkpoint inhibitor to receive approval for head and neck cancer.

Listen to the podcast below.

In the December podcast for The Journal of Community and Supportive Oncology, Dr David Henry discusses a round-up and review by Linda Bosserman, an Editor on the Journal, of the 2016 oncology landscape – from new therapy approvals, to practice pathways and value-based care, and the implementation of MACRA. Also included are Original Reports on patients’ retrospective assessment of palliative chemotherapy for lung or gastrointestinal cancers, social support needs among patients with advanced breast cancer, and quality of life after surgery for pleural malignant mesothelioma. As always, we focus on cutting edge care for the cancer patient, with two features, one by our regular contributor, Jane de Lartigue, who brings us up to date on new therapies for pancreatic cancer, and a second, practice-oriented article that reports on adopting a team approach for co-managing the clinical and palliative components in caring for our patients. Among the regular offerings, we have Case Reports on paraneoplastic Isaacs syndrome that led to diagnosis of small-cell lung cancer and unicentric Castleman disease that was disguised as a pancreatic neoplasm, and a Community Translations report on the approval of pembrolizumab as the first immune checkpoint inhibitor to receive approval for head and neck cancer.

Listen to the podcast below.

Mouse eating

Photo by Steve Berger

Intermittent fasting inhibits the development and progression of acute lymphoblastic leukemia (ALL), according to preclinical research published in Nature Medicine.

Fasting had an inhibitory effect in mouse models of T-cell and B-cell ALL but not acute myeloid leukemia (AML).

“This study using mouse models indicates that the effects of fasting on blood cancers are type-dependent and provides a platform for identifying new targets for leukemia treatments,” said study author Chengcheng “Alec” Zhang, PhD, of UT Southwestern Medical Center in Dallas, Texas.

“We also identified a mechanism responsible for the differing response to the fasting treatment.”

For this study, Dr Zhang and his colleagues created mouse models of acute leukemia—N-Myc B-ALL, activated Notch1 T-ALL, MLL-AF9 AML, and AML driven by the AML1-Eto9a oncogene—and tested the effects of various dietary restriction plans.

The team used green or yellow florescent proteins to mark and trace the leukemia cells so they could determine if the cells’ levels rose or fell in response to the fasting treatment.

“Strikingly, we found that, in models of ALL, a regimen consisting of 6 cycles of 1 day of fasting followed by 1 day of feeding completely inhibited cancer development,” Dr Zhang said.

At the end of 7 weeks, fasted mice with B-ALL had virtually no detectible cancerous cells—an average of 0.48%—compared to an average of 67.68% of cells found to be cancerous in the test areas of the non-fasted B-ALL mice.

Dr Zhang noted that, compared to B-ALL mice that ate normally, the mice on alternate-day fasting had dramatic reductions in the percentage of ALL cells in the bone marrow and spleen, as well as reduced numbers of white blood cells.

In addition, the spleens and lymph nodes in the fasted mice with B-ALL were similar in size to those of normal mice.

“Although initially cancerous, the few fluorescent cells that remained in the fasted mice after 7 weeks appeared to behave like normal cells,” Dr Zhang said. “Mice in the [B-ALL] model group that ate normally died within 59 days, while 75% of the fasted mice survived more than 120 days without signs of leukemia.”

Dr Zhang and his colleagues said they observed similar results in the T-ALL model but not the AML models. There was no decrease in leukemia cells among fasted mice with AML. And fasting actually shortened survival time in these mice.

Identifying the mechanism

Fasting is known to reduce the level of leptin, a cell signaling molecule created by fat tissue. In addition, previous studies have shown weakened activity by leptin receptors in humans with ALL. For those reasons, the researchers studied both leptin levels and leptin receptors in the mouse models.

The team found that mice with ALL showed reduced leptin receptor activity that increased with intermittent fasting.

“We found that fasting decreased the levels of leptin circulating in the bloodstream as well as decreased the leptin levels in the bone marrow,” Dr Zhang said. “These effects became more pronounced with repeated cycles of fasting. After fasting, the rate at which the leptin levels recovered seemed to correspond to the rate at which the cancerous ALL cells were cleared from the blood.”

The researchers also found that AML was associated with higher levels of leptin receptors that were unaffected by fasting, which could help explain why the fasting treatment was ineffective against this type of leukemia.

It also suggests a mechanism—the leptin receptor pathway—by which fasting exerts its effects in ALL, Dr Zhang said.

“It will be important to determine whether ALL cells can become resistant to the effects of fasting,” he noted. “It also will be interesting to investigate whether we can find alternative ways that mimic fasting to block ALL development.”

Given that this study did not involve drug treatment, researchers are discussing with clinicians whether the tested regimen might be able to move forward quickly to clinical trials.

Mouse eating

Photo by Steve Berger

Intermittent fasting inhibits the development and progression of acute lymphoblastic leukemia (ALL), according to preclinical research published in Nature Medicine.

Fasting had an inhibitory effect in mouse models of T-cell and B-cell ALL but not acute myeloid leukemia (AML).

“This study using mouse models indicates that the effects of fasting on blood cancers are type-dependent and provides a platform for identifying new targets for leukemia treatments,” said study author Chengcheng “Alec” Zhang, PhD, of UT Southwestern Medical Center in Dallas, Texas.

“We also identified a mechanism responsible for the differing response to the fasting treatment.”

For this study, Dr Zhang and his colleagues created mouse models of acute leukemia—N-Myc B-ALL, activated Notch1 T-ALL, MLL-AF9 AML, and AML driven by the AML1-Eto9a oncogene—and tested the effects of various dietary restriction plans.

The team used green or yellow florescent proteins to mark and trace the leukemia cells so they could determine if the cells’ levels rose or fell in response to the fasting treatment.

“Strikingly, we found that, in models of ALL, a regimen consisting of 6 cycles of 1 day of fasting followed by 1 day of feeding completely inhibited cancer development,” Dr Zhang said.

At the end of 7 weeks, fasted mice with B-ALL had virtually no detectible cancerous cells—an average of 0.48%—compared to an average of 67.68% of cells found to be cancerous in the test areas of the non-fasted B-ALL mice.

Dr Zhang noted that, compared to B-ALL mice that ate normally, the mice on alternate-day fasting had dramatic reductions in the percentage of ALL cells in the bone marrow and spleen, as well as reduced numbers of white blood cells.

In addition, the spleens and lymph nodes in the fasted mice with B-ALL were similar in size to those of normal mice.

“Although initially cancerous, the few fluorescent cells that remained in the fasted mice after 7 weeks appeared to behave like normal cells,” Dr Zhang said. “Mice in the [B-ALL] model group that ate normally died within 59 days, while 75% of the fasted mice survived more than 120 days without signs of leukemia.”

Dr Zhang and his colleagues said they observed similar results in the T-ALL model but not the AML models. There was no decrease in leukemia cells among fasted mice with AML. And fasting actually shortened survival time in these mice.

Identifying the mechanism

Fasting is known to reduce the level of leptin, a cell signaling molecule created by fat tissue. In addition, previous studies have shown weakened activity by leptin receptors in humans with ALL. For those reasons, the researchers studied both leptin levels and leptin receptors in the mouse models.

The team found that mice with ALL showed reduced leptin receptor activity that increased with intermittent fasting.

“We found that fasting decreased the levels of leptin circulating in the bloodstream as well as decreased the leptin levels in the bone marrow,” Dr Zhang said. “These effects became more pronounced with repeated cycles of fasting. After fasting, the rate at which the leptin levels recovered seemed to correspond to the rate at which the cancerous ALL cells were cleared from the blood.”

The researchers also found that AML was associated with higher levels of leptin receptors that were unaffected by fasting, which could help explain why the fasting treatment was ineffective against this type of leukemia.

It also suggests a mechanism—the leptin receptor pathway—by which fasting exerts its effects in ALL, Dr Zhang said.

“It will be important to determine whether ALL cells can become resistant to the effects of fasting,” he noted. “It also will be interesting to investigate whether we can find alternative ways that mimic fasting to block ALL development.”

Given that this study did not involve drug treatment, researchers are discussing with clinicians whether the tested regimen might be able to move forward quickly to clinical trials.

Mouse eating

Photo by Steve Berger

Intermittent fasting inhibits the development and progression of acute lymphoblastic leukemia (ALL), according to preclinical research published in Nature Medicine.

Fasting had an inhibitory effect in mouse models of T-cell and B-cell ALL but not acute myeloid leukemia (AML).

“This study using mouse models indicates that the effects of fasting on blood cancers are type-dependent and provides a platform for identifying new targets for leukemia treatments,” said study author Chengcheng “Alec” Zhang, PhD, of UT Southwestern Medical Center in Dallas, Texas.

“We also identified a mechanism responsible for the differing response to the fasting treatment.”

For this study, Dr Zhang and his colleagues created mouse models of acute leukemia—N-Myc B-ALL, activated Notch1 T-ALL, MLL-AF9 AML, and AML driven by the AML1-Eto9a oncogene—and tested the effects of various dietary restriction plans.

The team used green or yellow florescent proteins to mark and trace the leukemia cells so they could determine if the cells’ levels rose or fell in response to the fasting treatment.

“Strikingly, we found that, in models of ALL, a regimen consisting of 6 cycles of 1 day of fasting followed by 1 day of feeding completely inhibited cancer development,” Dr Zhang said.

At the end of 7 weeks, fasted mice with B-ALL had virtually no detectible cancerous cells—an average of 0.48%—compared to an average of 67.68% of cells found to be cancerous in the test areas of the non-fasted B-ALL mice.

Dr Zhang noted that, compared to B-ALL mice that ate normally, the mice on alternate-day fasting had dramatic reductions in the percentage of ALL cells in the bone marrow and spleen, as well as reduced numbers of white blood cells.

In addition, the spleens and lymph nodes in the fasted mice with B-ALL were similar in size to those of normal mice.

“Although initially cancerous, the few fluorescent cells that remained in the fasted mice after 7 weeks appeared to behave like normal cells,” Dr Zhang said. “Mice in the [B-ALL] model group that ate normally died within 59 days, while 75% of the fasted mice survived more than 120 days without signs of leukemia.”

Dr Zhang and his colleagues said they observed similar results in the T-ALL model but not the AML models. There was no decrease in leukemia cells among fasted mice with AML. And fasting actually shortened survival time in these mice.

Identifying the mechanism

Fasting is known to reduce the level of leptin, a cell signaling molecule created by fat tissue. In addition, previous studies have shown weakened activity by leptin receptors in humans with ALL. For those reasons, the researchers studied both leptin levels and leptin receptors in the mouse models.

The team found that mice with ALL showed reduced leptin receptor activity that increased with intermittent fasting.

“We found that fasting decreased the levels of leptin circulating in the bloodstream as well as decreased the leptin levels in the bone marrow,” Dr Zhang said. “These effects became more pronounced with repeated cycles of fasting. After fasting, the rate at which the leptin levels recovered seemed to correspond to the rate at which the cancerous ALL cells were cleared from the blood.”

The researchers also found that AML was associated with higher levels of leptin receptors that were unaffected by fasting, which could help explain why the fasting treatment was ineffective against this type of leukemia.

It also suggests a mechanism—the leptin receptor pathway—by which fasting exerts its effects in ALL, Dr Zhang said.

“It will be important to determine whether ALL cells can become resistant to the effects of fasting,” he noted. “It also will be interesting to investigate whether we can find alternative ways that mimic fasting to block ALL development.”

Given that this study did not involve drug treatment, researchers are discussing with clinicians whether the tested regimen might be able to move forward quickly to clinical trials.

 

 

Micrograph showing DLBCL

 

The chimeric antigen receptor (CAR) T-cell therapy JCAR017 has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and access to the European Medicines Agency’s (EMA) Priority Medicines (PRIME) program.

JCAR017 has gained access to the PRIME program as a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The breakthrough designation is for JCAR017 in the treatment of patients with relapsed/refractory, aggressive, large B-cell non-Hodgkin lymphoma, including DLBCL not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.

JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain. The product is being developed by Juno Therapeutics, Inc. and Celgene Corporation.

The breakthrough therapy designation and PRIME eligibility for JCAR017 were granted by the FDA and EMA, respectively, on the basis of early clinical results with JCAR017 in relapsed/refractory DLBCL.

Results from a phase 1 trial of JCAR017 in relapsed/refractory DLBCL and mantle cell lymphoma were recently presented at the 2016 ASH Annual Meeting (abstract 4192).

About the PRIME program

The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.

The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

 

 

Micrograph showing DLBCL

 

The chimeric antigen receptor (CAR) T-cell therapy JCAR017 has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and access to the European Medicines Agency’s (EMA) Priority Medicines (PRIME) program.

JCAR017 has gained access to the PRIME program as a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The breakthrough designation is for JCAR017 in the treatment of patients with relapsed/refractory, aggressive, large B-cell non-Hodgkin lymphoma, including DLBCL not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.

JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain. The product is being developed by Juno Therapeutics, Inc. and Celgene Corporation.

The breakthrough therapy designation and PRIME eligibility for JCAR017 were granted by the FDA and EMA, respectively, on the basis of early clinical results with JCAR017 in relapsed/refractory DLBCL.

Results from a phase 1 trial of JCAR017 in relapsed/refractory DLBCL and mantle cell lymphoma were recently presented at the 2016 ASH Annual Meeting (abstract 4192).

About the PRIME program

The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.

The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

 

 

Micrograph showing DLBCL

 

The chimeric antigen receptor (CAR) T-cell therapy JCAR017 has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and access to the European Medicines Agency’s (EMA) Priority Medicines (PRIME) program.

JCAR017 has gained access to the PRIME program as a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The breakthrough designation is for JCAR017 in the treatment of patients with relapsed/refractory, aggressive, large B-cell non-Hodgkin lymphoma, including DLBCL not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.

JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain. The product is being developed by Juno Therapeutics, Inc. and Celgene Corporation.

The breakthrough therapy designation and PRIME eligibility for JCAR017 were granted by the FDA and EMA, respectively, on the basis of early clinical results with JCAR017 in relapsed/refractory DLBCL.

Results from a phase 1 trial of JCAR017 in relapsed/refractory DLBCL and mantle cell lymphoma were recently presented at the 2016 ASH Annual Meeting (abstract 4192).

About the PRIME program

The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.

The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Shridevi Subramaniam

Photo courtesy of ESMO

SINGAPORE—Cancer survivors in Malaysia may have impaired health-related quality of life (HRQOL) and high levels of psychological distress 1 year after diagnosis, according to research presented at the ESMO Asia 2016 Congress.*

Of all the patients studied, those with lymphoma had the lowest global health score (according to the EORTC QLQ C30 questionnaire) and the highest levels of psychological distress (anxiety and depression).

“We urgently need new ways of supporting cancer survivors and addressing wider aspects of wellbeing,” said study investigator Shridevi Subramaniam, of the Clinical Research Centre, Ministry of Health Malaysia, in Kuala Lumpur.

“Instead of just focusing on clinical outcome, doctors must focus equally on quality of life for cancer patients, especially psychologically, financially, and socially.”

Patient population

Subramaniam and her colleagues assessed HRQOL in 1376 cancer patients who had survived 12 months from diagnosis. The patients’ mean age was 52, and 64% were female.

Patients had breast cancer (n=403), lymphomas (n=349), colorectal cancer (n=160), mouth cancer (n=108), and female reproductive cancer (n=91).

Forty-one percent of patients had late-stage cancer, 30% had early stage, and 29% had hematologic cancer. Twenty-eight percent of patients had comorbidities.

Thirty-five percent of patients underwent surgery, 73% received chemotherapy, 43% received radiotherapy, and 13% received hormonal therapy.

Forty-six percent of patients were treated at public hospitals, 48% were treated at academic hospitals, and 6% were treated at private hospitals.

Nearly three-quarters of patients (73%) had no insurance, 20% had private insurance, 5% had insurance via their employers, and 4% had other insurance. Forty-one percent of patients had low income status, 30% middle income, and 20% high income.

Overall HRQOL

The patients reported their HRQOL using the EORTC QLQ C30, Hospital Anxiety and Depression Scale, and EQ-5D questionnaire.

For the entire patient cohort, EORTC QLQ-Q30 scores were as follows:

• Mean global health score—53.0
• Mean physical function score—72.6
• Mean emotional function score—63.0
• Mean fatigue score—32.3
• Mean pain score—26.5

The patients’ mean generic HRQOL index score (according to EQ-5D) was 0.7. And a majority of patients reported anxiety (83.5%, n=949) and depression (79.1%, n=899).

HRQOL by cancer type

Anxiety and depression was most common among patients with lymphoma. These patients also had the lowest global health score. Subramaniam said these findings might be explained by side effects from aggressive treatment.

Mean global health scores were 33.3 for lymphoma patients, 59.4 for female breast cancer patients, 59.6 for colorectal cancer patients, 59.8 for patients with mouth cancer, and 67.8 for patients with female reproductive cancers.

The generic HRQOL index scores were 0.69 (colorectal), 0.73 (lymphoma, breast, and mouth), and 0.80 (reproductive).

The proportion of patients with anxiety was 94% (lymphoma), 87.4% (colorectal), 80.5% (breast), 72.6% (mouth), and 51.7% (reproductive).

The proportion of patients with depression was 86.7% (lymphoma), 80.9% (colorectal), 75.8% (mouth), 74.4% (breast), and 50.5% (reproductive).

Predictors of HRQOL

Subramaniam and her colleagues found several significant predictors of HRQOL.

Older patients had decreased physical function and global health, as well as increased pain and fatigue. Married patients had increased fatigue. And patients without comorbidities had increased physical and emotional function as well as decreased fatigue.

Compared with those treated at private hospitals, patients treated at academic hospitals had decreased physical and emotional functions and increased fatigue. Subramaniam said this could be due to long wait times at academic hospitals, which lead to worsening conditions and more pain and discomfort.

Compared to patients with high income status, those from low income groups had increased global health and physical and emotional functions, as well as decreased pain and fatigue. Subramaniam said this could be due to higher expectations among patients with higher incomes.

Compared to patients with early stage cancers, patients with hematologic and late stage cancers had decreased global health and physical function, as well as increased pain and fatigue. Subramaniam said this could be attributed to side effects of treatment.

She added that treatment side effects might also explain why patients who did not receive chemotherapy had higher global health scores.

Patients who didn’t receive radiotherapy were twice as likely as those who did to report psychological distress. And Subramaniam attributed this to a loss of hope among patients who were not treated.

Patients treated in public and academic hospitals were less likely to be psychologically distressed than those treated in private centers. Subramaniam said this could be related to financial distress.

In closing, Subramaniam said this study indicates that cancer survivors in Malaysia have impaired HRQOL, and many experience psychological distress. Therefore, clinicians should focus on “supporting patients throughout their whole cancer ‘journey,’ especially in their lives after treatment.”

*Abstract 496O_PR—“Health-related quality of life and psychological distress among cancer survivors in a middle-income Asian country.” (Information in the abstract differs from the presentation.)

Shridevi Subramaniam

Photo courtesy of ESMO

SINGAPORE—Cancer survivors in Malaysia may have impaired health-related quality of life (HRQOL) and high levels of psychological distress 1 year after diagnosis, according to research presented at the ESMO Asia 2016 Congress.*

Of all the patients studied, those with lymphoma had the lowest global health score (according to the EORTC QLQ C30 questionnaire) and the highest levels of psychological distress (anxiety and depression).

“We urgently need new ways of supporting cancer survivors and addressing wider aspects of wellbeing,” said study investigator Shridevi Subramaniam, of the Clinical Research Centre, Ministry of Health Malaysia, in Kuala Lumpur.

“Instead of just focusing on clinical outcome, doctors must focus equally on quality of life for cancer patients, especially psychologically, financially, and socially.”

Patient population

Subramaniam and her colleagues assessed HRQOL in 1376 cancer patients who had survived 12 months from diagnosis. The patients’ mean age was 52, and 64% were female.

Patients had breast cancer (n=403), lymphomas (n=349), colorectal cancer (n=160), mouth cancer (n=108), and female reproductive cancer (n=91).

Forty-one percent of patients had late-stage cancer, 30% had early stage, and 29% had hematologic cancer. Twenty-eight percent of patients had comorbidities.

Thirty-five percent of patients underwent surgery, 73% received chemotherapy, 43% received radiotherapy, and 13% received hormonal therapy.

Forty-six percent of patients were treated at public hospitals, 48% were treated at academic hospitals, and 6% were treated at private hospitals.

Nearly three-quarters of patients (73%) had no insurance, 20% had private insurance, 5% had insurance via their employers, and 4% had other insurance. Forty-one percent of patients had low income status, 30% middle income, and 20% high income.

Overall HRQOL

The patients reported their HRQOL using the EORTC QLQ C30, Hospital Anxiety and Depression Scale, and EQ-5D questionnaire.

For the entire patient cohort, EORTC QLQ-Q30 scores were as follows:

• Mean global health score—53.0
• Mean physical function score—72.6
• Mean emotional function score—63.0
• Mean fatigue score—32.3
• Mean pain score—26.5

The patients’ mean generic HRQOL index score (according to EQ-5D) was 0.7. And a majority of patients reported anxiety (83.5%, n=949) and depression (79.1%, n=899).

HRQOL by cancer type

Anxiety and depression was most common among patients with lymphoma. These patients also had the lowest global health score. Subramaniam said these findings might be explained by side effects from aggressive treatment.

Mean global health scores were 33.3 for lymphoma patients, 59.4 for female breast cancer patients, 59.6 for colorectal cancer patients, 59.8 for patients with mouth cancer, and 67.8 for patients with female reproductive cancers.

The generic HRQOL index scores were 0.69 (colorectal), 0.73 (lymphoma, breast, and mouth), and 0.80 (reproductive).

The proportion of patients with anxiety was 94% (lymphoma), 87.4% (colorectal), 80.5% (breast), 72.6% (mouth), and 51.7% (reproductive).

The proportion of patients with depression was 86.7% (lymphoma), 80.9% (colorectal), 75.8% (mouth), 74.4% (breast), and 50.5% (reproductive).

Predictors of HRQOL

Subramaniam and her colleagues found several significant predictors of HRQOL.

Older patients had decreased physical function and global health, as well as increased pain and fatigue. Married patients had increased fatigue. And patients without comorbidities had increased physical and emotional function as well as decreased fatigue.

Compared with those treated at private hospitals, patients treated at academic hospitals had decreased physical and emotional functions and increased fatigue. Subramaniam said this could be due to long wait times at academic hospitals, which lead to worsening conditions and more pain and discomfort.

Compared to patients with high income status, those from low income groups had increased global health and physical and emotional functions, as well as decreased pain and fatigue. Subramaniam said this could be due to higher expectations among patients with higher incomes.

Compared to patients with early stage cancers, patients with hematologic and late stage cancers had decreased global health and physical function, as well as increased pain and fatigue. Subramaniam said this could be attributed to side effects of treatment.

She added that treatment side effects might also explain why patients who did not receive chemotherapy had higher global health scores.

Patients who didn’t receive radiotherapy were twice as likely as those who did to report psychological distress. And Subramaniam attributed this to a loss of hope among patients who were not treated.

Patients treated in public and academic hospitals were less likely to be psychologically distressed than those treated in private centers. Subramaniam said this could be related to financial distress.

In closing, Subramaniam said this study indicates that cancer survivors in Malaysia have impaired HRQOL, and many experience psychological distress. Therefore, clinicians should focus on “supporting patients throughout their whole cancer ‘journey,’ especially in their lives after treatment.”

*Abstract 496O_PR—“Health-related quality of life and psychological distress among cancer survivors in a middle-income Asian country.” (Information in the abstract differs from the presentation.)

Shridevi Subramaniam

Photo courtesy of ESMO

SINGAPORE—Cancer survivors in Malaysia may have impaired health-related quality of life (HRQOL) and high levels of psychological distress 1 year after diagnosis, according to research presented at the ESMO Asia 2016 Congress.*

Of all the patients studied, those with lymphoma had the lowest global health score (according to the EORTC QLQ C30 questionnaire) and the highest levels of psychological distress (anxiety and depression).

“We urgently need new ways of supporting cancer survivors and addressing wider aspects of wellbeing,” said study investigator Shridevi Subramaniam, of the Clinical Research Centre, Ministry of Health Malaysia, in Kuala Lumpur.

“Instead of just focusing on clinical outcome, doctors must focus equally on quality of life for cancer patients, especially psychologically, financially, and socially.”

Patient population

Subramaniam and her colleagues assessed HRQOL in 1376 cancer patients who had survived 12 months from diagnosis. The patients’ mean age was 52, and 64% were female.

Patients had breast cancer (n=403), lymphomas (n=349), colorectal cancer (n=160), mouth cancer (n=108), and female reproductive cancer (n=91).

Forty-one percent of patients had late-stage cancer, 30% had early stage, and 29% had hematologic cancer. Twenty-eight percent of patients had comorbidities.

Thirty-five percent of patients underwent surgery, 73% received chemotherapy, 43% received radiotherapy, and 13% received hormonal therapy.

Forty-six percent of patients were treated at public hospitals, 48% were treated at academic hospitals, and 6% were treated at private hospitals.

Nearly three-quarters of patients (73%) had no insurance, 20% had private insurance, 5% had insurance via their employers, and 4% had other insurance. Forty-one percent of patients had low income status, 30% middle income, and 20% high income.

Overall HRQOL

The patients reported their HRQOL using the EORTC QLQ C30, Hospital Anxiety and Depression Scale, and EQ-5D questionnaire.

For the entire patient cohort, EORTC QLQ-Q30 scores were as follows:

• Mean global health score—53.0
• Mean physical function score—72.6
• Mean emotional function score—63.0
• Mean fatigue score—32.3
• Mean pain score—26.5

The patients’ mean generic HRQOL index score (according to EQ-5D) was 0.7. And a majority of patients reported anxiety (83.5%, n=949) and depression (79.1%, n=899).

HRQOL by cancer type

Anxiety and depression was most common among patients with lymphoma. These patients also had the lowest global health score. Subramaniam said these findings might be explained by side effects from aggressive treatment.

Mean global health scores were 33.3 for lymphoma patients, 59.4 for female breast cancer patients, 59.6 for colorectal cancer patients, 59.8 for patients with mouth cancer, and 67.8 for patients with female reproductive cancers.

The generic HRQOL index scores were 0.69 (colorectal), 0.73 (lymphoma, breast, and mouth), and 0.80 (reproductive).

The proportion of patients with anxiety was 94% (lymphoma), 87.4% (colorectal), 80.5% (breast), 72.6% (mouth), and 51.7% (reproductive).

The proportion of patients with depression was 86.7% (lymphoma), 80.9% (colorectal), 75.8% (mouth), 74.4% (breast), and 50.5% (reproductive).

Predictors of HRQOL

Subramaniam and her colleagues found several significant predictors of HRQOL.

Older patients had decreased physical function and global health, as well as increased pain and fatigue. Married patients had increased fatigue. And patients without comorbidities had increased physical and emotional function as well as decreased fatigue.

Compared with those treated at private hospitals, patients treated at academic hospitals had decreased physical and emotional functions and increased fatigue. Subramaniam said this could be due to long wait times at academic hospitals, which lead to worsening conditions and more pain and discomfort.

Compared to patients with high income status, those from low income groups had increased global health and physical and emotional functions, as well as decreased pain and fatigue. Subramaniam said this could be due to higher expectations among patients with higher incomes.

Compared to patients with early stage cancers, patients with hematologic and late stage cancers had decreased global health and physical function, as well as increased pain and fatigue. Subramaniam said this could be attributed to side effects of treatment.

She added that treatment side effects might also explain why patients who did not receive chemotherapy had higher global health scores.

Patients who didn’t receive radiotherapy were twice as likely as those who did to report psychological distress. And Subramaniam attributed this to a loss of hope among patients who were not treated.

Patients treated in public and academic hospitals were less likely to be psychologically distressed than those treated in private centers. Subramaniam said this could be related to financial distress.

In closing, Subramaniam said this study indicates that cancer survivors in Malaysia have impaired HRQOL, and many experience psychological distress. Therefore, clinicians should focus on “supporting patients throughout their whole cancer ‘journey,’ especially in their lives after treatment.”

*Abstract 496O_PR—“Health-related quality of life and psychological distress among cancer survivors in a middle-income Asian country.” (Information in the abstract differs from the presentation.)

NEW ORLEANS – Performing bariatric surgery prior to total knee or hip replacement instead of vice versa resulted in significantly shorter orthopedic surgical operating time and length of stay in an observational study, Emanuel E. Nearing II, MD, reported at Obesity Week 2016.

“We propose that strong consideration be given to bariatric surgery as a means of weight loss and BMI [body mass index] reduction in patients with obesity prior to total joint replacement,” he said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Bruce Jancin/Frontline Medical News

[email protected]
 

NEW ORLEANS – Performing bariatric surgery prior to total knee or hip replacement instead of vice versa resulted in significantly shorter orthopedic surgical operating time and length of stay in an observational study, Emanuel E. Nearing II, MD, reported at Obesity Week 2016.

“We propose that strong consideration be given to bariatric surgery as a means of weight loss and BMI [body mass index] reduction in patients with obesity prior to total joint replacement,” he said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Bruce Jancin/Frontline Medical News

[email protected]
 

NEW ORLEANS – Performing bariatric surgery prior to total knee or hip replacement instead of vice versa resulted in significantly shorter orthopedic surgical operating time and length of stay in an observational study, Emanuel E. Nearing II, MD, reported at Obesity Week 2016.

“We propose that strong consideration be given to bariatric surgery as a means of weight loss and BMI [body mass index] reduction in patients with obesity prior to total joint replacement,” he said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Bruce Jancin/Frontline Medical News

[email protected]