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Ixekizumab proves highly effective for palmoplantar, scalp psoriasis
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.
The primary results of UNCOVER-3 have been published. At week 60, at least 80% of patients on maintenance therapy with ixekizumab had a PASI 75 response and at least 73% were rated clear or almost clear (N Engl J Med. 2016 Jul 28;375[4]:345-56).
Dr. Menter and Dr. Reich presented new subgroup analyses focused specifically on palmoplantar and scalp psoriasis because these two expressions of the disease are very important in clinical practice, albeit for different reasons.
Scalp psoriasis is extremely common in patients with plaque psoriasis. In fact, nearly 91% of subjects in UNCOVER-3 had scalp involvement.
“That’s a higher percentage than we’re accustomed to seeing in daily practice. It suggests scalp psoriasis may be more common than previously thought in patients with moderate or severe psoriasis,” said Dr. Reich, professor of dermatology at Georg-August-University in Gottingen, Germany, and a partner at the Dermatologikum Hamburg.
At week 60, more than 77% of patients on ixekizumab achieved a Psoriasis Scalp Severity Index 100 response (PSSI 100), meaning they had complete resolution of their scalp psoriasis. More than 80% achieved a PSSI 90 response indicative of complete or near complete resolution of their scalp involvement, the dermatologist reported.
“I often tell my patients that it’s because of palmoplantar psoriasis that I have so many white hairs. It’s certainly a disease that none of us cope with well topically, phototherapy-wise, PUVA-wise, or with systemic therapy. All of the studies done to date with our systemic therapies show significantly lower effect on palmoplantar psoriasis than for psoriasis at other sites. When I did the REVEAL study for Humira [adalimumab], we published a week 16 PASI 75 rate of 71%. When we did the palmoplantar psoriasis cohort, it was less than 40%,” recalled Dr. Menter, who is chair of dermatology at Baylor University Medical Center, Dallas.
“Even though palmoplantar disease affects less than 5% of the body surface area, the quality of life impact for patients with significant palmoplantar pustular or plaque psoriasis is very significant,” Dr. Menter continued. “We’ve worked with our hand surgeons and our foot surgeons to show that the impairment equals that seen in patients with severe rheumatoid arthritis or osteoarthritis of the hands and feet. So it is a huge issue.”
He reported on the 115 UNCOVER-3 participants with palmoplantar involvement. Within 2 weeks after the first 80-mg dose of ixekizumab, recipients had a 60% improvement in their Palmoplantar Psoriasis Area and Severity Index (PPSI) scores.
“It was very dramatic. These are figures that we haven’t seen with methotrexate, with retinoids, or with TNF-alpha blockers,” according to Dr. Menter.
At week 12 in UNCOVER-3, patients randomized to ixekizumab at 80 mg every 2 weeks showed an 85% improvement from baseline in PPSI scores. Those on ixekizumab at 80 mg every 4 weeks had a 78% improvement from baseline, while patients on etanercept at 50 mg twice weekly showed a 52% improvement.
At 60 weeks, PPSI 100 response rates – that is, clear palms and soles – were 60%-70% in the various ixekizumab-treated groups.
“To me, the big issue now is what about palmoplantar pustulosis, a totally different disease, and a disease with equally serious issues for our patients. I’m looking forward to studies in that population. I sincerely hope these new agents such as ixekizumab will have a significant role to play,” he said.
Dr. Menter and Dr. Reich reported receiving research support from and serving as consultants to Eli Lilly, which sponsored the UNCOVER-3 trial and markets ixekizumab, as well as numerous other pharmaceutical companies.
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.
The primary results of UNCOVER-3 have been published. At week 60, at least 80% of patients on maintenance therapy with ixekizumab had a PASI 75 response and at least 73% were rated clear or almost clear (N Engl J Med. 2016 Jul 28;375[4]:345-56).
Dr. Menter and Dr. Reich presented new subgroup analyses focused specifically on palmoplantar and scalp psoriasis because these two expressions of the disease are very important in clinical practice, albeit for different reasons.
Scalp psoriasis is extremely common in patients with plaque psoriasis. In fact, nearly 91% of subjects in UNCOVER-3 had scalp involvement.
“That’s a higher percentage than we’re accustomed to seeing in daily practice. It suggests scalp psoriasis may be more common than previously thought in patients with moderate or severe psoriasis,” said Dr. Reich, professor of dermatology at Georg-August-University in Gottingen, Germany, and a partner at the Dermatologikum Hamburg.
At week 60, more than 77% of patients on ixekizumab achieved a Psoriasis Scalp Severity Index 100 response (PSSI 100), meaning they had complete resolution of their scalp psoriasis. More than 80% achieved a PSSI 90 response indicative of complete or near complete resolution of their scalp involvement, the dermatologist reported.
“I often tell my patients that it’s because of palmoplantar psoriasis that I have so many white hairs. It’s certainly a disease that none of us cope with well topically, phototherapy-wise, PUVA-wise, or with systemic therapy. All of the studies done to date with our systemic therapies show significantly lower effect on palmoplantar psoriasis than for psoriasis at other sites. When I did the REVEAL study for Humira [adalimumab], we published a week 16 PASI 75 rate of 71%. When we did the palmoplantar psoriasis cohort, it was less than 40%,” recalled Dr. Menter, who is chair of dermatology at Baylor University Medical Center, Dallas.
“Even though palmoplantar disease affects less than 5% of the body surface area, the quality of life impact for patients with significant palmoplantar pustular or plaque psoriasis is very significant,” Dr. Menter continued. “We’ve worked with our hand surgeons and our foot surgeons to show that the impairment equals that seen in patients with severe rheumatoid arthritis or osteoarthritis of the hands and feet. So it is a huge issue.”
He reported on the 115 UNCOVER-3 participants with palmoplantar involvement. Within 2 weeks after the first 80-mg dose of ixekizumab, recipients had a 60% improvement in their Palmoplantar Psoriasis Area and Severity Index (PPSI) scores.
“It was very dramatic. These are figures that we haven’t seen with methotrexate, with retinoids, or with TNF-alpha blockers,” according to Dr. Menter.
At week 12 in UNCOVER-3, patients randomized to ixekizumab at 80 mg every 2 weeks showed an 85% improvement from baseline in PPSI scores. Those on ixekizumab at 80 mg every 4 weeks had a 78% improvement from baseline, while patients on etanercept at 50 mg twice weekly showed a 52% improvement.
At 60 weeks, PPSI 100 response rates – that is, clear palms and soles – were 60%-70% in the various ixekizumab-treated groups.
“To me, the big issue now is what about palmoplantar pustulosis, a totally different disease, and a disease with equally serious issues for our patients. I’m looking forward to studies in that population. I sincerely hope these new agents such as ixekizumab will have a significant role to play,” he said.
Dr. Menter and Dr. Reich reported receiving research support from and serving as consultants to Eli Lilly, which sponsored the UNCOVER-3 trial and markets ixekizumab, as well as numerous other pharmaceutical companies.
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.
The primary results of UNCOVER-3 have been published. At week 60, at least 80% of patients on maintenance therapy with ixekizumab had a PASI 75 response and at least 73% were rated clear or almost clear (N Engl J Med. 2016 Jul 28;375[4]:345-56).
Dr. Menter and Dr. Reich presented new subgroup analyses focused specifically on palmoplantar and scalp psoriasis because these two expressions of the disease are very important in clinical practice, albeit for different reasons.
Scalp psoriasis is extremely common in patients with plaque psoriasis. In fact, nearly 91% of subjects in UNCOVER-3 had scalp involvement.
“That’s a higher percentage than we’re accustomed to seeing in daily practice. It suggests scalp psoriasis may be more common than previously thought in patients with moderate or severe psoriasis,” said Dr. Reich, professor of dermatology at Georg-August-University in Gottingen, Germany, and a partner at the Dermatologikum Hamburg.
At week 60, more than 77% of patients on ixekizumab achieved a Psoriasis Scalp Severity Index 100 response (PSSI 100), meaning they had complete resolution of their scalp psoriasis. More than 80% achieved a PSSI 90 response indicative of complete or near complete resolution of their scalp involvement, the dermatologist reported.
“I often tell my patients that it’s because of palmoplantar psoriasis that I have so many white hairs. It’s certainly a disease that none of us cope with well topically, phototherapy-wise, PUVA-wise, or with systemic therapy. All of the studies done to date with our systemic therapies show significantly lower effect on palmoplantar psoriasis than for psoriasis at other sites. When I did the REVEAL study for Humira [adalimumab], we published a week 16 PASI 75 rate of 71%. When we did the palmoplantar psoriasis cohort, it was less than 40%,” recalled Dr. Menter, who is chair of dermatology at Baylor University Medical Center, Dallas.
“Even though palmoplantar disease affects less than 5% of the body surface area, the quality of life impact for patients with significant palmoplantar pustular or plaque psoriasis is very significant,” Dr. Menter continued. “We’ve worked with our hand surgeons and our foot surgeons to show that the impairment equals that seen in patients with severe rheumatoid arthritis or osteoarthritis of the hands and feet. So it is a huge issue.”
He reported on the 115 UNCOVER-3 participants with palmoplantar involvement. Within 2 weeks after the first 80-mg dose of ixekizumab, recipients had a 60% improvement in their Palmoplantar Psoriasis Area and Severity Index (PPSI) scores.
“It was very dramatic. These are figures that we haven’t seen with methotrexate, with retinoids, or with TNF-alpha blockers,” according to Dr. Menter.
At week 12 in UNCOVER-3, patients randomized to ixekizumab at 80 mg every 2 weeks showed an 85% improvement from baseline in PPSI scores. Those on ixekizumab at 80 mg every 4 weeks had a 78% improvement from baseline, while patients on etanercept at 50 mg twice weekly showed a 52% improvement.
At 60 weeks, PPSI 100 response rates – that is, clear palms and soles – were 60%-70% in the various ixekizumab-treated groups.
“To me, the big issue now is what about palmoplantar pustulosis, a totally different disease, and a disease with equally serious issues for our patients. I’m looking forward to studies in that population. I sincerely hope these new agents such as ixekizumab will have a significant role to play,” he said.
Dr. Menter and Dr. Reich reported receiving research support from and serving as consultants to Eli Lilly, which sponsored the UNCOVER-3 trial and markets ixekizumab, as well as numerous other pharmaceutical companies.
EXPERT ANALYSIS FROM THE EADV CONGRESS
David Henry's JCSO podcast, December 2016
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.
Intermittent fasting fights ALL, not AML, in mice
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. 
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.
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.
JCAR017 gets PRIME access, breakthrough designation
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.
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.
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.
Why some patients relapse: The case for consolidation therapy in Hodgkin lymphoma
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.
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.
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.
Lymphoma patients report high levels of distress
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.)
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.)
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.)
Sleep Disorders
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The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Bariatric surgery or total joint replacement: which first?
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.
“A common complaint of patients presenting with obesity is that their osteoarthritis has limited their mobility and that their weight gain is secondary to that reduced mobility. They believe that a new joint will help them regain their mobility and then lose weight. Interestingly, this does not appear to be the case. In fact, the majority of patients in our study actually gained weight following joint replacement. Given that, these patients need to be weight-optimized prior to total joint replacement. Bariatric surgery is a durable way to facilitate this,” he continued.
Dr. Nearing presented a retrospective observational study of 102 patients who underwent either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy plus a total knee or hip replacement in the Gundersen system. Sixty-six patients had their bariatric surgery first, by a mean of 4.3 years, while the other 36 had arthroplasty a mean of 4.9 years before their bariatric surgery. The two groups were similar in terms of demographics and baseline comorbid conditions.
Patients who had their total joint replacement first had a mean preoperative BMI of 43.7 kg/m2 and a mean pre–bariatric surgery BMI of 46.3 kg/m2. The patients who had bariatric surgery first had a preoperative BMI of 49.6 kg/m2 and a mean pre–orthopedic surgery BMI of 37.6 kgm2. One year after joint replacement surgery, patients who had that operation first had a mean BMI of 43.9 kg/m2, compared with 37.8 kg/m2 for those who waited until after they underwent bariatric surgery.
Mean operative time for total joint replacement when it was the first operation was 113.5 minutes and substantially less at 71 minutes when it was done after bariatric surgery. Mean hospital length of stay for total joint replacement when it followed bariatric surgery was 2.9 days, a full day less than when joint replacement came first.
Rates of complications including skin or soft tissue infection, venous thromboembolism, hematoma, need for transfusion, and periprosthetic infection at 30 and 90 days didn’t differ between the two groups. Neither did the need for late reinterventions.
Dr. Nearing noted that a working group of the American Association of Hip and Knee Surgeons has conducted a review of the orthopedic surgery literature and concluded that all patients with a BMI of 30 kg/m2 or more undergoing total knee or hip arthroplasty are at increased risk for perioperative respiratory complications, thromboembolic events, delayed wound healing, infection, and need for joint revision surgery (J Arthroplasty. 2013 May;28[5]:714-21).
He observed that a retrospective study such as his cannot shed light on the optimal time interval for total joint replacement following bariatric surgery. That key question is being addressed by the ongoing prospective SWIFT (Surgical Weight-Loss to Improve Functional Status Trajectories Following Total Knee Arthroplasty) trial. The study hypothesis is that bariatric surgery prior to the knee replacement surgery will reduce risk and improve long-term outcomes and physical function.
Several audience member commented that, based upon their experience, they would have anticipated that complication rates would have been significantly lower in total joint replacement patients when that operation followed bariatric surgery.
“We were surprised, too,” Dr. Nearing replied. “I think the explanation is that at Gundersen we have three bariatric surgeons and only a handful of orthopedic surgeons, and we use protocols and pathways. We just routinely do our operations the same way each and every time.”
John M. Morton, MD, a former American Society for Metabolic and Bariatric Surgery president, commented that the Gundersen study findings sound a call for more cross-specialty collaboration in steering obese patients with severe knee or hip osteoarthritis to bariatric surgery first in order to maximize the results of the joint replacement surgery.
“I think we’re all seeing weight loss as another form of prehabilitation for other specialties. Our orthopedic colleagues are kind of like us – surgeons – so this seems to be a great place for us to partner with them,” said Dr. Morton, chief of bariatric and minimally invasive surgery at Stanford (Calif.) University.
Dr. Nearing reported having no financial interests relevant to his study.
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.
“A common complaint of patients presenting with obesity is that their osteoarthritis has limited their mobility and that their weight gain is secondary to that reduced mobility. They believe that a new joint will help them regain their mobility and then lose weight. Interestingly, this does not appear to be the case. In fact, the majority of patients in our study actually gained weight following joint replacement. Given that, these patients need to be weight-optimized prior to total joint replacement. Bariatric surgery is a durable way to facilitate this,” he continued.
Dr. Nearing presented a retrospective observational study of 102 patients who underwent either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy plus a total knee or hip replacement in the Gundersen system. Sixty-six patients had their bariatric surgery first, by a mean of 4.3 years, while the other 36 had arthroplasty a mean of 4.9 years before their bariatric surgery. The two groups were similar in terms of demographics and baseline comorbid conditions.
Patients who had their total joint replacement first had a mean preoperative BMI of 43.7 kg/m2 and a mean pre–bariatric surgery BMI of 46.3 kg/m2. The patients who had bariatric surgery first had a preoperative BMI of 49.6 kg/m2 and a mean pre–orthopedic surgery BMI of 37.6 kgm2. One year after joint replacement surgery, patients who had that operation first had a mean BMI of 43.9 kg/m2, compared with 37.8 kg/m2 for those who waited until after they underwent bariatric surgery.
Mean operative time for total joint replacement when it was the first operation was 113.5 minutes and substantially less at 71 minutes when it was done after bariatric surgery. Mean hospital length of stay for total joint replacement when it followed bariatric surgery was 2.9 days, a full day less than when joint replacement came first.
Rates of complications including skin or soft tissue infection, venous thromboembolism, hematoma, need for transfusion, and periprosthetic infection at 30 and 90 days didn’t differ between the two groups. Neither did the need for late reinterventions.
Dr. Nearing noted that a working group of the American Association of Hip and Knee Surgeons has conducted a review of the orthopedic surgery literature and concluded that all patients with a BMI of 30 kg/m2 or more undergoing total knee or hip arthroplasty are at increased risk for perioperative respiratory complications, thromboembolic events, delayed wound healing, infection, and need for joint revision surgery (J Arthroplasty. 2013 May;28[5]:714-21).
He observed that a retrospective study such as his cannot shed light on the optimal time interval for total joint replacement following bariatric surgery. That key question is being addressed by the ongoing prospective SWIFT (Surgical Weight-Loss to Improve Functional Status Trajectories Following Total Knee Arthroplasty) trial. The study hypothesis is that bariatric surgery prior to the knee replacement surgery will reduce risk and improve long-term outcomes and physical function.
Several audience member commented that, based upon their experience, they would have anticipated that complication rates would have been significantly lower in total joint replacement patients when that operation followed bariatric surgery.
“We were surprised, too,” Dr. Nearing replied. “I think the explanation is that at Gundersen we have three bariatric surgeons and only a handful of orthopedic surgeons, and we use protocols and pathways. We just routinely do our operations the same way each and every time.”
John M. Morton, MD, a former American Society for Metabolic and Bariatric Surgery president, commented that the Gundersen study findings sound a call for more cross-specialty collaboration in steering obese patients with severe knee or hip osteoarthritis to bariatric surgery first in order to maximize the results of the joint replacement surgery.
“I think we’re all seeing weight loss as another form of prehabilitation for other specialties. Our orthopedic colleagues are kind of like us – surgeons – so this seems to be a great place for us to partner with them,” said Dr. Morton, chief of bariatric and minimally invasive surgery at Stanford (Calif.) University.
Dr. Nearing reported having no financial interests relevant to his study.
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.
“A common complaint of patients presenting with obesity is that their osteoarthritis has limited their mobility and that their weight gain is secondary to that reduced mobility. They believe that a new joint will help them regain their mobility and then lose weight. Interestingly, this does not appear to be the case. In fact, the majority of patients in our study actually gained weight following joint replacement. Given that, these patients need to be weight-optimized prior to total joint replacement. Bariatric surgery is a durable way to facilitate this,” he continued.
Dr. Nearing presented a retrospective observational study of 102 patients who underwent either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy plus a total knee or hip replacement in the Gundersen system. Sixty-six patients had their bariatric surgery first, by a mean of 4.3 years, while the other 36 had arthroplasty a mean of 4.9 years before their bariatric surgery. The two groups were similar in terms of demographics and baseline comorbid conditions.
Patients who had their total joint replacement first had a mean preoperative BMI of 43.7 kg/m2 and a mean pre–bariatric surgery BMI of 46.3 kg/m2. The patients who had bariatric surgery first had a preoperative BMI of 49.6 kg/m2 and a mean pre–orthopedic surgery BMI of 37.6 kgm2. One year after joint replacement surgery, patients who had that operation first had a mean BMI of 43.9 kg/m2, compared with 37.8 kg/m2 for those who waited until after they underwent bariatric surgery.
Mean operative time for total joint replacement when it was the first operation was 113.5 minutes and substantially less at 71 minutes when it was done after bariatric surgery. Mean hospital length of stay for total joint replacement when it followed bariatric surgery was 2.9 days, a full day less than when joint replacement came first.
Rates of complications including skin or soft tissue infection, venous thromboembolism, hematoma, need for transfusion, and periprosthetic infection at 30 and 90 days didn’t differ between the two groups. Neither did the need for late reinterventions.
Dr. Nearing noted that a working group of the American Association of Hip and Knee Surgeons has conducted a review of the orthopedic surgery literature and concluded that all patients with a BMI of 30 kg/m2 or more undergoing total knee or hip arthroplasty are at increased risk for perioperative respiratory complications, thromboembolic events, delayed wound healing, infection, and need for joint revision surgery (J Arthroplasty. 2013 May;28[5]:714-21).
He observed that a retrospective study such as his cannot shed light on the optimal time interval for total joint replacement following bariatric surgery. That key question is being addressed by the ongoing prospective SWIFT (Surgical Weight-Loss to Improve Functional Status Trajectories Following Total Knee Arthroplasty) trial. The study hypothesis is that bariatric surgery prior to the knee replacement surgery will reduce risk and improve long-term outcomes and physical function.
Several audience member commented that, based upon their experience, they would have anticipated that complication rates would have been significantly lower in total joint replacement patients when that operation followed bariatric surgery.
“We were surprised, too,” Dr. Nearing replied. “I think the explanation is that at Gundersen we have three bariatric surgeons and only a handful of orthopedic surgeons, and we use protocols and pathways. We just routinely do our operations the same way each and every time.”
John M. Morton, MD, a former American Society for Metabolic and Bariatric Surgery president, commented that the Gundersen study findings sound a call for more cross-specialty collaboration in steering obese patients with severe knee or hip osteoarthritis to bariatric surgery first in order to maximize the results of the joint replacement surgery.
“I think we’re all seeing weight loss as another form of prehabilitation for other specialties. Our orthopedic colleagues are kind of like us – surgeons – so this seems to be a great place for us to partner with them,” said Dr. Morton, chief of bariatric and minimally invasive surgery at Stanford (Calif.) University.
Dr. Nearing reported having no financial interests relevant to his study.
AT OBESITY WEEK 2016
Key clinical point:
Major finding: When total joint replacement in obese patients was performed after bariatric surgery, mean hospital length of stay was a full day less than when the orthopedic surgery preceded the bariatric surgery.
Data source: This retrospective observational study included 102 obese patients who underwent bariatric surgery and total knee or hip replacement.
Disclosures: The study presenter reported having no financial conflicts of interest.
ADHD versus anxiety? An approach for pediatricians
This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.
Case summary
Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).
Discussion
1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.
2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.
3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.3
4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.
5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist4 which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.
Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.5 When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.6
Case follow-up
Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.
References
1. Genes Brain Behav. 2005;4(8):466-81.
2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.
3. Am J Psychiatry. 2015;172(7):630-7.
4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).
5. J Anxiety Disord. 1997;11(4):377-94.
6. J Abnorm Child Psychol. 2000;28(6):527-41.
Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at [email protected].
This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.
Case summary
Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).
Discussion
1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.
2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.
3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.3
4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.
5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist4 which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.
Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.5 When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.6
Case follow-up
Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.
References
1. Genes Brain Behav. 2005;4(8):466-81.
2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.
3. Am J Psychiatry. 2015;172(7):630-7.
4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).
5. J Anxiety Disord. 1997;11(4):377-94.
6. J Abnorm Child Psychol. 2000;28(6):527-41.
Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at [email protected].
This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.
Case summary
Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).
Discussion
1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.
2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.
3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.3
4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.
5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist4 which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.
Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.5 When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.6
Case follow-up
Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.
References
1. Genes Brain Behav. 2005;4(8):466-81.
2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.
3. Am J Psychiatry. 2015;172(7):630-7.
4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).
5. J Anxiety Disord. 1997;11(4):377-94.
6. J Abnorm Child Psychol. 2000;28(6):527-41.
Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at [email protected].
Tips and tricks for open laparoscopy
Visit the Society of Gynecologic Surgeons online: sgsonline.org
More videos from SGS:
- Complete colpectomy & colpocleisis: Model for simulation
- Natural orifice sacral colpopexy
- Alternative options for visualizing ureteral patency during intraoperative cystoscopy
- Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
- Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
- Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
- Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
- Laparoscopic cystectomy for large, bilateral ovarian dermoids
- Small bowel surgery for the benign gynecologist
Visit the Society of Gynecologic Surgeons online: sgsonline.org
More videos from SGS:
- Complete colpectomy & colpocleisis: Model for simulation
- Natural orifice sacral colpopexy
- Alternative options for visualizing ureteral patency during intraoperative cystoscopy
- Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
- Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
- Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
- Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
- Laparoscopic cystectomy for large, bilateral ovarian dermoids
- Small bowel surgery for the benign gynecologist
Visit the Society of Gynecologic Surgeons online: sgsonline.org
More videos from SGS:
- Complete colpectomy & colpocleisis: Model for simulation
- Natural orifice sacral colpopexy
- Alternative options for visualizing ureteral patency during intraoperative cystoscopy
- Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
- Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
- Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
- Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
- Laparoscopic cystectomy for large, bilateral ovarian dermoids
- Small bowel surgery for the benign gynecologist
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