Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Women who underwent bilateral salpingo-oophorectomy with a benign hysterectomy had a higher 10-year mortality rate across all ages than those who had hysterectomies alone, based on data from more than 140,000 individuals.

Although bilateral salpingo-oophorectomy (BSO) with hysterectomy has been shown to reduce the risk for ovarian cancer in women at increased risk, current guidelines are touting ovarian conservation, especially in premenopausal women, wrote Mathilde Gottschau, MD, of the Danish Cancer Society Research Center, Copenhagen, and colleagues. However, post-hysterectomy outcomes in women with and without BSO have not been well examined.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a nationwide registry of women in Denmark aged 20 years and older who underwent benign hysterectomies with BSO (22,974 women) and without BSO (120,011 women) between 1977 and 2017. The women were divided into subgroups based on age; those younger than 45 years were defined as premenopausal, those aged 45-54 years were defined as perimenopausal, those aged 55-64 were defined as early postmenopausal, and those aged 65 and older were defined as late menopausal.

The primary outcomes were hospitalization for cardiovascular disease, cancer incidence, and all-cause mortality over a median follow-up period of 22 years.

For women younger than 45 years, the 10-year cumulative risk for all cancer was lower with BSO than without, but the risk of overall cardiovascular disease was higher with BSO, with higher levels of ischemic heart disease and stroke, compared with women without BSO. The 10-year cumulative mortality was higher with BSO than without (2.16% vs. 1.94%).

For women aged 45-54 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO (risk difference, 0.73 percentage points) associated mainly with nonbreast cancer, and both 10-year and 20-year mortality were higher in those with BSO than those without.

For women aged 55-65 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO. Cumulative overall mortality was higher at 10 years for those with BSO, but lower at 20 years.

For women aged 65 years and older, both 10-year and 20-year cumulative overall cancer risk was higher with BSO than without (RD, 2.54 and 4.57 percentage points, respectively). Cumulative mortality was higher in the BSO group at 10 years, but lower at 20 years.

The study findings were limited by several factors including the use of age to determine menopausal status and the lack of genetic predisposition data, and the focus only on a relatively homogeneous population that may not be generalizable to other populations, the researchers noted.

However, the results were strengthened by the use of a nationwide registry and the long-term follow-up period, they said. The current study indicates that the health risks outweigh the potential benefits of BSO with benign hysterectomy for premenopausal women and supports the current guidelines for ovarian conservation in these women with low lifetime ovarian cancer risk, they said. For postmenopausal women, the data support a cautious approach to BSO given the lack of a clear survival benefit and cancer excess, they concluded.
 

Delayed diagnosis of ovarian cancers favors BSO

“The question of removing ovaries at the time of benign hysterectomy to prevent ovarian cancer in low-risk women has been widely debated,” which has contributed to the variation in incidence rates of unilateral and bilateral oophorectomy over time, wrote Elizabeth Casiano Evans, MD, of the University of Texas, San Antonio, and Deslyn T.G. Hobson, MD, of Wayne State University, Detroit, in an accompanying editorial.

Ovarian cancer often goes undiagnosed until an advanced stage, and BSO can significantly reduce risk in women with BRCA1 and BRCA2 mutations, they noted.

For women without increased risk, those who are premenopausal may wish to preserve ovarian function, but women also may benefit from improvements in a range of menopause-related symptoms including vasomotor and urogenital symptoms, sexual dysfunction, and psychiatric and cognitive symptoms, they said.

“In addition, salpingectomy alone has a role in significantly reducing ovarian cancer incidence without compromising ovarian function because the fallopian tube has been found to be at the origin of many ovarian cancer cases,” they noted. In the current study, “the crude ovarian cancer risk was lower with BSO” across all age groups, the editorialists said.

The choice of whether to include BSO at the time of benign hysterectomy is complicated, with many factors to consider, the editorialists wrote, and the current study supports the need for informed, shared decision-making between clinicians and patients.

The study was supported by the Danish Cancer Society’s Scientific Committee and the Mermaid Project. The researchers had no financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.
 

Women who underwent bilateral salpingo-oophorectomy with a benign hysterectomy had a higher 10-year mortality rate across all ages than those who had hysterectomies alone, based on data from more than 140,000 individuals.

Although bilateral salpingo-oophorectomy (BSO) with hysterectomy has been shown to reduce the risk for ovarian cancer in women at increased risk, current guidelines are touting ovarian conservation, especially in premenopausal women, wrote Mathilde Gottschau, MD, of the Danish Cancer Society Research Center, Copenhagen, and colleagues. However, post-hysterectomy outcomes in women with and without BSO have not been well examined.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a nationwide registry of women in Denmark aged 20 years and older who underwent benign hysterectomies with BSO (22,974 women) and without BSO (120,011 women) between 1977 and 2017. The women were divided into subgroups based on age; those younger than 45 years were defined as premenopausal, those aged 45-54 years were defined as perimenopausal, those aged 55-64 were defined as early postmenopausal, and those aged 65 and older were defined as late menopausal.

The primary outcomes were hospitalization for cardiovascular disease, cancer incidence, and all-cause mortality over a median follow-up period of 22 years.

For women younger than 45 years, the 10-year cumulative risk for all cancer was lower with BSO than without, but the risk of overall cardiovascular disease was higher with BSO, with higher levels of ischemic heart disease and stroke, compared with women without BSO. The 10-year cumulative mortality was higher with BSO than without (2.16% vs. 1.94%).

For women aged 45-54 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO (risk difference, 0.73 percentage points) associated mainly with nonbreast cancer, and both 10-year and 20-year mortality were higher in those with BSO than those without.

For women aged 55-65 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO. Cumulative overall mortality was higher at 10 years for those with BSO, but lower at 20 years.

For women aged 65 years and older, both 10-year and 20-year cumulative overall cancer risk was higher with BSO than without (RD, 2.54 and 4.57 percentage points, respectively). Cumulative mortality was higher in the BSO group at 10 years, but lower at 20 years.

The study findings were limited by several factors including the use of age to determine menopausal status and the lack of genetic predisposition data, and the focus only on a relatively homogeneous population that may not be generalizable to other populations, the researchers noted.

However, the results were strengthened by the use of a nationwide registry and the long-term follow-up period, they said. The current study indicates that the health risks outweigh the potential benefits of BSO with benign hysterectomy for premenopausal women and supports the current guidelines for ovarian conservation in these women with low lifetime ovarian cancer risk, they said. For postmenopausal women, the data support a cautious approach to BSO given the lack of a clear survival benefit and cancer excess, they concluded.
 

Delayed diagnosis of ovarian cancers favors BSO

“The question of removing ovaries at the time of benign hysterectomy to prevent ovarian cancer in low-risk women has been widely debated,” which has contributed to the variation in incidence rates of unilateral and bilateral oophorectomy over time, wrote Elizabeth Casiano Evans, MD, of the University of Texas, San Antonio, and Deslyn T.G. Hobson, MD, of Wayne State University, Detroit, in an accompanying editorial.

Ovarian cancer often goes undiagnosed until an advanced stage, and BSO can significantly reduce risk in women with BRCA1 and BRCA2 mutations, they noted.

For women without increased risk, those who are premenopausal may wish to preserve ovarian function, but women also may benefit from improvements in a range of menopause-related symptoms including vasomotor and urogenital symptoms, sexual dysfunction, and psychiatric and cognitive symptoms, they said.

“In addition, salpingectomy alone has a role in significantly reducing ovarian cancer incidence without compromising ovarian function because the fallopian tube has been found to be at the origin of many ovarian cancer cases,” they noted. In the current study, “the crude ovarian cancer risk was lower with BSO” across all age groups, the editorialists said.

The choice of whether to include BSO at the time of benign hysterectomy is complicated, with many factors to consider, the editorialists wrote, and the current study supports the need for informed, shared decision-making between clinicians and patients.

The study was supported by the Danish Cancer Society’s Scientific Committee and the Mermaid Project. The researchers had no financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.
 

Women who underwent bilateral salpingo-oophorectomy with a benign hysterectomy had a higher 10-year mortality rate across all ages than those who had hysterectomies alone, based on data from more than 140,000 individuals.

Although bilateral salpingo-oophorectomy (BSO) with hysterectomy has been shown to reduce the risk for ovarian cancer in women at increased risk, current guidelines are touting ovarian conservation, especially in premenopausal women, wrote Mathilde Gottschau, MD, of the Danish Cancer Society Research Center, Copenhagen, and colleagues. However, post-hysterectomy outcomes in women with and without BSO have not been well examined.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a nationwide registry of women in Denmark aged 20 years and older who underwent benign hysterectomies with BSO (22,974 women) and without BSO (120,011 women) between 1977 and 2017. The women were divided into subgroups based on age; those younger than 45 years were defined as premenopausal, those aged 45-54 years were defined as perimenopausal, those aged 55-64 were defined as early postmenopausal, and those aged 65 and older were defined as late menopausal.

The primary outcomes were hospitalization for cardiovascular disease, cancer incidence, and all-cause mortality over a median follow-up period of 22 years.

For women younger than 45 years, the 10-year cumulative risk for all cancer was lower with BSO than without, but the risk of overall cardiovascular disease was higher with BSO, with higher levels of ischemic heart disease and stroke, compared with women without BSO. The 10-year cumulative mortality was higher with BSO than without (2.16% vs. 1.94%).

For women aged 45-54 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO (risk difference, 0.73 percentage points) associated mainly with nonbreast cancer, and both 10-year and 20-year mortality were higher in those with BSO than those without.

For women aged 55-65 years, the 10-year cumulative cancer risk was higher in those with BSO than those without BSO. Cumulative overall mortality was higher at 10 years for those with BSO, but lower at 20 years.

For women aged 65 years and older, both 10-year and 20-year cumulative overall cancer risk was higher with BSO than without (RD, 2.54 and 4.57 percentage points, respectively). Cumulative mortality was higher in the BSO group at 10 years, but lower at 20 years.

The study findings were limited by several factors including the use of age to determine menopausal status and the lack of genetic predisposition data, and the focus only on a relatively homogeneous population that may not be generalizable to other populations, the researchers noted.

However, the results were strengthened by the use of a nationwide registry and the long-term follow-up period, they said. The current study indicates that the health risks outweigh the potential benefits of BSO with benign hysterectomy for premenopausal women and supports the current guidelines for ovarian conservation in these women with low lifetime ovarian cancer risk, they said. For postmenopausal women, the data support a cautious approach to BSO given the lack of a clear survival benefit and cancer excess, they concluded.
 

Delayed diagnosis of ovarian cancers favors BSO

“The question of removing ovaries at the time of benign hysterectomy to prevent ovarian cancer in low-risk women has been widely debated,” which has contributed to the variation in incidence rates of unilateral and bilateral oophorectomy over time, wrote Elizabeth Casiano Evans, MD, of the University of Texas, San Antonio, and Deslyn T.G. Hobson, MD, of Wayne State University, Detroit, in an accompanying editorial.

Ovarian cancer often goes undiagnosed until an advanced stage, and BSO can significantly reduce risk in women with BRCA1 and BRCA2 mutations, they noted.

For women without increased risk, those who are premenopausal may wish to preserve ovarian function, but women also may benefit from improvements in a range of menopause-related symptoms including vasomotor and urogenital symptoms, sexual dysfunction, and psychiatric and cognitive symptoms, they said.

“In addition, salpingectomy alone has a role in significantly reducing ovarian cancer incidence without compromising ovarian function because the fallopian tube has been found to be at the origin of many ovarian cancer cases,” they noted. In the current study, “the crude ovarian cancer risk was lower with BSO” across all age groups, the editorialists said.

The choice of whether to include BSO at the time of benign hysterectomy is complicated, with many factors to consider, the editorialists wrote, and the current study supports the need for informed, shared decision-making between clinicians and patients.

The study was supported by the Danish Cancer Society’s Scientific Committee and the Mermaid Project. The researchers had no financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.
 

As Parkinson's disease progresses, dopamine and dopamine agonists that control tremor and stiffness can wear off too early or cause dyskinesia when they peak in the bloodstream.  

In this ReCAP, Dr Michael Okun, professor and chair of neurology at the University of Florida, explains that adjustments to dose, timing, or delivery mode of these medications can smooth out some fluctuations. He reports that catechol-O-methyltransferase inhibitors, such as opicapone, tolcapone, and entacapone, can extend the effect of dopamine and the addition of amantadine or istradefylline can suppress dyskinesia. 

He points out that for other patients, surgical options, such as deep brain stimulation or focused ultrasound, can alter how the brain controls disordered movement or implanted pumps can better regulate the delivery of medication either subcutaneously or directly into the gut. 

--

Michael S. Okun, MD, Chair of Neurology, College of Medicine; Director Norman Fixel Institute, University of Florida, Gainesville, Florida 

Michael S. Okun, MD, has disclosed no relevant financial relationships

As Parkinson's disease progresses, dopamine and dopamine agonists that control tremor and stiffness can wear off too early or cause dyskinesia when they peak in the bloodstream.  

In this ReCAP, Dr Michael Okun, professor and chair of neurology at the University of Florida, explains that adjustments to dose, timing, or delivery mode of these medications can smooth out some fluctuations. He reports that catechol-O-methyltransferase inhibitors, such as opicapone, tolcapone, and entacapone, can extend the effect of dopamine and the addition of amantadine or istradefylline can suppress dyskinesia. 

He points out that for other patients, surgical options, such as deep brain stimulation or focused ultrasound, can alter how the brain controls disordered movement or implanted pumps can better regulate the delivery of medication either subcutaneously or directly into the gut. 

--

Michael S. Okun, MD, Chair of Neurology, College of Medicine; Director Norman Fixel Institute, University of Florida, Gainesville, Florida 

Michael S. Okun, MD, has disclosed no relevant financial relationships

As Parkinson's disease progresses, dopamine and dopamine agonists that control tremor and stiffness can wear off too early or cause dyskinesia when they peak in the bloodstream.  

In this ReCAP, Dr Michael Okun, professor and chair of neurology at the University of Florida, explains that adjustments to dose, timing, or delivery mode of these medications can smooth out some fluctuations. He reports that catechol-O-methyltransferase inhibitors, such as opicapone, tolcapone, and entacapone, can extend the effect of dopamine and the addition of amantadine or istradefylline can suppress dyskinesia. 

He points out that for other patients, surgical options, such as deep brain stimulation or focused ultrasound, can alter how the brain controls disordered movement or implanted pumps can better regulate the delivery of medication either subcutaneously or directly into the gut. 

--

Michael S. Okun, MD, Chair of Neurology, College of Medicine; Director Norman Fixel Institute, University of Florida, Gainesville, Florida 

Michael S. Okun, MD, has disclosed no relevant financial relationships

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

Bipolar disorder  is a multifaceted condition associated with an increased risk for hospitalization and suicide as well as high costs to society and family. 

In this ReCAP, Dr Martha Sajatovic, of the University Hospitals of Cleveland, discusses evidence of the short- and long-term consequences of bipolar disorder, including progressive neurologic impact such as changes in brain structure.  

She discusses two FDA-approved long-acting injectables  for bipolar disorder and considerations for their use, including their potential for first-line maintenance treatment and benefits for medication adherence.  

Finally, she considers challenges in the clinical use of the long-acting injectables, including insufficient caregiver involvement and lack of awareness of the drugs' availability. 

--

Martha Sajatovic, MD, Director, Neurological and Behavioral Outcomes Center, University Hospitals of Cleveland, Cleveland, Ohio 

Martha Sajatovic, MD, has disclosed the following relevant financial relationships: 

Received research grant from: Otsuka; International Society for Bipolar Disorders; National Institutes of Health 

Received income in an amount equal to or greater than $250 from: Otsuka; Janssen; Lundbeck; Teva; Neurelis 

Received royalties from: Springer Press; Johns Hopkins University Press 

Bipolar disorder  is a multifaceted condition associated with an increased risk for hospitalization and suicide as well as high costs to society and family. 

In this ReCAP, Dr Martha Sajatovic, of the University Hospitals of Cleveland, discusses evidence of the short- and long-term consequences of bipolar disorder, including progressive neurologic impact such as changes in brain structure.  

She discusses two FDA-approved long-acting injectables  for bipolar disorder and considerations for their use, including their potential for first-line maintenance treatment and benefits for medication adherence.  

Finally, she considers challenges in the clinical use of the long-acting injectables, including insufficient caregiver involvement and lack of awareness of the drugs' availability. 

--

Martha Sajatovic, MD, Director, Neurological and Behavioral Outcomes Center, University Hospitals of Cleveland, Cleveland, Ohio 

Martha Sajatovic, MD, has disclosed the following relevant financial relationships: 

Received research grant from: Otsuka; International Society for Bipolar Disorders; National Institutes of Health 

Received income in an amount equal to or greater than $250 from: Otsuka; Janssen; Lundbeck; Teva; Neurelis 

Received royalties from: Springer Press; Johns Hopkins University Press 

Bipolar disorder  is a multifaceted condition associated with an increased risk for hospitalization and suicide as well as high costs to society and family. 

In this ReCAP, Dr Martha Sajatovic, of the University Hospitals of Cleveland, discusses evidence of the short- and long-term consequences of bipolar disorder, including progressive neurologic impact such as changes in brain structure.  

She discusses two FDA-approved long-acting injectables  for bipolar disorder and considerations for their use, including their potential for first-line maintenance treatment and benefits for medication adherence.  

Finally, she considers challenges in the clinical use of the long-acting injectables, including insufficient caregiver involvement and lack of awareness of the drugs' availability. 

--

Martha Sajatovic, MD, Director, Neurological and Behavioral Outcomes Center, University Hospitals of Cleveland, Cleveland, Ohio 

Martha Sajatovic, MD, has disclosed the following relevant financial relationships: 

Received research grant from: Otsuka; International Society for Bipolar Disorders; National Institutes of Health 

Received income in an amount equal to or greater than $250 from: Otsuka; Janssen; Lundbeck; Teva; Neurelis 

Received royalties from: Springer Press; Johns Hopkins University Press 

Weight loss in otherwise healthy older adults is linked to an increased risk of mortality, even from conditions not typically associated with weight change, with a substantially stronger link in men versus women, suggesting the need for clinicians to be alert to such changes.

“Our study emphasizes the importance of weight loss even in relatively healthy individuals who are free from evident cardiovascular disease [CVD], dementia, physical disability, or life-limiting chronic illness,” first author Monira Hussain, MBBS, MPH, PhD, said in an interview.

“Clinicians should be aware that even minor weight loss of 5% or more in older adults without life-limiting illnesses can increase mortality risk,” Dr. Hussain said. “Regular monitoring of weight changes can help early identification of associated risks.”

The study was published online in JAMA Network Open.

The researchers noted that data on the significance of weight changes among older individuals who are otherwise relatively healthy and not diagnosed with life-limited diseases are limited, with the exception that “it is widely acknowledged that weight loss may precede a diagnosis of cancer.” But the association with the other types of non–cancer-related premature death is notable.

“In our study, weight loss also preceded an increased mortality from CVD and other causes, [such as] deaths from trauma, dementia, Parkinson disease, and other less common causes.”

Therefore, “a likely explanation for these findings is that weight loss can be an early prodromal indicator of the presence of various life-shortening diseases,” Dr. Hussain, of Monash University, Melbourne, and colleagues wrote.

In terms of why weight loss shows such a stronger link to mortality in older men, compared with women, Dr. Hussain speculated that this may be caused by “differences in body composition,” between the two sexes. “Men have a higher proportion of muscle and bone mass, and weight loss [in men] primarily involves loss of these tissues.”
 

10% weight loss quadrupled risk of premature death among men

To investigate this phenomenon, the researchers conducted a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial, which included information on a variety of body size parameters, such as weight and waist circumference, measured annually, from a large population of healthy individuals with no evident CVD, dementia, physical disability, or life-limiting chronic illness.

The 16,523 participants included in the study had a mean age of 75 years and 55.6% were women. During a mean follow-up of 4.4 years, 1,256 deaths occurred in the cohort.

Looking at rates of all-cause mortality, stratified by gender, the results showed that among men who had a 5%-10% decrease in weight over the course of the study, the risk of all-cause mortality was 33% higher than that of men who had a stable weight (less than 5% change; hazard ratio, 1.33).

Among men who had a more than 10% decrease in weight, the mortality risk was as much as 289%, or nearly four times higher compared with those with a stable weight (HR, 3.89).

For women, the mortality risk was also increased, however, to a lesser degree. A 5%-10% loss of body weight was associated with a 26% increased mortality risk (HR, 1.26), and a loss of more than 10% was linked to a 114% increased risk of all-cause mortality (HR, 2.14).

In terms of cancer-specific deaths, the risk was significantly increased only among men who had a greater than 10% weight decrease (HR, 3.49), while the increased risk in women was observed with a 5%-10% decrease in weight (HR, 1.44) as well as a more than 10% decrease (HR, 2.78).

The risk of CVD-specific death was significantly increased with a more than 10% decrease in weight in both sexes, but the risk was again higher among men (HR, 3.14) than women (HR, 1.92), compared with stable weight groups.

And the noncancer, non–CVD-specific mortality risk was nearly five times higher among men who had a more than 10% decrease in weight versus stable weight (HR, 4.98); however, the association was not significant among women (HR, 1.49).

Looking at the effects of change in waist circumference, a decrease of more than 10% was associated with a higher risk in all-cause mortality that was again higher for men (HR, 2.14) versus women (HR, 1.34); however, no link with all-cause mortality was observed with a less than 10% decrease in either sex.

A greater than 10% decrease in waist circumference was also associated with higher risk of cancer death for men and women, and higher noncancer, non-CVD death among men, but not women, while there was no association between waist circumference and CVD mortality in men or women.
 

Association with mortality remained after adjustment for hospitalization

The results persisted after adjustment for age, frailty status, baseline body mass index, country of birth, smoking, hypertension, diabetes, and hospitalization in the previous 24 months.

The adjustment for recent hospitalization was especially important for ruling out weight loss that may have occurred because of hospitalization for acute conditions that could have contributed to mortality, the authors noted.

The authors reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Weight loss in otherwise healthy older adults is linked to an increased risk of mortality, even from conditions not typically associated with weight change, with a substantially stronger link in men versus women, suggesting the need for clinicians to be alert to such changes.

“Our study emphasizes the importance of weight loss even in relatively healthy individuals who are free from evident cardiovascular disease [CVD], dementia, physical disability, or life-limiting chronic illness,” first author Monira Hussain, MBBS, MPH, PhD, said in an interview.

“Clinicians should be aware that even minor weight loss of 5% or more in older adults without life-limiting illnesses can increase mortality risk,” Dr. Hussain said. “Regular monitoring of weight changes can help early identification of associated risks.”

The study was published online in JAMA Network Open.

The researchers noted that data on the significance of weight changes among older individuals who are otherwise relatively healthy and not diagnosed with life-limited diseases are limited, with the exception that “it is widely acknowledged that weight loss may precede a diagnosis of cancer.” But the association with the other types of non–cancer-related premature death is notable.

“In our study, weight loss also preceded an increased mortality from CVD and other causes, [such as] deaths from trauma, dementia, Parkinson disease, and other less common causes.”

Therefore, “a likely explanation for these findings is that weight loss can be an early prodromal indicator of the presence of various life-shortening diseases,” Dr. Hussain, of Monash University, Melbourne, and colleagues wrote.

In terms of why weight loss shows such a stronger link to mortality in older men, compared with women, Dr. Hussain speculated that this may be caused by “differences in body composition,” between the two sexes. “Men have a higher proportion of muscle and bone mass, and weight loss [in men] primarily involves loss of these tissues.”
 

10% weight loss quadrupled risk of premature death among men

To investigate this phenomenon, the researchers conducted a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial, which included information on a variety of body size parameters, such as weight and waist circumference, measured annually, from a large population of healthy individuals with no evident CVD, dementia, physical disability, or life-limiting chronic illness.

The 16,523 participants included in the study had a mean age of 75 years and 55.6% were women. During a mean follow-up of 4.4 years, 1,256 deaths occurred in the cohort.

Looking at rates of all-cause mortality, stratified by gender, the results showed that among men who had a 5%-10% decrease in weight over the course of the study, the risk of all-cause mortality was 33% higher than that of men who had a stable weight (less than 5% change; hazard ratio, 1.33).

Among men who had a more than 10% decrease in weight, the mortality risk was as much as 289%, or nearly four times higher compared with those with a stable weight (HR, 3.89).

For women, the mortality risk was also increased, however, to a lesser degree. A 5%-10% loss of body weight was associated with a 26% increased mortality risk (HR, 1.26), and a loss of more than 10% was linked to a 114% increased risk of all-cause mortality (HR, 2.14).

In terms of cancer-specific deaths, the risk was significantly increased only among men who had a greater than 10% weight decrease (HR, 3.49), while the increased risk in women was observed with a 5%-10% decrease in weight (HR, 1.44) as well as a more than 10% decrease (HR, 2.78).

The risk of CVD-specific death was significantly increased with a more than 10% decrease in weight in both sexes, but the risk was again higher among men (HR, 3.14) than women (HR, 1.92), compared with stable weight groups.

And the noncancer, non–CVD-specific mortality risk was nearly five times higher among men who had a more than 10% decrease in weight versus stable weight (HR, 4.98); however, the association was not significant among women (HR, 1.49).

Looking at the effects of change in waist circumference, a decrease of more than 10% was associated with a higher risk in all-cause mortality that was again higher for men (HR, 2.14) versus women (HR, 1.34); however, no link with all-cause mortality was observed with a less than 10% decrease in either sex.

A greater than 10% decrease in waist circumference was also associated with higher risk of cancer death for men and women, and higher noncancer, non-CVD death among men, but not women, while there was no association between waist circumference and CVD mortality in men or women.
 

Association with mortality remained after adjustment for hospitalization

The results persisted after adjustment for age, frailty status, baseline body mass index, country of birth, smoking, hypertension, diabetes, and hospitalization in the previous 24 months.

The adjustment for recent hospitalization was especially important for ruling out weight loss that may have occurred because of hospitalization for acute conditions that could have contributed to mortality, the authors noted.

The authors reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Weight loss in otherwise healthy older adults is linked to an increased risk of mortality, even from conditions not typically associated with weight change, with a substantially stronger link in men versus women, suggesting the need for clinicians to be alert to such changes.

“Our study emphasizes the importance of weight loss even in relatively healthy individuals who are free from evident cardiovascular disease [CVD], dementia, physical disability, or life-limiting chronic illness,” first author Monira Hussain, MBBS, MPH, PhD, said in an interview.

“Clinicians should be aware that even minor weight loss of 5% or more in older adults without life-limiting illnesses can increase mortality risk,” Dr. Hussain said. “Regular monitoring of weight changes can help early identification of associated risks.”

The study was published online in JAMA Network Open.

The researchers noted that data on the significance of weight changes among older individuals who are otherwise relatively healthy and not diagnosed with life-limited diseases are limited, with the exception that “it is widely acknowledged that weight loss may precede a diagnosis of cancer.” But the association with the other types of non–cancer-related premature death is notable.

“In our study, weight loss also preceded an increased mortality from CVD and other causes, [such as] deaths from trauma, dementia, Parkinson disease, and other less common causes.”

Therefore, “a likely explanation for these findings is that weight loss can be an early prodromal indicator of the presence of various life-shortening diseases,” Dr. Hussain, of Monash University, Melbourne, and colleagues wrote.

In terms of why weight loss shows such a stronger link to mortality in older men, compared with women, Dr. Hussain speculated that this may be caused by “differences in body composition,” between the two sexes. “Men have a higher proportion of muscle and bone mass, and weight loss [in men] primarily involves loss of these tissues.”
 

10% weight loss quadrupled risk of premature death among men

To investigate this phenomenon, the researchers conducted a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial, which included information on a variety of body size parameters, such as weight and waist circumference, measured annually, from a large population of healthy individuals with no evident CVD, dementia, physical disability, or life-limiting chronic illness.

The 16,523 participants included in the study had a mean age of 75 years and 55.6% were women. During a mean follow-up of 4.4 years, 1,256 deaths occurred in the cohort.

Looking at rates of all-cause mortality, stratified by gender, the results showed that among men who had a 5%-10% decrease in weight over the course of the study, the risk of all-cause mortality was 33% higher than that of men who had a stable weight (less than 5% change; hazard ratio, 1.33).

Among men who had a more than 10% decrease in weight, the mortality risk was as much as 289%, or nearly four times higher compared with those with a stable weight (HR, 3.89).

For women, the mortality risk was also increased, however, to a lesser degree. A 5%-10% loss of body weight was associated with a 26% increased mortality risk (HR, 1.26), and a loss of more than 10% was linked to a 114% increased risk of all-cause mortality (HR, 2.14).

In terms of cancer-specific deaths, the risk was significantly increased only among men who had a greater than 10% weight decrease (HR, 3.49), while the increased risk in women was observed with a 5%-10% decrease in weight (HR, 1.44) as well as a more than 10% decrease (HR, 2.78).

The risk of CVD-specific death was significantly increased with a more than 10% decrease in weight in both sexes, but the risk was again higher among men (HR, 3.14) than women (HR, 1.92), compared with stable weight groups.

And the noncancer, non–CVD-specific mortality risk was nearly five times higher among men who had a more than 10% decrease in weight versus stable weight (HR, 4.98); however, the association was not significant among women (HR, 1.49).

Looking at the effects of change in waist circumference, a decrease of more than 10% was associated with a higher risk in all-cause mortality that was again higher for men (HR, 2.14) versus women (HR, 1.34); however, no link with all-cause mortality was observed with a less than 10% decrease in either sex.

A greater than 10% decrease in waist circumference was also associated with higher risk of cancer death for men and women, and higher noncancer, non-CVD death among men, but not women, while there was no association between waist circumference and CVD mortality in men or women.
 

Association with mortality remained after adjustment for hospitalization

The results persisted after adjustment for age, frailty status, baseline body mass index, country of birth, smoking, hypertension, diabetes, and hospitalization in the previous 24 months.

The adjustment for recent hospitalization was especially important for ruling out weight loss that may have occurred because of hospitalization for acute conditions that could have contributed to mortality, the authors noted.

The authors reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The new COVID-19 strain known as “Arcturus” has increased in the United States so much that it has been added to the Centers for Disease and Control’s watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization’s watchlist since the end of March. The CDC’s most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.

“It is causing increasing case counts in certain parts of the world, including India. We’re not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks,” Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

Arcturus has been causing a new symptom in children, Indian medical providers have reported.

“One new feature of cases caused by this variant is that it seems to be causing conjunctivitis, or red and itchy eyes, in young patients,” Dr. Binnicker said. “This is not something that we’ve seen with prior strains of the virus.”

More than 11,000 people in the United States remained hospitalized with COVID at the end of last week, and 1,327 people died of the virus last week, CDC data show. To date, 6.9 million people worldwide have died from COVID, the WHO says. Of those deaths, more than 1.1 million occurred in the U.S.

A version of this article originally appeared on WebMD.com.

The new COVID-19 strain known as “Arcturus” has increased in the United States so much that it has been added to the Centers for Disease and Control’s watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization’s watchlist since the end of March. The CDC’s most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.

“It is causing increasing case counts in certain parts of the world, including India. We’re not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks,” Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

Arcturus has been causing a new symptom in children, Indian medical providers have reported.

“One new feature of cases caused by this variant is that it seems to be causing conjunctivitis, or red and itchy eyes, in young patients,” Dr. Binnicker said. “This is not something that we’ve seen with prior strains of the virus.”

More than 11,000 people in the United States remained hospitalized with COVID at the end of last week, and 1,327 people died of the virus last week, CDC data show. To date, 6.9 million people worldwide have died from COVID, the WHO says. Of those deaths, more than 1.1 million occurred in the U.S.

A version of this article originally appeared on WebMD.com.

The new COVID-19 strain known as “Arcturus” has increased in the United States so much that it has been added to the Centers for Disease and Control’s watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization’s watchlist since the end of March. The CDC’s most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.

“It is causing increasing case counts in certain parts of the world, including India. We’re not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks,” Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

Arcturus has been causing a new symptom in children, Indian medical providers have reported.

“One new feature of cases caused by this variant is that it seems to be causing conjunctivitis, or red and itchy eyes, in young patients,” Dr. Binnicker said. “This is not something that we’ve seen with prior strains of the virus.”

More than 11,000 people in the United States remained hospitalized with COVID at the end of last week, and 1,327 people died of the virus last week, CDC data show. To date, 6.9 million people worldwide have died from COVID, the WHO says. Of those deaths, more than 1.1 million occurred in the U.S.

A version of this article originally appeared on WebMD.com.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.