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Chemo-Free Maintenance Strategies May Boost Survival in TNBC
TOPLINE:
METHODOLOGY:
- First-line standard therapy for advanced TNBC generally includes taxane- or platinum-based chemotherapy which poses challenging toxicities. Exploring chemotherapy-free maintenance strategies may provide adequate disease control and improve patient quality of life.
- The researchers evaluated 45 patients, at five sites in the Republic of Korea, the United States, and Singapore, with TNBC who had ongoing stable disease or complete/partial response from first- or second-line platinum-based chemotherapy.
- The patients were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 mg on day 1 every 4 weeks.
- The authors compared PFS with a historical control of continued platinum-based therapy. An improvement to 4 months with maintenance therapy was considered clinically significant.
TAKEAWAY:
- After a follow-up of 9.8 months, patients who received olaparib alone demonstrated median PFS of 4.0 months, and those who received the combination therapy had median PFS of 6.1 months.
- Clinical benefit rates, defined as stable disease for at least 24 weeks or complete/partial response, were reported in 44% of the monotherapy group and 36% of the combination therapy group.
- Sustained clinical benefit was evident irrespective of germline BRCA mutation or programmed death-ligand 1 status, although it tended to be associated with complete or partial response to prior platinum.
- Grade 3-4 adverse events were reported in nine patients (39%) in the olaparib arm and eight patients (36%) in the combination arm. No treatment-related deaths or new safety signals were observed.
IN PRACTICE:
“Maintenance regimens are rarely used in [triple-negative breast cancer] but offer the possibility of more tolerable long-term treatment avoiding some of the chemotherapy-related side effects of more aggressive regimens, as is standard in the first-line treatment of HER2-positive advanced breast cancer,” the researchers concluded.
SOURCE:
This study, led by Tira J. Tan from Duke-NUS Medical School, Singapore, was published online on January 18, 2024, in Clinical Cancer Research.
LIMITATIONS:
The main limitations were the small sample size and lack of a standard control arm. Most patients (76%) were Asian, limiting generalizability. The trial was not designed to compare olaparib monotherapy and olaparib plus durvalumab regimens.
DISCLOSURES:
AstraZeneca Pharmaceuticals LP supported this study. Several authors reported financial support from various sources.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- First-line standard therapy for advanced TNBC generally includes taxane- or platinum-based chemotherapy which poses challenging toxicities. Exploring chemotherapy-free maintenance strategies may provide adequate disease control and improve patient quality of life.
- The researchers evaluated 45 patients, at five sites in the Republic of Korea, the United States, and Singapore, with TNBC who had ongoing stable disease or complete/partial response from first- or second-line platinum-based chemotherapy.
- The patients were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 mg on day 1 every 4 weeks.
- The authors compared PFS with a historical control of continued platinum-based therapy. An improvement to 4 months with maintenance therapy was considered clinically significant.
TAKEAWAY:
- After a follow-up of 9.8 months, patients who received olaparib alone demonstrated median PFS of 4.0 months, and those who received the combination therapy had median PFS of 6.1 months.
- Clinical benefit rates, defined as stable disease for at least 24 weeks or complete/partial response, were reported in 44% of the monotherapy group and 36% of the combination therapy group.
- Sustained clinical benefit was evident irrespective of germline BRCA mutation or programmed death-ligand 1 status, although it tended to be associated with complete or partial response to prior platinum.
- Grade 3-4 adverse events were reported in nine patients (39%) in the olaparib arm and eight patients (36%) in the combination arm. No treatment-related deaths or new safety signals were observed.
IN PRACTICE:
“Maintenance regimens are rarely used in [triple-negative breast cancer] but offer the possibility of more tolerable long-term treatment avoiding some of the chemotherapy-related side effects of more aggressive regimens, as is standard in the first-line treatment of HER2-positive advanced breast cancer,” the researchers concluded.
SOURCE:
This study, led by Tira J. Tan from Duke-NUS Medical School, Singapore, was published online on January 18, 2024, in Clinical Cancer Research.
LIMITATIONS:
The main limitations were the small sample size and lack of a standard control arm. Most patients (76%) were Asian, limiting generalizability. The trial was not designed to compare olaparib monotherapy and olaparib plus durvalumab regimens.
DISCLOSURES:
AstraZeneca Pharmaceuticals LP supported this study. Several authors reported financial support from various sources.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- First-line standard therapy for advanced TNBC generally includes taxane- or platinum-based chemotherapy which poses challenging toxicities. Exploring chemotherapy-free maintenance strategies may provide adequate disease control and improve patient quality of life.
- The researchers evaluated 45 patients, at five sites in the Republic of Korea, the United States, and Singapore, with TNBC who had ongoing stable disease or complete/partial response from first- or second-line platinum-based chemotherapy.
- The patients were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 mg on day 1 every 4 weeks.
- The authors compared PFS with a historical control of continued platinum-based therapy. An improvement to 4 months with maintenance therapy was considered clinically significant.
TAKEAWAY:
- After a follow-up of 9.8 months, patients who received olaparib alone demonstrated median PFS of 4.0 months, and those who received the combination therapy had median PFS of 6.1 months.
- Clinical benefit rates, defined as stable disease for at least 24 weeks or complete/partial response, were reported in 44% of the monotherapy group and 36% of the combination therapy group.
- Sustained clinical benefit was evident irrespective of germline BRCA mutation or programmed death-ligand 1 status, although it tended to be associated with complete or partial response to prior platinum.
- Grade 3-4 adverse events were reported in nine patients (39%) in the olaparib arm and eight patients (36%) in the combination arm. No treatment-related deaths or new safety signals were observed.
IN PRACTICE:
“Maintenance regimens are rarely used in [triple-negative breast cancer] but offer the possibility of more tolerable long-term treatment avoiding some of the chemotherapy-related side effects of more aggressive regimens, as is standard in the first-line treatment of HER2-positive advanced breast cancer,” the researchers concluded.
SOURCE:
This study, led by Tira J. Tan from Duke-NUS Medical School, Singapore, was published online on January 18, 2024, in Clinical Cancer Research.
LIMITATIONS:
The main limitations were the small sample size and lack of a standard control arm. Most patients (76%) were Asian, limiting generalizability. The trial was not designed to compare olaparib monotherapy and olaparib plus durvalumab regimens.
DISCLOSURES:
AstraZeneca Pharmaceuticals LP supported this study. Several authors reported financial support from various sources.
A version of this article appeared on Medscape.com.
Two-Step Strategy Improves Early-Stage Ovarian Cancer Detection
TOPLINE:
a new analysis with a 21-year follow-up found.
METHODOLOGY:
- Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
- In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
- Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
- Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.
TAKEAWAY:
- Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
- Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
- Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
- The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).
IN PRACTICE:
“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.
LIMITATIONS:
This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.
SOURCE:
This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.
DISCLOSURES:
This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.
A version of this article appeared on Medscape.com.
TOPLINE:
a new analysis with a 21-year follow-up found.
METHODOLOGY:
- Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
- In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
- Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
- Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.
TAKEAWAY:
- Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
- Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
- Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
- The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).
IN PRACTICE:
“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.
LIMITATIONS:
This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.
SOURCE:
This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.
DISCLOSURES:
This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.
A version of this article appeared on Medscape.com.
TOPLINE:
a new analysis with a 21-year follow-up found.
METHODOLOGY:
- Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
- In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
- Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
- Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.
TAKEAWAY:
- Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
- Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
- Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
- The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).
IN PRACTICE:
“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.
LIMITATIONS:
This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.
SOURCE:
This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.
DISCLOSURES:
This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.
A version of this article appeared on Medscape.com.
Testosterone Replacement Therapy and Prostate Cancer Risk
TOPLINE:
Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.
METHODOLOGY:
- Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
- The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
- The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
- Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.
TAKEAWAY:
- The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
- The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
- The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
- Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.
IN PRACTICE:
In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”
SOURCE:
This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.
LIMITATIONS:
These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.
DISCLOSURES:
This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.
METHODOLOGY:
- Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
- The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
- The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
- Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.
TAKEAWAY:
- The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
- The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
- The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
- Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.
IN PRACTICE:
In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”
SOURCE:
This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.
LIMITATIONS:
These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.
DISCLOSURES:
This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.
METHODOLOGY:
- Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
- The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
- The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
- Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.
TAKEAWAY:
- The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
- The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
- The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
- Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.
IN PRACTICE:
In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”
SOURCE:
This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.
LIMITATIONS:
These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.
DISCLOSURES:
This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
Unexplained collapse unveils rare blood disorder
This case report was published in the New England Journal of Medicine.
Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.
The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.
During the examination, her vital signs were within normal ranges.
The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.
Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.
In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).
Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.
After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.
While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.
A version of this article first appeared on Medscape.com.
This case report was published in the New England Journal of Medicine.
Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.
The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.
During the examination, her vital signs were within normal ranges.
The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.
Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.
In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).
Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.
After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.
While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.
A version of this article first appeared on Medscape.com.
This case report was published in the New England Journal of Medicine.
Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.
The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.
During the examination, her vital signs were within normal ranges.
The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.
Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.
In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).
Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.
After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.
While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Early cryoprecipitate fails to improve trauma hemorrhage outcomes
TOPLINE:
(MHP).
METHODOLOGY:
- CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
- A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
- A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
- The primary outcome was all-cause mortality at 28 days.
TAKEAWAY:
- Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
- In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
- Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.
IN PRACTICE:
According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.
SOURCE:
The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).
LIMITATIONS:
There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.
DISCLOSURES:
The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.
A version of this article first appeared on Medscape.com.
TOPLINE:
(MHP).
METHODOLOGY:
- CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
- A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
- A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
- The primary outcome was all-cause mortality at 28 days.
TAKEAWAY:
- Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
- In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
- Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.
IN PRACTICE:
According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.
SOURCE:
The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).
LIMITATIONS:
There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.
DISCLOSURES:
The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.
A version of this article first appeared on Medscape.com.
TOPLINE:
(MHP).
METHODOLOGY:
- CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
- A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
- A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
- The primary outcome was all-cause mortality at 28 days.
TAKEAWAY:
- Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
- In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
- Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.
IN PRACTICE:
According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.
SOURCE:
The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).
LIMITATIONS:
There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.
DISCLOSURES:
The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.
A version of this article first appeared on Medscape.com.