Venous Thromboembolism Risk in Hematological Malignancies Post-Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: A Meta-Analysis of Phase 2 and Phase 3 Clinical Trials.

Chimeric Antigen Receptor T-cell (CAR-T) therapy uses genetically engineered T-cells with specific binding sites. This therapy allows for tumor specificity and durable treatment responses for patients with hematological malignancies. In this review, we study the risk of venous thromboembolism (VTE) associated with CAR-T therapy. We searched the National Institutes of Health library, Cochrane Library Databases, ClinicalTrials.gov database, and medical literature search engines PubMed and Google Scholar for Phase 2 and Phase 3 drug-efficacy and safety trials to determine the aggregate incidence and risk of VTE treated with CAR-T. Of 1127 search results, nine studies were identified and included in our meta-analysis. Of the 1017 patients who received therapy, 805 patients (79.15%) experienced some degree of CRS, and 122 patients (11.9%) experienced severe CRS (higher than grade 3). Only three out of one thousand and seventeen patients were reported to have experienced venous thromboembolism. Our study did not find a statistically significant association between increased VTE incidence (OR = 0.0005, 95% CI [0.0001, 0.0017]) and CRS/ICANS (p < 0.0001). There was a 0.0050 (95% confidence interval [0.0019, 0.0132]) relative risk for VTE. In our study, we did not find a statistically significantly increased risk of developing VTE despite CRS and underlying malignancy, which have been associated with increased risk of VTE

Venous Thromboembolism in Metastatic Uterine Leiomyosarcoma: A Case Report and Review of the Literature

We report an unusual case of extensive deep vein thrombosis (DVT) and pulmonary embolism (PE) in the setting of metastatic uterine leiomyosarcoma. Recognition of the associated sequelae of this condition may improve short- and long-term outcomes. A 56-year-old black female with a history of uterine leiomyosarcoma diagnosed incidentally after total abdominal hysterectomy for fibroid uterus without initiation of chemoradiation treatment presented to the emergency department complaining of generalized weakness and progressively worsening stridor for 2 weeks. The patient was experiencing shortness of breath, dysphagia, and hoarseness. Physical exam was remarkable for rhonchi but was otherwise normal. Diagnostic imaging via CT of the abdomen, pelvis, and chest revealed DVTs of the left common and external iliac veins, the superior mesenteric artery, multiple pulmonary emboli of the right pulmonary artery, several nodular lesions within the lungs, and scattered peritoneal necrotic lesions, which were suspicious for metastatic disease. Additionally, CT of the neck showed an exophytic mass protruding into the airway from the subglottic region and thyromegaly with bilateral thyroid lobe nodules. The patient was subsequently started on Eliquis and chemotherapy. The rarity of this case is rooted in the extent of the patient's DVTs and PEs secondary to hypercoagulability in metastatic cancer. This presentation should be further evaluated to exclude thrombophilias or underlying malignancies. Drawing from the lessons of this case will help guide future clinical management regarding the care of metastatic uterine leiomyosarcoma

Neurocysticercosis: An Easy to Miss Diagnosis in Non-Endemic Regions

A 29-year-old male presented with swollen gums and stomatitis for the past two months. History revealed that he had moved to the United States from India six years ago and had a first episode of generalized tonic-clonic seizure with confusion and loss of consciousness. Meningioma of the brain was diagnosed, and a Gamma Knife excision of the meningioma was planned. The patient refused to proceed with the surgery and came back to India for a second opinion. Upon repeat MRI scan, the neurosurgeon revised the diagnosis to neurocysticercosis (NCC), and the patient was treated with albendazole, prednisolone, and phenytoin and recovered completely. Hence an unnecessary brain surgery was avoided. The complaint of stomatitis and gingival hypertrophy was due to the side effects of phenytoin. NCC remains a major public health problem in developing countries, and it should be considered as a differential diagnosis in patients from NCC endemic regions

Duet of Death: Biventricular Thrombus in a Methamphetamine User.

We present the case of a 60-year-old male who developed an ischemic stroke due to left ventricular (LV) thrombus emboli as a complication of methamphetamine-induced cardiomyopathy. The patient had a history of methamphetamine abuse, hypertension, and ischemic stroke with no residual deficits presented with new onset slurred speech, left-sided weakness, and numbness for two hours. Computed tomography (CT) of the head showed no acute changes, and a tissue plasminogen activator was given in the emergency department within 30 minutes of arrival. Urine drug screen (UDS) was positive for methamphetamine, and magnetic resonance imaging (MRI) of the brain showed acute cortical infarcts in the right frontal lobe and parietal lobe and chronic infarct in the left occipital lobe. Transthoracic echocardiography showed bilateral ventricular thrombus and severely reduced ejection fraction of 20-25%. The patient had no evidence of thrombophilia and was started on a heparin drip for thrombus and goal-directed medical therapy for heart failure with reduced ejection fraction (HFrEF). Upon discharge, the patient was prescribed the oral anticoagulant rivaroxaban. The LV thrombus emboli were attributed to causing ischemic stroke. This case highlights the potential risk of ischemic stroke due to LV thrombus emboli in patients with methamphetamine-induced cardiomyopathy

A Meta-Analysis to Assess the Efficacy of HER2-Targeted Treatment Regimens in HER2-Positive Metastatic Colorectal Cancer (mCRC).

Recent trials provide evidence that HER2 is a potential new target for patients with colorectal cancer. While HER2-positive tumors do not show a very encouraging response to anti-HER2-positive agents like trastuzumab alone, promising results have been observed when combined with other synergistically acting tyrosine kinase inhibitors (TKIs). Our meta-analysis was conducted following the Cochrane Handbook and written following the PRISMA guidelines. The protocol was registered on PROSPERO with the registration number CRD42022338935. After a comprehensive search for relevant articles, 14 CTs were identified and uploaded to Rayyan, and six trials were ultimately selected for inclusion. The meta-analysis revealed that a median of three prior lines of therapy was used before enrolling in the six trials comprising 238 patients with HER2-positive metastatic colorectal cancer (mCRC). The pooled objective response rate (ORR) and disease control rate (DCR) were 31.33% (95% confidence interval [CI] 24.27-38.39) and 74.37% (95% CI 64.57-84.17), respectively. The pooled weighted progression-free survival (PFS) was 6.2 months. The pooled ORR and DCR meta-analysis indicate a significant response to HER2-targeted therapy in this patient in HER2-positive mCRC. Additionally, a pooled PFS of 6.2 months suggests that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes in this population

Risks of hypertension and thromboembolism in patients receiving bevacizumab with chemotherapy for colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three-drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first-line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life-threatening side effects such as severe hypertension (HTN) (5%-18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%-4.6%), and gastrointestinal perforation (0.3%-2.4%). This meta-analysis aims to evaluate the additive risk of BVZ-induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. METHODS: Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ-chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. RESULTS: The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy-only group. CONCLUSION: BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy-only group. Our findings are significant as they provide vital information in analyzing the risk-benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities

Risks of hypertension and thromboembolism in patients receiving bevacizumab with chemotherapy for colorectal cancer: A systematic review and meta‐analysis

Abstract Background Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three‐drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first‐line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life‐threatening side effects such as severe hypertension (HTN) (5%–18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%–4.6%), and gastrointestinal perforation (0.3%–2.4%). This meta‐analysis aims to evaluate the additive risk of BVZ‐induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. Methods Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ‐chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. Results The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy‐only group. Conclusion BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy‐only group. Our findings are significant as they provide vital information in analyzing the risk–benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities

A Meta-Analysis to Assess the Efficacy of HER2-Targeted Treatment Regimens in HER2-Positive Metastatic Colorectal Cancer (mCRC)

Recent trials provide evidence that HER2 is a potential new target for patients with colorectal cancer. While HER2-positive tumors do not show a very encouraging response to anti-HER2-positive agents like trastuzumab alone, promising results have been observed when combined with other synergistically acting tyrosine kinase inhibitors (TKIs). Our meta-analysis was conducted following the Cochrane Handbook and written following the PRISMA guidelines. The protocol was registered on PROSPERO with the registration number CRD42022338935. After a comprehensive search for relevant articles, 14 CTs were identified and uploaded to Rayyan, and six trials were ultimately selected for inclusion. The meta-analysis revealed that a median of three prior lines of therapy was used before enrolling in the six trials comprising 238 patients with HER2-positive metastatic colorectal cancer (mCRC). The pooled objective response rate (ORR) and disease control rate (DCR) were 31.33% (95% confidence interval [CI] 24.27–38.39) and 74.37% (95% CI 64.57–84.17), respectively. The pooled weighted progression-free survival (PFS) was 6.2 months. The pooled ORR and DCR meta-analysis indicate a significant response to HER2-targeted therapy in this patient in HER2-positive mCRC. Additionally, a pooled PFS of 6.2 months suggests that HER2-targeted treatment regimens are associated with a meaningful improvement in survival outcomes in this population