Use of romiplostim for antineoplastic therapy-induced thrombocytopenia in gynecologic and breast cancers.

Objective: Romiplostim is used to treat chemotherapy-induced thrombocytopenia in a variety of tumor types; however, few studies have examined its use in breast and gynecologic cancers. We evaluated platelet response and durability of response to romiplostim in patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia. Methods: We retrospectively identified 33 patients with gynecologic or breast cancer who received romiplostim between 07/1/2021-07/31/2022 at an academic cancer center. Results: Thirty-three patients met inclusion criteria; 26 (79 %) had breast cancer, 4 (12 %) had ovarian cancer, and 3 (9 %) had endometrial cancer. Twenty patients (61 %) experienced treatment delays and 12 (36 %) required dose reductions prior to starting romiplostim for chemotherapy-induced thrombocytopenia, with some patients experiencing both. Eleven patients (33 %) did not undergo a dose reduction or delay prior to initiation of romiplostim. Median platelet count prior to romiplostim therapy was 53 k/mcL (range, 40.5-78.8). Median platelet count within 3 weeks following initiation of romiplostim was 147 k/mcL (range, 31-562). Twenty-one patients (64 %) achieved platelet correction within 3 weeks, of whom 10 (48 %) resumed anticancer therapy and maintained platelet levels above 100 k/mcL at 8 weeks. Twelve patients did not achieve platelet correction within 3 weeks of romiplostim initiation; 4 (33 %) required a treatment change secondary to persistent thrombocytopenia, 3 (25 %) required a treatment dose reduction, 3 (25 %) were deemed too ill to continue therapy, and 2 (17 %) required a treatment delay. Conclusions: Romiplostim facilitated the resumption of anticancer therapy in 64 % of patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia.

Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy: a meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy.

BACKGROUND: Chimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for thrombotic and bleeding outcomes are lacking. OBJECTIVES: We performed a systematic review and meta-analysis in patients who received CAR T-cell therapy for an underlying hematologic malignancy with the objective to: a) assess the thrombosis and bleeding risk associated with CAR T-cell therapy, b) assess the impact of CRS and ICANS on the risks of thrombosis and bleeding, and c) assess the safety of anticoagulant or antiplatelet use in the period following treatment with CAR T-cell therapy. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to February 2022 for studies reporting thrombotic or bleeding outcomes in patients receiving CAR T-cell therapy. Pooled event rates were calculated using a random-effects model. We performed subgroup analyses stratified by follow-up duration, CAR T-cell target antigen, and underlying hematologic malignancy. RESULTS: We included 47 studies with a total of 7040 patients. High heterogeneity between studies precluded reporting of overall pooled rates of thrombotic and bleeding events. In studies with follow-up duration of ≤6 months, the pooled incidence of venous thrombotic events was 2.4% (95% CI, 1.4%-3.4%; I2 = 0%) per patient-month, whereas the rate was 0.1% (95% CI, 0%-0.1%; I2 = 0%) per patient-month for studies with longer follow-up periods (>6 months). The pooled incidences of any bleeding events per patient-month in studies with follow-up duration of ≤6 months and >6 months were 1.9% (95% CI, 0.6%-3.1%; I2 = 78%) and 0.3% (95% CI: 0%-0.8%, I2 = 40%), respectively. Secondary analyses by CAR T-cell target antigen, underlying malignancy, and primary outcome of the studies did not reveal significant differences in the rates of thromboembolism, any bleeding events, or major bleeding events. CONCLUSION: The risk of both thrombosis and bleeding following CAR T-cell therapy appears to be highest in the initial months following infusion.

Comparison of direct oral anticoagulants versus low-molecular-weight heparin in primary and metastatic brain cancers: a meta-analysis and systematic review.

BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known. OBJECTIVES: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs low-molecular-weight heparin (LMWH). METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n = 1638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup. RESULTS: The pooled RR for ICH in patients receiving DOACs vs those receiving LMWH was 0.65 (95% CI, 0.36-1.17; P = .15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = .003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with the type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = .80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants. CONCLUSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

Management of chemotherapy-induced thrombocytopenia: guidance from the ISTH Subcommittee on Hemostasis and Malignancy.

Thrombocytopenia is a common adverse effect of chemotherapy. The development of chemotherapy-induced thrombocytopenia (CIT) is influenced by cancer type and therapy, occurring in approximately one-third of patients with a solid tumor diagnosis and half of all patients with a hematologic malignancy. CIT may complicate the administration of chemotherapy, leading to therapeutic delays or dose reductions. This guidance document, presented by the International Society on Thrombosis and Haemostasis (ISTH) Subcommittee on Hemostasis and Malignancy, provides a comprehensive summary of the evidence and offers direction on the use of thrombopoietin receptor agonists (TPO-RAs) in various settings of CIT, including solid tumors, acute myeloid leukemia, stem cell transplant, and lymphoma. Studies have shown that TPO-RAs can improve platelet counts in CIT, but the clinical benefits of TPO-RA in terms of reducing bleeding, limiting platelet transfusion, avoiding chemotherapy delay, or dose reduction are uncertain. Further research is needed to optimize the selection of appropriate indications and study design to manage thrombocytopenia following chemotherapy.

Venous Thromboembolism in Total Hip and Total Knee Arthroplasty.

Importance: The optimal pharmacologic thromboprophylaxis agent after total hip and total knee arthroplasty is uncertain and consensus is lacking. Quantifying the risk of postoperative venous thromboembolism (VTE) and bleeding and evaluating comparative effectiveness and safety of the thromboprophylaxis strategies can inform care. Objective: To quantify risk factors for postoperative VTE and bleeding and compare patient outcomes among pharmacological thromboprophylaxis agents used after total hip and knee arthroplasty. Design, Setting, and Participants: This retrospective cohort study used data from a large health care claims database. Participants included patients in the United States with hip or knee arthroplasty and continuous insurance enrollment 3 months prior to and following their surgical procedure. Patients were excluded if they received anticoagulation before surgery, received no postsurgical pharmacological thromboprophylaxis, or had multiple postsurgery thromboprophylactic agents. In a propensity-matched analysis, patients receiving a direct oral anticoagulant (DOAC) were matched with those receiving aspirin. Exposures: Aspirin, apixaban, rivaroxaban, enoxaparin, or warfarin. Main Outcomes and Measures: The primary outcome was 30-day cumulative incidence of postdischarge VTE. Other outcomes included postdischarge bleeding. Results: Among 29 264 patients included in the final cohort, 17 040 (58.2%) were female, 27 897 (95.2%) had inpatient admissions with median (IQR) length of stay of 2 (1-2) days, 10 948 (37.4%) underwent total hip arthroplasty, 18 316 (62.6%) underwent total knee arthroplasty; and median (IQR) age was 59 (55-63) years. At 30 days, cumulative incidence of VTE was 1.19% (95% CI, 1.06%-1.32%) and cumulative incidence of bleeding was 3.43% (95% CI, 3.22%-3.64%). In the multivariate analysis, leading risk factors associated with increased VTE risk included prior VTE history (odds ratio [OR], 5.94 [95% CI, 4.29-8.24]), a hereditary hypercoagulable state (OR, 2.64 [95% CI, 1.32-5.28]), knee arthroplasty (OR, 1.65 [95% CI, 1.29-2.10]), and male sex (OR, 1.34 [95% CI, 1.08-1.67]). In a propensity-matched cohort of 7844 DOAC-aspirin pairs, there was no significant difference in the risk of VTE in the first 30 days after the surgical procedure (OR, 1.14 [95% CI, 0.82-1.59]), but postoperative bleeding was more frequent in patients receiving DOACs (OR, 1.36 [95% CI, 1.13-1.62]). Conclusions and Relevance: In this cohort study of patients who underwent total hip or total knee arthroplasty, underlying patient risk factors, but not choice of aspirin or DOAC, were associated with postsurgical VTE. Postoperative bleeding rates were lower in patients prescribed aspirin. These results suggest that thromboprophylaxis strategies should be patient-centric and tailored to individual risk of thrombosis and bleeding.

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer.

Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100 K/µL at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio (SHR) 2.4, P=0.02) and CRNMB (17.9% vs. 9.6%, SHR 2.0, P=0.01). Thrombocytopenia did not impact recurrent VTE (9.8% vs. 7.4%, SHR 1.3, P=0.37) nor overall mortality (21.8% vs. 26.0%, HR 0.9, P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs 0, p.

The unfolded protein response links ER stress to cancer-associated thrombosis.

Thrombosis is a common complication of advanced cancer, yet the cellular mechanisms linking malignancy to thrombosis are poorly understood. The unfolded protein response (UPR) is an ER stress response associated with advanced cancers. A proteomic evaluation of plasma from patients with gastric and non-small cell lung cancer who were monitored prospectively for venous thromboembolism demonstrated increased levels of UPR-related markers in plasma of patients who developed clots compared with those who did not. Release of procoagulant activity into supernatants of gastric, lung, and pancreatic cancer cells was enhanced by UPR induction and blocked by antagonists of the UPR receptors inositol-requiring enzyme 1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK). Release of extracellular vesicles bearing tissue factor (EVTFs) from pancreatic cancer cells was inhibited by siRNA-mediated knockdown of IRE1α/XBP1 or PERK pathways. Induction of UPR did not increase tissue factor (TF) synthesis, but rather stimulated localization of TF to the cell surface. UPR-induced TF delivery to EVTFs was inhibited by ADP-ribosylation factor 1 knockdown or GBF1 antagonism, verifying the role of vesicular trafficking. Our findings show that UPR activation resulted in increased vesicular trafficking leading to release of prothrombotic EVTFs, thus providing a mechanistic link between ER stress and cancer-associated thrombosis.

Application of Machine Learning to the Prediction of Cancer-Associated Venous Thromboembolism.

Venous thromboembolism (VTE) is a common and impactful complication of cancer. Several clinical prediction rules have been devised to estimate the risk of a thrombotic event in this patient population, however they are associated with limitations. We aimed to develop a predictive model of cancer-associated VTE using machine learning as a means to better integrate all available data, improve prediction accuracy and allow applicability regardless of timing for systemic therapy administration. A retrospective cohort was used to fit and validate the models, consisting of adult patients who had next generation sequencing performed on their solid tumor for the years 2014 to 2019. A deep learning survival model limited to demographic, cancer-specific, laboratory and pharmacological predictors was selected based on results from training data for 23,800 individuals and was evaluated on an internal validation set including 5,951 individuals, yielding a time-dependent concordance index of 0.72 (95% CI = 0.70-0.74) for the first 6 months of observation. Adapted models also performed well overall compared to the Khorana Score (KS) in two external cohorts of individuals starting systemic therapy; in an external validation set of 1,250 patients, the C-index was 0.71 (95% CI = 0.65-0.77) for the deep learning model vs 0.66 (95% CI = 0.59-0.72) for the KS and in a smaller external cohort of 358 patients the C-index was 0.59 (95% CI = 0.50-0.69) for the deep learning model vs 0.56 (95% CI = 0.48-0.64) for the KS. The proportions of patients accurately reclassified by the deep learning model were 25% and 26% respectively. In this large cohort of patients with a broad range of solid malignancies and at different phases of systemic therapy, the use of deep learning resulted in improved accuracy for VTE incidence predictions. Additional studies are needed to further assess the validity of this model.

Targeting thiol isomerase activity with zafirlukast to treat ovarian cancer from the bench to clinic.

Thiol isomerases, including PDI, ERp57, ERp5, and ERp72, play important and distinct roles in cancer progression, cancer cell signaling, and metastasis. We recently discovered that zafirlukast, an FDA-approved medication for asthma, is a pan-thiol isomerase inhibitor. Zafirlukast inhibited the growth of multiple cancer cell lines with an IC50 in the low micromolar range, while also inhibiting cellular thiol isomerase activity, EGFR activation, and downstream phosphorylation of Gab1. Zafirlukast also blocked the procoagulant activity of OVCAR8 cells by inhibiting tissue factor-dependent Factor Xa generation. In an ovarian cancer xenograft model, statistically significant differences in tumor size between control vs treated groups were observed by Day 18. Zafirlukast also significantly reduced the number and size of metastatic tumors found within the lungs of the mock-treated controls. When added to a chemotherapeutic regimen, zafirlukast significantly reduced growth, by 38% compared with the mice receiving only the chemotherapeutic treatment, and by 83% over untreated controls. Finally, we conducted a pilot clinical trial in women with tumor marker-only (CA-125) relapsed ovarian cancer, where the rate of rise of CA-125 was significantly reduced following treatment with zafirlukast, while no severe adverse events were reported. Thiol isomerase inhibition with zafirlukast represents a novel, well-tolerated therapeutic in the treatment of ovarian cancer.

Antiplatelet medications and intracranial hemorrhage in patients with primary brain tumors.

BACKGROUND: Spontaneous intracranial hemorrhage (ICH) is a frequent and severe consequence of primary brain tumors. The safety of antiplatelet medications in this patient population is undefined. OBJECTIVE: The primary objective was to determine whether antiplatelet medications are associated with an increased risk of ICH in patients with primary brain tumors. PATIENTS/METHODS: We performed a matched, retrospective cohort study of patients with the diagnosis of primary brain tumor treated at our institution between 2010 and 2021. Radiographic images of all potential ICH events underwent blinded review. The primary end point of the study was the cumulative incidence of ICH at 1 year after tumor diagnosis. RESULTS AND CONCLUSIONS: A total of 387 patients with primary brain tumors were included in the study population (130 exposed to antiplatelet agents, 257 not exposed). The most common malignancy was glioblastoma (n = 256, 66.1%). Among the intervention cohort, 119 patients received aspirin monotherapy. The cumulative incidence of any ICH at 1 year was 11.0% (95% CI, 5.3-16.6) in those receiving antiplatelet medications and 13.0% (95% CI, 8.5-17.6) in those not receiving antiplatelet medications (Gray test, p = 0.6). The cumulative incidence of major ICH was similar between the cohorts (3.3% in antiplatelet cohort vs 2.9% in control cohort, p = 1.0). This study did not identify an increased incidence of ICH in patients with primary brain tumors exposed to antiplatelet medications.

The bridging conundrum: perioperative management of direct oral anticoagulants for venous thromboembolism.

Most patients diagnosed with venous thromboembolism (VTE) are currently treated with direct oral anticoagulants (DOACs). Before an invasive procedure or surgery, clinicians face the challenging decision of how to best manage DOACs. Should the DOAC be held, for how long, and are there instances where bridging with other anticoagulants should be considered? Although clinical trials indicate that most patients taking DOACs for atrial fibrillation do not require bridging anticoagulation, the optimal strategy for patients with a history of VTE is undefined. In this review, we present a case-based discussion for DOAC interruption perioperatively in patients receiving anticoagulation for management of VTE.

The prevalence of thrombocytopenia in patients with acute cancer-associated thrombosis.

Venous thromboembolism (VTE) and thrombocytopenia are frequently encountered complications in patients with cancer. Although there are several studies evaluating the safety and efficacy of anticoagulation regimens in patients with cancer-associated thrombosis (CAT) with thrombocytopenia, there is a paucity of data assessing the scope of the concurrent diagnoses. This study evaluates the prevalence of thrombocytopenia among patients with acute CAT. A retrospective cohort analysis of adult patients with cancer was conducted at Beth Israel Deaconess Medical Center between 2010 and 2021 with CAT (acute VTE within 6 months after new diagnosis of malignancy). VTE included acute deep vein thrombosis, pulmonary embolism, abdominal or intrathoracic venous thrombosis, and cerebral sinus thrombosis. The lowest platelet count within 2 weeks of (before or after) the index VTE event was identified to assess the frequency and grade of concurrent thrombocytopenia. We identified 3635 patients with CAT (80% solid tumors, 18% hematologic malignancies, and 2% multiple concurrent cancer diagnoses). Thrombocytopenia (defined as platelet count <100 000/µL) occurred in 22% (95% CI 21%-24%) of patients with CAT with solid tumors diagnoses and 47% (95% CI 43%-51%) of patients with CAT and hematologic malignancies. Severe thrombocytopenia (platelet count <50 000/µL) occurred in 7% (95% CI 6%-8%) of patients with solid tumors and 30% (95% CI 27%-34%) of patients with hematologic malignancies. Concurrent diagnoses of CAT and thrombocytopenia are very common, especially among patients with hematologic malignancies.

Evidence-Based Minireview: Full dose, modified dose, or no anticoagulation for patients with cancer and acute VTE and thrombocytopenia.

Co-incident venous thromboembolism and thrombocytopenia are frequent in patients with active malignancies. The optimal approach for anticoagulation in patients with cancer and thrombocytopenia is not established. Different strategies are often utilized including dose-reduced anticoagulation dictated by degree of thrombocytopenia or transfusing platelets in order to facilitate therapeutic anticoagulation. This minireview provides an overview of the data and we outline our approach toward anticoagulation in patients with venous thromboembolism and thrombocytopenia in the setting of cancer.

Peri-procedure management of antithrombotic agents and thrombocytopenia for common procedures in oncology: Guidance from the SSC of the ISTH.

Patients with cancer have an increased risk of thrombosis requiring anticoagulants and/or antiplatelet agents, and they can also encounter thrombocytopenia due to cancer itself or cancer therapies. They often undergo many procedures such as tissue or bone marrow biopsies, placement of central access lines, diagnostic or therapeutic draining procedures, lumbar puncture, and more. Management of antithrombotic agents or thrombocytopenia around the time of these procedures is highly variable. In this document, the Hemostasis and Malignancy Subcommittee of the International Society on Thrombosis and Haemostasis aims to provide useful practice guidance in the management of antithrombotic agents and thrombocytopenia around the time of common procedures in patients with cancer.

Challenges in anticoagulation for patients with brain tumors.

Venous thromboembolism (VTE) is a common complication in patients with primary and metastatic brain cancer. Treatment of thrombosis in these patients must be balanced against the risk of intracranial hemorrhage (ICH). A number of cohort studies conducted over the last several years have assessed the risk of ICH in patients with primary or secondary brain tumors in the setting of anticoagulation. Anticoagulation with warfarin or low-molecular weight heparin significantly increases the risk of ICH in the setting of primary brain cancers. In contrast, therapeutic anticoagulation does not appear to alter the risk of ICH among patients with metastatic brain tumors. This review summarizes current data regarding anticoagulant and antiplatelet therapy in patients with brain tumors, including emerging data on direct-acting oral anticoagulants, and other related topics, such as the use of inferior vena cava filters and resumption of anticoagulation following ICH.

The impact of warfarin on overall survival in cancer patients.

Venous thromboembolism (VTE) is a common complication in patients with cancer. Warfarin has largely been replaced by low-molecular-weight heparin (LMWHs) and direct oral anticoagulants (DOACs) as the standard of care in cancer-associated VTE. The survival benefit of these anticoagulants over warfarin in the cancer population was not demonstrated in clinical trials, possibly due to insufficient sample size and limited follow-up duration. There are emerging population-based studies suggesting that warfarin may be associated with improved overall survival in cancers and may have a protective effect against certain types of cancers. Warfarin may exert its anti-neoplastic properties through both coagulation pathway -dependent and -independent mechanisms, the latter of which are mediated by inhibition of the Gas6-AXL signaling pathway. Further research should emphasize on identifying clinical and laboratory predictors of beneficial effects of warfarin. In this review article, we summarize and update the current evidence regarding the potential impact of warfarin on the overall survival of cancer patients and incidence of cancer, as well as review the potential mechanism of such effect and future perspectives.

Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study.

BACKGROUND: Direct oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established. METHODS AND FINDINGS: Utilizing the United States' Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied. CONCLUSIONS: In this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.

Standardization of risk prediction model reporting in cancer-associated thrombosis: Communication from the ISTH SSC subcommittee on hemostasis and malignancy.

Since the development of the Khorana score to predict risk of cancer-associated venous thromboembolism (VTE), many modified and de novo risk prediction models (RPMs) have been proposed. Comparison of the prognostic performance across models requires comprehensive reporting and standardized methods for model development, validation and evaluation. To improve the standardization of RPM reporting, the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) tool was published in 2015. To better understand the quality of reporting and development of RPMs for cancer-associated VTE, we performed a literature search of published RPMs and assessed each model using the TRIPOD checklist. Our results yielded 29 RPMs for which 30 items were evaluated. There was a non-significant (p = 0.15) improvement in reporting of the 30 items in the post-TRIPOD era (81%) versus the pre-TRIPOD era (75%). Of seven items (title, sample size, missing data handling, baseline demographics, methods and results for model performance, and supplemental resources) with the lowest reporting in the pre-TRIPOD era (<70%), there was an average improvement of 22% in the post-TRIPOD era. Only two of the 22 studies published in the post-TRIPOD era acknowledged compliance with TRIPOD. Informed by the results of this assessment, the Scientific and Standardization Committee (SSC) Subcommittee on Hemostasis & Malignancy of the International Society on Thrombosis and Hemostasis (ISTH) advocates for standardization of four key elements of RPMs for cancer-associated VTE: (1) inclusion of the TRIPOD checklist, (2) clear definition of the derivation population, with justification of sample size, (3) clear definition of predictors, and (4) external validation prior to implementation.