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Background: Patients with suspected deep vein thrombosis (DVT) are typically referred to the emergency department for immediate evaluation. To enhance efficiency, our hospital implemented a regional, general practitioner (GP)-driven DVT care pathway, deferring diagnostic evaluation to a scheduled outpatient DVT clinic appointment the following day. Patients receive a single dose anticoagulant from their GP to prevent thrombosis progression while awaiting diagnostic workup. This prospective study aimed to evaluate the safety and patient preferences regarding the DVT care pathway and the type of single dose anticoagulant (low-molecular-weight heparin (LMWH) vs. direct oral anticoagulant (DOAC))., Methods: Patients enrolled in the DVT care pathway between June 2021 and July 2023 were eligible. Until July 2022, LMWH was administered, and thereafter, the protocol recommended DOAC as the single dose anticoagulant. Patients completed questionnaires, incorporating patient-reported outcome and experience measures (PROMs/PREMs), during their DVT clinic visit and after five days. The primary endpoint was bleeding events within 72 h of receiving the single dose anticoagulant., Results: Of 460 included patients, 229 received LMWH and 231 received DOAC as the single dose anticoagulant. DVT was confirmed in 24.8 % of patients. No major or clinically relevant non-major bleeding were reported. LMWH was associated with more minor bleedings (22.3 % vs. DOAC 13.4 %), primarily attributed to injection site hematomas. Patients reported high satisfaction with the DVT care pathway (96.5 %) and generally preferred DOAC over LMWH., Conclusion: Deferring diagnostic evaluation for DVT using a single dose of either LMWH or DOAC in a real-world population is deemed safe. Considering practical advantages, patient preferences, and fewer skin hematomas, we favor DOACs as the single dose anticoagulant in this care pathway., Competing Interests: Declaration of competing interest I have read the journal's policy and the authors of this manuscript have the following competing interests: H.C. has received research grants from Bayer and consulting fees from Alveron, Galapagos, and Novostia, and is a stockholder with Coagulation Profile, outside the submitted work. D.J.L.T. has received research grants from Bayer, consulting fees from Amarin and Novartis, and honoraria for lectures from Bayer and Sanofi, and is a board member of the Dutch Society of Hypertension, outside the submitted work. I.H.Y.L., Y.A., J.I.A.W., R.J.C.A.M.G., M.B.I.L., K.K., Jo.P., Ja.P., J.B., K.S.G.J., R.J.W.K., and G.J.M.M. declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent., Methods: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID)., Results: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients., Conclusion: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CAMS serves on advisory boards for Sanofi and Janssen and on speakers' bureaus for Sanofi, Celgene, BMS and Takeda. GJT served as advisor for Novartis. PFY has received payments for lectures from Janssen and Amgen and support for travel expenses from Janssen. RJWK has received support for travel expenses from Novartis and serves on an advisory board of Novartis. PS has received research support from Janssen, Amgen, BMS, Celgene and Karyopharm; and serves on advisory boards for Celgene, Janssen, Amgen, Karyopharm, BMS and Pfizer. NWCJD has received research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, Cellectis and BMS, all paid to their institution; and serves on advisory boards for Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, Bayer, Adaptive, and Servier, all paid to their institution. HMB serves on an advisory board for Pfizer and has received research support from BMS-Celgene, all paid to their institution. DGJC has received payments for lectures for Takeda, and received financial support for travel expenses from Servier, all outside the submitted work. SZ has received research support from Janssen and the Dutch Cancer Society, all paid to their institution; and serves on advisory boards for Janssen, BMS, Oncopeptides, and Sanofi, all paid to their institution. Others: All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Kazimierz Groen: BMS and Beigene: speakers bureau (no personal funding). Febe Smits: No conflicts of interest. Kazem Nasserinejad: No conflicts of interest. Mark‐David Levin: Support for attending meetings and/or travel: Janssen, Takeda. Josien C. Regelink: No conflicts of interest. Gert‐Jan Timmers: Participation on an Advisory Board: Novartis; Travel, Accommodations, Expenses; Novartis, Janssen. Esther G. M. de Waal: No conflicts of interest. Matthijs Westerman: No conflicts of interest. Gerjo A. Velders: No conflicts of interest. Koen de Heer: No conflicts of interest. Rineke B. L. Leys: No conflicts of interest. Roel J. W. van Kampen: No conflicts of interest. Claudia A. M. Stege: Speaker's Bureau: Sanofi, Celgene/Bristol Myers Squibb, Takeda; Consulting or Advisory Role: Sanofi, Janssen. Maarten R. Seefat: No conflicts of interest. Inger S. Nijhof: Payment or honoraria for lectures, presentations, or educational events: Janssen, Celgene/Bristol Myers Squibb, Sanofi. Ellen van der Spek: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Janssen. Saskia K. Klein: No conflicts of interest. Niels W. C. J. van de Donk: Consulting or Advisory Role: Janssen, Celgene, Bristol Myers Squibb, Novartis, Amgen, Servier, Takeda, Bayer, Roche, Pfizer, Abbvie, Adaptive (no personal funding); Research Funding: Janssen, Celgene, Amgen, Novartis, Bristol Myers Squibb, Cellectis. Paula F. Ypma: Payment or honoraria for presentations: Janssen; Support for attending meetings and/or travel: Janssen. Sonja Zweegman: Consulting or Advisory Role: Janssen‐Cilag, Takeda, Celgene/Bristol Myers Squibb, Sanofi, Oncopeptides (no personal funding); Research Funding: Janssen, Takeda.

Background: Patients with suspected deep venous thrombosis (DVT) are typically referred to the emergency department (ED) for immediate evaluation. However, this often contributes to ED overcrowding and necessitates round-the-clock sonographic examinations. Therefore, we implemented a regionwide care pathway for deferring diagnostic workup of suspected DVT until the following day. Patients receive a single anticoagulant dose from their general practitioner (GP) to prevent progression of DVT in the interval between referral and diagnostic evaluation. The next day, patients undergo comprehensive evaluation at our outpatient DVT clinic, including venous ultrasound. This retrospective study aims to provide real-world data on the safety of this care pathway regarding the occurrence of bleeding complications and pulmonary embolism (PE)., Methods: We included all GP-referred patients with suspected DVT in 2018 and 2019. Patients with absolute contraindications to deferred evaluation or anticoagulation were excluded. The primary endpoint was the occurrence of bleeding complications. Secondary endpoints included PE events and all-cause mortality within seven days following DVT evaluation., Results: Among 1,024 included patients, DVT was confirmed in 238 patients (23.2%) and superficial thrombophlebitis in 98 patients (9.6%). No bleeding events were recorded in patients in whom DVT was ruled out. PE was confirmed in eight patients on the same day as DVT evaluation (0.8%, 95%CI 0.4-1.6) and in six patients within seven days following DVT evaluation (0.6%, 0.2-1.3%). No deaths occurred during this timeframe., Conclusion: This real-world study observed a very low incidence of bleeding complications and PE events, indicating that this care pathway of deferred DVT workup is safe and may offer a more streamlined diagnostic approach for patients with suspected DVT., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10)., (© 2024. The Author(s).)

Background: The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients., Methods: In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297., Findings: Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment., Interpretation: Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate-fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate-fit patients., Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited., Competing Interests: Claudia Stege. Speaker's Bureau: Sanofi, Celgene/Bristol Myers Squibb, Takeda. Consulting or Advisory Role: Sanofi, Janssen. Marie-Christiane Vekemans. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, Janssen, Takeda, Bristol Myers Squibb/Celgene. Consulting or Advisory Role: Amgen, Celgene-Bristol Myers Squibb, Janssen, Takeda, Sanofi, Pfizer, GlaxoSmithKline, Menarini. Ka-Lung Wu. Consulting or Advisory Role: Pfizer, Janssen, Bristol Myers Squibb. Niels W. C. J. van de Donk. Consulting or Advisory Role: Janssen, Celgene, Bristol Myers Squibb, Novartis, Amgen, Servier, Takeda, Bayer, Roche, Pfizer, Abbvie, Adaptive. Research Funding: Janssen, Celgene, Amgen, Novartis, Bristol Myers Squibb, Cellectis. Gert Jan Timmers. Participation on an Advisory Board: Novartis. Travel, Accommodations, Expenses: Novartis, Janssen. Ellen van der Spek. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Janssen. Pieter Sonneveld. Participation on a Data Safety Monitoring Board or Advisory Board: Celgene, Janssen, Amgen, Bristol Myers Squibb, Karyopharm Therapeutics, Pfizer. Research Funding: Janssen, Amgen, Bristol Myeres Squibb/Celgene, Karyopharm Therapeutics, Pfizer. Inger S. Nijhof. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Janssen, Celgene/Bristol Myers Squibb, Sanofi. Mark-David Levin. Support for attending meetings and/or travel: Janssen, Takeda. Paula F. Ypma. Payment or honoraria for presentations: Janssen. Support for attending meetings and/or travel: Janssen. Sonja Zweegman. Consulting or Advisory Role: Janssen-Cilag, Takeda, Celgene/Bristol Myers Squibb, Sanofi, Oncopeptides (no personal funding). Research Funding: Janssen, Takeda. No other potential conflicts of interest were reported., (© 2023 The Author(s).)

Purpose: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex)., Methods: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years., Results: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles., Conclusion: Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance., Competing Interests: Ellen van der SpekOther Relationship: Amgen Alain KentosConsulting or Advisory Role: Amgen, Sanofi, Janssen-Cilag Niels W. C. J. van de DonkConsulting or Advisory Role: Janssen, Celgene, Bristol Myers Squibb, Novartis, Amgen, Servier, Takeda, BayerSpeakers' Bureau: Janssen Research & Development, Celgene, Amgen, Bristol Myers SquibbResearch Funding: Janssen, Celgene, Amgen, Novartis, Bristol Myers Squibb, Cellectis Esther G. M. de WaalSpeakers' Bureau: CelgeneTravel, Accommodations, Expenses: Roche Marie-Christiane VekemansConsulting or Advisory Role: Amgen, Celgene, Bristol Myers Squibb, Janssen, TakedaTravel, Accommodations, Expenses: Amgen, Bristol Myers Squibb, Teva, Janssen Gert Jan TimmersConsulting or Advisory Role: Daiichi Sankyo Ned, Janssen-CilagSpeakers' Bureau: Novartis, ServierTravel, Accommodations, Expenses: Gilead Sciences Paul A. F. GeertsHonoraria: SanofiConsulting or Advisory Role: Janssen-Cilag Inger S. NijhofConsulting or Advisory Role: Janssen, Celgene/Bristol Myers Squibb Pieter SonneveldConsulting or Advisory Role: Celgene, Janssen, Amgen, Karyopharm Therapeutics, CARsgen TherapeuticsResearch Funding: Janssen, Amgen, Skyline Diagnostics Mark-David LevinHonoraria: AbbVie, Celgene, Janssen, TakedaTravel, Accommodations, Expenses: Takeda, Janssen Sonja ZweegmanConsulting or Advisory Role: Janssen-Cilag, Takeda, Celgene, Sanofi, OncopeptidesResearch Funding: Janssen-Cilag, Takeda, CelgeneTravel, Accommodations, Expenses: Janssen-Cilag, Takeda, CelgeneNo other potential conflicts of interest were reported.

Purpose: We aimed to evaluate quality of life (QoL) using the European Quality of Life Five-Dimensions questionnaire (EQ-5D-3L) in a real-world cohort of Dutch advanced breast cancer (ABC) patients. Secondary, we reported differences in QoL between subgroups of patients based on age, comorbidity, tumor-, and treatment characteristics, and assessed the association of duration of metastatic disease and time to death with QoL., Methods: ABC patients who attended the outpatient clinic between October 2010 and May 2011 were asked to fill out the EQ-5D-3L questionnaire. Patient-, disease-, and treatment characteristics were obtained from the medical files. Health-utility scores were calculated. Subgroups were described and compared for utility scores by parametric and non-parametric methods., Results: A total of 92 patients were included with a median utility score of 0.691 (Interquartile range [IQR] 0.244). Patients ≥ 65 years had significantly worse median utility scores than younger patients; 0.638 versus 0.743, respectively (p = 0.017). Moreover, scores were significantly worse for patients with versus those without comorbidity (medians 0.620 versus 0.725, p = 0.005). Utility scores did not significantly differ between subgroups of tumor type, type of systemic treatment, number of previous palliative treatment(s), or number or location of metastatic site(s). The remaining survival was correlated with utility scores (correlation coefficient (r) = 0.260, p = 0.0252), especially in the subgroup < 65 years (r = 0.340, p = 0.0169), whereas there was no significant correlation with time since metastatic diagnosis (r = - 0.106, p = 0.3136)., Conclusion: Within this real-world cross-sectional study, QoL was significantly associated with age, comorbidity, and remaining survival duration. The observation of a lower QoL in ABC patients, possibly indicating the last period of life, may assist clinical decision-making on timing of cessation of systemic antitumor therapy.

Background: The prevalence of inflammatory bowel disease (IBD) is increasing and, consequently, more IBD patients will develop cancer with need for cancer-associated chemotherapy. Physicians are therefore confronted with whether they should continue, stop, or restart IBD medication in relation with chemotherapy. The current strategy in our hospital is to discontinue immunomodulating IBD medication, comprising corticosteroids, anti-tumour necrosis factor (anti-TNF), and other immunosuppressives, before starting chemotherapy., Methods: Out of 1826 patients with IBD, we analyzed 41 IBD patients who received chemotherapy between January 2006-2017. The primary endpoint was the effect of chemotherapy on IBD course, assessed by number of exacerbations and use of IBD medication. The paired-samples t-test and Wilcoxon Signed-Rank test were performed., Results: The mean number of IBD exacerbations of 0.3 (0.0-0.6) per 5 years after chemotherapy was lower compared to 1.4 (0.8-1.9) exacerbations per 5 years before chemotherapy exposure (P < 0.01). In terms of IBD medication, there was a decrease in the number of patients using mesalazine (47% vs 71%, P < 0.01) or corticosteroids (9% vs 32%, P = 0.02) in a time span of 5 years after compared to 5 years before chemotherapy. There was also a trend of less use of immunosuppressives (anti-TNF 0% vs 15%, P = 0.25; thiopurines 12% vs 34%, P = 0.13)., Conclusions: Cancer-associated chemotherapy is associated with a more benign course of IBD that may contribute to the decision to discontinue anti-TNF or other immunosuppressives in relation to cancer-associated treatment both before the start of chemotherapy, as well as reinitiating aggressive immunosuppressives for IBD afterwards.

Introduction: The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial., Methods: A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted., Results: In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of €56,213 and €52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of €155,261 per QALY gained. In the trial scenario, the ICER amounted to €278,711 per QALY gained., Conclusion: According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: We assessed the real world costs and cost-effectiveness of the addition of trastuzumab in HER2 positive early breast cancer compared to chemotherapy alone in the Dutch daily practice as opposed to the results based on trial data and based on a subset of patients that were treated according to the guidelines., Patients and Methods: In a cohort study, we included all patients with stage I-III invasive breast cancer treated with curative intent in 5 Dutch hospitals between 2005 and 2007 ( n =2684).We assessed three scenarios: a real-world scenario, a trial scenario and a guideline scenario, with costs and effectiveness based on either the cohort study, the published trials or the guidelines. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves (CEACs) were constructed., Results: Costs were €243,216 and €239,657 for trastuzumab and no trastuzumab for the real world scenario, €224,443 and €218,948 for the guideline scenario and €253,666 and €265,116 for the trial scenario. The QALYs were 0.827, 0.861, 0.993 for the real world, guideline and trial scenario. The corresponding ICERs were €4,304, €6,382 and dominance, respectively. CEACs showed that the probability that trastuzumab is cost-effective is ≥99% in each scenario., Conclusion: Adjuvant trastuzumab in the real world can be considered cost-effective., Competing Interests: CONFLICTS OF INTEREST There is no conflict of interest.