Real-world total cost of care by line of therapy in relapsed/refractory diffuse large B-cell lymphoma.

AIMS: There are multiple recently approved treatments and a lack of clear standard-of-care therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While total cost of care (TCC) by the number of lines of therapy (LoTs) has been evaluated, more recent cost estimates using real-world data are needed. This analysis assessed real-world TCC of R/R DLBCL therapies by LoT using the IQVIA PharMetrics Plus database (1 January 2015-31 December 2021), in US patients aged ≥18 years treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or an R-CHOP-like regimen as first-line therapy. METHODS: Treatment costs and resources in the R/R setting were assessed by LoT. A sensitivity analysis identified any potential confounding of the results caused by the impact of the COVID-19 pandemic on healthcare utilization and costs. Overall, 310 patients receiving a second- or later-line treatment were included; baseline characteristics were similar across LoTs. Inpatient costs represented the highest percentage of total costs, followed by outpatient and pharmacy costs. RESULTS: Mean TCC per-patient-per-month generally increased by LoT ($40,604, $48,630, and $59,499 for second-, third- and fourth-line treatments, respectively). Costs were highest for fourth-line treatment for all healthcare resource utilization categories. Sensitivity analysis findings were consistent with the overall analysis, indicating results were not confounded by the COVID-19 pandemic. LIMITATIONS: There was potential misclassification of LoT; claims data were processed through an algorithm, possibly introducing errors. A low number of patients met the inclusion criteria. Patients who switched insurance plans, had insurance terminated, or whose enrollment period met the end of data availability may have had truncated follow-up, potentially resulting in underestimated costs. CONCLUSION: Total healthcare costs increased with each additional LoT in the R/R DLBCL setting. Further improvements of first-line treatments that reduce the need for subsequent LoTs would potentially lessen the economic burden of DLBCL.

Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats.

Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study's findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels.

Pulmonary lesions in early response assessment in pediatric Hodgkin lymphoma: prevalence and possible implications for initial staging.

BACKGROUND: Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification. OBJECTIVE: This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging. MATERIALS AND METHODS: A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes. RESULTS: Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common. CONCLUSION: New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.

Treatment patterns and costs among US patients with diffuse large B-cell lymphoma not treated with 2L stem cell transplantation.

Aim: To assess treatment patterns, healthcare resource utilization (HCRU), and costs for patients with diffuse large B-cell lymphoma (DLBCL) who did not receive stem cell transplantation in second-line. Patients & methods: An administrative MarketScan® database study to assess DLBCL claims from 01/01/2009-30/09/2020. Results: Most patients (n = 750) received rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in first-line (86.8%) and rituximab (39.5%) or bendamustine ± rituximab ± other (16.3%) in second-line. Over half were hospitalized (mean duration: 16.5 (standard deviation [SD]: 25.8) days per patient per year). Mean medical/pharmacy costs were US$141,532 per patient per year (SD: $189,579), driven by DLBCL-related claims. Conclusion: Healthcare resource utilization and costs for DLBCL-related claims were due to hospitalizations and outpatient visits. Novel therapies to reduce clinical and economic burdens are needed.

Adding a Gene Expression Profile Test to Aid Differential Diagnosis and Treatment in Aggressive Large B-Cell Lymphoma: An Early Exploratory Economic Evaluation.

BACKGROUND AND OBJECTIVE: Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies. METHODS: Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted. RESULTS: The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero. CONCLUSIONS: Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests.

Assessment of early anthracycline-induced cardiotoxicity and liver injury with T2 and T2* mapping in rabbit models.

OBJECTIVES: To evaluate the early prevalence of anthracycline-induced cardiotoxicity (AIC) and anthracycline-induced liver injury (AILI) using T2 and T2* mapping and to explore their correlations. MATERIALS AND METHODS: The study included 17 cardiotoxic rabbits that received weekly injections of doxorubicin and magnetic resonance imaging (MRI) every 2 weeks for 10 weeks. Cardiac function and T2 and T2* values were measured on each period. Histopathological examinations for two to five rabbits were performed after each MRI scan. The earliest sensitive time and the threshold of MRI parameters for detecting AIC and AILI based on these MRI parameters were obtained. Moreover, the relationship between myocardial and liver damage was assessed. RESULTS: Early AIC could be detected by T2 mapping as early as the second week and focused on the 7th, 11th, and 12th segments of left ventricle. The cutoff value of 46.64 for the 7th segment had the best diagnostic value, with an area under the curve (of 0.767, sensitivity of 100%, and specificity of 52%. T2* mapping could detect the change in iron content for early AIC at the middle interventricular septum and AILI as early as the sixth week (p = 0.014, p = 0.027). The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver (r = 0.39, p = 0.002). CONCLUSION: T2 and T2* mapping showed value one-stop assessment of AIC and AILI and could obtain the earliest MRI diagnosis point and optimal parameter thresholds for these conditions. CLINICAL RELEVANCE STATEMENT: Anthracycline-induced cardiotoxicity could be detected by T2 mapping as earlier as the second week, mainly focusing on the 7th, 11th, and 12th segments of left ventricle. Combined with T2* mapping, hepatoxicity and supplementary cardiotoxicity were assessed by one-stop scan. KEY POINTS: • MRI screening time of cardiotoxicity was as early as the second week with focusing on T2 values of the 7th, 11th, and 12th segments of left ventricle. • T2* mapping could be used as a complement to T2 mapping to evaluate cardiotoxicity and as an effective index to detect iron change in the early stages of chemotherapy. • The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver, indicating that iron content in the liver and heart increased with an increase in the chemotherapeutic drugs.

Circulating-tumor DNA Assessment in Diffuse Large B-cell Lymphoma to Determine Up-front Stem Cell Transplantation: A Pilot Study.

BACKGROUND/AIM: This study evaluated the possibility of clinical use of circulating-tumor DNA (ctDNA) as a biomarker to determine up-front autologous stem cell transplantation (auto-SCT) for patients with high-risk diffuse large B-cell lymphoma (DLBCL) in practice. PATIENTS AND METHODS: To explore the dynamics of ctDNA in DLBCL, blood samples were collected sequentially before and after treatment from patients with newly diagnosed DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. To conduct ctDNA genotyping and ctDNA monitoring simultaneously, targeted sequencing by cancer personalized profiling using deep sequencing was used. RESULTS: Ten patients between the ages of 50 and 60 years were enrolled. Based on the international prognostic index (IPI), seven patients were classified as high-IPI-risk group, and three patients were classified as low-IPI-risk group. The IPI risk group correlated with total metabolic tumor volume. All patients completed six cycles of R-CHOP chemotherapy, and seven patients achieved complete response. Changes in ctDNA mutation numbers did not correlate with changes in PET scan images and treatment response. In most high-risk patients, new mutations appeared in ctDNA after completion of chemotherapy that conceivably marked resistant clones. Notably, disease relapse did not occur in high-risk patients with poor prognostic mutations who underwent autologous SCT. CONCLUSION: ctDNA monitoring was meaningful in high-risk patients. Moreover, ctDNA and well-known prognostic factors should be considered in the decision making for auto-SCT. If a new genetic mutation in ctDNA with a negative prognosis would emerge during treatment, high-risk patients should consider auto-SCT.

Spindle Monitor: A Tool for Real-Time Assessment and Concurrent Treatment of Postoperative Tumor Prognosis.

Cancer surgery remains a mainstay in clinical treatment. However, the efficacy of subsequent therapies largely depends on the precise evaluation of postoperative prognoses, underscoring the critical need for a comprehensive and accurate assessment of surgical outcomes. Nanoprobes targeting tumors offer a promising solution for visual prognostic assessment. In this study, we developed a "Spindle Monitor" system, designated as APPADs (Au NBPs@PDA-pep-AS1411-Dox), composed of core-shell nanoparticles. The core was made up of gold nanobipyramids (Au NBPs), coated with polydopamine (PDA), and subsequently loaded with peptide chains, AS1411, and doxorubicin (Dox). Upon deployment in the acidic tumor microenvironment (TME), APPADs released substantial amounts of Dox, initiating the apoptotic process. This triggered the activity of caspase-3, which is a crucial executor in the apoptotic pathway. Consequently, DEVD, a specific recognition site for caspase-3, was cleaved, enabling the disconnection of FITC-conjugated peptide chains and the recovery of fluorescence. Through assessing this fluorescence imaging effect, local laser irradiation could be precisely guided to the postoperative site, facilitating a synergistic combination of photothermal therapy and chemotherapy. Specifically, our "Spindle Monitor" APPADs had been validated to achieve accurate fluorescence imaging in vitro and in vivo, which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.

Cost-effectiveness of response-adapted therapy (RAT) for advanced Hodgkin's Lymphoma compared with conventional treatment in India: a Markov-model based analysis.

Cost effectiveness analysis of interim positron emission tomography (PET-2, done after 2 cycles of chemotherapy) based response adaptive therapy (RAT) approaches in advanced Hodgkin lymphoma (aHL) are not available from an Indian perspective. We used a five-year decision analytics model to assess the cost-effectiveness of the two RAT approaches [(escalation (RAT-1) or de-escalation (RAT-2)] compared with standard care (SOC) in aHL (mean age:35 years). Modelling data was derived from secondary sources and sensitivity analyses were performed to assess the robustness of the model. Net monetary benefit (NMB) gained from RAT2 in Indian rupees (INR) (INR 2,26,896) was higher than the RAT1 (INR 1,83,138) when compared with SOC. Proportion achieving the complete response after initial treatment (CR1) was the key determining factor for the RAT1/2 dominance over SOC. Despite higher initial input costs, response-adapted therapy of aHL was cost-effective by minimizing the cost incurred and disutility experienced during relapse and salvage.

Despite higher initial costs, response-adapted therapy based on the interim PET scan after 2 cycles of chemotherapy was more cost-effective when compared to standard therapy with 6 cycles of ABVD in patients with advanced Hodgkin's lymphoma. Among the RAT approaches, de-escalation (RAT-2) had better cost-effectiveness than the escalation approach (RAT-1).

US cost-effectiveness analysis of polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma.

AIMS: We evaluated the pharmacoeconomic value of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) in previously untreated diffuse large B-cell lymphoma (DLBCL) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MATERIALS AND METHODS: A 3-state partitioned survival model was used to estimate life years (LYs), quality-adjusted LYs (QALYs), and cost impacts of Pola-R-CHP versus R-CHOP. Analyses utilized mixture-cure survival modelling, assessed a lifetime horizon, discounted all outcomes at 3% per year, and examined both payer and societal perspectives. Progression-free survival, overall survival (OS), drug utilization, treatment duration, adverse reactions, and subsequent treatment inputs were based on data from the POLARIX study (NCT03274492). Costs included drug acquisition/administration, adverse reaction management, routine care, subsequent treatments, end-of-life care, and work productivity. RESULTS: Incremental cost-effectiveness ratios of Pola-R-CHP versus R-CHOP were $70,719/QALY gained and $88,855/QALY gained from societal and payer perspectives, respectively. The $32,824 higher total cost of Pola-R-CHP versus R-CHOP was largely due to higher drug costs ($122,525 vs $27,694), with cost offsets including subsequent treatment (-$52,765), routine care (-$1,781), end-of-life care (-$383), and work productivity (-$8,418). Pola-R-CHP resulted in an increase of 0.47 LYs and 0.46 QALYs versus R-CHOP. Pola-R-CHP was cost-effective in 60.9% and 58.0% of simulations at a willingness-to-pay threshold of $150,000/QALY gained from societal and payer perspectives, respectively. LIMITATIONS: There was uncertainty around the OS extrapolation in the model, and costs were derived from different sources. Recommended prophylactic medications were not included; prophylactic use of granulocyte colony-stimulating factor for all patients was assumed to be equal across treatment arms in POLARIX. Work productivity loss was estimated from a general population and was not specific to patients with DLBCL. CONCLUSION: Pola-R-CHP was projected to be cost-effective versus R-CHOP in previously untreated DLBCL, suggesting that Pola-R-CHP represents good value relative to R-CHOP in this setting.

Cost-effectiveness of combination therapy of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone for previously untreated diffuse large B-cell lymphoma in Japan.

AIM: The POLARIX trial showed that Pola + R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone) prolongs progression-free survival (PFS) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), the conventional standard of care, with a similar safety profile. However, Pola + R-CHP has not been evaluated from the viewpoint of health economics in Japan. This study evaluates the cost-effectiveness of Pola + R-CHP for previously untreated DLBCL from a Japanese public healthcare payer's perspective. METHODS: A partitioned survival analysis model was constructed to estimate lifetime costs and effectiveness of Pola + R-CHP and R-CHOP in previously untreated DLBCL who had an International Prognostic Index score (IPI) score of ≥2. A parametric survival model was applied to data analyzed in the POLARIX trial to estimate the lifetime overall survival (OS) and PFS for each treatment. The parameters required for the model were based on the results of a literature search and expert opinion. RESULTS: The incremental cost-effectiveness ratio (ICER) of Pola + R-CHP vs. R-CHOP was JPY2,710,238 per quality-adjusted life year (QALY), less than the ICER of JPY7.5 million per QALY that is considered to be cost-effective based on the threshold of the Japanese cost-effectiveness evaluation system. One-way sensitivity analysis showed that the parameters influencing the results of the analysis were median PFS and the total cost per regimen of salvage chemotherapy, patient weight, and patient age. Probabilistic sensitivity analysis showed that the probability of Pola + R-CHP having superior cost-effectiveness was 99.2% when the reference value was JPY7.5 million. The results of scenario analysis suggested that prolongation of PFS was an important factor in the evaluation of cost-effectiveness in previously untreated DLBCL with or without prolongation of OS. CONCLUSIONS: This study suggests that Pola + R-CHP is a cost-effective treatment for previously untreated DLBCL in Japan under the public health insurance system.

[Risk assessment and prophylactic treatment strategies for central nervous system relapse of diffuse large B-cell lymphoma].

Rituximab treatment significantly improved the outcomes of diffuse large B-cell lymphoma (DLBCL). A central nervous system (CNS) relapse remains a serious and fatal event for patients with DLBCL; therefore, the clinical question of the optimal treatment regimen for reducing the risk of CNS relapse remains unknown. The CNS-International Prognostic Index was identified as a predictive model for CNS relapse. No factors can completely predict CNS relapse although several reports regarding high-risk factors for CNS relapse have been reported. In practice, intrathecal methotrexate (MTX) and high-dose MTX therapy have been used for CNS prophylaxis. Unfortunately, evidence of the optimal therapy for CNS prophylaxis in patients with DLBCL remains lacking. This study aimed to review CNS relapse assessment and discuss study results with clinical impacts on CNS prophylaxis treatment strategies in DLBCL.

Doxorubicin-Fe(III)-Gossypol Infinite Coordination Polymer@PDA:CuO2 Composite Nanoparticles for Cost-Effective Programmed Photothermal-Chemodynamic-Coordinated Dual Drug Chemotherapy Trimodal Synergistic Tumor Therapy.

To achieve the maximum therapeutic effects and minimize adverse effects of trimodal synergistic tumor therapies, a cost-effective programmed photothermal (PTT)-chemodynamic (CDT)-coordinated dual drug chemotherapy (CT) trimodal synergistic therapy strategy in chronological order is proposed. According to the status or volumes of the tumors, the intensity and time of each therapeutic modality are optimized, and three modalities are combined programmatically and work in chronological order. The optimal synergistic therapy begins with high-intensity PTT for 10 min to ablate larger tumors, followed by medium-intensity CDT for several hours to eliminate medium-sized tumors, and then low-intensity coordinated dual drugs CT lasts over 48 h to clear smaller residual tumors. Composite nanoparticles, made of Fe-coordinated polydopamine mixed with copper peroxide as the cores and their surface dotted with lots of doxorubicin-Fe(III)-gossypol infinite coordination polymers (ICPs), have been developed to implement the strategy. These composite nanoparticles show excellent synergistic effects with the minimum dose of therapeutic agents and result in nearly 100% tumor inhibition for mice bearing PC-3 tumors and no observed recurrence within 60 days of treatment. The ratios of the different therapeutic agents in the composite nanoparticles can be adjusted to accommodate different types of tumors with this cost-effective programmed trimodal therapy strategy.

Cost-Effectiveness of Pharmacologic Treatment Options for Women With Endocrine-Refractory or Triple-Negative Metastatic Breast Cancer.

PURPOSE: Treatments for endocrine-refractory or triple-negative metastatic breast cancer (mBC) are modestly effective at prolonging life and improving quality of life but can be extremely expensive. Given these tradeoffs in quality of life and cost, the optimal choice of treatment sequencing is unclear. Cost-effectiveness analysis can explicitly quantify such tradeoffs, enabling more informed decision making. Our objective was to estimate the societal cost-effectiveness of different therapeutic alternatives in the first- to third-line sequences of single-agent chemotherapy regimens among patients with endocrine-refractory or triple-negative mBC. METHODS: Using three dynamic microsimulation models of 10,000 patients each, three cohorts were simulated, based upon prior chemotherapy exposure: (1) unexposed to either taxane or anthracycline, (2) taxane- and anthracycline-exposed, and (3) taxane-exposed/anthracycline-naive. We focused on the following single-agent chemotherapy regimens as reasonable and commonly used options in the first three lines of therapy for each cohort, based upon feedback from oncologists treating endocrine-refractory or triple-negative mBC: (1) for taxane- and anthracycline-unexposed patients, paclitaxel, capecitabine (CAPE), or pegylated liposomal doxorubicin; (2) for taxane- and anthracycline-exposed patients, Eribulin, CAPE, or carboplatin; and (3) for taxane-exposed/anthracycline-naive patients, pegylated liposomal doxorubicin, CAPE, or Eribulin. RESULTS: In each cohort, accumulated quality-adjusted life-years were similar between regimens, but total societal costs varied considerably. Sequences beginning first-line treatment with paclitaxel, carboplatin, and CAPE, respectively, for cohorts 1, 2, and 3, had lower costs and similar or slightly better outcomes compared with alternative options. CONCLUSION: In this setting where multiple single-agent chemotherapy options are recommended by clinical guidelines and share similar survival and adverse event trajectories, treatment sequencing approaches that minimize costs early may improve the value of care.

Cost-Effectiveness of PET Directed Versus Combined Modality Therapy for Early-Stage Favorable Hodgkin's Lymphoma.

INTRODUCTION: The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Recent treatment de-escalation trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET) and have suggested a detriment in progression free survival (PFS) for patients who do not receive radiation therapy (RT) but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy versus standard of care CMT. METHODS: This study used a cost-effectiveness Markov model simulating 5 year outcomes for 1 million patients with early-stage HL treated with either PET-directed therapy consisting of 2 cycles of ABVD chemotherapy ± ISRT or CMT consisting of 2 cycles of ABVD + ISRT. Patients progressed to no evidence of disease, progression of disease (PD), or death. Patients with PD underwent salvage therapy with high dose chemotherapy and stem cell transplant (HDC-SCT). The primary outcome measured was the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were performed. RESULTS: We found that PET-directed therapy and CMT strategies were associated with costs of $47,362 and $41,167, respectively. The CMT strategy was equally as effective as the PET-directed therapy strategy with QALYs of 3.4. On 1-way sensitivity analyses, the model was most sensitive to CMT and HDC-SCT costs. Two-way sensitivity analyses showed the model was sensitive to the relative costs of these treatments. CONCLUSION: For patients with early-stage HL, CMT is the cost-effective strategy as compared with PET-directed therapy.

Adding rituximab to chemotherapy for diffuse large B-cell lymphoma patients in Indonesia: a cost utility and budget impact analysis.

BACKGROUND: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used to treat patients with diffuse large B-cell lymphoma (DLBCL) under National Health Insurance (NHI) scheme in Indonesia. This study aims to estimate its cost-effectiveness and budget impact. METHODS: We conducted a cost utility analysis using Markov model over a lifetime horizon, from a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital data. Direct non-medical costs, indirect costs, and utility data were primarily gathered by interviewing the patients. We applied 3% discount rate for both costs and effect. All monetary data are converted into USD (1 USD = IDR 14,000, 2019). Probabilistic sensitivity analysis was performed. In addition, from a payer perspective, budget impact analysis was estimated using price reduction scenarios. RESULTS: The incremental cost-effectiveness ratio (ICER) of R-CHOP was USD 4674/LYG and 9280/QALY. If we refer to the threshold three times the GDP per capita (USD 11,538), R-CHOP could thus be determined as a cost-effective therapy. Its significant health benefit has contributed to the considerable ICER result. Although the R-CHOP has been considered a cost-effective intervention, the financial consequence of R-CHOP if remain in benefit package under National Health Insurance (NHI) system in Indonesia is considerably substantial, approximately USD 35.00 million with 75% price reduction scenario. CONCLUSIONS: As a favorable treatment for DLBCL, R-CHOP ensures value for money in Indonesia. Budget impact analysis provides results which can be used as further consideration for decision-makers in matters related to benefit packages.

Eficacia y seguridad de doxorrubicina liposomal en el tratamiento médico de mama metastásico con progresión de dos o más lineas de tratamiento / Efficacy and safety of liposomal doxorubicin in the medical treatment of metastatic breast with progression of two or more lines of treatment

ANTECEDENTES: Como parte de las funciones de UFETS inciso e: "Evaluar las tecnologías sanitarias ya existentes en la entidad, y proponer estrategias para su uso eficiente y/o reposición", se ha elaborado el presente informe sobre doxorrubicina liposomal en el tratamiento de cáncer de mama metastásico con progresión de dos o más líneas de tratamiento. ESTRATEGIA DE BÚSQUEDA DE INFORMACIÓN: a) Pregunta Clínica: En pacientes con cáncer de mama metastásico que progresaron a 2 o más líneas de tratamiento ¿Cuál es la eficacia y seguridad de doxorrubicina liposomal como monoterapia? b) La estrategia de búsqueda sistemática de información científica para el desarrollo del presente informe se realizó siguiendo las recomendaciones de la Pirámide jerárquica de la evidencia propuesta por Haynes y se consideró los siguientes estudios: Sumarios y guías de práctica clínica. Revisiones sistemáticas y/o meta-análisis. Ensayos Controlados Aleatorizados (ECA). Estudios Observacionales (cohortes, caso y control, descriptivos). INFORMACIÓN QUE SOPORTE LA RELEVANCIA PARA LA SALUD PÚBLICA: El cáncer de mama se constituye por el crecimiento y proliferación celular anormal que se origina en el tejido mamario, a nivel de los conductos o lobulillos, denominándose carcinoma ductal y Iobulillar respectivamente. El cáncer de mama afecta a una de cada 10 mujeres, con una edad promedio al diagnóstico de 62 años. En 2014, en Perú el cáncer de mama constituyó la segunda causa de muerte asociada a cáncer en mujeres. Se registra una tasa de mortalidad de 10.7 por 100 000 mujeres, representando el 18.3% de todas las neoplasias malignas en mujeres según el Registro de Cáncer de Lima Metropolitana. Aunque sólo un 10% de las pacientes se presentan inicialmente con enfermedad metastásica (etapa IV), entre 30 y 80% de los pacientes con enfermedad loco-regional inicial (etapas I-III) recaerán a los 10 años del diagnóstico. La sobrevida global de pacientes con cáncer de mama es de 90% a 5 años; sin embargo, en el subgrupo con cáncer de mama metastásico, la sobrevida a 5 años es de sólo 20%, con una mediana. de 2 a 4 años. En el Perú, el INEN4 registra más de 1400 casos nuevos de cáncer mama anualmente, siendo los registros en el Perú casos nuevos de 7000 al año, por lo que representa una gran carga de pacientes al año que ingresan a la institución. En las últimas décadas, en el manejo de cáncer de mama metastásico se introdujeron nuevos agentes quimioterapéuticos; la innovación ha provocado una modesta mejoría en las tasas de supervivencia, y aunque el cáncer de mama metastásico es incurable, los objetivos del tratamiento son el alivio de los síntomas, extender la supervivencia y mejorar la calidad de vida. El conocimiento de los subtipos de cáncer (tipo luminal, tipo HER2+, o triple negativo) ha permitido un tratamiento más dirigido5 . En estados avanzados del cáncer de mama se ofrece como tratamiento la terapia hormonal, quimioterapia, medicamentos de terapia dirigida, (trastuzumab, pertuzumab), inmunoterapia, entre otros. La doxorrubicina convencional es un agente antineoplásico de antraciclina utiliza para cáncer de mama y cáncer de ovario. La doxorrubicina y otras antraciclinas inducen citotoxicidad a través de varios mecanismos, principalmente con intercalación entre los pares de bases de ADN6 . Esto interfiere con la cadena de elongación mediante la inhibición del ADN polimerasa y puede inhibir la síntesis de proteínas debido a los efectos en la ARN polimerasa. Adicionalmente a ello, producen cardiotoxicidad irreversible, de manera dependiente de la dosis y a través de la generación de radicales libres, el daño de ADN y la muerte celular de los miocardiocitos y las células progenitoras cardiacas. Doxorrubicina liposomal se presenta como una opción menos cardiotóxica e igual de efectiva que la doxorrubicina convencional. El presente informe analizará la eficacia y seguridad de doxorrubicina liposomal como tratamiento de cáncer de mama metastásico con progresión de dos o más líneas de tratamiento. DISCUSIÓN: Tomando los criterios para un marco de valor de la Health Technology Assessment International (2018) para la toma de decisiones y formulación de la recomendación, se describe: La calidad de la evidencia encontrada es baja. La evidencia analizada ha consistido en revisión sistemática con meta análisis, los cuales encabezan la pirámide de calidad de evidencia, así como estudios observacionales, GPC y ETS de agencias reconocidas. La revisión sistemática encontró que el uso de cladribina en LCV tiene buena respuesta completa y parcial en los pacientes, sin embargo, se debe valorar también los eventos adversos. Esta revisión tuvo sesgo de selección, alta heterogenidad, sesgo de publicación por lo que obtuvo muy bajo nivel de evidencia. Los estudios observacionales encontrados tuvieron muy bajo nivel de evidencia, pues se realizaron evaluación del mundo real en un solo sitio por lo que el tamaño de muestra de los estudios es pequeño, además de alta heterogeneidad en dosis y características de los pacientes. Una evaluación económica en la región no se tiene, sin embargo, en Reino Unido se realizó una, en la cual, las estimaciones de costo de los análogos de purina son muy parecidos, y ambos logran tener similar AVAC en la población tratada. En el marco temporal y de probabilidades incluyen recaídas y progresión, sin embargo, se basan en evidencia local de Reino Unido. La magnitud del beneficio al momento es incierta, debido a una falta de comparador. Se tiene una ligera experiencia en el INEN, donde los tres pacientes con LCV que recibieron cladribina han logrado una respuesta parcial al momento. Se tiene aceptación por parte de los médicos tratantes para continuar el uso de cladribina en LCV. Se cuenta con el personal profesional en salud capacitado, y con los insumos para administrarla. Luego de la discusión, el panel concluye que doxorrubicina liposomal es una opción como tratamiento de CMM y se puede usar en dos escenarios: en pacientes que progresaron a dos o más líneas sin exposición previa, y en pacientes con progresión a dos o más líneas mayores a 12 meses de exposición a antraciclinas. CONCLUSIONES: El cáncer de mama metastásico tiene bajo nivel de sobrevida, y es una enfermedad heterogénea en el tratamiento. Doxorubicina aparece como un tratamiento convencional muy usado, pero con alta cardiotoxicidad que puede limitar el tratamiento. Doxorubicina liposomal se muestra como una alternativa para reducir la cardiotoxicidad. Se hizo una búsqueda de evidencia para evaluar el uso de doxorrubicina liposomal posterior a dos líneas de tratamiento en cáncer de mama metastásico. Doxorubicina liposomal fue evaluada en estudios de pacientes que habían recibido antraciclinas previamente y habían progresado, encontrando que la SLP y SG fue similar al uso de doxorubicina convencional, sin embargo, menos eventos cardiotóxicos. En un estudio, de 274 pacientes, el beneficio clínico de doxorubicina liposomal fue del 37,2 % (IC del 95 %, 32,4-42,0). El beneficio clínico se vio mayor en ILA>12 meses (40,7% frente a 29,2 % P = 0,078). Se encontró un resumen de un estudio económico, comparando doxorrubicina liposomal con la convencional encontrando que, doxorrubicina liposomal puede llevar a un ahorro de costos, en un marco temporal de 6 años. Finalmente, luego del análisis y discusión por parte del panel, se decidió por mayoría la aprobación de la tecnología sanitaria doxorubicina liposomal en los siguientes escenarios: en pacientes que progresaron a dos o más líneas sin exposición previa, y en pacientes con progresión a dos o más líneas mayores a 12 meses de exposición a antraciclinas.

The Clinical Desire for Pressurized Intraperitoneal Aerosol Chemotherapy in South Korea: An Electronic Survey-based Study.

BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.

The clinical and economic burden of peripheral T-cell lymphoma: a systematic literature review.

Aim: To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). Methods: A systematic literature review was conducted in November 2020 following best practice methodology. Results: Fifty-five clinical studies were included, mostly investigating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or 'CHOP-like' regimens, with combination regimens showing similar effectiveness to CHOP alone. Aside from the combination of brentuximab vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP), other available treatments showed no statistically significant benefit over CHOP in terms of overall or progression-free survival in overall PTCL patients. The mean monthly cost per patient in the USA ranged from 6328 to US$9356 based on six studies. One economic evaluation demonstrated A+CHP to be a more cost-effective treatment option than CHOP. Conclusion: Further research is needed to understand the humanistic and cost impact of frontline treatment for PTCL and its specific subtypes.

Plain language summary Peripheral T-cell lymphoma (PTCL) is an aggressive cancer that develops from white blood cells called T cells, which are an important part of the immune system. There is limited knowledge on the impact PTCL has on patients and their families. This systematic review of 55 clinical studies was conducted to further understand how safe and effective current treatments are for patients with newly diagnosed PTCL, how these treatments and disease impact their quality of life, and the economic impact of treatment and disease. Chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP]) was the most commonly studied regimen, but had limited effectiveness and a notable side effect profile. A newer treatment option, brentuximab vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP) was the only treatment to show a significant added benefit over CHOP for patients, with side effects that were comparable to those of CHOP. Six studies assessed the economic impact of PTCL, the majority of which were focused on the USA, and found the mean monthly cost per patient to be 6328­US$9356. No studies were identified that assessed the impact of PTCL or its treatment on quality of life. Further research is needed to understand the impact of frontline PTCL treatment on patients and their families.