Úvod: Liečba chronickej lymfocytovej leukémie (CLL) naďalej prechádza veľmi dynamickým vývojom. Chemoimunoterapia, ktorá bola hlavnou kostrou liečby, je do značnej miery nahradená cieľovými molekulami, ktoré sú účinnejšie a bezpečnejšie. Cieľ: Retrospektívna analýza vlastných dát na zhodnotenie výsledkov CLL pacientov liečených inovatívnou nechemoterapeutickou liečbou chemo-free. Materiál a metódy: V období od januára 2016 do septembra 2021 sme do štúdie zahrnuli 83 pacientov s chronickou lymfocytovou leukémiou, ktorí boli liečení na našom pracovisku. Celkovo 63 pacientov dostalo ibrutinib (15,9 % v prvej línii) a 20 pacientov dostalo venetoklax +/– rituximab (85 % v monoterapii a 5 % v prvej línii). Medián veku bol 64 rokov (rozsah 39–81 rokov). Každá skupina mala medián dvoch predchádzajúcich línií liečby (rozsah 1–6). Medián sledovania bol 31 mesiacov pri ibrutinibe a 23 mesiacov pri venetoklaxe. Výsledky: Väčšina pacientov odpovedala na liečbu s celkovou mierou odpovede (overall response rate – ORR) 92 % pri ibrutinibe a 90 % pri venetoklaxe. Miera kompletnej remisie bola vyššia pri venetoklaxe (relatívne riziko – RR = 2,02; 95% CI: 1,16–3,5; p = 0,012). Trojročné prežívanie bez progresie (progression-free survival – PFS) a celkové prežívanie (overall survival – OS) bolo 82 a 83 % pri ibrutinibe, 80 a 80 % pri venetoklaxe. Nežiaduce účinky boli väčšinou mierne alebo stredne závažné. Záver: V našej práci sme konštatovali, že nové molekuly ibrutinib a venetoklax poskytujú porovnateľné výsledky u pacientov s CLL liečených mimo klinického skúšania.

Introduction: Treatment of chronic lymphocytic leukaemia (CLL) continues to develop dramatically. Chemoimmunotherapy that historically represented the golden standard of treatment has been largely replaced by molecular-targeted therapies that are more effective and safer. Objective: A retrospective study to evaluate the efficacy and safety of innovative „chemo-free“ therapy (ibrutinib and venetoclax) in patients with CLL. Material and methods: from January 2016 to September 2021, 83 patients with chronic lymphocytic leukaemia treated in our institute were included in the study. A total of 63 patients received ibrutinib (15.9% in front-line setting) and 20 patients received venetoclax +/– rituximab (85% as monotherapy and 5% in front-line setting). The median age was 64 years (range 39–81 years). Each group had a median of two prior lines of therapy (range 1–6). The median follow-up was 31 months for ibrutinib and 23 months for venetoclax. Results: the majority of patients responded to treatment with an overall response rate (ORR) of 92% for ibrutinib and 90% for venetoclax. The rate of complete remission was higher with venetoclax (relative risk – RR = 2.02, 95% CI: 1.16–3.5; P = 0.012). The 3-year progression-free survival (PFS) and overall survival (OS) were 82% and 83% for ibrutinib, 80% and 80% for venetoclax respectively. The majority of side effects reported were relatively mild to moderate. Conclusion: In our study, we demonstrate that novel agents, ibrutinib and venetoclax provide comparable results in patients with CLL treated outside clinical trials.

• Klíčová slova
• Ibrutinib, venetoklax,
• MeSH
• adenin * analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• chronická lymfatická leukemie * farmakoterapie   imunologie   MeSH
• cílená molekulární terapie MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sulfonamidy * aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

Výdaje zdravotních pojišťoven za zdravotní péči se každoročně pohybují ve výši 250 miliard korun českých. Významnou část tvoří položky za léčivé přípravky, a to více než 50 miliard korun českých. Tyto vysoké náklady jsou důvodem, proč plátci a regulátoři požadují před uhrazením nějaké nové zdravotní intervence důkazy prokazující dostatečnou klinickou účinnost, bezpečnost a nákladovou efektivitu. Data z randomizovaných klinických studií, která jsou standardně k dispozici v okamžiku vstupu nové molekuly na trh, nejsou často dostačující v té míře, aby poskytla požadované informace o tom, že nová terapie přináší požadovaný benefi t jak pro pacienty, tak i pro plátce. Studie přináší pouze parametry spojené s účinností, bezpečností a předpokládanou délkou léčby, které neposkytují plátcům velkou jistotu v odhadech týkajících se hodnoty nové terapie. Sběr dat v reálné klinické praxi může prokázat reálnou klinickou hodnotu nové zdravotní intervence, neboť zahrnuje větší soubory parametrů než v klinických studiích. Takový sběr přináší informace z různých subpopulací pacientů a jen tato data mohou identifi kovat efekt nové terapie za horizont registrační klinické studie. Sběr dat z reálné klinické praxe rovněž umožňuje kombinovat údaje z různých datových zdrojů, což může přinést novou kvalitu. Využitím údajů z reálné klinické praxe můžeme získat informace o epidemiologických trendech, dostupnosti zdravotní péče, obvyklých léčebných postupech, adherenci k léčbě a příležitostech na zlepšení zdravotní péče. Tato data mohou být ve spolupráci s plátci využita k identifi kaci neúčinné terapie nebo naopak k nalezení nových segmentů trhu, kde může být nová terapie uplatněna.

Total healthcare expenditures in the Czech Republic are around 250 billion CZK annualy. Drugs represent roughly 20 percent of these costs or around 50 billion CZK annually. That has led payers (HCIs) and regulators (MoH, SÚKL) to require data that demonstrate the cost-effectiveness of a medicine before agreeing to pay for it. Data from randomized clinical trials which are available at time of entry of new molecules to the market are not suffi cient to provide such an information, it may be diffi cult using conventional trial data alone to demonstrate that new expensive drugs provide real value relative to their cost. Payers concerns are related to the uncertainty in terms of effi cacy, safety and length of therapy. Real-world evidence (RWE) program can help to pharmaceutical companies, physicians, payers and healthcare providers to determine the effectiveness, safety and cost benefit of a medicine using the records of thousands of patients in real clinical practice. It makes use of very large data sets to identify how new drugs perform beyond the scope of clinical trials. RWE also allows providers, payers and pharma companies to integrate data from multiple sources, e.g. data from clinical registries, payers data, epidemiology data etc. Linking data from various databases can bring new insights and quality. Using RWE data we can gain insights into epidemiological trends, equity in terms of access to the therapy, treatment patterns, patient adherence and disease management opportunities. These can be used to find treatment inefficiencies and/or for new market segments identification. Using these data, pharmaceutical companies can work with stakeholders to determine exactly who benefits from new expensive therapies. When the evidence shows that a specific group of patients will have benefits from these medicines, then payers are much more willing to reimburse it.

• MeSH
• kontrola nákladů MeSH
• léčivé přípravky ekonomika   MeSH
• náklady a analýza nákladů ekonomika   MeSH
• náklady na léky * MeSH
• náklady na zdravotní péči MeSH
• sběr dat MeSH
• všeobecné zdravotní pojištění ekonomika   MeSH
• Publikační typ
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

• Klíčová slova
• RWE, BIG DIP, real time insights, business decisions, visual analytics,
• MeSH
• big data MeSH
• data mining MeSH
• elektronické zdravotní záznamy * MeSH
• farmaceutický průmysl MeSH
• informační management * MeSH
• lékařská informatika * MeSH
• lidé MeSH
• manažerské informační systémy MeSH
• metody pro podporu rozhodování MeSH
• sektor zdravotní péče trendy   MeSH
• šíření informací MeSH
• Check Tag
• lidé MeSH

We assessed the outcomes of pomalidomide and dexamethasone treatment in relapsed/refractory multiple myeloma (RRMM) patients with ≥1 prior line of therapy. We analyzed the data of all RRMM patients treated with pomalidomide and dexamethasone at nine Czech centers between 2013 and 2018. The source of the data was the Registry of Monoclonal Gammopathies of the Czech Republic. Primary endpoints included response rates based on International Myeloma Working Group criteria and survival measures, including progression-free survival (PFS) and overall survival (OS). Secondary endpoints were toxicities and previous treatment patterns, including refractory to lenalidomide, and their impact on final outcomes. The overall response rate was 51.8% and the clinical benefit rate (including patients with minimal response) was 67.1%, with 0.6% of complete responses, 8.5% of very good partial responses, and 42.1% of partial responses (PR). Overall, 16.5% of patients had a minimal response, and 32.3% had stable disease /progression. Median PFS was 8.8 months and the median OS was 14.2 months. In patients who achieved ≥PR, the median PFS and OS were significantly longer compared to non-responders (median PFS (12.1 vs. 4.5 months, p≤0.001 respectively), median OS (22.1 vs. 7.7 months, p≤0.001, respectively). The most frequent adverse events (AEs) were neutropenia (29.9%) and anemia (18.9%), non-hematological AEs included infections (14.6%) and fatigue (7.3%). Our analysis confirmed the effectiveness of pomalidomide and dexamethasone in a real-world setting. This therapy achieved reasonable outcomes comparable to the data from clinical trials even though this was an unbiased cohort of patients.

• MeSH
• dexamethason terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• rutinně sbírané zdravotní údaje MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/refractory MM on novel agent-based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients' treatment approaches.

• MeSH
• disparity zdravotní péče MeSH
• interpretace statistických dat * MeSH
• klinické zkoušky jako téma * MeSH
• komorbidita MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   epidemiologie   mortalita   terapie   MeSH
• prognóza MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• biometrie metody   přístrojové vybavení   MeSH
• Evropská unie MeSH
• financování organizované MeSH
• lidé MeSH
• monitorování fyziologických funkcí metody   přístrojové vybavení   využití   MeSH
• obuv normy   škodlivé účinky   MeSH
• počítačové zpracování signálu MeSH
• protézy a implantáty normy   škodlivé účinky   využití   MeSH
• telemetrie metody   přístrojové vybavení   využití   MeSH
• výzkumný projekt trendy   MeSH
• Check Tag
• lidé MeSH

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

• MeSH
• autologní transplantace škodlivé účinky   MeSH
• dospělí MeSH
• lidé MeSH
• monoklonální gamapatie nejasného významu * komplikace   diagnóza   terapie   MeSH
• nemoci ledvin * etiologie   patologie   terapie   MeSH
• paraproteinemie * diagnóza   MeSH
• prekancerózy * MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Provenance is information describing the lineage of an object, such as a dataset or biological material. Since these objects can be passed between organizations, each organization can document only parts of the objects life cycle. As a result, interconnection of distributed provenance parts forms distributed provenance chains. Dependant on the actual provenance content, complete provenance chains can provide traceability and contribute to reproducibility and FAIRness of research objects. In this paper, we define a lightweight provenance model based on W3C PROV that enables generation of distributed provenance chains in complex, multi-organizational environments. The application of the model is demonstrated with a use case spanning several steps of a real-world research pipeline - starting with the acquisition of a specimen, its processing and storage, histological examination, and the generation/collection of associated data (images, annotations, clinical data), ending with training an AI model for the detection of tumor in the images. The proposed model has become an open conceptual foundation of the currently developed ISO 23494 standard on provenance for biotechnology domain.

• Publikační typ
• časopisecké články MeSH

In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.

• MeSH
• kombinované vakcíny MeSH
• lidé MeSH
• meningokokové infekce * epidemiologie   prevence a kontrola   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Anglie MeSH
• Austrálie MeSH
• Nizozemsko MeSH

Hairy cell leukemia (HCL) and HCL-like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real-world setting. We analyzed 225 HCL and 26 HCLv patients with median follow-up of 67.9 months (HCL) and 20.1 months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5 years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, BRAF V600E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front-line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine-based regimen (91.2%). Overall response rate (ORR) was higher in cladribine-treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second-line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first-line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10-year TTNT was estimated at 74.1%. HCLv patients who underwent first-line treatment had a median TTNT of 56 months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5 years. These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed.

• MeSH
• dospělí MeSH
• kladribin terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vlasatobuněčná leukemie * diagnóza   farmakoterapie   patologie   mortalita   terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH