Smoldering multiple myeloma (SMM) is an asymptomatic precursor to active multiple myeloma (MM). The aim of this study was to report clinical characteristics and outcomes of patients with SMM stratified based on their risk of progression to MM using the Mayo 20/2/20 criteria. Data were leveraged from the Czech Myeloma Group Registry of Monoclonal Gammopathies (RMG). Key outcomes included progression-free survival from SMM diagnosis to active MM diagnosis or death (PFS), progression-free survival from SMM diagnosis to progression on first line (1 L) MM treatment or death (PFS2), and overall survival (OS). Of 498 patients, 174 (34.9%) were classified as high risk and 324 (65.1%) as non-high risk. Median follow-up was approximately 65 months. During follow-up, more patients in the high-risk vs non-high-risk group received 1 L MM treatment (76.4% vs 46.6%, p < 0.001). PFS, PFS2, and OS were significantly shorter in high-risk vs non-high-risk patients (13.2 vs 56.6 months, p < 0.001; 49.9 vs 84.9 months, p < 0.001; 93.2 vs 131.1 months, p = 0.012, respectively). The results of this study add to the growing body of evidence that patients with high-risk vs non-high-risk SMM have significantly worse outcomes, including OS.

• MeSH
• doba přežití bez progrese choroby MeSH
• doutnající mnohočetný myelom * diagnóza   epidemiologie   terapie   MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   epidemiologie   terapie   MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Lenalidomide (LEN) is an immunomodulator with clinical activity against myeloma cells. Based on the pivotal phase 3 trials MM-009 and MM010, the combination of lenalidomide and dexamethasone(DEX) was approved for patients with multiple myeloma who received at least one prior therapy. Here, we evaluated LEN/DEX therapy in unselected population and subsequently in selected sub-groups of patients with relapsed/refractory multiple myeloma followed in the Registry of Monoclonal Gammopathies of the Czech Myeloma Group. Altogether 858 patients were treated with LEN/DEX in the Czech Republic and Slovakia until end of 2017. The analyzed sub-groups were defined as patients with high risk cytogenetic aberrations and patients with relapsed and refractory MM. The overall response rate (ORR; partial remission or better response, PR) in the whole group of patients was 46.3% for all lines of therapy, 26.4% for high-risk group and 32.1% for relapsed and refractory group. Medians of overall survival (OS) in the same cohorts were as follows: 25.6, 15.7 and 18.5 months, progression free survival (PFS) was: 11.2, 6.4 and 9.0 months respectively. The most common adverse events were hematologic and infectious. In conclusion we found that our results correlated with those found in other studies in terms of response rates, survival measures, and also of treatment toxicity.

• MeSH
• analýza přežití MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• dexamethason * škodlivé účinky   terapeutické užití   MeSH
• lenalidomid * škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• registrace * statistika a číselné údaje   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

INTRODUCTION: Real-world data on patient outcomes and treatment patterns in multiple myeloma (MM) are limited. MATERIALS AND METHODS: The present noninterventional, observational, retrospective analysis of prospectively collected Czech patient medical record data from the Registry of Monoclonal Gammopathies estimated real-world outcomes in adults with a diagnosis of symptomatic MM made between May 2007 and June 2014. RESULTS: In total, 2446 patients had initiated first-line treatment. The median overall survival since the diagnosis (primary endpoint) was 50.3 months (95% confidence interval, 46.1-54.5 months) and decreased with each successive treatment line. A similar trend was observed for progression-free survival and the depth of response. In line with European guidelines and clinical practice, bortezomib-, thalidomide-, and lenalidomide-based regimens were most commonly used across all treatment lines (42.3%, 28.9%, and 18.4%, respectively). In the first line, bortezomib and thalidomide were used most often, with lenalidomide the most commonly used agent in the relapse setting (second to fourth lines). Exploratory analyses revealed that younger age (≤ 65 years), lower international staging system stage, and previous stem cell transplantation were associated with significant improvements in overall and progression-free survival, especially in the early treatment lines. CONCLUSION: The present study is the first analysis of Czech data from the Registry of Monoclonal Gammopathies, and it provides important insights into the real-world management of MM for physicians and healthcare providers.

• MeSH
• analýza přežití MeSH
• bortezomib terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• lenalidomid terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom mortalita   patologie   terapie   MeSH
• následné studie MeSH
• prospektivní studie MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• registrace statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• thalidomid terapeutické užití   MeSH
• transplantace kmenových buněk * MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVES: We conducted an adjusted comparison of progression-free survival (PFS) and overall survival (OS) for daratumumab monotherapy versus standard of care, as observed in a real-world historical cohort of heavily pretreated multiple myeloma patients from Czech Republic. METHODS: Using longitudinal chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, patient-level data from the RMG was pooled with pivotal daratumumab monotherapy studies (GEN501 and SIRIUS; 16 mg/kg). RESULTS: From the RMG database, we identified 972 treatment lines in 463 patients previously treated with both a proteasome inhibitor and an immunomodulatory drug. Treatment initiation dates for RMG patients were between March 2006 and March 2015. The most frequently used treatment regimens were lenalidomide-based regimens (33.4%), chemotherapy (18.1%), bortezomib-based regimens (13.6%), thalidomide-based regimens (8.0%), and bortezomib plus thalidomide (5.3%). Few patients were treated with carfilzomib-based regimens (2.5%) and pomalidomide-based regimens (2.4%). Median observed PFS for daratumumab and the RMG cohort was 4.0 and 5.8 months (unadjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.94-1.39), respectively, and unadjusted median OS was 20.1 and 11.9 months (unadjusted HR, 0.61; 95% CI, 0.48-0.78), respectively. Statistical adjustments for differences in baseline characteristics were made using patient-level data. The adjusted HRs (95% CI) for PFS and OS for daratumumab versus the RMG cohort were 0.79 (0.56-1.12; p = .192) and 0.33 (0.21-0.52; p < .001), respectively. CONCLUSIONS: Adjusted comparisons between trial data and historical cohorts can provide useful insights to clinicians and reimbursement decision makers on relative treatment efficacies in the absence of head-to-head comparison studies for daratumumab monotherapy.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• kohortové studie MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

Východiska: Monoklonální gamapatie nejasného významu (monoclonal gammopathy of undetermined significance – MGUS) a doutnající mnohočetný myelom (smouldering multiple myeloma – SMM) jsou prekancerózními stadii mnohočetného myelomu (MM). MM je malignita plazmatických buněk s mediánem přežití od 5 do 7 let. MM tvoří zhruba 10 % diagnóz v oblasti hematoonkologie. Pacienti a metody: Na datech z 19 českých center zadaných v Registru monoklonálních gamapatií (Registry of Monoclonal Gammopathies – RMG) byla provedena popisná analýza. Výsledky: Za posledních 10 let sběru dat, spolu s retrospektivně zadanými daty pacientů diagnostikovaných před založením registru, registr disponuje daty o 7 467 pacientech se asymptomatickou nebo symptomatickou formou MM. Validační kritéria pro analýzu splňovalo 2 506 pacientů s MGUS, 400 pacientů s SMM a 4 378 pacientů s MM. Medián délky sledování pacientů byl 4,3 roku u MGUS a 2,4 roku u SMM. Celkové roční riziko progrese z MGUS do maligního onemocnění bylo 1,7 %. Riziko progrese z SMM do MM bylo nejvyšší první roky po diagnóze; za celou dobu sledování bylo riziko progrese 16,6 % každý rok. Medián délky sledování od diagnózy MM byl 2,8 roku. Medián celkového přežití (overall survival – OS) od diagnózy byl 5,7 roku. Medián OS od zahájení léčby/doby bez progrese klesl z 60,5/21,0 měsíce u 1. linie léčby na 34,3/12,4 měsíce u 2. linie, 22,6/8,9 měsíce u 3. linie a 13,8/5,8 měsíce u 4. nebo vyšší linie léčby. Díky dostupnosti nových léků pro léčbu MM v České republice došlo v posledním desetiletí k dramatickým změnám v léčebných postupech. Závěr: RMG je registr určený pro sběr klinických dat týkajících se diagnózy, léčby, jejích výsledků a přežití pacientů s monoklonálními gamapatiemi. RMG je cenným zdrojem dat z reálné klinické praxe.

Background: Monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) are premalignant stages of multiple myeloma (MM). MM is a malignancy of plasma cells, which is associated with a median overall survival of 5 to 7 years. MM accounts for approximately 10% of hematological malignancies. Patients and Methods: Descriptive analysis of data from 19 Czech centres collected in the Registry of Monoclonal Gammopathies (RMG) was performed. Results: Over the last 10 years of prospective collection of data, together with retrospectively recorded data on patients diagnosed before the registry establishment, data on 7,467 patients with either asymptomatic or symptomatic form of MM have been gathered. Validation criteria for the analysis were met by 2,506 MGUS patients, 400 SMM patients and 4,738 MM patients. The median duration of follow-up was 4.3 years in MGUS patients and 2.4 years in SMM patients. The overall risk of progression from MGUS to malignancy was 1.7% per year. The risk of progression from SMM to MM was highest in the 1st years after diagnosis: overall, this risk was 16.6% per year. The median duration of follow-up was 2.8 years in MM patients. The median overall survival from the diagnosis was 5.7 years. The median OS from treatment initiation/progression-free survival decreased from 60.5/21.0 months in the 1st line therapy to 34.3/12.4 months in the 2nd line therapy, 22.6/8.9 months in the 3rd line therapy and 13.8/5.8 months in the 4th or higher line therapies. Thanks to the availability of novel drugs for MM treatment in the Czech Republic, treatment strategies have changed dramatically over the last decade. Conclusion: RMG is a registry designated for the collection of data on diagnosis, treatment, treatment results and survival of patients with monoclonal gammopathies in the long-term follow-up. RMG is a valuable source of data from real clinical practice.

• MeSH
• adresáře jako téma MeSH
• interpretace statistických dat MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   terapie   MeSH
• monoklonální gamapatie nejasného významu * diagnóza   MeSH
• přežití MeSH
• progrese nemoci MeSH
• sběr dat MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

Monoclonal gammopathy of undetermined significance is a pre-malignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little is known about the molecular mechanism of malignant transformation. We performed whole exome sequencing together with comparative genomic hybridization plus single nucleotide polymorphism array analysis in 33 flow-cytometry-separated abnormal plasma cell samples from patients with monoclonal gammopathy of undetermined significance to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in monoclonal gammopathy of undetermined significance than in myeloma (P<10-4) and we identified six genes that were significantly mutated in myeloma (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) within the monoclonal gammopathy of undetermined significance dataset. We also found a positive correlation with increasing chromosome changes and somatic gene mutations. IGH translocations, comprising t(4;14), t(11;14), t(14;16) and t(14;20), were present in 27.3% of cases and in a similar frequency to myeloma, consistent with the primary lesion hypothesis. MYC translocations and TP53 deletions or mutations were not detected in samples from patients with monoclonal gammopathy of undetermined significance, indicating that they may be drivers of progression to myeloma. Data from this study show that monoclonal gammopathy of undetermined significance is genetically similar to myeloma, however overall genetic abnormalities are present at significantly lower levels in monoclonal gammopathy of undetermined significant than in myeloma.

• MeSH
• lidé MeSH
• lidské chromozomy genetika   MeSH
• mnohočetný myelom genetika   patologie   MeSH
• monoklonální gamapatie nejasného významu genetika   patologie   MeSH
• nádorové proteiny genetika   MeSH
• průtoková cytometrie MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH