Diffuse large B-cell lymphoma (DLBCL) represents a curable disease with a 60-70% chance of cure with current R-CHOP chemoimmunotherapy. However, 30-40% of patients are refractory or relapsing. Many attempts failed to improve the outcome of DLBCL patients, including the intensification of R-CHOP regimen, consolidation, or maintenance therapy since the introduction of R-CHOP in 2000. Better understanding of both molecular biology of lymphoma cells and the tumor microenvironment raised the hope for future improvement of DLBCL patients' survival. Novel molecular findings have initiated clinical trials exploring targeted therapy based on driver genetic alterations with an intent to improve survival of high-risk subsets of patients. But the preliminary results remain ambiguous. The approach "agnostic" to specific molecular alterations of lymphoma cell includes antibody-drug conjugates (especially polatuzumab vedotin), immunotherapy comprising different antibodies with immunomodulatory effect (tafasitamab, lenalidomide), and T-cell engaging therapy (bispecific antibodies, early use of CAR T-cell). This approach could increase the cure rates and change the current therapeutic paradigm. However, better prognostic stratification, smarter designs of clinical trials, modification of endpoints including the use of ctDNA are needed. This review covers the complexity of DLBCL management.

• Klíčová slova
• R-CHOP, agnostic therapy, diffuse large B-cell lymphoma, first-line therapy, polatuzumab vedotin, tailored therapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. CONCLUSIONS: The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

• MeSH
• analýza přežití MeSH
• biologické markery analýza   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• difúzní velkobuněčný B-lymfom diagnóza   farmakoterapie   mortalita   patologie   MeSH
• doxorubicin aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocyty patologie   MeSH
• monocyty patologie   MeSH
• myší monoklonální protilátky aplikace a dávkování   MeSH
• počet leukocytů MeSH
• prednison aplikace a dávkování   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• rituximab MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• vinkristin aplikace a dávkování   MeSH
• výzkumný projekt statistika a číselné údaje   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
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cyklofosfamid MeSH
• doxorubicin MeSH
• myší monoklonální protilátky MeSH
• prednison MeSH
• R-CHOP protocol MeSH Prohlížeč
• rituximab MeSH
• vinkristin MeSH

Carbohydrate antigen-125 (CA-125) was established as a prognostic marker in cancer, especially in ovarian carcinoma. Many recent studies have also reported on the prognostic significance of CA-125 in patients with different types of lymphoma, but only a few studies have been carried out in patients treated with rituximab or high-dose therapy. The prognostic impact of CA-125 on a large cohort of patients with follicular lymphoma (FL) has not been studied. This study analyzed the prognostic significance of CA-125 levels in 116 prospectively enrolled patients with previously untreated FL. It showed that the CA-125 level at the time of treatment initiation correlates with the clinical stage, number of involved nodal areas, bulky disease, hemoglobin level, beta-2 microglobulin level, and lactate dehydrogenase level. Patients with CA-125 >35 U/mL had significantly shorter progression-free (p < 0.001) and overall (p = 0.025) survival rates. Cox regression analysis identified high CA-125 levels as a prognostic factor for overall (HR 3.04, p = 0.05) and progression-free (HR 3.55, p < 0.001) survival rates independent of FLIPI score variables. CA-125 levels may help to refine risk assessment in the modern immunotherapy era.

• MeSH
• analýza přežití MeSH
• antigen CA-125 krev   MeSH
• dospělí MeSH
• folikulární lymfom diagnóza   mortalita   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• radioterapie MeSH
• senioři MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CA-125 MeSH