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1.
Br J Haematol ; 202(1): 40-47, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36971061

RESUMO

Idelalisib (idela), a phosphatidylinositol 3-kinase inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, were the first oral targeted agents approved for relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). However, no randomised trials of idelalisib plus rituximab (R-idela) versus ibrutinib have been conducted. Therefore, we performed a real-world retrospective analysis of patients with R/R CLL treated with R-idela (n = 171) or ibrutinib (n = 244). The median age was 70 versus 69 years, with a median of two previous lines. There was a trend towards higher tumour protein p53 (TP53) aberrations and complex karyotype in the R-idela group (53% vs. 44%, p = 0.093; 57% vs. 46%, p = 0.083). The median progression-free survival (PFS) was significantly longer with ibrutinib (40.5 vs. 22.0 months; p < 0.001); similarly to overall survival (OS; median 54.4 vs. 37.7 months, p = 0.04). In multivariate analysis, only PFS but not OS remained significantly different between the two agents. The most common reasons for treatment discontinuation included toxicity (R-idela, 39.8%; ibrutinib, 22.5%) and CLL progression (27.5% vs. 11.1%). In conclusion, our data show significantly better efficacy and tolerability of ibrutinib over R-idela in patients with R/R CLL treated in routine practice. The R-idela regimen may still be considered a reasonable option in highly selected patients without a suitable treatment alternative.


Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Idoso , Rituximab , Estudos Retrospectivos , Recidiva , Sistema de Registros
2.
Onco Targets Ther ; 15: 1481-1501, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36510607

RESUMO

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.

3.
Eur J Haematol ; 109(2): 162-165, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35502609

RESUMO

OBJECTIVES: Polatuzumab vedotin with bendamustine and rituximab (Pola-BR) was approved for treatment of transplant-ineligible patients with relapsed/refractory DLBCL (R/R DLBCL). However, the number of patients treated in the GO29365 trial including the extension cohort was limited, and more data evaluating the efficacy of this treatment regimen is needed. METHODS: We analyzed 21 patients with R/R DLBCL to determine real-life efficacy and safety of Pola-BR regimen. Data of all patients entered the database of the NiHiL project (NCT03199066). RESULTS: Median overall survival was 8.7 months, and progression-free survival 3.8 months. The overall response rate was 33%. Grade 3-4 neutropenia was detected in 29%, thrombocytopenia in 38%, anemia in 19%, infections in 24% cases, and peripheral neuropathy in 5%. Discontinuation of treatment was caused by progression in 50%, adverse events in 31%, and intended bridging to CAR-T therapy in 19%. CONCLUSION: Although the outcome of patients is worse than in GO29365 trial, the use of Pola-BR regimen in the real world demonstrates tolerable toxicity profile and efficacy in transplant-ineligible patients with R/R DLBCL. Moreover, this regimen might represent a perspective option as a bridge to CAR-T therapy.


Assuntos
Imunoconjugados , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Rituximab
4.
Oncol Lett ; 19(3): 2413-2421, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194741

RESUMO

The molecular pathogenesis of thymoma remains largely unknown. It has been recently demonstrated, that activation of Wnt signaling pathway leads to increased incidence of thymoma in murine models. The present study investigated the activation of molecules of the Wnt signaling pathway in human thymoma. A total of 112 thymoma cases with complete clinical and follow-up data and 8 controls were included in the present study. Patients with thymoma and controls were examined immunohistochemically for ß-catenin and E-cadherin. The mRNA expression levels of CTNNB1, CCND1, MYC, AXIN2 and CDH1 were analyzed by reverse transcription-quantitative PCR. Immunohistochemically, ß-catenin and E-cadherin were overexpressed in neoplastic cells of all thymomas. In type A, B1 and non-invasive type B2 thymoma, both molecules were located in the cytoplasm, in contrast to invasive type B2 and B3 thymoma, where membranous immunopositivities were observed. mRNA expression levels of genes involved in the Wnt pathway and of E-cadherin were significantly increased in both type A and B thymoma compared with controls; increasing gradually from type B1 to B3, and with higher stage of disease. In recurrent type B thymoma, the mRNA expression of the molecules was significantly higher. Despite the activation of Wnt pathway in indolent type A thymoma, the negative feedback of the pathway was preserved by overexpression of inhibitory molecule axin2, which was not overexpressed in type B thymoma. In summary, the Wnt pathway was activated in human thymoma and may contribute to oncogenesis. Detection of molecules of the Wnt pathway may be of diagnostic and prognostic value.

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