RESUMEN
Abstract Background Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. Objective The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. Method Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens. Results Median age was 64-years old and 58% were female patients. The median follow-up was 42 months. The progression free survival (PFS) at this time was 63% and overall survival (OS), 66%. In the patients with tumors expressing Myc proto-oncogene protein (MYC) and B-cell lymphoma 2 (BCL2), assessed by immunohistochemistry (IHC), known as dual protein expressers, median post-progression survival was 31 (15-45) months. An increased proliferative index were associated with a high rate of progression (hazard ratio 2.31 [95% confidence interval [1.05-5.12]; p = 0.04). The cell of origin (COO), identified by IHC, was not able to predict PFS (p = 0.76). The MYD88 L265P mutation was present in 10.8% (9/83) of patients and did not show a prognostic correlation. Conclusion In conclusion, the MYD88 mutation, although an important tool for diagnosis and a possible target drug, presented at a low frequency and was not a prognostic marker in this population.
Asunto(s)
Biomarcadores de Tumor , Linfoma de Células B Grandes Difuso , Factor 88 de Diferenciación Mieloide , MutaciónRESUMEN
Objetivo: Comparar o impacto orçamentário de obinutuzumabe + clorambucila (GClb), rituximabe + clorambucila (RClb), ofatumumabe + clorambucila (OClb) ou clorambucila (Clb) na primeira linha de tratamento (1L) e suas respectivas opções de segunda linha (2L) recomendadas por consenso brasileiro e internacional para adultos com leucemia linfoide crônica (LLC) não tratados previamente e inelegíveis à dose completa de fludarabina (slow-go). Métodos: A análise foi conduzida a partir do desfecho de tempo para próxima terapia (TPPT) na perspectiva do Sistema de Saúde Suplementar (SSS). Apenas custos de aquisição de medicamentos foram considerados, incluindo posologia de bulas registradas. Regimes de tratamento de 2L considerados foram RClb ou ibrutinibe. As curvas de TPPT foram obtidas do estudo CLL11 e COMPLEMENT 1. Resultados: Em horizonte temporal de cinco anos, GClb demonstrou benefício econômico, quando comparado com RClb, OClb e Clb, sendo o potencial de savings por paciente de R$ 80 mil, R$ 149 mil e R$ 284 mil, respectivamente. Adicionalmente, em cinco anos, verificou-se que a adoção de GClb na 1L para pacientes com LLC pode promover economia de R$32 milhões para SSS quando comparado com RClb e Clb, uma vez que seu intervalo livre de tratamento é mais longo do que o das tecnologias comparadas, o que posterga o início do tratamento de 2L. Conclusões: Apesar de o preço unitário de obinutuzumabe e o custo de tratamento inicial de GClb serem superiores aos de RClb, OClb e Clb, o tratamento de 1L com GClb pode promover benefícios econômicos em longo prazo, consequentes dos resultados clínicos favoráveis da associação de GClb no tratamento da LLC.
Objective: To compare the budget impact of obinutuzumab + chlorambucil (GClb), rituximab + chlorambucil (RClb), ofatumumabe + chlorambucil (OClb) or chlorambucil (Clb) in first line treatment (1L) and their respective therapeutic options in second line (2L), recommended by a Brazilian and international consensus for adults with chronic lymphocytic leukemia (CLL), with no previous treatment and classified as ineligible to full dose fludarabine treatment (slow-go). Methods: The analysis was conducted based on the outcome time to next treatment (TPPT) under the perspective of the Brazilian Private Healthcare System (SSS). Only drug acquisition costs were considered, including dosage from registered labels. RClb and ibrutinib were considered as 2L treatment regimens. The TPPT curves were obtained from the CLL11 and COMPLEMENT 1 studies. Results: Considering a five-year time horizon, GClb demonstrated economic benefit when compared to RClb, OClb and Clb, with potential savings per patient of R$ 80 thousand, R$ 149 thousand and R$ 284 thousand, respectively. Additionally, in five years, the adoption of GClb as 1L for patients with CLL can promote an economy of R$ 32 million to the SSS when compared to RClb and Clb, since the GClb treatment free interval is longer than the compared technologies, which delays the beginning of the more costly 2L treatment. Conclusions: Although the unitary obinutuzumab price and the cost of initial GClb treatment are greater than RClb, OClb and Clb, 1L treatment with GClb can promote economic benefits in the long term, resulting from the favorable clinical results of GClb association in CLL treatment.