RESUMO
This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.
RESUMO
Obinutuzumab is a fully humanized monoclonal antibody against CD20 used in the treatment of chronic lymphocytic leukemia. Fatal cardiovascular events have been described, but only in patients with known cardiovascular records. We report the case of an adult male with a high-risk chronic lymphocytic leukemia who developed subendocardial injury, with no evidence of coronary atherosclerosis, during the first administration of obinutuzumab.
El obinutuzumab es un anticuerpo monoclonal completamente humanizado contra CD20, empleado en el tratamiento de leucemia linfocítica crónica. Los eventos cardiovasculares fatales han sido descritos, pero solo en pacientes con antecedentes cardiovasculares conocidos. Presentamos el caso de un hombre adulto con diagnóstico de leucemia linfocítica crónica de alto riesgo que desarrolló injuria subendocárdica, sin evidencia de aterosclerosis coronaria, durante la primera infusión de obinutuzumab.
Assuntos
Aterosclerose , Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígenos CD20/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , MasculinoRESUMO
Resumen El obinutuzumab es un anticuerpo monoclonal completamente humanizado contra CD20, empleado en el tratamiento de leucemia linfocítica crónica. Los eventos cardiovasculares fatales han sido des critos, pero solo en pacientes con antecedentes cardiovasculares conocidos. Presentamos el caso de un hombre adulto con diagnóstico de leucemia linfocítica crónica de alto riesgo que desarrolló injuria subendocárdica, sin evidencia de aterosclerosis coronaria, durante la primera infusión de obinutuzumab.
Abstract Obinutuzumab is a fully humanized monoclonal antibody against CD20 used in the treat ment of chronic lymphocytic leukemia. Fatal cardiovascular events have been described, but only in patients with known cardiovascular records. We report the case of an adult male with a high-risk chronic lymphocytic leukemia who developed subendocardial injury, with no evidence of coronary atherosclerosis, during the first administration of obinutuzumab.
RESUMO
Objetivo: O objetivo deste estudo foi avaliar a custo-efetividade da terapia obinutuzumabe + quimioterapia (GQT) versus quimioterapia (QT) em pacientes com leucemia linfoide crônica (LLC) sem tratamento prévio classificados como inelegíveis à dose completa de fludarabina (slow-go) na perspectiva do Sistema Único de Saúde (SUS). Métodos: Um modelo de Markov foi desenvolvido para acompanhar os pacientes com LLC durante o curso da doença, em um horizonte de tempo de 20 anos. Os desfechos de sobrevida livre de progressão (SLP) e sobrevida global (SG) foram avaliados respectivamente em termos de anos de vida livres de progressão (AVLP) e anos de vida ganhos (AVG). O custo de tratamento incluiu os custos de aquisição de medicamentos, manejo de eventos adversos e acompanhamento. Os dados de eficácia foram obtidos dos estudos CLL11 e CLL5. Resultados: O custo de tratamento incremental foi de R$ 72.565. Os valores de SLP para GQT e QT foram, respectivamente, 3,3 e 1,1 AVLP. Para SG, o GQT resultou em uma efetividade de 5,7 e QT 4,3 AVG. Os resultados de RCEI foram de R$ 32.477/SLP e R$ 52.252/AVG. Conclusão: A terapia GQT é uma opção que proporciona benefícios clínicos superiores quando comparada à QT e pode ser considerada custo-efetiva no tratamento de LLC em pacientes não elegíveis a doses completas de fludarabina.
Objective: The objective of the study was to evaluate the cost-effectiveness of obinutuzumab + chemotherapy (GQT) versus chemotherapy (QT) in patients with chronic lymphocytic leukemia (CLL) without previous treatment, classified as ineligible to full dose of fludarabine (slow-go) under the perspective of Brazilian Public Healthcare System (SUS). Methods: A Markov model was developed to follow the patients with CLL through the disease course, in a time horizon of 20 years. The evaluated outcomes were progression free life years (PFLY) and life years gained (LY). The treatment cost included drug acquisition, adverse events management and patient follow-up. Efficacy data were obtained from CLL11 and CLL5 studies. Results: Incremental treatment cost was R$ 72,565. PFS for GQT and QT were respectively 3.3 and 1.1 PFLY. For LY, GQT resulted in an effectiveness of 5.7 and QT 4.3. ICER were R$ 32,477/PFLY and R$ 52,252/LY. Conclusion: GQT therapy is an option that promotes superior clinical benefits when compared to QT, and it can be considered cost-effective in the treatment of CLL in patients not eligible to full doses of fludarabine.
Assuntos
Humanos , Sistema Único de Saúde , Leucemia Linfoide , Análise Custo-Benefício , Tratamento FarmacológicoRESUMO
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.