Eficácia e segurança de Rituximabe comparado a outras drogas no tratamento de vasculites sistêmicas: revisão rápida de evidências / Efficacy and safety of Rituximab compared to other drugs in the treatment of systemic vasculitides: rapid response review of evidence

Objetivo: descrever as evidências disponíveis na literatura científica sobre eficácia e segurança do rituximabe comparado a diferentes tratamentos. Materiais e métodos: é uma revisão rápida de evidências científicas para tomada de decisão informada por evidências em políticas e práticas de saúde. Conclusão: o Rituximabe tem eficácia e segurança similares à da Ciclofosfamida, para terapia de indução de remissão e para manutenção da remissão e, para pacientes com doença recidivante, o Rituximabe é mais eficaz que a Ciclofosfamida para manter a remissão. Para terapia de manutenção, Rituximabe é mais eficaz que Azatioprina, com perfil de segurança similar. Diferentes regimes de dosagem do Rituximabe tem eficácia e segurança similar para terapia de manutenção. O Infliximabe parece ser superior ao Rituximabe nos desfechos de eficácia (indução e manutenção da remissão).

Objective: to describe the evidence available in the scientific literature on the efficacy and safety of rituximab compared to different treatments. Materials and Methods: is a rapid review of scientific evidence for evidence-informed decision making in health policy and practice. Conclusion: Rituximab has similar efficacy and safety to Cyclophosphamide, for remission induction therapy and for maintenance of remission, and for patients with relapsing disease, Rituximab is more effective than Cyclophosphamide in maintaining remission. For maintenance therapy, Rituximab is more effective than Azathioprine, with a similar safety profile. Different dosing regimens of Rituximab have similar efficacy and safety for maintenance therapy. Infliximab appears to be superior to Rituximab in efficacy outcomes (induction and maintenance of remission).

Maintenance rituximab in newly diagnosed mantle cell lymphoma patients: a real world analysis from the Czech lymphoma study group registry†.

We analyzed 495 MCL patients from the Czech Lymphoma Study Group data registry. With the median follow-up of 4.4 years, 51.7% patients progressed or relapsed and 34.1% died. Five-year overall survival reached 65.3% and five-year progression free survival 44.1% of the patients. Maintenance rituximab (MR) after first line therapy improved overall and progression free survival compared to the patients under observation only (both p < .001). Elevated beta-2-microglobulin (p = .003), presence of systemic symptoms (p = .002), ECOG >0 (p = .003), age (p = .014), and MIPI (p < .001) were associated with MR failure. Patients who did not achieve complete remission have had two-fold higher risk of MR failure (p < .001). Autologous stem cell transplant reduced the risk of MR failure by 69% (p < .001). The MIPI and the beta-2-microglobulin were identified as independent predictors of MR failure (p = .02 and p = .03, respectively). Patients who relapsed/progressed on MR reached shorter OS calculated from the MR start compared to patients without failure (HR = 15.0; p < .001).

Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy.

PURPOSE: Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAb) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. EXPERIMENTAL DESIGN: Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs. RESULTS: We demonstrate that CD20 expression on ibrutinib was rapidly and persistently downregulated (median reduction 74%, day 28, P < 0.001) compared with baseline. Concomitantly, CD20 mRNA was decreased concurrent with reduced NF-κB signaling. An NF-κB binding site in the promoter of MS4A1 (encoding CD20) and downregulation of CD20 by NF-κB inhibitors support a direct transcriptional effect. Ex vivo, tumor cells from patients on ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P < 0.001); however, opsonization by the complement protein C3d, which targets cells for phagocytosis, was relatively maintained. Expression of decay-accelerating factor (CD55) decreased on ibrutinib, providing a likely mechanism for the preserved C3d opsonization. In addition, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy. CONCLUSIONS: Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal antitumor effects of such combinations requires further investigation.

Clinical and economic aspects of the use of rituximab in non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) consists of a group of neoplasias involving mainly B cells and represents 90% of all lymphomas. The current available therapy is based on chemotherapy associated with the monoclonal antibody rituximab (Mab Thera(r)), which targets the CD20 protein, present in over 80% of NHL mature B cells. Recent clinical reports show a preference for combining the benefits of immunotherapy and adjuvant chemotherapy, thus generating safe and effective alternative treatments. The current review aimed at evaluating various aspects related to the use of rituximab for NHL, highlighting the possible inhibitory mechanisms of cell proliferation, the achieved clinical results, and the expected clinical and economic outcomes of treatments. The results from clinical tests indicate the need for a better understanding of the critical mechanisms of action of this antibody, which may maximize its therapeutic efficacy. This therapy not only represents a viable option to treat most types of NHLs, especially when associated with conventional chemotherapy, but also offers cost-utility and cost-effectiveness advantages.

O Linfoma não-Hodgkin (LNH) consiste em um grupo de neoplasias envolvendo, principalmente, as células B e representa 90% de todos os linfomas. A terapia atual disponível é baseada em quimioterapia associada ao anticorpo monoclonal rituximabe (Mab Thera(r)), que tem como alvo a proteína CD20, presente em mais de 80% das células B maduras do LNH. Recentes relatórios clínicos mostram preferência para combinar os benefícios da quimioterapia adjuvante e imunoterapia, gerando alternativas de tratamentos seguro e eficaz. O trabalho de revisão teve por objetivo avaliar vários aspectos relacionados à aplicação do rituximabe no LNH, destacando os possíveis mecanismos inibitórios da proliferação celular, os resultados clínicos obtidos e as implicações clínicas e econômicas esperadas para o tratamento. Os resultados de testes clínicos indicam a necessidade de uma melhor compreensão dos mecanismos críticos de ação deste anticorpo, que poderão maximizar a sua eficácia terapêutica. Essa terapia não representa apenas uma opção viável para o tratamento da maioria dos tipos de LNH, principalmente quando associado à quimioterapia convencional, mas, também, oferece vantagens em termos de custo-utilidade e custo-efetividade.