Prevention and management of obinutuzumab‐associated toxicities: Australian experience

Abstract

Patients with chronic lymphocytic leukaemia (CLL) are typically diagnosed at an advanced age and may have multiple coexisting conditions, augmenting the challenges of treating their CLL. Aggressive cytotoxic therapies are often poorly tolerated in this patient population.Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody indicated in combination with chlorambucil for previously untreated CLL. The approval of this drug was based on the pivotal CLL11 trial, which demonstrated longer progression-free survival vs. rituximab/chlorambucil and chlorambucil alone in patients with significant co-existing medical conditions and/or poor renal function. However, a higher risk of infusion-related reactions (IRRs) was demonstrated with obinutuzumab-based therapy.We highlight important nursing care considerations to help prevent and successfully manage IRRs and other important adverse events, to improve the treatment experience of patients receiving obinutuzumab infusions and to enable them to complete their treatment and receive optimal benefit. Premedication, drug handling, dosing, administration, monitoring and documentation are discussed.

Anticorpos monoclonais no tratamento oncológico: revisão de literatura para o atendimento ao paciente e manejo das reações infusionais

“…As fontes bibliográficas selecionadas foram publicadas, em sua maioria, em 2013 (23,07%) e 2015 (26,9%), seguidos por 2014 (19,2%), 2012 (19,2%), 2016 (11,5%) e 2011 (3,8%), demostrando que o tema de pesquisa é recente e pouco discutido nas áreas médicas. Em geral, os anticorpos que correspondem aos alvos dos estudos são o Obinutuzumab 3,5,[8][9][10][11][12] (26,9%), seguido pelo Rituximab 9,11,[13][14][15] (19,2%), Bevacizumab [16][17] (7,6%), Daratumumab 4,18 (7,6%), Cetuximab [19][20] (7,6%), Trastuzumab 21 (3,8%), Ipilimumab 22 (3,8%), Ocrelizumab 23 (3,8%), Brentuximab 24 (3,8%) e Ingatuzumab 25 (3,8%).…”

“…Dentre as referências bibliográficas do tema, o tipo de estudo predominante é o prospectivo (30,7%) 4,8,9,13,18,28,5 . Foram revisados, também, estudos retrospectivos (26,9%) 3,14,16,17,21 e, em menor número, os estudos de coorte (19,2%) 5,12,22,25 , relatos de caso 19,20,24 (11,5%), revisão bibliográfica 11,26 (7,6%), estudo caso-controle 23 (3,8%).…”

“…Obinutuzumab é um mAb humanizado de imunoglobulina G1 tipo II anti-CD20 que promove o aumento da morte celular direta e diminui a ativação do complemento 3,8,9 . É principalmente indicado para leucemia linfocítica crônica, linfoma não-Hodgkin e doenças hematológicas CD20 positivas 5 .…”

“…Rituximab [13][14] Receptor CD20 nos Linfócitos B 32-77% calafrios, febre, náuseas, hipotensão, rash, angioedema, dispneia Estudos acerca do Obinutuzumab evidenciaram que os pacientes que receberam a primeira infusão apresentaram reação infusional com maior frequência quando comparada aos pacientes nas infusões subsequentes 4,8 . Durante a primeira administração, ocorre a liberação de citocinas pró-inflamatórias, em particular IL-6 e IL-8, as quais são acompanhadas pela redução das células natural killers.…”

Rethinking the INN system for therapeutic antibodies

“…For example, obinutuzumab has been glycoengineered to increase its binding to FcγRIIIA (and FcγRIIIB), and this modification could explain the higher number of cytokine release syndromes and chronic neutropenias, in comparison to ritixumab 29 . Furthermore, mydriasis and impaired accommodation has been more frequently observed in patients with neuroblastoma receiving the anti-GD2 hu14.18K322A antibody than in patients receiving dinutuximab, an anti-GD2 IgG1 antibody 30 .…”