1.Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab.
Dawson K1, Moran M2, Guindon K1, Wan H3. Clin J Oncol Nurs. 2016 Apr 1;20(2):E41-8. doi: 10.1188/16.CJON.E41-E48.
BACKGROUND: In patients with previously untreated chronic lymphocytic leukemia (CLL) and comorbidities, treatment with the glycoengineered, type II anti-CD20 monoclonal antibody obinutuzumab (Gazyva®) (GA101) plus chlorambucil (Leukeran®) was associated with superior outcomes to rituximab (Rituxan®) plus chlorambucil, with a similar safety profile. However, a higher occurrence of infusion-related reactions (IRRs) was reported with obinutuzumab. These reactions typically require additional management.
2.Chronic lymphocytic leukemia therapy: new targeted therapies on the way.
Vitale C1, Burger JA1. Expert Opin Pharmacother. 2016 Apr 12:1-13. [Epub ahead of print]
INTRODUCTION: The critical role of the tissue microenvironment and B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL) pathogenesis, and the clinical success of targeted agents that disrupt BCR signaling are currently changing the CLL landscape. Three new drugs were recently approved for CLL therapy, and other agents are in late development. Areas covered: In this review, we summarize data on promising new targeted drugs for CLL. The heterogeneous mechanisms of actions of these molecules are described, such as the inhibition of BCR signaling, direct targeting of CD20 molecules on the CLL cell surface, and BCL-2 inhibition. We present preclinical and clinical data from phase I to III studies in order to describe efficacy and side effect profile of these new drugs. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings. Expert opinion: Ibrutinib and idelalisib are challenging the role of chemo-immunotherapy in CLL therapy in the frontline and relapsed disease settings.
3.Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2 selective antagonist idasanutlin (RG7388).
Herting F1, Herter S2, Friess T1, Muth G1, Bacac M2, Sulcova J2, Umana P2, Dangl M1, Klein C2. Eur J Haematol. 2016 Mar 19. doi: 10.1111/ejh.12756. [Epub ahead of print]
OBJECTIVES: To investigate whether the glycoengineered, type II anti-CD20 monoclonal antibody obinutuzumab (GA101) combined with the selective MDM2 antagonist idasanutlin (RG7388) offers superior efficacy to monotherapy in treating B-lymphoid malignancies in preclinical models METHODS: The combined effect of obinutuzumab or rituximab plus idasanutlin on direct cell death/apoptosis induction and antibody-dependent cellular cytotoxicity (ADCC) was evaluated using p53 wild-type Z-138 and DoHH-2 lymphoma cells. Furthermore, whole blood B-cell depletion was analysed, and tumour growth inhibition was evaluated in subcutaneous xenograft models RESULTS: Idasanutlin induced concentration-dependent death of Z-138 and DoHH-2 cells. At concentrations >10-100 nM, idasanutlin enhanced obinutuzumab-induced death of DoHH-2 and Z-138 cells without negatively impacting obinutuzumab-mediated ADCC, natural killer cell activation, or whole blood B-cell depletion.