An Evidence-based Review of Anti-CD20 Antibody-containing Regimens for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Diffuse Large B-cell Lymphoma, or Follicular Lymphoma

Abstract

Combination regimens with anti-CD20 agents might improve the outcomes of patients with relapsed or refractory B-cell malignancies; however, the available comparative clinical evidence is limited. The present review assessed the reported evidence on the efficacy of anti-CD20 monoclonal antibodies combined with chemotherapy for patients with relapsed or refractory chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), or diffuse large B-cell lymphoma (DLBCL), using a rapid evidence assessment approach. MEDLINE, Embase, and the Cochrane Library were searched from January 1, 1997 to July 14, 2017 (English language only). The data identified from randomized controlled trials or single-arm prospective studies are reported as descriptive study summaries, grouped by anti-CD20 agent and outcome (overall response rate, including complete response and partial response; duration of response; survival, including overall survival and progression-free survival). Of 56 included reports, 32 reported on CLL/small lymphocytic lymphoma, 15 on FL, and 11 on DLBCL. Within the study period, 40, 11, and 7 studies evaluated rituximab, ofatumumab, and obinutuzumab, respectively. Substantially more data were available for rituximab-based combination regimens than for either ofatumumab or obinutuzumab. Moreover, substantial heterogeneity was recorded in the study design and backbone chemotherapy. Thus, the available data are inconclusive regarding any potential similarities or differences in efficacy among these anti-CD20 agents for each respective disease. More importantly, only 1 direct comparison among the anti-CD20 agents was identified, emphasizing the need for head-to-head randomized controlled trials of these drugs to inform clinical decision-making for patients with relapsed or refractory B-cell lymphoproliferative disorders.

Pre-Therapeutic Total Lesion Glycolysis on [18F]FDG-PET Enables Prognostication of 2-Year Progression-Free Survival in MALT Lymphoma Patients Treated with CD20-Antibody-Based Immunotherapy

“…The randomized, multicenter IELSG-19 trial suggested that PFS and EFS (event-free survival) were comparable between MALT lymphoma patients that received CD20-antibodybased immunotherapy with rituximab (monotherapy) and those that received standard cytostatic chemotherapy with chlorambucil [17]. Unlike rituximab, the fully humanized, second-generation CD20-antibody ofatumumab can bind both the small and large extracellular loop of CD20 [18]; it has already been approved by the FDA (Food and Drug Administration) for the treatment of chronic lymphocytic leukemia, and has shown promise in different lymphoma subtypes, although head-to-head comparisons with rituximab in randomized controlled trials are presently still lacking [19]. In our study, TLG demonstrated a potential utility as a prognostic biomarker in the CD20-antibody group: the dichotomized TLG enabled the identification of a Blow-risk population^in which not a single patient showed progression within the 2-year observation period, suggesting a very favorable response to this type of treatment (Fig.…”

Leveraging Heterogeneity in Systemic Lupus Erythematosus for New Therapies

“…Despite the failure of rituximab in clinical trials, CD20 is still considered a critical candidate to target pan B cells. Repurposing of obinutuzumab, a type II monoclonal antibody against CD20, approved for adults with follicular lymphoma and chronic lymphocytic leukemia [91], shows promise as a next-generation B cell depletion therapy for SLE. Obinutuzumab was fast tracked by the FDA for adults with proliferative lupus nephritis.…”

Monoclonal Antibody Therapies in Multiple Myeloma: A Challenge to Develop Novel Targets

“…CD20 is a transmembrane phosphoprotein expressed on committed B lymphoid cells through the all stages of their development, but its expression is reduced in plasma cells. Rituximab, a chimeric murine/human anti-CD20 monoclonal IgG 1 κ antibody targeting CD20 on B cells, is currently indicated for the treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) [39]. It exerts significant activity in combination with cytotoxic anticancer drugs.…”

“…In hematological malignancies, rituximab, a chimeric murine/human anti-CD20 monoclonal IgG 1 κ antibody or of atumumab, a humanized anti-CD20 monoclonal IgG 1 κ antibody, targeting CD20 on B cells, is currently indicated for the treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). It exerts significant activity in combination with cytotoxic anticancer drugs [38, 39].…”