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Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20⁺ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

ABSTRACT: Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20⁺ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20⁺ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P?=?0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13-1.48, P?131I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. ⁹⁰Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47-6.43, P?=?0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20⁺ B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, ⁹⁰Y-ibritumomab tiuxetan increases ORR.

SUBMITTER: Luo C

PROVIDER: S-EPMC7864901 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20<sup>+</sup> B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

Luo Chengxin C Wu Guixian G Huang Xiangtao X Ma Yanni Y Zhang Yali Y Song Qiuyue Q Xie Mingling M Sun Yanni Y Huang Yarui Y Huang Zhen Z Hou Yu Y Xu Shuangnian S Chen Jieping J Li Xi X

Scientific reports 20210205 1

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20<sup>+</sup> B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are ...[more]

PMID: 33547368

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Project description:The possibility to deliver radioisotopes directly to tumor cells by using monoclonal antibodies has become a promising concept for the elimination of small tumor nodules or single disseminated tumor cells. The alpha-particle emitter Bismut-213 which has a high linear energy transfer and a very short path length appears to be able to kill cells by only few nuclear hits. Bismut-213 based alpha-immunotherapy treatment is currently proved in clinical trials for AML, NHL and preclinically for CLL and multiple myeloma. Because little is known about the biological effects of alpha radiation we examined the molecular effects of the alpha emitter Bismut-213 in malignant and normal B-cells. In this study, we used the cell line Karpas 422 (K422) which had been derived from a malignant B-cell Non-Hodgkin’s lymphoma as well as normal primary CD19+ B-cells which had been selected immunomagnetically from peripheral blood. For the delivery and binding of the alpha emitter we used the monoclonal antibody rituximab which targets the CD20 receptor of malignant and normal B-cells. The lymphoma cell line K422 was incubated in vitro with Bismut-213-CD20 with 100 µCi and 200 µCi respectively, for 46 min (1 half life time of the alpha emitter) or 24 h. Immunomagnetically isolated CD19+ cells from healthy donors were incubated in vitro with Bismut-213-CD20 with 100 µCi or 200 µCi, for 46 min. Gene expression profiles of irradiated cells were analysed using cDNA oligonucleotide arrays (Affymetrix Human Genome Focus Arrays) comprising 8,793 genes and compared with those from untreated control cells. Following normalization significantly altered genes were identified by using the variance stabilization normalization (VSN) method and the significance analysis of microarrays (SAM) algorithm. Differentially expressed genes were defined to exhibit a fold change of 1,4 and higher or 0,7 and lower and a q-value of 5% or lower compared to the genes of the untreated control cells. Irradiated K422 cells with 100 µCi showed 42 differential expressed genes after 46 minutes (one half life time) and 451 deregulated genes after exposure of 24 hours. A similar response could be observed at an exposure of 200 µCi (50 differentially expressed genes after 46 min; 485 genes after 24 h). Hence, a severe radiation induced response could not be detected before 24 hours. 200 µCi irradiated CD19+ cells showed 67 differentially expressed genes after 46 minutes compared to the untreated CD19+ cells (for 100 µCi: 42 differentially expressed genes). By performing cluster analyses the irradiated cells exhibited a distinct homogenous molecular phenotype in comparison to not irradiated cells. Alpha irradiated cells showed transcriptional activation of DNA repair genes. Furthermore, both examined cell types showed up-regulated genes which are known to play a role in general and oxidative stress response. Surprisingly, up-regulation of interferon-stimulated genes in K422 cells could be observed. Because of the transcriptional activation of genes regulating the G1-S- cell cycle transition the supposition came up that the irradiated K422 do progress into the S-phase of the cell cycle and arrest in the S- or G2/M-phase. In contrast to the K422 cells the primary CD19+ B-cells revealed transcriptional activation of cell cycle inhibitors which is an already known reaction following ionizing radiation but no apoptosis associated genes could be observed. In spite of the massive cytotoxic damages which are assumed referring to the gene expression data the K422 cells appear to be able to activate several defense mechanisms in a precise manner. Hence, the malignant K422 cells exhibit a larger amount as well as more various responses than the CD19+ cells. This might be due to the tumorigenic transformation of the malignant cells that exhibit probably more effective defense strategies than the CD19+ cells. The balance between the therapeutic effect of alpha radiation on malignant cells and the damaging effect on normal cells is an essential issue and it is of important clinical relevance concerning radioimmunotherapy with alpha radiation. Keywords: time course and dose dependency

Dataset Information

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20⁺ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

Publications

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20<sup>+</sup> B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

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Dataset Information

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

Publications

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20<sup>+</sup> B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20⁺ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.