Trial reportJournal of immunology (Baltimore, Md. : 1950)2014
Induced resistance to ofatumumab-mediated cell clearance mechanisms, including complement-dependent cytotoxicity, in chronic lymphocytic leukemia.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Risk-adapted, ofatumumab-based chemoimmunotherapy and consolidation in treatment-naïve chronic lymphocytic leukemia: a phase 2 study.Leukemia & lymphoma · 2021Trial
- A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG-ACRIN cancer research group (E1908).American journal of hematology · 2016Trial
- Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.American journal of hematology · 2014Trial
- Efficacy of high-frequency low-dose rituximab and acalabrutinib in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Antibody-mediated phagocytosis in cancer immunotherapy.Immunological reviews · 2023Review
- Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions.Leukemia research · 2023Article
- A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.Frontiers in immunology · 2023Article
- Article
- Review
- Complement Activation in the Treatment of B-Cell Malignancies.Antibodies (Basel, Switzerland) · 2020Review
- Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance.Blood · 2020Article
- The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs.Antibodies (Basel, Switzerland) · 2020Review
- Ofatumumab and Complement Replacement in Relapsed/Refractory Chronic Lymphocytic Leukemia.Journal of hematology · 2020Article
- The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy.Haematologica · 2020Review
- High-resolution quantification of discrete phagocytic events by live cell time-lapse high-content microscopy imaging.Journal of cell science · 2020Article
- Monitoring of the Complement System Status in Patients With B-Cell Malignancies Treated With Rituximab.Frontiers in immunology · 2020Article
- Mutations resulting in the formation of hyperactive complement convertases support cytocidal effect of anti-CD20 immunotherapeutics.Cancer immunology, immunotherapy : CII · 2019Article
- Anaphylatoxin C3a: A potential biomarker for esophageal cancer diagnosis.Molecular and clinical oncology · 2018Article
- Complement in cancer: untangling an intricate relationship.Nature reviews. Immunology · 2018Review
- B-chronic lymphocytic leukemia showed triple transformation, to diffuse large B cell, CD20-negative, and T-cell neoplasm during ofatumumab treatment: a case report.BMC clinical pathology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Ofatumumab (OFA), a human CD20-targeting mAb, kills B lymphocytes using the innate immune system including complement-dependent cytotoxicity (CDC). The efficacy of OFA in patients with chronic lymphocytic leukemia (CLL) is limited by drug resistance, which is not well characterized. To better understand mechanisms of resistance, we prospectively studied CLL cells isolated from blood samples collected before and after in vivo exposure to the initial dose of OFA therapy in 25 patients undergoing their first treatment for progressive CLL. As previously reported, OFA therapy rapidly decreased the absolute lymphocyte count, CD20 expression by CLL cells, and serum complement levels. We now show that after administration of the first dose of OFA, there was a modest rebound in the absolute lymphocyte count and serum complement levels, but substantial ongoing loss of CD20 expression by CLL cells. These post-OFA treatment CLL cells were highly resistant to OFA-mediated CDC but retained sensitivity to alemtuzumab-mediated CDC in vitro. Posttherapy serum OFA levels correlated inversely with both the amount of pretreatment circulating cell-bound CD20 and with the decrease in this value following treatment. In vitro OFA-mediated CDC did not predict clinical responses, and the patients with first-dose reactions to OFA did not have markers of increased complement activation in vivo. We propose that optimal efficacy of CD20- targeted therapy for CLL requires determining an mAb dose size and frequency that optimizes CLL killing without exceeding the capacity of the cytotoxic mechanisms and thus minimizes loss of CD20 expression in the surviving CLL cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.