Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions

Moore, Jeremiah; Bloom, Paige C.; Chu, Charles C.; Bruno, Jennifer E.; Herne, Christine A.; Baran, Andrea; Quataert, Sally A.; Mosmann, Timothy R.; Taylor, Ronald P.; Wallace, Danielle; Elliott, Michael R.; Barr, Paul M.; Zent, Clive S.

doi:10.1016/j.leukres.2023.107072

Cited by 2 publications

(2 citation statements)

References 44 publications

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“…Macrophage hypophagia could explain our recent observation that treatment naïve CLL patients receiving their first dose of rituximab as a slow intravenous infusion at 25 mg/h have a rapid (<1 h) clearance of ~80% of circulating CLL cells followed by no further clearance with ongoing infusion of rituximab 61,93 . These data are compatible with “exhaustion” of innate immune cytotoxicity and compatible with the onset of hypophagia.…”

Section: Factors Limiting Adcp Efficacymentioning

confidence: 57%

Antibody‐mediated phagocytosis in cancer immunotherapy

Van Wagoner,

Rivera‐Escalera,

Jaimes‐Delgadillo

et al. 2023

Immunological Reviews

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SUMMARYUnconjugated monoclonal antibodies (mAbs) have revolutionized the treatment of many types of cancer. Some of these mAbs promote the clearance of malignant cells via direct cytotoxic effects. More recently, antibody‐dependent cellular phagocytosis (ADCP) has been appreciated as a major mechanism of action for a number of widely used mAbs, including anti‐CD20 (rituximab, obinutuzumab), anti‐HER2 (trastuzumab), and anti‐CD38 (daratumumab). However, as a monotherapy, these ADCP‐inducing mAbs produce insufficient levels of cytotoxicity in vivo and are not curative. As a result, these mAbs are most effectively used in combination therapies. The efficacy of these mAbs is further hampered by the apparent development of drug resistance by many patients. Here we will explore the role of ADCP in cancer immunotherapy and discuss the key factors that could limit the efficacy of ADCP‐inducing mAbs in vivo. Finally, we will discuss current insights and approaches being applied to overcome these limitations.

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Section: Factors Limiting Adcp Efficacymentioning

confidence: 57%

Antibody‐mediated phagocytosis in cancer immunotherapy

Van Wagoner,

Rivera‐Escalera,

Jaimes‐Delgadillo

et al. 2023

Immunological Reviews

Self Cite

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“…The issue of IRRs to rituximab has become a major obstacle that cannot be ignored. At present, the mechanisms of IRRs have been mainly attributed to rituximab-induced cytokine release syndrome, which involves the release of TNF-α, IL-1 and IL-6 in the blood ( 17 ). Rising levels of cytokines trigger a series of symptoms of inflammatory response, including fever, chills, rigors, rash, headache, hypotension, breathlessness, bronchospasm, nausea, vomiting and even allergic shock ( 8 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

A novel prednisone premedication protocol significantly decreases infusion‑related reactions of rituximab in newly diagnosed diffuse large B‑cell lymphoma

Ding

Leng

Gu³

et al. 2023

Oncol Lett

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Rituximab is a widely used anti-CD20 monoclonal antibody with a high incidence of infusion-related reactions (IRRs) during administration. Reducing the incidence of IRRs remains problematic in hematological practices. In the present study, a novel strategy of a prednisone pretreatment regimen was designed similar to the combination of rituximab, cyclophosphamide, epirubicin, vincristine and prednisone (R-CHOP) with the aim of exploring the effect on the incidence of IRRs to rituximab in patients with diffuse large B-cell lymphoma (DLBCL). A prospective, randomized (1:1) and controlled study was conducted in three regional hospitals in two groups (n=44 for each group): i) A control group treated with standard R-CHOP-like regimen; and ii) a group receiving a prednisone-pretreatment, modified R-CHOP-like protocol for newly diagnosed patients with DLBCL. The primary endpoint was to assess the incidence of IRRs to rituximab, as well as the association of IRRs with the efficacy of treatment. The second endpoint involved clinical outcomes. The total incidence of IRRs to rituximab in the treatment group was significantly lower compared with that in the control group (15.9 vs. 43.2%; P=0.0051). The different grade incidence of IRRs was lower in the treatment group compared with that in the control group (P=0.0053). In total, 29.5% of patients (26/88) experienced >1 IRR episode. The incidence of IRRs in the pre-treatment group was decreased compared with that in the control group in the 1st cycle (15.9 vs. 43.2%; P=0.0051) and 2nd cycle (6.8 vs. 27.3%; P=0.0107). The overall response rate was similar between the two groups (P>0.05). Median progression-free survival and median overall survival time were not statistically distinct between the two groups (P=0.5244 and P=0.5778, respectively). Grade ≥III toxicities mainly included vomiting and nausea (<20%), leukopenia and granulocytopenia (<20%), and alopecia (<25%). No death events were reported. Apart from IRRs to rituximab, the incidence of other adverse events was similar in both groups. The novel prednisone-pretreatment R-CHOP-like protocol in the present study significantly decreased the total and different grade incidences of IRRs to rituximab among newly diagnosed patients with DLBCL. This clinical trial was retrospectively registered with the Chinese Clinical Trial Registry (registration number, ChiCTR2300070327; date of registration, 10 April 2023).

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Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions

Cited by 2 publications

References 44 publications

Antibody‐mediated phagocytosis in cancer immunotherapy

Antibody‐mediated phagocytosis in cancer immunotherapy

A novel prednisone premedication protocol significantly decreases infusion‑related reactions of rituximab in newly diagnosed diffuse large B‑cell lymphoma

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