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Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
Lenzilumab was approved by the FDA for compassionate use in COVID-19 patients with moderate or serious COVID-19 pneumonia. Lenzilumab, was authorized to be used as a first-line care alternative in hospitalized patients [33]. GM-CSF neutralization with lenzilumab was safe and associated with clinical benefits related to oxygen demand, and cytokine storm in high-risk patients with serious pneumonia [34].
Antibodies to watch in 2022
Published in mAbs, 2022
Hélène Kaplon, Alicia Chenoweth, Silvia Crescioli, Janice M. Reichert
Initiated in May 2020 and completed in March 2021, the LIVE-AIR trial assessed the potential for lenzilumab to improve the likelihood of ventilator-free survival beyond standard supportive care in hospitalized subjects with severe COVID-19.37 The study enrolled 520 adult patients who experienced blood oxygen saturation of less than or equal to 94%, or required low-flow supplemental oxygen, or high-flow oxygen support, or non-invasive positive pressure ventilation; and were hospitalized but did not require invasive mechanical ventilation. Patients were randomized to receive three infusions of either 600 mg lenzilumab or placebo, with each 1-h infusion separated by 8 h over a 24-h period. All patients received standard of care, including dexamethasone (or other steroids) and/or remdesivir. The study’s primary endpoint, survival without ventilation measured through d 28 following treatment, was met (hazard ratio (HR): 1.54; 95% CI: 1.02–2.32, P = 0.0403). The Kaplan–Meier estimates for invasive mechanical ventilation and/or death in the lenzilumab vs. placebo arms were 15.6% (95% CI: 11.5–20.9) vs. 22.1% (95% CI: 17.4–27.9), respectively.37
Assessment and management of cytokine release syndrome and neurotoxicity following CD19 CAR-T cell therapy
Published in Expert Opinion on Biological Therapy, 2020
Cassie K. Chou, Cameron J. Turtle
As we understand more about the underlying pathophysiology of CRS and ICANS, targeted therapies and preventive measures might be better utilized in severe CRS and/or ICANS. Other drugs targeting cytokines that are elevated in patients with severe CRS and/or neurotoxicity are being explored in pre-clinical and early phase clinical trials. There are case reports of the use of siltuximab, a monoclonal anti-IL-6 antibody that is currently FDA approved to treat multicentric Castleman’s disease, to treat CRS [62,63]. Anakinra is a recombinant IL-1 receptor antagonist that is approved by the FDA for treatment of adults with rheumatoid arthritis and cryopyrin-associated periodic syndromes and has been used to treat macrophage activation syndrome and HLH [64–66]. Lenzilumab is a monoclonal GM-CSF neutralizing antibody that is currently in pre-clinical development for CAR-T cell-associated toxicities [35]. Modulating CAR-T cell responsiveness is another attractive strategy to ameliorate toxicities. Dasatinib has been shown to suppress CAR-T cell function in a dose-dependent and reversible manner in a mouse model without additional toxicity [67]. Robust efficacy data to support the routine use of these agents in humans are not available. Ablation of infused CAR-T cells is another strategy that is often considered to treat CAR-T cell-dependent toxicities; however, there is no good data to demonstrate that CAR-T cell ablation in humans will mitigate CRS and/or neurotoxicity [68,69].
Clinical and economic benefits of lenzilumab plus standard of care compared with standard of care alone for the treatment of hospitalized patients with COVID-19 in the United States from the hospital perspective
Published in Journal of Medical Economics, 2022
Adrian Kilcoyne, Edward Jordan, Allen Zhou, Kimberly Thomas, Alicia N. Pepper, Dale Chappell, Miyuru Amarapala, Avery Hughes, Melissa Thompson
Lenzilumab is a novel Humaneeredi anti-human GM-CSF monoclonal antibody that directly binds GM-CSF, thereby preventing its downstream signaling15. The Phase 3 LIVE-AIR trial (NCT04351152) is a randomized, double-blind, placebo-controlled study designed to evaluate early intervention with lenzilumab compared with placebo, both in combination with standard of care (SOC), in newly hospitalized patients with COVID-19 pneumonia who have an oxygen saturation (SpO2) ≤94% on room air or require supplemental oxygen but have not progressed to IMV15. Preliminary results of the LIVE-AIR trial showed that lenzilumab significantly improved the likelihood of achieving survival without ventilation (SWOV) (sometimes referred to as ventilator-free survival) by day 28 compared with placebo15. SWOV is a robust composite endpoint used in many of the recent COVID-19 studies that are less prone to favor treatments with discordant effects on survival and days free of ventilation while avoiding the need for sample sizes approaching those of mortality trials to enable timely availability of study results21. Lenzilumab plus SOC was most efficacious as measured by SWOV in the groups of patients aged <85 years with CRP levels <150 mg/L, and patients aged <85 years with CRP levels <150 mg/L receiving remdesivir, compared with SOC alone22. C-reactive protein is an important marker of systemic inflammation and elevated levels of CRP are associated with poor clinical outcomes among patients with severe COVID-1915,22–24; therefore, preliminary findings from the LIVE-AIR trial suggest that lenzilumab may be particularly effective when used as an early intervention in hospitalized patients.