Inhaled Sargramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor) for COVID-19-Associated Acute Hypoxemia: Results of the Phase 2, Randomized, Open-Label Trial (iLeukPulm).

INTRODUCTION: Granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein produced in the lung, is essential for pulmonary host defense and alveolar integrity. Prior studies suggest potential benefits in several pulmonary conditions, including acute respiratory distress syndrome and viral infections. This trial evaluated the effect of the addition of inhaled sargramostim (yeast-derived, glycosylated recombinant human GM-CSF) to standard of care (SOC) on oxygenation and clinical outcomes in patients with COVID-19-associated acute hypoxemia. MATERIALS AND METHODS: A randomized, controlled, open-label trial of hospitalized adults with COVID-19-associated hypoxemia (oxygen saturation <93% on ≥2 L/min oxygen supplementation and/or PaO2/FiO2 <350) randomized 2:1 to inhaled sargramostim (125 mcg twice daily for 5 days) plus SOC versus SOC alone. Institutional SOC before and during the study was not limited. Primary outcomes were change in the alveolar-arterial oxygen gradient (P(A-a)O2) by day 6 and the percentage of patients intubated within 14 days. Safety evaluations included treatment-emergent adverse events. Efficacy analyses were based on the modified intent-to-treat population, the subset of the intent-to-treat population that received ≥1 dose of any study treatment (sargramostim and/or SOC). An analysis of covariance approach was used to analyze changes in oxygenation measures. The intubation rate was analyzed using the chi-squared test. All analyses are considered descriptive. The study was institutional review board approved. RESULTS: In total, 122 patients were treated (sargramostim, n = 78; SOC, n = 44). The sargramostim arm experienced greater improvement in P(A-a)O2 by day 6 compared to SOC alone (least squares [LS] mean change from baseline [SE]: -102.3 [19.4] versus -30.5 [26.9] mmHg; LS mean difference: -71.7 [SE 33.2, 95% CI -137.7 to -5.8]; P = .033; n = 96). By day 14, 11.5% (9/78) of sargramostim and 15.9% (7/44) of SOC arms required intubation (P = .49). The 28-day mortality was 11.5% (9/78) and 13.6% (6/44) in the sargramostim and SOC arms, respectively (hazard ratio 0.85; P = .76). Treatment-emergent adverse events occurred in 67.9% (53/78) and 70.5% (31/44) on the sargramostim and SOC arms, respectively. CONCLUSIONS: The addition of inhaled sargramostim to SOC improved P(A-a)O2, a measure of oxygenation, by day 6 in hospitalized patients with COVID-19-associated acute hypoxemia and was well tolerated. Inhaled sargramostim is delivered directly to the lung, minimizing systemic effects, and is simple to administer making it a feasible treatment option in patients in settings where other therapy routes may be difficult. Although proportionally lower rates of intubation and mortality were observed in sargramostim-treated patients, this study was insufficiently powered to demonstrate significant changes in these outcomes. However, the significant improvement in gas exchange with sargramostim shows this inhalational treatment enhances pulmonary efficiency in this severe respiratory illness. These data provide strong support for further evaluation of sargramostim in high-risk patients with COVID-19.

A prospective crossover pilot study to evaluate the use of a topical wound gel in patients with cutaneous toxicity caused by epidermal growth factor receptor inhibitors.

One of the dose-limiting toxicities of epidermal growth factor receptor inhibitors (EGFRIs) is a papulopustular rash that is often pruritic and painful. Secondary skin infection can occur from scratching to relieve the pruritus. Studies suggest that this rash might be a surrogate marker for efficacy; therefore, effective rash management is needed to allow patients to use EGFRIs without unnecessary dose modifications. In this single-center, prospective, crossover study, we evaluated the use of a topical gel (Regenecare Wound Gel) for relieving the pruritus and pain of EGFRI-induced rash among oncology patients. The secondary end points were patient satisfaction, adverse effects, and EGFRI dose modifications. At the occurrence of grade 2 skin rash, patients started applying the study gel to the right side of their face; after 1 week, they began applying it to both sides of their face for up to an additional 5 weeks. Each week, providers performed a facial evaluation and patients rated their symptoms and satisfaction on questionnaires. Of the 20 patients enrolled, 13 were evaluable. Reduction in itch at the end of week 1 was greater on the right (treated) side in 69% of patients greater on the left (untreated) side in 8%, and the same in 23% (P = 0.01). The pattern was similar for pain, but the differences were not significant. On average, patients rated the gel as being moderately to extremely effective for alleviating symptoms, improving rash appearance, and promoting healing and found it easy to apply. No adverse effects were documented. Four patients (31%) required EGFRI dose modifications because of rash. Taken together, these findings suggest that the topical wound gel is effective in relieving rash-associated itching in patients receiving EGFRIs and is associated with high patient satisfaction.

Managing colorectal cancer liver metastases.

The treatment of resectable colorectal cancer metastases to the liver has undergone changes with the addition of active chemotherapeutic agents, innovations and definition in the surgical procedures, understanding of the benefits and toxicities of the surgical and chemotherapeutic (cytotoxic and biologic) interventions, and use of the team approach. Patients are initially evaluated for the overall risk of their disease, which includes the standard parameters for disease recurrence and blends in disease and patient comorbidities and likelihood of surgical success. Advanced imaging techniques are mandatory in the initial evaluation. Rather than approaching the patient with sequential, independent therapies and handoff from specialist to specialist, a continuous interaction is required. This article outlines the initial consultation, required team components, surgical decision-making, and use of cytotoxic and biologic agents. The implication is that the best outcomes can only be achieved with the use of all modalities.