Clinical and economic benefits of lenzilumab plus standard of care compared with standard of care alone for the treatment of hospitalized patients with Coronavirus Disease 19 (COVID-19) from the perspective of National Health Service England

PurposeEstimate the clinical and economic benefits of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of hospitalized COVID-19 patients from the National Health Service (NHS) England perspective. MethodsA cost calculator was developed to estimate the clinical benefits and costs of adding lenzilumab to SOC in newly hospitalized COVID-19 patients over 28 days. The LIVE-AIR trial results informed the clinical inputs: failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included drug acquisition and administration for lenzilumab and remdesivir and hospital resource costs based on level of care required. Clinical and economic benefits per weekly cohort of newly hospitalized patients were also estimated. ResultsIn all populations examined, specified clinical outcomes were improved with lenzilumab plus SOC over SOC treatment alone. In a base case population aged <85 years with C-reactive protein (CRP) <150 mg/L, with or without remdesivir, adding lenzilumab to SOC was estimated to result in per-patient cost savings of {pound}1,162. In a weekly cohort of 4,754 newly hospitalized patients, addition of lenzilumab to SOC could result in 599 IMV uses avoided, 352 additional lives saved, and over {pound}5.5 million in cost savings. Scenario results for per-patient cost savings included: 1) aged <85 years, CRP <150 mg/L, and receiving remdesivir ({pound}3,127); 2) Black patients with CRP <150 mg/L ({pound}9,977); and 3) Black patients from the full population ({pound}2,369). Conversely, in the full mITT population, results estimated additional cost of {pound}4,005 per patient. ConclusionFindings support clinical benefits for SWOV, mortality, time to recovery, time in ICU, time on IMV, and ventilator use, and an economic benefit from the NHS England perspective when adding lenzilumab to SOC for hospitalized COVID-19 patients.

Radiotherapy and Immunotherapy Combinations for Lung Cancer.

PURPOSE OF REVIEW: Positive results from recent immunotherapy trials of non-small cell lung cancer (NSCLC) have coincided with a greater appreciation for the impact of radiation therapy (RT) on tumor immunity. Here, we summarize key clinical findings and ongoing efforts to combine immunotherapy and RT for the treatment of NSCLC. RECENT FINDINGS: The role of immunotherapy for NSCLC has expanded significantly following the pivotal approvals of nivolumab and pembrolizumab for metastatic NSCLC, maintenance durvalumab in unresectable stage III NSCLC, and atezolizumab for metastatic NSCLC. Several small early-phase trials have demonstrated the ability of RT to elicit clinically significant tumor immunity. These positive findings support current trial efforts combining RT with immunotherapy for NSCLC. Recently initiated trials of RT and immunotherapy hold significant promise in expanding the therapeutic options for NSCLC. Optimization of therapy will require careful patient selection to yield meaningful improvements in clinical outcomes.

Generating antitumor immunity by targeted radiation therapy: Role of dose and fractionation.

Accumulating evidence supports the role of radiation therapy in the induction of antitumor immunity. With recent advancements in stereotactic radiation therapy, there is increasing appreciation that, when combined with immune checkpoint blockade, the type of radiation dose and fractionation regimen selected may both influence local tumor control and also affect the generation of immune responses that are important for systemic control. Although a broad range of radiation dose and fractionation schema have been tested in both the preclinical and clinical settings, recent preclinical evidence suggests the existence of a dose per fraction threshold beyond which radiation becomes less effective in generating tumor immune responses. Such a threshold seems to be tumor dependent, probably reflecting different genetic mutations of cancer. In this review we discuss the key preclinical and clinical evidence relating to radiation dose and fractionation considerations. Future clinical trials should focus on identifying optimal radiation dose and fractionation schedules, which may depend on the clinical context.