ABSTRACT
Context: Pegcetacoplan (PEG) is a C3 complement inhibitor recently approved by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PEG was superior to eculizumab (ECU;C5-inhibitor) in improving hemoglobin levels at week 16 during the phase 3 PEGASUS trial (NCT03500549) in patients with suboptimal response to prior ECU treatment. Objective: We report on efficacy and safety of PEG and results from a post hoc time-aligned analysis based on start of PEG dosing. Design: Eighty PNH patients (≥18 years, hemoglobin levels <10.5 g/dL despite stable ECU treatment [≥3 months]) were enrolled. Following a 4-week run-in, patients were randomized (1:1) to PEG or ECU monotherapy for the randomized controlled period (RCP) through week 16, before initiating an open-label period (OLP) through week 48, where ECU patients completed a second run-in before switching to PEG monotherapy (ECU-to-PEG), and PEG patients continued PEG monotherapy (PEG-to-PEG). Key endpoints included change from baseline (CFB) in hemoglobin levels and incidence of adverse events (AEs). Timepoints were manually aligned based on start of PEG dosing (PEG-to-PEG: day 1;ECU-to-PEG: week 20) to compare changes in hemoglobin levels between groups. Results: PEG-to-PEG patients achieved sustained improvements in hemoglobin levels at week 16 through the OLP (week 48 mean hemoglobin level: 11.3 g/dL;CFB: 2.5 g/dL). ECU-to-PEG patients displayed improved hemoglobin levels during the OLP (week 48 mean hemoglobin level: 11.6 g/dL;CFB: 2.9 g/dL). Timepoint alignment demonstrated no significant difference (p=0.64) between improvements in hemoglobin levels at 28 and 48 weeks among PEG-to-PEG and ECU-to-PEG groups, respectively. Thirty percent of patients reported a serious AE, 6% possibly PEG-related. Common AEs for PEG-treated patients were injection site reactions (36%), hemolysis (24%), and diarrhea (21%). Twelve patients (15%) discontinued PEG due to AEs: 3 in RCP, 8 in OLP, 1 during follow-up, including one death due to COVID-19, unrelated to PEG. Conclusions: PEG-treated patients experienced sustained improvements in hemoglobin levels at week 48, and the safety profile of PEG was consistent with previously reported data. The treatment effect of PEG on hemoglobin levels over time was similar between PEG-to-PEG and ECU-to-PEG groups. Thus, PEG represents a new effective therapeutic option for PNH patients.
ABSTRACT
INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.