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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, hematologic disease characterized by complement-mediated hemolysis. PNH symptoms include anemia and debilitating fatigue. In the phase 3 PEGASUS trial (NCT03500549), pegcetacoplan demonstrated superiority over eculizumab in improving hemoglobin levels in adults with PNH. However, improvement in fatigue symptoms, measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and time to improvement are also valuable to clinicians considering treatment options. This analysis elucidates the time to achieve a clinically meaningful FACIT-Fatigue response. This post hoc analysis compared pegcetacoplan to eculizumab in time to 1) a clinically meaningful response (≥3-point FACIT-Fatigue improvement; additionally, ≥5-point improvement) and 2) FACIT-Fatigue normalization through Week 16 using the Kaplan-Meier curve and log-rank test. PEGASUS enrolled 80 patients ≥18 years of age with PNH (hemoglobin <10.5 g/dL at screening; stable eculizumab treatment ≥3 months). Patients completed a 4-week eculizumab+pegcetacoplan run-in period followed by 1:1 randomization to pegcetacoplan (n=41; 1,080 mg subcutaneously twice weekly) or eculizumab (n=39) through Week 16. FACIT-Fatigue is a 5-point Likert scale instrument (scores 0-52), where a ≥3-point increase is considered clinically meaningful. FACIT-Fatigue normalization was achieved when patient scores reached the general population mean of ≥43.6 (Cella, et al. Cancer. 2002). Other outcome measures included a ≥5-point improvement in the FACIT-Fatigue score (Cella, et al. Blood. 2021). The Kaplan-Meier analysis demonstrated that pegcetacoplan patients achieve a clinically meaningful response at a significantly faster rate than eculizumab-treated patients. At Week 2, a higher probability of ≥3-point improvement (80.49%), ≥5-point improvement (68.29%), and FACIT-Fatigue normalization (37.50%) was observed in the pegcetacoplan group compared to the eculizumab group (45.71%, 34.29%, and 21.43%, respectively). Within Week 16, FACIT-Fatigue ≥3-point improvement was observed in 36/41 pegcetacoplan patients and 16/36 eculizumab patients (P<0.0002). FACIT-Fatigue ≥5-point improvement was observed in 33/41 pegcetacoplan patients and 12/36 eculizumab patients (log-rank test P<0.0002). FACIT-Fatigue normalization was achieved by 23/32 pegcetacoplan patients and 6/29 eculizumab patients (log-rank test P<0.0086). Patients with PNH treated with pegcetacoplan had significantly higher probabilities of displaying clinically meaningful improvements in their FACIT-Fatigue scores and achieving rapid FACIT-Fatigue normalization than eculizumab-treated patients. Copyright © 2022 Elsevier Inc. All rights reserved.


Dharmik Desai, Jesse Fishman, Xuan Zhang. MDS-136 Rapid Time to a Clinically Meaningful Response in FACIT-Fatigue Scores With Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria: A Kaplan-Meier Analysis from the PEGASUS Trial. Clinical lymphoma, myeloma & leukemia. 2022 Oct;22 Suppl 2:S306

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PMID: 36163948

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