Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey.

In 2021, 47,412 HCT (19,806 (42%) allogeneic and 27,606 (58%) autologous) in 43,109 patients were reported by 694 European centers. 3494 patients received advanced cellular therapies, 2524 of which were CAR-T treatments, an additional 3245 received DLI. Changes compared to the previous year were CAR-T treatment (+35%), allogeneic HCT +5.4%, autologous HCT +3.9%, more pronounced in non-malignant disorders. Main indications for allogeneic HCT were myeloid malignancies 10,745 (58%), lymphoid malignancies 5127 (28%) and non-malignant disorders 2501 (13%). Main indications for autologous HCT were lymphoid malignancies 22,129 (90%) and solid tumors 1635 (7%). In allogeneic HCT, use of haploidentical donors decreased by -0.9% while use of unrelated and sibling donors increased by +4.3% and +9%. Cord blood HCT decreased by -5.8%. Pediatric HCT increased overall by +5.6% (+6.9% allogeneic and +1.6% autologous). Increase in the use of CAR-T was mainly restricted to high-income countries. The drop in HCT activity reported in 2020 partially recovered in 2021, the second year of the SARS-CoV-2 pandemic. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual EBMT report reflects current activities useful for health care resource planning.

Efficacy and Safety at 48 Weeks of Pegcetacoplan in Adult Paroxysmal Nocturnal Hemoglobinuria Patients with Suboptimal Response to Prior Eculizumab Treatment

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.