Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled complement activation that leads to hemolysis and thrombosis. Clinical outcomes have dramatically improved with administering terminal and proximal complement inhibitors (CIs). However, these treatments come at the cost of increasingthe risk of severe infection, especially from encapsulated bacteria. This has created compulsory vaccination recommendations by regulatory authorities to patients with PNH on CIs treatment. Material and methods: An adaptation of the Delphi consensus process involving a group of experts in the field of hematology, infectious diseases, and vaccinology was used to develop Polish vaccination recommendations for patients with PNH treated with CIs. The experts reviewed 16 proposed statements, rating each from 1 to 9 in 3 rounds (1-3 denoted as "disagree", 4-6 as "neutral" and 7-9 as "agree"). A final decision on statements that were converged to strong or even moderate agreement was taken into practice. Results: A Delphi process ended with convergence into consensus all 16 prepared statements. Recommendations include routine immunization against meningococcus (MenACWY, MenB) in patients on proximal and terminal CIs, extended immunization against Streptococcus pneumoniae and Haemophilus influenzae type b in patients on proximal CIs, and the use of antibiotic prophylaxis against meningococcal infection in patients where the institution of CI therapy cannot be delayed until vaccines have been given. Annual immunizations against influenza and COVID-19 are also recommended. Conclusions: These consensus guidelines emphasize the paramount importance of optimal immunization for PNH patients treated with CIs. Completing vaccination schedules and implementing prophylactic strategies may significantly reduce the risk of severe, potentially life-threatening infections, thus allowingfor safer and more effective management of the disease.
7535 Background: In patients with NDMM, therapy after ASCT aims to deepen remission and prolong survival. Although lenalidomide (R) monotherapy after ASCT is well established, the impact of combination therapy on survival remains to be established. Interim results of the ATLAS study suggested that extended KRd after ASCT treatment prolongs progression-free survival (PFS) compared with R alone in patients with NDMM (Dytfeld et al, Lancet Oncol. 2023; 24:139–150). Here we provide the results from the primary analysis of the ATLAS study. Methods: This international, open-label phase 3 study randomly assigned adults with NDMM who completed induction and had stable disease or better after ASCT 1:1 to KRd or R alone as maintenance therapy. Randomization was stratified by post-transplant response, presence or absence of ≥1 high-risk cytogenetic abnormality, and by country. For the KRd group, patients with standard-risk cytogenetics and measurable residual disease (MRD) negativity at 10 -5 after cycle 6 were switched to R maintenance after cycle 8; remaining patients continued KRd up to 36 cycles and then switched to R. The preplanned primary endpoint was PFS. Secondary endpoints included overall survival (OS), MRD negativity, response rate, and safety. Results: At data cutoff (21 Oct 2024), median follow up was 5.7 years. The median number of treatment cycles initiated was 35 and 31 for KRd and R, respectively. After cycle 8, 40 of 81 patients on KRd switched to R. The 4-year PFS rate with KRd was superior to R (67.5% vs 36.8%; HR 0.46 [95% CI: 0.30, 0.70]; p=0.0002). The PFS benefit was consistent across subgroups, including high-risk cytogenetics (HR 0.52 [95% CI: 0.24, 1.1]) and MRD-positive status at randomization (HR 0.52 [95% CI: 0.29, 0.93)]. Median PFS was 72.8 months and 37.3 months in the KRd and R groups, respectively. The 4-year OS rate also was increased with KRd vs R (84.3% vs 79.2%; HR 0.49 [95% CI: 0.26, 0.90]; p=0.02). The depth of response improved across all response categories; the rate of MRD <10 - 5 and at least a complete response as best response was 74% and 51% (OR 2.7 [95% CI: 1.5, 5.1]; (p=0.002), and 12-month sustained MRD-negativity was 48% and 24% (OR 2.9 [95% CI 1.5, 5.5]; p=0.001) for KRd and R, respectively. No new safety signals were observed (Table). Conclusions: The ATLAS phase 3 study demonstrated superior PFS as well as longer OS with MRD-directed, risk-stratified KRd treatment compared with R alone in patients with NDMM after ASCT. Extended KRd maintenance treatment may represent a new standard of care. Clinical trial information: NCT02659293 . Treatment emergent adverse events. Patients, n (%) KRd(n=91) R(n=87) Any grade 89 (98) 83 (95) Grade ≥3 72 (79) 64 (74) Grade 5 2 (2.2) a 2 (2.3) b Any serious adverse event 29 (32) 20 (23) a Lung infection (n=2). b Lung/Covid infection (n=1); heart failure (n=1).
