Session: 508. Bone Marrow Failure: Acquired: Poster III
Hematology Disease Topics & Pathways:
Bone Marrow Failure Syndromes, Paroxysmal Nocturnal Hemoglobinuria, Diseases
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease. Parker described three phenotypes: Classic PNH (C-PNH), PNH associated with another bone marrow disorder (BMD-PNH), and subclinical PNH associated with another bone marrow disorder (BMD-SCPNH). Virtually all research of complement inhibitors is focused on C-PNH, while BMD-PNH remains a poorly studied phenotype. The main objective of this study was to analyze survival of BMD-PNH patients compared to that in C-PNH.
This is a multi-center retrospective study. We analyzed the outcomes of patients diagnosed with PNH from March 1990 to January 2022 in three hospitals in Mexico. PNH was classified according to Parker´s criteria. We compared clinical characteristics between patients with C-PNH and BMD-PNH. Univariate and multivariate analyses were performed to assess the impact of PNH phenotype on overall survival and Kaplan Meier curves were plotted to compare survival between groups.
We found 106 patients diagnosed with PNH, of which 6 patients with the BMD-SCPNH phenotype were excluded. We analyzed 100 patients, median age 49 years (37.5-59), 50% female, C-PNH 72% (n=72), BMD-PNH 28% (n=28). Relevant differences between groups (C-PNH vs BMD-PNH) include serum LDH median 1,147 vs 256 U/L, p=0.001, LDH ≥1.5 SLN 72.2% vs 26.08%, p=0.001, clone size 78.7% vs 18.8%, and platelets median 120x109 U/L vs 13x109U/L, p=0.0001. In the BMD-PNH group, 46.42% (n=13), had a clone size ≥50%, 7.14% (n=2) presented thrombotic events, and 21.42% (n=6) had high disease burden.
Regarding treatment agents (C-PNH vs BMD-PNH), complement inhibitor use was reported in 30.55% (n=22) vs only 3.57% (n=1), p=0.003, and anticoagulation treatment was also more frequent in C-NPH, 47.22% vs 7.14%, p=0.001. Use of bone marrow failure treatment (immunosuppressants and/or androgens) was frequent in the BMD-PNH group, 96.43%, n=27.
Table 1 describes pronostic factors found to influence survival. Of note, overall survival of BMD-PNH was considerably lower: median 1y (CI95%; 0-2.4h) vs 10y (CI95%;6.6-13.3y), p=0.012, as presented in Fig 1. In the multivariate analysis, lack of either complement inhibitor (HR 4.64; 95% CI, 1.66-12.94, p=0.003) or lack anticoagulation treatment was independently associated with increased mortality (HR 2.00; 95%CI 1.24-3.25, p=0.005).
We found that BMD-PNH patients had a notably inferior survival, and infrequently received agents considered to be standard in C-PNH treatment. Interestingly, 21.42% of BMD-PNH had a high disease burden, a frequent indication of complement inhibitor use in C-PNH. Since specific treatment of BMD-PNH hasn’t been defined (that is, beyond immunosuppression and/or androgens), use of complement inhibitor therapy could be a promising option. To our knowledge, clinical trial information of complement inhibitors in BMD-PNH patients is currently lacking.
Disclosures: Alvarez: Novartis,: Speakers Bureau; AbbVie: Speakers Bureau; Bristol: Speakers Bureau; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Teva: Speakers Bureau. Demichelis: Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Teva: Consultancy; Gilead: Consultancy; ASH: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Apodaca: Asofarma: Speakers Bureau.
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