Prognostic Impact of Beta 2 Microglobulin in Patients with Immunoglobulin Light-Chain Amyloidosis Undergoing Autologous Hematopoietic Stem Cell Transplantation
Authors: Afrough Aimaz , Srour Samer A. , Bashir Qaiser , Saini Neeraj , Hosing Chitra , Popat Uday R. , Kebriaei Partow , Shpall Elizabeth J. , Delgado Ruby , Murphy Regan , Manasanch Elisabet E. , Lee Hans C. , Kaufman Gregory P. , Patel Krina K. , Thomas Sheeba K. , Weber Donna M. , Orlowski Robert Z. , Champlin Richard E. , Qazilbash Muzaffar H. 
Published: November 2020

Background: Risk stratification for Immunoglobulin light chain amyloidosis (AL) has been refined with advances in the understanding of disease biology. Although nonspecific, beta 2 microglobulin (β2M) levels correlate with disease burden and are considered a prognostic marker in several hematologic malignancies. Recently, we and others have shown the association of β2M levels with survival in AL. In this study, we evaluated the role of β2M as a predictor of outcome for high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) in patients with AL.
Methods: We identified 175 consecutive patients with AL who received auto-HCT between 2009 and 2019 at our institution. A β2M≥3.5 mg/L, regardless of renal function status was used as a cutoff value. Hematologic and organ responses were evaluated according to the Consensus Guidelines for AL. Revised Mayo staging system was utilized for Cardiac staging.
Results: The median age at auto-HCT was 60 years (range, 27 to 77). Of 175 patients, 153 (87%) had a β2M value available, of whom 57 (37%) had a β2M ≥ 3.5 mg/L. There were no significant differences in baseline characteristics between the 2 groups, except for the higher level of LDH, worse renal function, and more patients with renal involvement in the β2M ≥ 3.5 group, and more patients with lambda light chain type in the β2M &lt;3.5 group (Table 1). The median follow-up from auto-HCT was 38 months (range; 1 to 124). One-year non-relapse mortality (NRM) was 2%. The 1-year NRM was 5% (n=3) and 1% (n=1) in patients with β2M≥3.5, and β2M&lt;3.5, respectively (p=0.115). Hematologic CR after auto-HCT was seen in 21 (37%), and 38 (40%) patients with β2M≥3.5 and β2M&lt;3.5, respectively (p=0.864). Organ response (OR) after auto-HCT was seen in 36 (73%), and 65 (71%) patients with β2M≥3.5 and β2M&lt;3.5, respectively (p=1.00).
The 3-year progression-free survival (PFS) was 66%, and 74% in patients with β2M≥3.5, and β2M&lt;3.5 (p=0.17) (Figure 1A).The 3-year overall survival (OS) was 73%, ad 89% in patients with β2M≥3.5, and β2M&lt;3.5 (p=0.009) (Figure 1B). On Cox-regression multivariate analysis, cardiac involvement with AL (p=0.043), and β2M≥3.5 (p=0.029) were associated with a shorter OS.
Conclusion: In this single-center retrospective analysis, we showed that high serum β2M is associated with shorter OS. β2M may be incorporated as a prognostic marker for AL if these findings are confirmed in larger studies.

Disclosures
Bashir: Acrotech: Research Funding; StemLine: Research Funding; Celgene: Research Funding; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Novartis: Other: Served on advisory board; Jazz: Consultancy; Ziopharm: Other: Research Support; Kite: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Amgen: Other: Research Support. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Manasanch:Sanofi: Research Funding; Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Merck: Research Funding; JW Pharma: Research Funding; Novartis: Research Funding. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Cellectis: Research Funding; Nektar: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding. Thomas:BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Genentech: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Champlin:Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy; Actinium: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties. Qazilbash:Angiocrine: Research Funding; Bioline: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding.