The Integrated Glasgow Prognostic- and Cytogenetic Risk Score (CytoGPS) at Diagnosis Is a Strong and Independent Predictor of Survival in Transplant-Eligible Patients with Multiple Myelom
Authors: Witte Hanno Maximilian , Biersack Harald , Riecke Armin , Bonorden Bastian , Kopelke Svenja , Merz Hartmut , Bernard Veronica , Lehnert Hendrik , Kull Miriam , Fetscher Sebastian , Gebauer Niklas 
Published: October 2019

Abstract
Abstract
Introduction: Immunity and inflammatory response impact tumor microenvironment and progression of malignancies. Metabolic and inflammatory parameters of the peripheral blood, and ratios of the latter, correlate with outcome in cancer patients. There exist several established inflammation-based scores of prognostic significance including the Glasgow-prognostic-score (GPS; integrating serum-CRP (>10 mg/L: 1pt) and albumin (< 35g/L: 1 pt).
Methods: In this retrospective multi-center study we investigated the prognostic capabilities of an integrated scoring system including GPS and information on cytogenetic high-risk aberrations as determined by FisH (CytoGPS) in transplant-eligible MM patients as a complementary resource for risk-stratification. Patients with MM admitted to our institutions between January 2000 and July 2017 were screened and established prognostic factors were assessed. CytoGPS was calculated as conventional GPS score plus one additional point for high-risk cytogenetics. Statistical evaluation resulted in three significantly divergent groups in terms of clinical outcome (Group I: 0-1 pts.; group II. 2 pts.; III: 3 pts.). Characteristics significantly associated with OS or PFS were included in a proportional-hazard-model. The study was approved by the local ethics committee.
Results: Following initial assessment we identified 212 eligible and fully evaluable as well as transplant eligible patients. Centralized review of pathology and cytogenetic reports was conducted and central hematopathology assessment was performed in 163/212 (76.9%) cases. All patients included in the study proceeded to high-dose melphalan and subsequent autologous stem cell transplantation. Median age at diagnosis was 59 years (range 35 - 76 years) with a median follow-up of 76 months. Mean GPS was 0.849, with a mean CytoGPS of 0.472. Multivariate analysis revealed ISS (HR = 1.677, 95% CI = 1.035 - 2.716, p = 0.036) and CytoGPS but not R-ISS to be the only independent predictors of OS and CytoGPS constituted the only independent predictor of PFS (OS: HR = 2.172; 95% CI = 1.607 - 2.936 p = 0.001; PFS: HR = 1.517; 95% CI = 1.174 - 1.960, p = 0.001). The impact of CytoGPS on OS and PFS is presented in Figure 1.
Discussion: There is growing evidence stating a drastic impact of systemic inflammatory scores and cytogenetic data on clinical outcome in various malignancies including lymphoma and solid tumors. Our data show that baseline CytoGPS, integrating both these aspects, correlates with rates of relapse and refractory disease across all primary stages of MM in transplant-eligible patients. Upon multivariate analysis these effects were preserved with prognostic impact beyond established prognosticators. CytoGPS constitutes a promising means of risk-stratification in MM requiring further validation.
Acknowledgments
The authors would like to thank Mr. Jan Kroenke (ASH-Member) for the sponsorship of this abstract.
Figure 1: Overall and Progression-free Survival in transplant-eligible Multiple Myeloma patients according to CytoGPS (Log-rank: A: p < 0.0001, B: p = 0.0001).

Disclosures
No relevant conflicts of interest to declare.