The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia

Markus Pfirrmann,François Guilhot,Richard E Clark,Sonja Heibl,Anna Turkina,Rüdiger Hehlmann,Martin Höglund,Ulla Olsson‐Strömberg ,Daniela Žáčková ,Andreas Hochhaus,Edgar Faber,Andrey Zaritskey,Michele Baccarani,Francisco Cervantes,Laimonas Griškevičius ,Hele Everaus,Witold Prejzner,Irena Preložnik Zupan ,Susanne Saußele ,Michael Lauseker,Gert J Ossenkoppele ,Andrija Bogdanović ,Boris Labar,Adriana Coliță ,Perttu Koskenvesa,Joerg Hasford,Fausto Castagnetti,Tomasz Sacha,Verena S Hoffmann

doi:10.1038/s41375-020-0931-9

Abstract

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.

Highlights

For patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores were addressed by the most recent European LeukemiaNet (ELN) recommendations [1]
Compared with the low-risk group (n = 3037, 59%), the cumulative incidence probabilities of dying because of CML were significantly higher in the intermediate- (n = 1449, 28%, Sokal non-low-risk patients were hardly different (SHR): 2.584 [95% confidence interval (CI): 1.795–3.721]) and the high-risk groups (n = 668, 13% SHR: 5.667 [95% confidence interval (95% CI): 3.912–8.209]) of the EUTOS Long-Term Survival (ELTS) score, with both P < 0.0001 (Fig. 4a)
First described over 30 years ago, the Sokal score remains popular for risk group discrimination, despite suggesting that, at diagnosis, more than 20% of chronicphase patients are at high-risk with respect to overall survival (OS)—even in the presence of tyrosine kinase inhibitor (TKI)—and despite the availability of the ELTS score developed in imatinib-treated patients [6]

Summary

Introduction

For patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores were addressed by the most recent European LeukemiaNet (ELN) recommendations [1]. In 1984, the Sokal score was developed to allocate chemotherapy-treated patients into three risk groups of approximately equal size predicting significantly different overall survival (OS) probabilities [2, 3]. In 1998, the Euro score was proposed to discriminate OS between three risk groups of patients treated

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