A Prognostic Classifier Based on Early Platelet Drop in Lower-Risk MDS: a Study from the European Leukemianet Lower-Risk MDS (EUMDS) Registry

Raphael Itzykson, Simon Crouch, Alex Smith, Argiris Symeonidis, Eva Hellstrom-Lindberg, Guillermo Sanz, Jaroslav Cermak, Reinhard Stauder, Luca Malcovati, Ulrich Germing, Moshe Mittelman, Saskia Langemeijer, Krzysztof Madry, Aurelia Tatic, Mette Skov Holm, Antonio Medina de Almeida, Aleksandar Savic, Njetočka Gredelj-Šimec, Elisa Luño Fernandez, Dominic CulliganAgnes Guerci Bresler, Corine van Marrewijk, David T. Bowen, T. M. M de Witte, Pierre Fenaux

Research output: Contribution to journal › Meeting abstract › peer-review

Abstract

Context: Prognosis of lower-risk (IPSS low/int-1) MDS is heterogeneous. Current prognostic systems rely on steady-state values for cytopenias. Capturing the dynamics of these parameters could yield additional prognostic information. We analyzed the prognostic relevance of relative drop (\ in neutrophil (ANC) and platelet (PLT) counts during the first six months follow-up of lower-risk MDS patients included in the EUMDS registry.Methods: TheEUMDS registry includes prospectively patients (pts) within the first 100 days of diagnosis of lower-risk (IPSS low/intermediate-1) MDS. We performed a landmark analysis of overall survival (OS) in pts with a visit at 6±1 months from inclusion to assess the prognostic relevance of a relative drop in ANC and PLT over the first 6 months follow-up. Relative ANC and PLT drops were defined as: (ANC at landmark - ANC at inclusion) / ANC at inclusion, respectively (resp) for PLT.Results: As of Sept 2016,1,800 patients with ≥5 months follow-up were included in the registry. 807 patients with a second visit at 6±1 months from inclusion were analyzed. Reasons for exclusion from this cohort were: no visit within the strict limits of 6±1 month (n=904), no PLT count at baseline (n=40) or 6-month visit (n=20), and no follow-up beyond 6-month visit (n=19). Median age was 73 yr, IPSS-R was very-low, low, intermediate or higher in 26\ 43\4\\ resp. Median time to landmark was 183 days. Median follow-up from landmark was 37.8 months. Median relative drop in ANC and PLT was 5.2\.6\ resp. At landmark, 41 patients (5\ received treatments affecting ANC or PLT (hypomethylating agents, lenalidomide or hydroxycarbamide). Excluding them did not affect results. Relative ANC and PLT drop were dichotomized at the 25\ transfusion dependency (TD) at inclusion (OR=1.7, p=0.02) as the main predictor of 6-month relative PLT drop \gt; 25\ while higher baseline ANC as a continuous value was associated with 6-month ANC drop \gt;25\10-4). The latter suggests that the dynamic range of ANC does not allow uniform assessment of ANC drop in all MDS patients.In univariate analysis, a relative drop in PLT \gt;25\HR=2.3, p\lt;10-4) was associated with shorter OS after the 6-month landmark (median 29.2 months vs 57.1 in pts with PLT drop ≤25\ p\lt;10-4), and increased cumulative incidence of progression (CIP: standardized HR: 2.5, p\lt;10-4), while relative ANC drop \gt;25\standardized HR: 1.5, p=0.03), without significant impact on OS (p=0.12). The adverse prognosis of relative PLT drop was observed regardless of baseline IPSS-R or absolute PLT count at inclusion or landmark.We subsequently divided our cohort in a training (n=403) and a validation (n=404) set to derive a prognostic model applicable at the 6-month landmark. Variables included age, gender and IPSS-R at inclusion, RBC-TD, steady-state PLT and ANC values at landmark, and relative PLT and ANC drop (with the 25\. Cox models with variable selection by penalized regression identified older age (p\lt;10-4), RBC-TD at landmark (p\lt;10-4) and relative PLT drop \gt;25\p=0.005) as independent prognostic factors. We built a simple age-independent 6-month EUMDS classifier based on RBC-TD at landmark and relative PLT drop \gt;25\ where patients with none (53\, either (31\ or both criteria (16\ had median OS from landmark of 71, 42 and 19 months, resp, p\lt;10-4). The classifier performed equally well in the validation set (p\lt;10-4). A sensitivity analysis relaxing the timing of landmark drop was carried on an 'extended cohort' of 1610 (89\ registry pts with a second visit within ten months of inclusion. This analysis confirmed the adverse prognostic value of a relative PLT drop \gt;25\0 months of diagnosis of lower-risk MDS and the broad applicability of the EUMDS classifier, regardless of baseline IPSS-R risk (Figure).Conclusion: Early drop in platelets during the first 6 months of follow-up holds prognostic significance in lower-risk MDS. A 6-month classifier based on RBC-TD at 6 month and a relative platelet drop greater than 25\risk MDS independently from IPSS-R.Itzykson: Novartis: Research Funding; Janssen: Research Funding. Sanz: Gamida Cell: Research Funding. Germing: Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Almeida: Novartis: Consultancy; Celgene: Consultancy; Bristol Meyer Squibb: Honoraria; Alexion: Honoraria; Servier: Consultancy. Fenaux: Astex: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.
Original languageUndefined/Unknown
Pages (from-to)158
Number of pages1
JournalBlood
Volume130
Issue numberSuppl. 1
DOIs
Publication statusPublished - 1 Dec 2017
Event59th ASH Annual Meeting & Exposition - Atlanta, Georgia, United States
Duration: 9 Dec 2017 → 12 Dec 2017

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