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404 The Prognostic Value for Survival of Self-Reported Fatigue in Patients with Newly Diagnosed Myelodysplastic Syndromes: An International Prospective Observational Study By the Gimema

Program: Oral and Poster Abstracts
Type: Oral
Session: 908. Outcomes Research: Myeloid Malignancies: Patient Reported Outcomes and their Association with Clinical Outcomes in Patients with Myeloid Malignancies
Hematology Disease Topics & Pathways:
Research, MDS, Clinical Research, Health outcomes research, Chronic Myeloid Malignancies, Patient-reported outcomes, Diseases, Real-world evidence, Myeloid Malignancies
Saturday, December 7, 2024: 4:15 PM

Fabio Efficace, PhD1*, Wael Al Essa2*, Uwe Platzbecker, MD3, Pasquale Niscola, MD4*, Giuseppe A Palumbo5*, Giovanni Caocci, MD6, Serena Puglia1*, Francesco Sparano1*, Massimo Breccia7*, Mario Luppi8*, Reinhard Stauder, MD, MSc9, Alessandra Ricco10*, Duska Petranovic11*, Frederic Baron12*, Maria Teresa Voso, MD13, Chiara Frairia, MD14*, Isabella Capodanno, MD15*, Chiara Sarlo16*, Rosangela Invernizzi17*, Claudio Fozza, MD18*, Maribel Doro19* and Marco Vignetti, MD1*

1Data Center and Health Outcomes Research Unit, Italian Group for Adult Haematologic Diseases (GIMEMA), Rome, Italy
2Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
3Clinic and Policlinic of Hematology and Cellular Therapy, Oncology and Hemostaseology, University Hospital, Leipzig, Germany
4Hematology Unit, Sant'Eugenio Hospital, Rome, Italy
5Dipartimento di Scienze Mediche, Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia,” University of Catania, Catania, Italy
6University of Cagliari, Monserrato, Italy
7Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
8University of Modena and Reggio Emilia, AOU Modena, Modena, Italy
9Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria
10Hematology and Transplants Unit, University of Bari, Bari, Italy
11Department of Hematology, Clinical Hospital Center Rijeka, Rijeka, HRV
12Department of Hematology, CHU de Liège, University of Liege, Liege, Belgium
13Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
14Department of Oncology, Division of Hematology, AOU Città della Salute e della Scienza, Turin, Italy
15Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy
16Hematology and Stem Cell Transplantation Unit, University Campus Bio-Medico, Rome, Italy
17Department of Internal Medicine, San Matteo IRCCS Policlinic Foundation, University of Pavia, Pavia, Italy
18Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
19Unidade de Hematologia, Hemoterapia e Oncologia (UHHO), Serviço de Transplante de Medula Óssea (STMO), Complexo Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil

BACKGROUND

The ability to accurately predict survival in patients with myelodysplastic syndromes (MDS) is critical to guide treatment decisions. Although well-established prognostic indices are available, very limited data exists on the potential prognostic value for survival of patient-reported outcomes (PRO) in the MDS setting.

OBJECTIVE

We performed a prospective observational study to investigate whether the assessment of self-reported fatigue severity during the diagnostic workup could predict overall survival (OS) beyond baseline key factors, including the Revised International Prognostic Scoring System (IPSS-R).

METHODS: Adult patients with newly diagnosed MDS were consecutively enrolled in a large international prospective observational study involving 53 centers across 11 countries. Overall survival was defined from the date of MDS diagnosis to death from any cause. At study entry patients were classified according to the IPSS-R and also completed a PRO assessment, including the EORTC QLQ-C30. The prognostic value of the EORTC QLQ-C30 self-reported fatigue scale (i.e., 3 items) and the IPSS-R categories were analyzed using univariate and multivariate Cox proportional hazards models, checking the proportionality assumption. The following key variables were included in the starting univariate model: time since diagnosis, sex, living arrangements, transfusion dependency, ECOG performance status, HCT comorbidity index and white blood cell count. We also explored how to integrate self-reported fatigue into the scoring algorithm of the IPSS-R to increase its predictive accuracy. To this end, two thresholds for fatigue were identified, one for the higher-risk group and one for the lower-risk group by the IPSS-R. This resulted in a new risk-score classification, i.e. the FA-IPSS-R. Differences among Kaplan-Meier OS estimation of the newly developed risk group categories (by combining self-reported fatigue plus the IPSS-R risk group classification) were assessed by log-rank test. Statistical significance for all tests was set as α=0.05.

RESULTS: Overall, 927 patients with MDS were enrolled between November 2008 and December 2018. The IPSS-R was available for 902 patients, who had a median age of 73 years (IQR 66-79). Of these, 521 (58%) were classified as higher-risk and 381 (42%) as lower-risk by the IPSS-R. At baseline, 142 (16%) patients were transfusion-dependent and 488 (54%) had ≥ 1 comorbidities. We observed 457 deaths, and the median OS was 30 months (95% confidence interval [CI], 26-35). The median OS was 68 months (95% CI, 56-82) and 19 months (95% CI, 17-21) for patients with IPSS-R lower and higher-risk disease, respectively. In multivariate analysis, baseline factors independently associated with reduced OS were ECOG performance status ≥ 2 (hazard ratio [HR] 1.733, 95% CI 1.347–2.230; p<0.001), transfusion dependency (HR 1.267, 95% CI 1.001–1.604; p=0.049), higher-risk IPSS-R score (HR 2.938, 95% CI 2.336–3.695; p<0.001) and a higher score for self-reported fatigue (HR 1.080, 95% CI 1.040–1.120; p<0.001). The latter translates into an 8% increase in the hazard of death for every 10-point increase (i.e., higher severity) in the fatigue scale (ranging from 0 to 100) of the EORTC QLQ-C30. We then aimed to incorporate fatigue into the IPSS-R scoring system to investigate whether it could enhance its predictive accuracy. Integration of fatigue severity into the two broad IPSS-R risk categories (i.e. lower- and higher-risk) yielded four risk group categories, with statistically significant different OS (p<0.001). Two-year OS for patients with the lowest FA-IPSS-R risk was 80.8% (95% CI, 75.5-86.6) and only 31.6% (95% CI, 25.1-39.7) for those with the highest FA-IPSS-R risk. By integrating the EORTC QLQ-C30 fatigue severity into the standard IPSS-R (i.e., five risk groups), the FA-IPSS-R scoring algorithm generated six group categories with distinct survival outcomes (p<0.001).

CONCLUSION

Our findings suggest that self-reported fatigue severity provides independent prognostic information for OS in patients with lower and higher risk MDS disease. Integration of a brief self-assessment of fatigue during the diagnostic workup of MDS may also enhance the predictive accuracy of the IPSS-R. Further analyses are needed to finalize the development of a patient-centric prognostic index combining fatigue and the IPSS-R.

Disclosures: Efficace: Novartis: Consultancy; AbbVie: Consultancy; Incyte: Consultancy; JAZZ Pharmaceuticals: Consultancy; Daiichi Sankyo: Research Funding. Platzbecker: Amgen: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Research Funding; Curis: Consultancy, Honoraria, Research Funding; Geron: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Novartis: Consultancy, Research Funding. Palumbo: Astrazeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Other: Travel expenses, Speakers Bureau; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Other: Travel expenses; Stemline Menarini: Other: Travel expenses; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; Incyte: Speakers Bureau. Breccia: AOP: Honoraria; GSK: Honoraria; BMS: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Luppi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Istituto Gentili: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Stauder: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees. Voso: Celgene/BMS: Other: Research support, Advisory Board, Speakers Bureau; Astellas: Speakers Bureau; Abbvie: Speakers Bureau; Jazz: Other: Advisory Board, Speakers Bureau; Syros: Other: Advisory Board; Astra Zeneca: Speakers Bureau; Novartis: Other: Research support, Speakers Bureau. Fozza: Sanofi: Research Funding; Soby: Consultancy; Amgen: Research Funding; BMS: Research Funding. Vignetti: Vertex: Honoraria; Isheo: Honoraria; Edrea: Honoraria; Arhea: Honoraria; Mattioli Health: Honoraria; Novartis: Honoraria; Astrazeneca: Honoraria; Abbvie: Honoraria; Dephaforum SRL: Honoraria.

*signifies non-member of ASH