Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN + AZA vs PBO + AZA patients had longer TTD in GHS/QoL (P = 0.066) and fatigue (P = 0.189), and significantly longer TTD in PF (P = 0.028) and HS-VAS (P < 0.001). VEN + LDAC vs PBO + LDAC patients had significantly longer TTD in GHS/QoL (P = 0.011), PF (P = 0.020), and fatigue (P = 0.004), and a trend in HS-VAS (P = 0.057). Approximately 43%, 35%, 32%, and 18% of patients treated with VEN + AZA, AZA + PBO, VEN + LDAC, or LDAC + PBO, respectively, saw improvements >MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.

AbbVie Inc North Chicago IL USA

Abramson Cancer Center University of Pennsylvania Philadelphia PA USA

Almazov National Medical Research Center Saint Petersburg Russian Federation

Australian Center for Blood Diseases The Alfred Hospital and Monash University Melbourne Australia

Department of Hematology and Cell Therapy Aichi Cancer Center Nagoya Japan

Department of Hematology Shaare Zedek Medical Center Faculty of Medicine Hebrew University of Jerusalem Jerusalem Israel

Department of Hematology University Hospital Dubrava University of Zagreb School of Medicine Zagreb Croatia

Department of Internal Medicine and Hematology University Hospital Kralovske Vinohrady and 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Internal Medicine China Medical University Hospital Taichung Taiwan

Department of Internal Medicine Division of Hematology and Oncology University of California Davis School of Medicine Sacramento CA USA

Department of Internal Medicine Division of Hematology Ondokuz Mayıs University Faculty of Medicine Samsun Turkey

Department of Leukemia Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston TX USA

Department of Oncology Hematology and Bone Marrow Transplantation With Section Pneumology Hubertus Wald University Cancer Center University Medical Center Hamburg Eppendorf Hamburg Germany

Genentech Inc South San Francisco CA USA

Hematology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Hospital Universitario y Politécnico La Fe Valencia Spain

National and Kapodistrian University of Athens Medical School Laiko General Hospital Athens Greece

Norton Cancer Institute Louisville KY USA

Princess Margaret Cancer Centre and University of Toronto Toronto ON Canada

Seoul National University Hospital Seoul Republic of Korea

Service d'Hématologie Centre Hospitalier Universitaire de Toulouse Institut Universitaire du Cancer de Toulouse Oncopole Université de Toulouse 3 Paul Sabatier Toulouse France

The Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital Zhengzhou China

Zobrazit více v PubMed

Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review, 1975-2017, National Cancer Institute. Bethesda, MD, based on November 2019 SEER data submission, posted to the SEER website, April 2020 [Available from: https://seer.cancer.gov/archive/csr/1975_2017/.

Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47. doi: 10.1182/blood-2016-08-733196. PubMed DOI PMC

Levis M. Midostaurin approved for FLT3-mutated AML. Blood. 2017;129:3403–06. doi: 10.1182/blood-2017-05-782292. PubMed DOI

Yu B, Liu D. Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia. Biomark Res. 2019;7:24. doi: 10.1186/s40364-019-0175-x. PubMed DOI PMC

Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015;125:767–74. doi: 10.1182/blood-2014-08-551499. PubMed DOI

Song X, Peng Y, Wang X, Chen Y, Jin L, Yang T, et al. Incidence, survival, and risk factors for adults with acute myeloid leukemia not otherwise specified and acute myeloid leukemia with recurrent genetic abnormalities: analysis of the surveillance, epidemiology, and end results (SEER) database, 2001–2013. Acta Haematologica. 2018;139:115–27. doi: 10.1159/000486228. PubMed DOI

Thein MS, Ershler WB, Jemal A, Yates JW, Baer MR. Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer. 2013;119:2720–7. doi: 10.1002/cncr.28129. PubMed DOI PMC

Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, et al. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 Trial. J Clin Oncol. 2016;34:972–9. doi: 10.1200/JCO.2015.64.0060. PubMed DOI

Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007;109:1114–24. doi: 10.1002/cncr.22496. PubMed DOI

Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–99. doi: 10.1182/blood-2015-01-621664. PubMed DOI PMC

Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670–7. doi: 10.1200/JCO.2011.38.9429. PubMed DOI PMC

Stein EM, DiNardo CD, Pollyea DA, Schuh AC. Response kinetics and clinical benefits of nonintensive AML therapies in the absence of morphologic response. Clin Lymphoma Myeloma Leuk. 2020;20:e66–e75. doi: 10.1016/j.clml.2019.11.017. PubMed DOI

AbbVie. VENCLEXTA [Prescribing information] Available from: https://www.rxabbvie.com/pdf/venclexta.pdf.

US Food Drug Administration. FDA approves venetoclax in combination for AML in adults [Available from: https://www.fda.gov/drugs/fda-approves-venetoclax-combination-aml-adults.

DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N. Engl J Med. 2020;383:617–29. doi: 10.1056/NEJMoa2012971. PubMed DOI

DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133:7–17. doi: 10.1182/blood-2018-08-868752. PubMed DOI PMC

Richard-Carpentier G, DiNardo CD. Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy. Ther Adv Hematol. 2019;10:2040620719882822. doi: 10.1177/2040620719882822. PubMed DOI PMC

Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135:2137–45. doi: 10.1182/blood.2020004856. PubMed DOI PMC

Wei AH, Strickland SA, Jr., Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: Results from a phase Ib/II study. J Clin Oncol. 2019;37:1277–84. doi: 10.1200/JCO.18.01600. PubMed DOI PMC

Winters AC, Gutman JA, Purev E, Nakic M, Tobin J, Chase S, et al. Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Blood Adv. 2019;3:2911–19. doi: 10.1182/bloodadvances.2019000243. PubMed DOI PMC

Buckley SA, Jimenez-Sahagun D, Othus M, Walter RB, Lee SJ. Quality of life from the perspective of the patient with acute myeloid leukemia. Cancer. 2018;124:145–52. doi: 10.1002/cncr.30982. PubMed DOI PMC

Mamolo CM, Cappelleri JC, Hoang CJ, Kim R, Hadfield A, Middleton C, et al. A real-world, cross-sectional, community survey of symptoms and health-related quality of life of adults with acute myeloid leukemia. Future Oncol. 2019;15:1895–909. doi: 10.2217/fon-2018-0842. PubMed DOI

Tomaszewski EL, Fickley CE, Maddux L, Krupnick R, Bahceci E, Paty J, et al. The patient perspective on living with acute myeloid leukemia. Oncol Ther. 2016;4:225–38. doi: 10.1007/s40487-016-0029-8. PubMed DOI PMC

Korol EE, Wang S, Johnston K, Ravandi-Kashani F, Levis M, van Nooten F. Health-related quality of life of patients with acute myeloid leukemia: a systematic literature review. Oncol Ther. 2017;5:1–16. doi: 10.1007/s40487-016-0039-6. PubMed DOI PMC

Deschler B, Ihorst G, Platzbecker U, Germing U, März E, de Figuerido M, et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98:208–16. doi: 10.3324/haematol.2012.067892. PubMed DOI PMC

Forsythe A, Kwon CS, Bell T, Smith TA, Arondekar B. Health-related quality of life in acute myeloid leukemia patients not eligible for intensive chemotherapy: results of a systematic literature review. Clinicoecon Outcomes Res. 2019;11:87–98. doi: 10.2147/CEOR.S187409. PubMed DOI PMC

Oliva EN, Nobile F, Alimena G, Ronco F, Specchia G, Impera S, et al. Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians. Haematologica. 2011;96:696–702. doi: 10.3324/haematol.2010.036715. PubMed DOI PMC

Stauder R, Lambert J, Desruol-Allardin S, Savre I, Gaugler L, Stojkov I, et al. Patient-reported outcome measures in studies of myelodysplastic syndromes and acute myeloid leukemia: Literature review and landscape analysis. Eur J Haematol. 2020;104:476–87. doi: 10.1111/ejh.13389. PubMed DOI PMC

Efficace F, Kemmler G, Vignetti M, Mandelli F, Molica S, Holzner B. Health-related quality of life assessment and reported outcomes in leukaemia randomised controlled trials–a systematic review to evaluate the added value in supporting clinical decision making. Eur J Cancer. 2008;44:1497–506. doi: 10.1016/j.ejca.2008.03.017. PubMed DOI

Cannella L, Caocci G, Jacobs M, Vignetti M, Mandelli F, Efficace F. Health-related quality of life and symptom assessment in randomized controlled trials of patients with leukemia and myelodysplastic syndromes: what have we learned? Crit Rev Oncol Hematol. 2015;96:542–54. doi: 10.1016/j.critrevonc.2015.07.012. PubMed DOI

Horvath Walsh LE, Rider A, Piercy J, Pike J, Wilson S, Pandya BJ, et al. Real-world impact of physician and patient discordance on health-related quality of life in US patients with acute myeloid leukemia. Oncol Ther. 2019;7:67–81. doi: 10.1007/s40487-019-0094-x. PubMed DOI PMC

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76. doi: 10.1093/jnci/85.5.365. PubMed DOI

Cella D, Lai JS, Jensen SE, Christodoulou C, Junghaenel DU, Reeve BB, et al. PROMIS fatigue item bank had clinical validity across diverse chronic conditions. J Clin Epidemiol. 2016;73:128–34. doi: 10.1016/j.jclinepi.2015.08.037. PubMed DOI PMC

Garcia SF, Cella D, Clauser SB, Flynn KE, Lad T, Lai JS, et al. Standardizing patient-reported outcomes assessment in cancer clinical trials: a patient-reported outcomes measurement information system initiative. J Clin Oncol. 2007;25:5106–12. doi: 10.1200/JCO.2007.12.2341. PubMed DOI

Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20:1727–36. doi: 10.1007/s11136-011-9903-x. PubMed DOI PMC

Oppe M, Devlin NJ, van Hout B, Krabbe PF, de Charro F. A program of methodological research to arrive at the new international EQ-5D-5L valuation protocol. Value Health. 2014;17:445–53. doi: 10.1016/j.jval.2014.04.002. PubMed DOI

Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16:139–44. doi: 10.1200/JCO.1998.16.1.139. PubMed DOI

Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health Qual Life Outcomes. 2007;5:70. doi: 10.1186/1477-7525-5-70. PubMed DOI PMC

Sekeres MA, Stone RM, Zahrieh D, Neuberg D, Morrison V, De Angelo DJ, et al. Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia. 2004;18:809–16. doi: 10.1038/sj.leu.2403289. PubMed DOI

Sekeres MA, Lancet JE, Wood BL, Grove LE, Sandalic L, Sievers EL, et al. Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. Haematologica. 2013;98:119–28. doi: 10.3324/haematol.2012.066613. PubMed DOI PMC

Kornblith AB, Herndon JE, 2nd, Silverman LR, Demakos EP, Odchimar-Reissig R, Holland JF, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002;20:2441–52. doi: 10.1200/JCO.2002.04.044. PubMed DOI

Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29:1987–96. doi: 10.1200/JCO.2010.30.9245. PubMed DOI

Storey S, Gray TF, Bryant AL. Comorbidity, physical function, and quality of life in older adults with acute myeloid leukemia. Curr Geriatr Rep. 2017;6:247–54. doi: 10.1007/s13670-017-0227-8. PubMed DOI PMC

Kantarjian H, Issa J-PJ, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, et al. Decitabine improves patient outcomes in myelodysplastic syndromes. Cancer. 2006;106:1794–803. doi: 10.1002/cncr.21792. PubMed DOI

Buckley SA, Kirtane K, Walter RB, Lee SJ, Lyman GH. Patient-reported outcomes in acute myeloid leukemia: where are we now? Blood Rev. 2018;32:81–87. doi: 10.1016/j.blre.2017.08.010. PubMed DOI

Kayastha N, Wolf SP, Locke SC, Samsa GP, El-Jawahri A, LeBlanc TW. The impact of remission status on patients’ experiences with acute myeloid leukemia (AML): an exploratory analysis of longitudinal patient-reported outcomes data. Support Care Cancer. 2018;26:1437–45. PubMed PMC

El-Jawahri A, Abel GA, Traeger L, Waldman L, Markovitz N, VanDusen H, et al. Quality of life and mood of older patients with acute myeloid leukemia (AML) receiving intensive and non-intensive chemotherapy. Leukemia. 2019;33:2393–402. doi: 10.1038/s41375-019-0449-1. PubMed DOI

Gnanasakthy A, Mordin M, Clark M, DeMuro C, Fehnel S, Copley-Merriman C. A review of patient-reported outcome labels in the United States: 2006 to 2010. Value Health. 2012;15:437–42. doi: 10.1016/j.jval.2011.11.032. PubMed DOI

DeMuro C, Clark M, Doward L, Evans E, Mordin M, Gnanasakthy A. Assessment of PRO label claims granted by the FDA as compared to the EMA (2006–2010) Value Health. 2013;16:1150–55. doi: 10.1016/j.jval.2013.08.2293. PubMed DOI

Velikova G, Coens C, Efficace F, Greimel E, Groenvold M, Johnson C, et al. Health-related quality of life in EORTC clinical trials—30 years of progress from methodological developments to making a real impact on oncology practice. Eur J Cancer. 2012;10:141–49. doi: 10.1016/S1359-6349(12)70023-X. DOI

Buckley SA, Halpern AB, Othus M, Jimenez-Sahagun D, Walter RB, Lee SJ. Development and validation of the AML-QOL: a quality of life instrument for patients with acute myeloid leukemia. Leuk Lymphoma. 2020;61:1158–67. doi: 10.1080/10428194.2019.1709838. PubMed DOI

Salas M, Henderson M, Wientzek-Fleischmann A, Islam Z, Tu N, Bilitou A, et al. Validated instruments of quality of life (QOL) in patients with acute myeloid leukemia (AML) and other cancers. Front Pharm. 2020;11:1109. doi: 10.3389/fphar.2020.01109. PubMed DOI PMC