Quality of Life to Predict Outcome for Older AML
Quality of Life to Predict Outcome for Older AML
Abstract & Commentary
By Andrew S. Artz, MD, MS, Division of Hematology/Oncology, University of Chicago. Dr. Artz reports no relationships relevant to this field of study.
Synopsis: Investigators prospectively assessed quality of life in newly diagnosed AML patients 60 years and older using the EORTC QLC-C30 and QOL-E surveys. Among the 113 patients enrolled, 42.4% underwent intensive induction chemotherapy and 57.6% received palliative treatment. Self-rated quality of life did not correlate with physician-rated performance status or induction chemotherapy. Lower self-report functional status predicted higher mortality, even after adjusting for age, treatment, and comorbidity. Patient-reported quality of life may be an independent prognostic factor for AML outcomes.
Source: Oliva E, et al. Quality of life in elderly patients with acute myeloid leukemia: Patients may be more accurate than physicians. Haematologica 2011;35:696-702.
Acute myeloid leukemia (AML) generally occurs in older adults, with a median age at diagnosis older than 65 years of age. Studies consistently demonstrate poor long-term outcomes even among fit elderly receiving induction chemotherapy on clinical trials or major university programs.1 Survival deteriorates for each decade of age and for performance status limitations.1 Elderly patients not only manifest more resistant and high-risk disease, but induction therapy exacts a greater toxicity burden related to reduced physiologic reserve. Typical health measures employed by oncologists include age, performance status, and more recently comorbidity. However, these parameters may not optimally capture health impairments that influence toxicity or survival, presenting challenges in determining prognosis and selecting treatment intensity.
The authors prospectively assessed patient-reported quality of life (QOL) using the QOL-E questionnaire, a previously validated tool for myelodysplastic syndrome.2,3 The QOL-E scores can range from 0–100 with a score < 60 considered subjective poor health. In addition, another more widely used QOL instrument in Europe, the EORTC-QLQ, was administered.
They studied 113 patients 60 years and older diagnosed with de novo AML. The mean age was 71.7 years and ECOG PS was good (0 or 1) in 101 (89%). At least one comorbid condition requiring treatment prior to an AML diagnosis existed in 68/113 (60.1%). As expected, hypertension, cardiac disease, and diabetes accounted for the majority of conditions. Treating physicians were unaware of the QOL scores. The majority (57.6%) were assigned palliative treatment while 42.4% received intensive chemotherapy. Patients 70 years and older were less likely to receive intensive therapy (P = 0.007). Blast count in the blood and marrow did not differ between patients receiving intensive treatment vs palliative care, suggesting perceived patient fitness and age most strongly influenced treatment selection. Comorbid conditions were more prevalent among older adults. QOL scores across the various domains of the instruments (e.g., functional, social, fatigue) did not differ for patients undergoing intensive therapy vs palliative treatment despite older age or more comorbidity among patients receiving palliative care. However, QOL scores at diagnosis showed a strong association with survival. Patients reporting low scores (i.e., < 60) only achieved median survival of 15 weeks compared to 55 weeks (P = 0.002) for patients demonstrating better QOL.
After adjusting for age, disease, and treatment, both instruments maintained their prognostic value. Physician-rated performance status did not accurately identify poor patient-reported physical function. Specifically, among patients rated in excellent health as gauged by a PS of 0 (i.e., normal), 27% reported a low score on physical function by EORTC and 33% by QOL-E. Among those with normal PS, impaired QOL score still was associated with worse survival. The value of QOL appeared greatest in adults 70 years and older. In contrast, for patients 60-69 years receiving intensive therapy, baseline QOL-E functional measures showed no association with survival (P = 0.617).
Commentary
Standard therapy for AML remains intensive induction therapy. However, the majority of AML patients are older, have high rates of early death with induction, and rarely achieve long-term disease control.4,5 Fitness for induction therapy is determined primarily by patient age and physician-rated PS. Subtle but significant limitations in physiologic reserve may not be captured by standard oncologic evaluation. Comorbidity tools using scores such as the HCT-CI have become more widespread and may enhance estimates of early death after AML induction.6 The introduction of new therapies, in addition to standard cytarabine and anthracycline, increases the need for better assessment as physicians must select from a larger menu of treatments.7-11
In this study, the authors prospectively administered two QOL instruments to 113 consecutive AML patients. Treatment decisions were independent of QOL assessment. The authors report several important findings. A significant number of patients showed impaired QOL, including around 30% reporting poor physical function despite having an ECOG PS of 0. Moreover, QOL scores did not differ for patients assigned to intensive treatment or palliative treatment, indicating that subjective QOL did not influence treatment decisions and likely was not well appreciated by physicians. As expected, age older than 70 years and the presence of comorbidity were associated with treatment assigned. Finally, impaired QOL predicted for worse survival, independent of treatment, age, or comorbidity.
As a single institutional study, the data require confirmation. Nevertheless, these findings add to a growing body of literature showing self-report QOL may serve not only as an important outcome, but impaired QOL at baseline independently portends for inferior survival. The results are not surprising. Particularly for AML, oncologists generally have only recently recognized the need to immediately determine fitness. Further, patients may not volunteer important information about health or function for fear that treatment will be withheld. QOL tools provide validated measures that may enable physicians to better collect and incorporate detailed and prognostically valuable patient information. These tools also may be less prone to the natural bias of patients to optimistically report how well they function to the treating physician. Numerous QOL tools are under study and thus we have a paucity of data for using a specific instrument for a specific disease. Future clinical trials, especially in the cooperative groups, should incorporate QOL instruments that would permit more definitive conclusions. Thus, a specific QOL tool and algorithm cannot be recommended at present for AML. However, physicians may want to more directly inquire patients about the self-report function. For example, in our practice, we ask specific questions about daily activity and whether the level of activity has changed. Such data compliment results from disease status and standard tools of age, PS, and comorbidity.
In summary, poor self-report QOL in older AML patients is independent of treatment, age, or comorbidity and is associated with worse survival. Future studies are needed to clarify how to integrate specific QOL tools into prognostic discussions and treatment decisions. At a minimum, physicians should be more aware of patients' perceived health status at the time of AML diagnosis.
References
1. Appelbaum FR, et al. Age and acute myeloid leukemia. Blood 2006;107:3481-3485.
2. Oliva EN, et al. More concern about transfusion requirement when evaluating quality of life in anemic patients. J Clin Oncol 2002;20:3182-3183; author reply 3183-3184.
3. Oliva EN, et al. Darbepoetin alfa for the treatment of anemia associated with myelodysplastic syndromes: Efficacy and quality of life. Leuk Lymphoma 2010;51:1007-1014.
4. Kantarjian H, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010;116:4422-4429.
5. Juliusson G. Most 70- to 79-year-old patients with acute myeloid leukemia do benefit from intensive treatment. Blood 2011;117:3473-3474.
6. Giles FJ, et al. The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. Br J Haematol 2007;136:624-627.
7. Faderl S, et al. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood 2008;112:1638-1645.
8. Larson RA, et al. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia 2002;16:1627-1636.
9. Fenaux P, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010;28:562-569.
10. Lowenberg B, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009;361:1235-1248.
11. Cashen AF, et al. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol 2010;28:556-561.
Investigators prospectively assessed quality of life in newly diagnosed AML patients 60 years and older using the EORTC QLC-C30 and QOL-E surveys. Among the 113 patients enrolled, 42.4% underwent intensive induction chemotherapy and 57.6% received palliative treatment. Self-rated quality of life did not correlate with physician-rated performance status or induction chemotherapy. Lower self-report functional status predicted higher mortality, even after adjusting for age, treatment, and comorbidity. Patient-reported quality of life may be an independent prognostic factor for AML outcomes.Subscribe Now for Access
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