Table 6.
Considerations for risk stratification and treatments for older adults with AML
| Patient risk category | Characteristics | Treatment Considerations (Clinical trials preferred) |
|---|---|---|
| Frail | Poor oncology performance status (ECOG PS score ≥3) Major comorbidity (i.e. HCT CI>2) Impairment in ADLs |
High treatment-related mortality (particularly for adults >75 years) Favorable Tumor Biology*: Consider lower intensity therapy (HMAs, low- dose Ara-C). Patients with poor PS (particularly aged 60-75) but without end stage comorbidity may consider intensive treatment if risks/benefits are consistent with goals of care. Intermediate/Unfavorable: Consider best supportive care including palliative care consultation if available versus lower intensity therapy (HMAs, low- dose Ara-C). Clinical trials targeting frail patients are needed; randomized evidence is lacking. |
| Vulnerable | ECOG Performance status score 0-2 Absence of major comorbidity (HCT CI≤2) Presence of: Impairment in IADLs/ self-reported mobility Impaired physical performance (SPPB<9) Impaired cognition (3MS score <77) High symptom burden (fatigue, pain) |
Outcomes for this subgroup are poorly defined in clinical trials due to lack of characterization. In non-randomized studies this group is at risk for shorter survival compared to fit patients. Favorable Tumor Biology: Consider intensive therapy. Intermediate/Unfavorable: Consider intensive therapy if risks and benefits are consistent with goals of care versus lower intensity therapies (HMAs, low-dose Ara-C). Consider enhanced supportive care targeting vulnerabilities such as early physical therapy for impaired mobility. Clinical trials are needed to validate definitions of vulnerability and to test treatment and supportive care strategies to improve outcomes in this group. |
| Fit | ECOG performance status score 0-1 Minimal comorbidity (i.e. HCT CI<1) Absence of any above mentioned risk factors |
Best evidence suggests fit older adults derive benefit from aggressive therapy. Favorable Tumor Biology: Intensive therapy should be offered. Intermediate/Unfavorable: Consider intensive treatment with possible RIC allogeneic HSCT if risks/benefits consistent with goals of care versus lower intensity therapies (HMAs, low-dose Ara-C). Future clinical trials should compare investigational therapies to standard intensive treatment among fit older adults. |
Abbreviations: ECOG=Eastern Cooperative Oncology Group; PS= performance status; HCT-CI=Hematopoietic Cell Transplantation Comorbidity Index; ADLs=activities of daily living; TRM=treatment-related mortality; HMA=hypomethylating agent; Ara-C= cytarabine; IADLs=instrumental activities of daily living; SPPB=Short Physical Performance Battery: 3MS=Modified Mini-Mental State Exam; RIC=reduced intensity conditioning; HSCT= hematopoietic stem cell transplant.
Favorable Tumor Biology: inv(16), t(16; 16), t(8;21), t(15;17); Intermediate-risk: normal cytogenetics, +8 alone, t(9; 11), other non-defined: Unfavorable: Complex (≥3 clonal abnormalities), −5, 5q-, −7, 7q-, abnormalities of 11q, inv(3), t(3;3), t(6;9). In the normal cytogenetic category, NPM1 mutation in the absence of FLT3-ITD or isolated biallelic CEBPA mutation confers better risk versus presence of FLT3-ITD which confers worse risk.
Adapted from Klepin et al. J Clin Oncol 2014 2014 Aug 20;32(24):2541-52.