Adverse events in acute myeloid leukemia (AML) treatment

AML treatment often includes intense chemotherapy regimes, at induction, through consolidation and possibly following allogeneic stem cell transplantation for treatment of relapse. The highly cytotoxic treatment of AML can lead to adverse effects (AE) that continue long-term.

In their 2019 publication, Crossnohere et al.,¹ present the results of a national US survey of side effects during and after treatment for AML. The group used an instrument, previously developed and piloted under the leadership of the Leukemia and Lymphoma Society (LLS), to prioritize the concerns of AML patients.^2,3 Data was collected on patient issues such as decision-making, treatment delivery, physical impacts, and psychosocial effects. The group aimed to report the prevalence and severity of these AE.

Study design and patient demographics:

• A retrospective study of patients over 18 years old with an AML diagnosis, and/or current/former caregivers
• Out of 6,841 survey-containing emails that were sent out, 1,182 individuals completed the survey including; 901 patients, 159 caregivers of living patients, and 122 caregivers of deceased patients

Table 1. Participant characteristics and clinical characteristics (1)

Survey participant characteristics
		N(%)
Participant role	Patient Caregiver of living patient Caregiver of deceased patient	901 (76.2) 159 (13.5) 122 (10.3)
Age (mean years, range)		54.7 (19-87)
Gender	Female	689 (64.5)
Race/ethnicity	White/Caucasian Black/African American Other	939 (87.9) 40 (3.7) 80 (8.4)
Education	Less than college degree College degree or higher	365 (34.2) 702 (65.8)
Insurance	Private insurance	820 (76.9)
Clinical characteristics of patients
Years since diagnosis (range)		7.3 (1-40)
Treatment (all that apply)	Chemotherapy Allogeneic stem cell transplantation	1165 (99.0) 719 (57.7)
Disease status	In remission	1002 (86.0)

Results:

• 87% of participants reported at least one severe short-term AE and 33% reported one or more severe long-term AE, 11% of participants reported no short or long-term AE

Figure 1. Prevalence and severity of AML treatment side effects

• 87% of participants experienced severe short-term effects, 33% reported severe long-term effects
• Only 11% of respondents did not have any severe effects
• On average, the most severe short-term AE was hair loss and the most severe long-term AE was fatigue. Authors found a moderate correlation between short-term and long-term severity scores (r=0.41, p<0.001).
• There were similarities between the prevalence of severe short-term AEs reported by patients and caregivers (mouth sores, diarrhea, nausea, rashes), patients reported more severe hair loss (p=0.01) and caregivers reported more severe infections (p<0.001)
• Caregivers were significantly more likely than patients to report severe long-term AE (51% vs 29%, Chi²=43.9, p<0.001) and reported that fatigue, neuropathy and organ dysfunction as more severe, though reported a similar severity for chemobrain
• Gender differences were noted in the AE profiles of AML patients, with females being more likely to have severe forms of nausea, diarrhea, infection, mouth sores, rashes and hair loss
• Age differences were also noted, with those diagnosed at ≤55 years old being more likely to have severe forms of nausea, diarrhea, infection, mouth sores, and hair loss
• Analysis of patients who were not in remission found that compared to patients in remission they were more likely to have a severe AE such as infection, organ damage, neuropathy, fatigue, and chemobrain
• Patients who were diagnosed <5 years ago, when compared to patients diagnosed ≥5 years ago, were more likely to have severe forms of nausea, diarrhea, infection, rashes, and hair loss
• The prevalence of severe AE showed no variation by patient race or patient insurance type

Conclusion

The authors found that severe short-term effects of chemotherapy were extremely common in AML patients. Severe long-term effects were more commonly reported by caregivers. The prevalence of certain AEs also showed significant gender and age bias. The researchers concluded that the study of patient experience in this way could aid in the identification of areas of unmet need and drive patient-centered treatment development, as the patients are the ‘true experts of their disease experiences’. Their work has highlighted that there are a significant patient and caregiver burden associated with AML treatments and that this should be a priority for further patient-focussed drug development.