Despite Low Disease Recurrence, Long-Term AML Survivors Require Preventative Care
Many patients with acute myeloid leukemia (AML) achieve complete remission (CR) after induction chemotherapy; however, just 30% of patients maintain CR for three years or longer. Long-term outcomes for those who do maintain CR are largely unknown. Results from a new study have shown that new medical problems frequently occur, and patients require routine surveillance and preventative measures. Catherine Kendall Major, BS, of the MD Anderson Cancer Center in Lakeland, TN, discussed the findings at the ASH Annual Meeting on December 3, 2018.
Researchers performed a chart review to identify patients with AML who achieved CR for at least three years after initial chemotherapy and allogeneic hematopoietic cell transplantation (alloHCT). They included 2,779 patients who were treated at their institution between 2000 and 2015; 1,686 patients (61%) achieved CR, and 455 (27%) maintained first CR for at least three years. Patients who maintained CR received chemotherapy alone (n = 309) or chemotherapy plus alloHCT (n = 146).
The median time from the initiation of induction chemotherapy to first CR was 29 days (range = 10–207 days). At baseline, 27% of patients had hypertension, 16% had dyslipidemia, 10% had pulmonary disease, 9% had cardiac disease, 9% had diabetes, 5% had depression, 5% had renal disease, 5% had gastroesophageal reflux disease (GERD), 5% had hypothyroidism, 4% had anxiety, and 1% had osteopenia or osteoporosis.
Eleven percent of patients had late relapse, including 14% of those treated with chemotherapy alone and 6% of those treated with alloHCT. Relapses occurred after a median CR duration of six years (range = 3–12 years) for those receiving chemotherapy alone and seven years (range = 4–12 years) for those receiving alloHCT.
Researchers observed a change in karyotype in 51% of patients who relapsed after chemotherapy alone and 56% of those who relapsed after alloHCT. The most common new cytogenetic abnormalities were 7qdel (22%), trisomy 8 (11%), and 5qdel (7%). The two most common changes in mutational status were FLT3-ITD and FLT3-D835. At relapse, 7% of patients had a TP53 mutation; however, TP53 status at diagnosis was unknown.
More than half of patients (54%) achieved second CR after late relapse: 51% of patients receiving chemotherapy alone and 67% receiving alloHCT. The median duration of second CR was 18 months (range = 3–127 months) and 15 months (range = 7–23 months), respectively.
The median survival after relapse was 10 months for those receiving chemotherapy alone versus 14 months for those undergoing alloHCT. Among patients initially treated with chemotherapy alone, 30% of those who relapsed underwent alloHCT, and four patients who originally underwent transplant received a second one.
At three years, the researchers observed the following new comorbidities: hypertension (15%), osteopenia/osteoporosis (15%), renal disease (14%), pulmonary disease (11%), hematologic complications (11%), dyslipidemia (9%), GERD (8%), cardiac ailments (7%), depression (7%), anxiety (6%), diabetes (6%), and hypothyroidism (4%).
Seventeen percent of patients experienced second malignancies, the most common of which were skin cancer (7%), prostate cancer (2%), breast cancer (1%), and lymphoma (1%).
The median survival for the entire long-term CR cohort was 10.7 years (range = 0.1–14.3 years), including 10.7 years (range = 0.1–14.3 years) for those receiving chemotherapy alone and 12.7 years (range = 0.1–12.7 years) for those undergoing alloHCT. The most common causes of death for patients who relapsed after alloHCT were relapsed AML (33%), secondary complications from second alloHCT (22%), and infection (11%), while the most common causes for the chemotherapy group were relapsed AML (47%), secondary complications from alloHCT (14%), and second malignancy (2%).
The most common causes of death for those in the alloHCT cohort were transplant-related complications (2%), malignancy (< 1%), and myocardial infarction ([MI], < 1%), whereas the most common causes for the chemotherapy cohort were malignancy (2%), MI (< 1%), and pneumonia (< 1%).