Page 75 - Haematologica August 2018

Decitabine and plerixafor in elderly AML
blasts was 54% (range 6-99%) and 15% of patients had a baseline white blood cell count greater than 30x109/L. Forty-five percent of patients had impaired hepatic or renal function at study entry. Twenty percent of patients had received prior treatment with azacitidine.
Patients were evenly distributed among the three plerix- afor dosing cohorts and received a median of 3 cycles of decitabine and one cycle of plerixafor. Thirty-two percent (n=21) of patients received more than 3 cycles of decitabine and more than one cycle of plerixafor.
Safety
Grade 3 and 4 adverse events were as expected for older AML patients and included myelosupression in all patients, febrile neutropenia (65%), bacteremia (30%), and respiratory infections (23%). While myelosuppression was common, there were no episodes of unexpectedly prolonged myelosuppression in the absence of residual AML. Grade 1 and 2 adverse events observed in more than 20% of patients included, in ascending order of frequency: depression (23%), anxiety (26%), limb-related pain (29%), anorexia (30%), fever (30%), peripheral edema (33%), infection (36%), elevated creatinine (46%), nausea (48%), fatigue (51%), constipation (52%), skin disorders (53%), diarrhea (58%), and elevated bilirubin (83%) (Table 2). Grade 1 and 2 insomnia was unique to plerixafor-contain- ing cycles and was experienced by 56.1% of patients. There was no clinically significant hyperleukocytosis caused by plerixafor. There was one episode of dose-lim-
Figure 2. Mutational profile of patients studied. Each column indicates a patient, while each row indicates a gene tested (right label) and the per- cent of patients mutated for each gene (left label). Each mutation is col- ored according to the mutation type(s) present. Bar plots show the num- ber of mutations per patient (top) and the total number of mutations per gene (right).
Table 2. Grade 1/2 adverse events observed in over 20% of subjects, regardless of drug attribution.
Depression Anxiety Limb-related pain Anorexia
Fever
Peripheral edema
Infection
Elevated creatinine
Nausea
Fatigue
Constipation
Skin disorders
Insomnia
Diarrhea
Elevated bilirubin
N: number.
N (%)
16 (23) 18 (26) 20 (29) 21 (30) 21 (30) 23 (33) 25 (36) 32 (46) 33 (48) 35 (51) 36 (52) 37 (53) 39 (56) 40 (58) 57 (83)
iting toxicity, renal insufficiency, in the 810 μg/kg cohort, but this was not clearly related to plerixafor. Still, this event, combined with the clinical impression of increased insomnia and increased non-serious gastrointestinal com- plaints in the 810 μg/kg cohort, led us to recommend 675
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