Comorbidities Indexes In Patients Treated with 5-Azacitidine Are a An Useful and Easily Applicable Tool to Refine Prognostic Evaluation

Abstract 606

Myelodysplastic syndromes (MDS) are affecting mainly elderly patients, and age is considered per se a negative prognostic factor. Most of the elderly patients have comorbidity that presumably negatively impact the overall survival and quality of life and may influence response to therapy. A subanalysis of a recently concluded international trial demonstrated that MDS patients aged > 75 yrs treated with azacitidine have a significantly longer overall survival respect to best supportive care treated patients (Seymour, 2010).

We analyzed whether presence and number of comorbidities could have an impact on response and management of azacitidine treatment in elderly and very elderly patients treated in our Center, outside clinical trials. We evaluated outcome, survival and type of response, as well as adverse events in all patients.

We analyzed 59 elderly MDS patients (IPSS INT-1 15/59, INT-2 32/59 and High 12/59) treated with Azacitidine 75 mg/kg/day sc for 5 days every 28. Mean number of cycles was 9 (range:2-42). Mean age was 69 yrs (50-82); 30% of patients (18/59) were >= 75 yrs and 39% of the latter (7/18) >= 80 yrs.

We also evaluated Charlson comorbidity index (CCI) (10 patients scored =<1, 44 patients 2 or 3, and 5 patients >= 4), the Cumulative Illness Rating Scale (CIRS) (25 patients scored =<1, 25 patients 2 or 3 and 9 patients >= 4) and the Adult Comorbidity Evaluation-27 (ACE-27) (13 patients scored =<1, 43 patients 2,3 or 4 and 3 patients >=5).

Overall response rate (HI, CR and PR) according IWG criteria 2006 was 49.1%, stable disease was obtained in 37.1 % of MDS patients. We demonstrated by Fisher test that these IWG responses did not correlate with age.

We also evaluated CCI, CIRS, and the ACE-27 in relation to age and to hematological response and no correlation was showed. Hematological or non hematological adverse events were presented by 34% and 36% of patients, respectively. Adverse events were uniformly distributed independently from age. Median overall survival (OS) of our patient cohort was 21 months. Median OS in patients < 75yrs (20 monthts) and >= 75 yrs (16 months) was not significantly different (p value > 0.65).

OS in patients with higher CCI, CIRS, and the ACE-27 was respectly 10 months, 6,5 months and 6 months.

5 patients presented renal failure, but treatment with standard dose aza did not worsen creatinine clearance.

Very elderly patients with comorbidities may be treated with success with azacitidine, without any substantial increase in AE. Nevertheless comorbidities negatively influence overall survival. Evaluation of comorbidities with validated indexes is an useful and easily applicable tool to refine prognostic evaluation. ACE-27, although more complex, seems to give best prognostic evaluation.