Azacitidine In Compassionate Use: Response to Therapy, Survival, and Prognostic Factors In 200 Patients Diagnosed with MDS or AML

Abstract

2933 Introduction: Survival analysis need of large period of time for getting results. Survival subrogates variables provide with earlier data for clinical decisions. The current treatment paradigm is nowadays how the quality of the different treatment responses impact in patient's survival with the new treatment options. Azacitidine (AZA) is a hypomethilating agent which was available for clinical trials or compassionate use in Spain before receiving it marketing authorization in May 2009. We present the final analysis from those patients diagnosed with mielodysplastic syndromes (MDS) or acute myeloid leukemia (AML) selected from a longitudinal, multicenter Spanish patient registry. Materials and Methods: This analysis retrospectively gathers clinical data about the treatment, disease progression and survival of patients with MDS or AML who had received AZA 75mg/m2 in compassionate use conditions, with a dosage regimen documented. Three different dosage regimens at the beginning of each 28-day cycle were used; group A: days 1–5 (M-F)/group B: days 1–5, 8–9 (M-F, M-Tu)/group C: days 1–7 (M-Su). Survival analysis was stratified by patients' basal conditions, dosage schedule and best response after 4th and 6th cycles. Results: Data were collected from 200 patients with MDS or AML according to the WHO diagnostic criteria. Basal data, effectiveness results and data from haematological tolerance are mainly summarized in table 1. Median survival time was 706 days (95% CI 588–1093) in those patients who achieved a response versus 225 days (95% CI 156–319) in those who did not. Survival analysis showed differences based on the best response achieved (p<0.0001), the response achieved after the 4th cycle (p<0.0001) and the response achieved after the 6th cycle (p<0.0001). Survival Hazard Ratios based on the best response, the responses after 4th and 6th cycles are summarized in table 2. Figures 1 and 2 shows survival curves based on best response after 4 and 6 cycles of therapy. Conclusions: These in routine clinical practice data confirms those survival data previously published. Although results of AZA-001 show CR is sufficient but not necessary to prolong OS; our data shows an increase in the risk of not being alive when decreasing the quality of the best response achieved by patients during the treatment. To achieve the best response after the 4th cycle could be an AZA treatment goal. Percentages (Chi-Square Test, Exact's Fisher Test, LR Test according to application criteria met), Median +/− IQR (Kruskal-Wallis Test) or Median +/− Std (T-Test) when applicable. Disclosures: García: Celgene: Research Funding. de Miguel LLorente:Celgene: Speakers Bureau. Bargay:Celgene: Research Funding. Ramos:Celgene: Speakers Bureau. Sanz:Celgene: Speakers Bureau. Sánchez:Celgene: Speakers Bureau.

Azacitidine has limited activity in ‘real life’ patients with MDS and AML: a single centre experience

“…This was mainly associated with financial problems and the reimbursement policy in our country. In other series, however, the therapy was usually not stopped unless a CR was achieved [6,7,[11][12][13][14]. Gore et al [16], reported of delayed responses that occurred beyond 9 months in patients who continued to use Aza-C.…”

“…12, 13, published the Spanish Aza‐C registry results with three different treatment schedules of azacitidine [ group A : Aza‐C 75 mg/m 2 on days 1–5 (every 28 days); group B : Aza‐C 75 mg/m 2 on days 1–5, 8–9 (every 28 days) and group C : Aza‐C 75 mg/m 2 on days 1–7 (every 28 days)]. In their retrospective analysis of 200 patients with MDS and AML the overall response rates ranged between 42.5% and 63.2%, without any statistically significant difference between the three schedules 12. When they analysed the 181 MDS only patients, however, they found overall response rates of 37.7%, 70.6% and 52.2% for groups A, B and C, respectively.…”

“…This was mainly associated with financial problems and the reimbursement policy in our country. In other series, however, the therapy was usually not stopped unless a CR was achieved 6, 7, 11–14. Gore et al .…”

“…Recently, Garcia et al published the results of different Aza-C dosing schedules in 200 MDS and AML patients included in the multicenter Spanish azacitidine registry. The overall response rates of the three different dosage regimens were found between 42.5% and 63.2% when MDS and AML patients were evaluated together [12]. In MDS, only group response rates with different dosage regimens were between 38% and 71% [13].…”

Treatment with 5-Azacytidine improves clinical outcome in high-risk MDS patients in the ‘real life’ setting: A single center observational study

“…In their retrospective analysis, the ORR was 42.5% for 5 days, 63.2% for 5/2/2, and 56.4% for 7 consecutive days without any significant difference between the three schedules. 16 However, when the analysis was restricted only to 181 patients with MDS they reported ORR of 37.7% for 5 days, 70.6% for 5/2/2, and 52% for 7 consecutive days, respectively. 17 The higher ORR that have been reported in the previous two studies using the 5/2/2 schedule could be due to the inclusion of lower-risk patients compared to our study group: 59 and 70% were L-R and INT-1 by IPSS in these studies, respectively, while in our study only INT-2 and H-R patients were included.…”