Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey

Abstract

Objectives: We evaluated azacitidine (Vidaza H ) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. Methods: This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. Results: The median age of patients was 74.7 (range: 43.9-87.8) years; 69.4% had MDS, 26.5% had primary or secondary AML, and 4.1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67.3%, 28.6%, and 18.4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n529), 41.4% had CR, PR, or HI, 41.4% had SD, and 17.2% had TF. Among AML patients (n59), 44.4% had CR or PR, 33.3% had SD, and 22.2% had TF. TI was observed in 14/32 (43.8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0.571 (0.422-0.696). Conclusions: Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study)

“…The superior 2‐year OS rate seen in the AZA‐001 trial could further be confirmed in a subgroup analysis of elderly patients with a median age of 78, revealing a 2‐year survival of 55% . Our results are more in line with data reported in other non‐interventional studies (14.1 months vs 13.4 months Bernal, 16 months Beguin and 17.1 months Voso, 13,5 months Itzyskon).…”

“…The objective response rate (ORR) observed in our study was higher than reported in the pivotal AZA‐001 study (41.6% vs 29%) but comparable to the results from the non‐interventional studies published by Beguin et al (41.4%) and Itzyskon et al (43%). Voso et al reported even higher ORR (56.5%) . The difference in ORR found in this non‐interventional study compared to randomized clinical trials can be explained by the heterogeneity in evaluating response criteria; the non‐interventional study setting per se limits the comparability to clinical trial data.…”

“…Several further analyses have been subsequently performed on the basis of the AZA‐001 data . In addition, a number of noninterventional studies have been published including data from a registry in Spain that retrospectively analyzed the effectiveness in 251 unselected high‐risk MDS patients, a postmarketing survey in 49 high‐risk MDS patients in Belgium, a retrospective analysis on 196 Italian patients with MDS, and a multicenter patient cohort (n = 282) from a patient‐named compassionate program in France . The primary objective of our study was PFS.…”

Real Life Data on Efficacy and Safety of Azacitidine Therapy for Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia

“…Interestingly, the authors observed neither CR nor PR in their AML/CMML patients. Unexpectedly high CR rate after AZA treatment was demonstrated for “real life” Belgian patients; 41% for MDS/CMML and 44% for AML with estimated 1-year OS of 57% [13].…”

Evaluation of azacitidine in patients with transplant‑ineligible myelodysplastic syndromes and acute myeloid leukemia with myelodysplasia‑related changes in a Japanese clinical setting

“…We suggest that this mortality rate may thus reflect the real-world setting. Beguin et al (13) reported that six of 99 patients died of AEs, though they did not describe the AEs in detail.…”