The effects of continued azacitidine treatment cycles on response in higher-risk patients with myelodysplastic syndromes: An update

Abstract

The international, phase III, multi-centre AZA-001 trial demonstrated azacitidine (AZA) is the first treatment to significantly extend overall survival (OS) in higher risk myelodysplastic syndromes (MDS) patients (Fenaux (2007) Blood 110 817). The current treatment paradigm, which is based on a relationship between complete remission (CR) and survival, is increasingly being questioned (Cheson (2006) Blood 108 419). Results of AZA-001 show CR is sufficient but not necessary to prolong OS (List (2008) Clin Oncol 26 7006). Indeed, the AZA CR rate in AZA-001 was modest (17%), while partial remission (PR, 12%) and haematological improvement (HI, 49%) were also predictive of prolonged survival. This analysis was conducted to assess the median number of AZA treatment cycles associated with achievement of first response, as measured by IWG 2000-defined CR, PR or HI (major + minor). The number of treatment cycles from first response to best response was also measured.

Azacitidine for the treatment of lower risk myelodysplastic syndromes

“…These data are consistent with the benefit of continued azacitidine treatment observed in patients with higher risk MDS. 40 Altogether, these observations highlight the possible benefit of maintaining patients with MDS on azacitidine therapy in the absence of undue toxicity or signs of progressive disease.…”

The role of azacitidine in the management of myelodysplastic syndromes (MDS)

“…48 Continuation of azacitidine therapy led to a higher IWG response category in 43% of responding patients and these patients received a median of 8 additional azacitidine courses. 67 The median duration of hematological response (CR, PR or any hematologic improvement) in the AZA-001 trial was 13.6 months. In a small retrospective study, the outcome of patients with higher-risk MDS treated with a limited number of azacitidine cycles was analyzed.…”

“…Similarly, in the AZA-001 trial the median number of cycles until first response was 3, with 50% of responding patients showing an effect after 2 courses and 87% of patients achieving a response by cycle six. 67 Best response was achieved after a median of 4 cycles. On the basis of these results, it becomes evident that terminating therapy if no response is seen after a few cycles would be premature and prevent many patients from benefiting from azacitidine treatment.…”

Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group

“…In the AZA-001 trial, cycle range was 1-39 with a median of nine cycles [13]. Continuation of azacitidine treatment led to a higher IWG response category in 48% of responding patients, and these patients received a median of eight additional azacitidine courses [38]. The median duration of hematological response (CR, PR, or any hematologic improvement) in the AZA-001 trial was 13.6 months.…”