The outcome of patients with high‐risk MDS achieving stable disease after treatment with 5‐azacytidine: A retrospective analysis of the Hellenic (Greek) MDS Study Group

Abstract

The demethylating factor 5-azacytidine (5-AZA) improves survival in intermediate-2 and high-risk myelodysplastic syndrome (MDS) patients [according to the International Prognostic Score System (IPSS)] responding to treatment. However, the outcome of patients achieving stable disease (SD) is unclear. This retrospective study of the Hellenic MDS Study Group included 353 intermediate-2 or high IPSS risk patients treated with 5-AZA. Forty-four out of 86 (51.6%) patients achieving SD and continuing treatment with 5-AZA showed a lower risk of transformation of MDS to acute myeloid leukemia (AML) and increased overall survival (OS), compared to SD patients who discontinued the treatment (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 15 months, 95% CI = 10.4-19.6, P < .001; estimated median OS = 20 months, 95% CI = 5.5-34.5 vs 11 months, 95% CI = 5.8-16.2, P < .001). Moreover, SD patients continuing treatment with 5-AZA had no differences in AML-free survival compared to patients showing response to 5-AZA (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 31 months, 95% CI = 23.6-38.4, P = .45; estimated median OS 20 months, 95% CI = 5.5-34.5 vs 25 months, 95% CI = 21.3-28.7, P = .50). In conclusion, MDS patients achieving SD in the first 6 months of treatment with 5-AZA as best response should continue receiving 5-AZA as they may benefit from prolonged treatment.

Azacytidine failure revisited: an appraisal based on real life data from the MDS registry of the Hellenic Myelodysplastic Syndrome Study Group (HMDS).

“…However, patients who continued AZA had still significantly longer OS even when the analysis was adjusted for gender, disease subtype at the time of AZA discontinuation and the post-HMA model (p=0.02), though both patient groups received comparable therapies after AZA discontinuation (supplementary Tables 3 and 4). In line with these findings, our group has recently shown that patients with stable disease as best response benefited significantly by the continuation of AZA compared to the ones who stopped treatment 13. By contrast, prolonged survival was recently reported in patients who stopped AZA or decitabine without disease progression, but the study cohort consisted mainly of IPSS low-risk patients, most of whom discontinued treatment for extra medical causes 14…”

Low serum albumin level deteriorates prognosis in azacitidine-treated myelodysplastic syndromes patients – results of the PALG study ‘PolAZA’

“…Hematologic improvement, including cases with CR and PR classified as erythroid response (HI-E), was observed in 51%, neutrophil response (HI-N) in 36%, and platelet response (HI-P) in 48% of patients. Median time to response was 3 months (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Platelet doubling after the first cycle was documented in 18% of patients.…”

“…A large randomized trial AZA-001 showed survival benefit of azacitidine treatment when compared with conventional treatments with a median survival 24.5 months [1]. On the other hand, overall survival was shorter in smaller randomized trials and real-life studies (15-20 and 13-17 months, respectively) [2][3][4]. In this context, both pre-treatment as well as on-treatment risk stratification and identification of factors predicting response and prognosis seem to be of special value.…”

MRD Monitoring by Multiparametric Flow Cytometry in AML: Is It Time to Incorporate Immune Parameters?

“…However, the current prognostic assessment of AML cannot precisely predict the curative potential of chemotherapy alone or accurately estimate the benefit of alloSCT strategies. In addition, the advent of targeted therapies has, in several cases, disconnected the quality of response from survival benefit, thus adding another layer of complexity to the prognostic assessment of AML [ 4 , 5 ]. According to the latest ELN criteria [ 6 ] an AML patient is considered to be in complete remission (CR) if all of the above criteria are fulfilled: bone marrow blasts <5%; absence of circulating blasts or blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10 9 /L (1000/μL); and platelet count ≥100 × 10 9 /L (100,000/μL).…”