Evidence for Selective Benefit of Sequential Treatment With Hypomethylating Agents in Patients With Myelodysplastic Syndrome

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

“…Regarding the above patients, 5/11 evaluable cases were low and 6/11 high risk by post-HMA, whereas 4 discontinued AZA because of relapse after an initial response, 2 for disease progression, 2 for toxicity, 2 for failure to achieve a response after 4 cycles and one by his own decision. The overall response rate with second-line decitabine after AZA failure ranges from 19.4% to 63%2,11,12 and the median OS from 7.3 to 17.8 months, but the small patient cohorts, the heterogeneous definitions of AZA failure and the obvious selection biases, preclude the identification of predictive factors for response in decitabine. Therefore, though selected patients who failed AZA may benefit from second line decitabine, no solid recommendation can be made, also considering the toxicity and cost of decitabine treatment.…”

Cost–effectiveness of treatments for high-risk myelodysplastic syndromes after failure of first-line hypomethylating agent therapy

“…Whether the MDS patients who are HMA nonresponders benefit from these approaches remains a controversial issue [43]. There might be a small benefit of sequential switching of HMA with one small retrospective analysis showing an overall response rate of 40% in decitabine-failed patients switched to azacitidine and 19% response rate in azacitidine-failed patients switched to decitabine [44]. Of note, in 40-67% of second-line patients switching HMA, the disease continued to progress with no improvement in survival.…”

Hypomethylating Agents in Treatment of Myelodysplastic Syndrome

“…-patients with clinically significant thrombocytopenia and/or neutropenia. It has been shown that hypomethylating agents, in particular AZA, prolong the survival of patients, regardless of age, FAB or WHO subtype of the disease, the percentage of blast and karyotype (although some researchers have noted a better result in patients with the presence of -7/del7q) [13], significantly lower the risk of transformation in the AML, and not only reduce the transfusion dependence of patients, but also prolong the duration of the response in the previously treated patients [14,15].…”

“…The overall survival rate in patients with high risk MDS after failure of therapy with azacitidine or decitabine is 5.6 and 4.3 months respectively [41]. In a report by the Moffitt group, the overall survival time after ineffectiveness of azacitidine, analyzed in 280 patients with low-risk MDS, was 18.5 months (95 % confidence interval, 13.5-23.5 months), and decreased in patients with intermediate risk MDS according to IPSS down to 15 months [14]. Another retrospective analysis of 59 patients with IPSS low risk MDS with primary or secondary azacitidine ineffectiveness showed similarly low overall survival rates in these patients -16.7 months.…”