Decitabine As Salvage Therapy for Relapse of AML and MDS after Allogeneic Stem Cell Transplantation - a Retrospective Multicenter Analysis on Behalf of the German Cooperative Transplant Study Group

Background:

During the last years, based on its efficacy and favourable toxicity profile the hypomethylating agent (HMA) Azacitidine (Aza) has proven to be a valuable treatment option for patients with AML or MDS who relapse after allo-SCT. In contrast to Aza, reports on the use of Decitabine (DAC), the second HMA approved in Europe for the treatment of AML, as salvage therapy for relapse after allo-SCT are scarce covering a total of 9 patients so far. This prompted us to perform a retrospective survey in order to gather more experience on the use of DAC after allo-SCT.

Patients and Methods:

Retrieving information from the EBMT Med-A form and a study-specific questionnaire we were able to analyze data of 36 patients (median age 56 years, range 21-72 years) from 6 German transplant centers who had received at least one cycle of DAC for the treatment of relapse of AML (n=29) or MDS (n=7) after allo-SCT. Median time to haematological (n=34) or molecular (n=2) relapse was 370 days (range 43-2623 days).

Results:

Overall, DAC was the first treatment for relapse in 16 pts (44%), whereas 20 pts (56%) had previously received one (n=14), two (n=2) or three (n=4) lines of salvage therapy for relapse after allo-SCT. This included 16 pts treated with Aza, 3 pts with intensive chemotherapy and 2 pts with radiation. Five pts had received a second allo-SCT and 9 pts donor lymphocyte infusions (DLI) before DAC therapy.

Patients received a median of 2 DAC cycles (range, 1-10) with 24 pts (67%) treated with the approved dose of 20 mg/m² for 5 days and 12 pts (33%) treated with 20 mg/m² for 10 days based on the local policy of the individual transplant center. In addition to DAC, DLI (median number of DLI =1, range: 1-5) were administered to 22 pts (61%).

Following treatment with DAC +/- DLI the median survival was 5 months (range 1 - 40 months). Six pts achieved a complete remission (CR, 17%) and 3 pts achieved a partial remission (PR, 8%) leading to an overall response rate of 25%. Median time to documentation of CR was 157 days (range: 47-255 days) and 4 DAC cycles (range: 1-8 cycles). Of 6 patients achieving CR after DAC, 3 had received DAC as first salvage therapy and 3 had previously received Aza, including 2 pts not responding to Aza and 1 patient switched to DAC therapy due to Aza intolerability. With a median follow-up of 12 months (range: 5-40 months), 3 of 6 patients remain in ongoing remission for 4, 23, and 33 months respectively without any further antileukemic therapy, while the other 3 patients died in remission due to infectious complications after second transplant.

The 2-year overall survival rate of the entire group as calculated from the start of DAC therapy was 9%. Incidence and severity of acute GvHD (overall: 19%, grade I: 3%, grade II: 8%, grade III: 5%, grade IV: 0%, missing: 3%) and chronic GvHD (overall: 6%, limited 6%, extensive 0%) were low and mild.

Conclusion:

Our analysis shows, that also the second HMA DAC exerts relevant clinical efficacy in patients with AML or MDS relapsing after allo-SCT and can induce durable remissions in individual pts. Given the heterogeneity of our patient group and the limitations of a retrospective analysis this asks for confirmation in a prospective trial.