Outcome of Patients (pts) with Acute Myeloid Leukemia (AML) Evolving From Myelodysplastic Syndromes (MDS) Post Hypomethyling Agents (HMA) Failure

Outcome of pts with secondary AML evolving from MDS is dismal. HMA are standard of care for pts with MDS. We have previously reported a median survival of 4 months post HMA failure. The impact of salvage chemotherapy on pts with AML evolving from MDS post HMA failure is unknown.

Assess the impact of salvage chemotherapy on pts with AML evolving from MDS post HMA on survival.

We reviewed 64 consecutive pts with AML evolving from MDS and treated at MDACC with HMA in clinical trials between on 1/2003 and 7/2012. Response assessment followed standard criteria. Overall survival (OS) was measured from the time of therapy till the time of death or last follow-up.

64 pts with a median age of 63 years (range, 38–82) were assessed, with 39 % older than 65 years. At the time of MDS diagnosis, 13 (20%) had a high International Prognostic System Score (IPSS), 31 (48%) had an intermediate 2 IPSS score, 16 (25%) had an intermediate-1 risk IPSS score and 1(2%) had a low-risk IPSS. Thirty-seven patients (57%) had complex cytogenetics. Prior to progression into AML, 51 pts (80%) received decitabine based regimen and 13 (20%) received azacitidine based regimen. Responses to HMA were as follows: 18 pts (28%) achieved a complete remisson (CR) and an additional 2 pts (3%) achieved CR with incomplete platelet recovery (CRp), for an overall response rate (ORR) of 31%. After progression to AML, all 64 pts (100%) received at least 1 salvage regimen, 32 (50%) received 2 or more salvage regimens and 12 pts (18%) received 3 more salvage regimens. Twenty-nine pts received high-dose cytarabine (HDAC)-based regimen as first salvage and 5 as second salvage. Thirty-six pts received investigational agents at time of first relapse. Of the 34 pts who received HDAC, 7 (20%) achieved CR. Of the 36 who received investigational agents at first relapse, 8 achieved CR and 1 patient achieved CRp, for an ORR of 25%. 12 pts underwent allogeneic or cord stem transplantation, 5 of them had active disease at time of receiving the transplant, and 7 were in CR: five after HDAC containing regimens, and 2 after other agents. Median duration of response was 27 months (range, 2 to 81) after 1^st salvage and 5 months (range, 0 to 74) after 2nd salvage. With a median follow-up of 52 months from transformation into AML, 5 (8%) pts remained alive, 3 of them in CR. The median OS after HMA failure is 6.4 months with a 1-year survival of 23% and a 2-year survival of 8%.

The outcome of pts with AML evolving from MDS post HMA failure is poor with a median survival of 6.4 months. Response rate to salvage chemotherapy with HDAC is low (21%). These pts constitute a distinct population from those with secondary AML and should benefit from more innovative approaches.

Ravandi:Eisai: Honoraria.