Outcome of Patients (pts) with Acute Myeloid Leukemia (AML) Evolving From Myelodysplastic Syndromes (MDS) Post Hypomethyling Agents (HMA) Failure
Authors: Ghanem Hady , Kantarjian Hagop M. , Manero Guillermo Garcia , Ravandi Farhad , Cortes Jorge E. , Takahashi Koichi , O'Brien Susan M. , Pierce Sherry A. , Kadia Tapan M. , Jabbour Elias J. 
Published: October 2019

Abstract
Abstract 3600

Introduction:
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.

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

Methods:
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.

Results:
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 1st 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%.

Conclusion:
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.

Disclosures:
Ravandi: Eisai: Honoraria.