Favorable Survival Outcomes in Acute Myeloid Leukemia (AML) Patients (pts) Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT) without Achieving Complete Remission (CR) to Non-Intensive Chemotherapy

Abstract

<h3>Introduction</h3> HMA-based therapy is increasingly used as a bridge to potentially curative HCT in pts with AML. Historically, the correlation between traditional treatment response categories and survival has been analyzed primarily in the setting of intensive therapy and not in the context of newer or more gentle regimens. We hypothesized that traditional response criteria may not predict outcomes in the setting of non-intensive chemotherapy followed by HCT. <h3>Objectives</h3> To examine the correlation of response with survival in AML pts undergoing HCT after HMA-based therapy. <h3>Methods</h3> All AML pts undergoing HCT from June 2015 through May 2019 following frontline or salvage HMA-based therapy at our institution were reviewed. Responses prior to HCT were categorized as morphologic CR, CRi (CR with incomplete hematologic recovery), MLFS (morphologic leukemia-free state), or refractory. MRD (measurable residual disease) status was evaluated by flow cytometry and/or molecular testing. Pt, disease, and treatment characteristics were summarized. The Kaplan-Meier method estimated overall (OS) and relapse-free survival (RFS) from time of HCT. <h3>Results</h3> 37 pts received HMAs, 19 in the frontline setting. Median age at HCT was 64 years (range, 28-80); 62% of pts were male. NCCN risk categories at diagnosis were 22% favorable, 43% intermediate, and 35% unfavorable. FLT3-ITD mutations were present in 22% of pts, FLT3-TKD 3%, NPM1 16%, and TP53 13%. 73% received azacitidine, 16% decitabine, and 11% azacitidine followed by decitabine; 23 pts (62%) received HMA monotherapy, and 14 (38%) received concomitant sorafenib, venetoclax, lenalidomide, or midostaurin. Prior to HCT, 32% achieved CR, 30% CRi, 30% MLFS, and 8% were refractory. Of 34 pts evaluable for MRD, 53% achieved MRD negativity. Median follow-up from HCT for the entire cohort was 16.0 months; 1-year OS was 85%, 2-year OS 61%, and median OS was 35.7 months. CR/CRi pts had no OS or PFS advantage over non-CR/CRi patients (2-year OS 57% vs. 65%, p=0.214; 2-year PFS 52% vs. 53%, p=0.793; Figure 1, left panels). Pts with negative MRD exhibited a trend toward improved OS and PFS at 2-year mark (OS: 79% vs. 58%, p=0.090; PFS: 72% vs. 35%, p=0.118; Figure 1, right panels). <h3>Conclusions</h3> AML pts not achieving CR with HMA-based therapy can have favorable survival outcomes following HCT. Traditional response categories may not accurately predict survival in the setting of HMA-based therapy used prior to HCT. These results warrant validation in a larger, prospective study.