Outcome Of Patients With Myelodysplastic Syndrome (MDS) With Bone Marrow Blasts Between 10-30% Treated With Hypomethylating Agents Versus Intensive Chemotherapy
Authors: Nazha Aziz , Kantarjian Hagop M. , Jabbour Elias , DiNardo Courtney D. , Borthakur Gautam , Daver Naval G. , Faderl Stefan H. , Ning Jing , Qiao Wei , Ravandi Farhad , Kadia Tapan M. , Pierce Sherry R. , Cortes Jorge E. , Garcia-Manero Guillermo 
Published: October 2019

Abstract

Background
In 2001, the World Health Organization modified the French-American-British (FAB) classification for myelodysplastic syndrome (MDS) by folding the refractory anemia with excess blasts in transformation (RAEB-t) category into acute myeloid leukemia (AML). Whether this group of patients (pts) should be treated with AML versus MDS therapy remains controversial. A subset analysis of the AZA-001 trial showed that azacitidine prolongs overall survival (OS) in elderly pts with low blasts AML (bone marrow blasts [BM] 20-30%).

Aim
To compare the clinical outcome and OS of patients with MDS or AML with BM blasts between 10-30%, treated with hypomethylating agents (HMA) vs intensive chemotherapy (IC).

Patients and Methods
We conducted a retrospective analysis of newly diagnosed pts with MDS (or AML by WHO) and BM blasts between 10-30% treated with either HMA (alone or in combination with investigational therapies) or IC on clinical trials. Eligibility was based on pt characteristics and specific protocol inclusion criteria. A univariate Cox proportional hazards regression model was used to evaluate the overall effects of treatments and outcome (remission duration (RD), and OS). Then a regression model with the interactions between treatments and baseline covariates were used for subgroup analysis. The final model was obtained by a stepwise selection using 0.05 as a cut off of significant values.

Results
330 patients were included in the final analysis, with 93 (28%) HMA-treated pts and 237 (72%) pts treated with IC. Clinical characteristics at diagnosis are summarized in Table1. The overall response rate (ORR= CR+CR p) was 42% for the pts who treated with HMA and 60% for pts treated with IC (P = 0.01). The median RD was similar between the two groups (14.7 mos (m) vs. 14.7 mos, respectively, P = 0.74). Early induction mortality was also similar among the two groups (4-week mortality was 5% vs. 7%, respectively, and the 8-week mortality was 10% vs. 13 %, respectively). With median follow up of 37 mos (range, 1-94 mos), the median OS was 18.8 mos for pts who treated with HMA vs. 14.6 mos for pts treated with IC (P = 0.32). Moreover, the BM blasts percentage did not impact the overall outcome. In multivariate analysis, treatment with IC was associated with worse OS compared to HMA (HR 2.09, 95% CI 2.07-3.17, P = 0.003) but not for RD (HR 0.43, 95% CI 0.89-2.68, P = 0.13).

Conclusion
Although patients with MDS or AML with BM blasts between 10-30% initially achieve a higher ORR when treated with IC compared to HMA-based therapy, the OS was better for pts treated with HMA after accounting for all other covariates. Interestingly, BM blast percentages within this cohort did not impact overall outcome suggesting that pts with BM blasts 20-30% may achieve better outcome with MDS therapy.

Disclosures:
No relevant conflicts of interest to declare.