Comparative Analysis of An Azacytidine Versus Azacytidine-HSCT Approach for the Treatment of Older Patients with AML/MDS
Authors: Potter Victoria T , Tindell Victoria J , Kesse-Adu Rachel , Hayden Janet , Pasipanodya Patience , Reiff-Zall Laura , Marsh Judith C. W. , Pagliuca Antonio , Ho Aloysius Y , Lim ZiYi , Mufti Ghulam J. 
Published: October 2019

Abstract
Abstract 2375
While allogeneic HSCT remains the only curative option for patients with MDS, it is associated with considerable morbidity and mortality. 5-azacytidine (5-aza) has been shown to improve the overall survival (OS) of patients with int-2/high risk MDS when compared with best supportive care and conventional chemotherapy. The feasibility of 5-aza in the pre-transplant setting has been demonstrated allowing disease remission induction whilst minimising the toxicity of “induction” chemotherapy. However the additional benefit gained by patients receiving HSCT post 5-aza as compared to patients who receive continuous 5-aza therapy remains to be determined.
We report on our single centre experience on the use of 5-aza in a cohort of 71 patients receiving 5-aza as de-novo therapy for high risk MDS/AML. The patients were classified into 2 cohorts. 41 patients received 5-aza in a non-intensive group (defined as patients with advanced age or significant co-morbidities precluding them from HSCT) and 30 patients received 5-aza induction therapy with the intention of proceeding to an allogeneic HSCT (intensive group). Patients in the non-intensive group were significantly older at start of 5-aza therapy than the intensive group (median age: 72 yrs vs 62 yrs, p=<0.01). There was no difference in the proportion of patients with advanced disease (int-2/high IPSS or AML) between groups (non-intensive: 80% vs intensive: 76%, p=0.76). Similarly, there was no significant difference in blast percentage at diagnosis or karyotype risk group between the non-intensive and intensive groups.
In the intensive group, the median no. of cycles of 5-aza administered was 7(range 1–30). Out of 30 patients, 15(50%) patients did not proceed to transplant. 14 of these patients had disease progression while on 5-aza, out of which 11 patients received conventional chemotherapy. None of these 11 patients proceeded to HSCT primarily as a result of refractory MDS/AML or chemotherapy toxicity. 15(50%) patients attained a morphological remission (<5% bone marrow blasts) post-5-aza and eventually received a RIC HSCT (including two patients who received umbilical cord blood transplants). All transplanted patients had durable engraftment and the incidence of GVHD at 1 year post-transplant was 50%. At last follow-up, 6 patients who received HSCT were still alive. The actuarial OS at 1 yr post transplant was 35%+/&minus;7%. Among the 41 patients in the non-intensive group, the median number of cycles of 5-aza received was 7 (range:1-46). At last follow-up, 8 patients (19%) were alive with 7 patients receiving ongoing 5 aza. The main reason for cessation of therapy was disease progression.
In summary, only 50% of patients commencing 5-aza in the intensive group were subsequently able to receive an allogeneic HSCT. While the non-intensive group consisted of older patients, the median OS from start of 5-azacytidine was 22 months for both intensive and non-intensive groups. The 1 yr and 2 yr actuarial OS was 57%+/&minus;8% and 24%+/&minus;8% for the non-intensive group and 76%+/&minus;8% and 17%+/&minus;8% for the intensive group (p=0.76). While the development of RIC regimens has facilitated the expansion of allogeneic HSCT to older patients with AML/MDS, these findings suggest that in certain patients with co-morbidities, non-intensive novel therapies may be a preferable therapeutic option. Further studies in older AML/MDS patients to evaluate the benefit of novel agents such as 5-azacytidine when compared with HSCT are warranted.

Disclosures:
Mufti: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.