Progress Findings On a Novel Treatment Strategy Using Prolonged, Low-Dose Cytarabine and Thioguanine in Combination with Peg-Filgrastim for Acute Myeloid Leukaemia in Elderly Patients
Authors: Arthur Christopher , Wong Charmaine , Aubrey Brandon , Liu Eunice , Stevenson William , Soo Gary , Coyle Luke , Fay Keith , Greenwood Matthew , Mackinlay Naomi , Ward Christopher M 
Published: October 2019

Abstract
Abstract 3612
The incidence of Acute Myeloid Leukaemia increases with age and advanced age is a major adverse prognostic marker. Elderly patients treated with intensive chemotherapy experience high treatment-related mortality, low rates of remission and early relapse. Elderly patients are often unsuitable for intensive chemotherapy due to multiple medical comorbidities and poor risk disease, so have limited treatment options. Our centre is using a novel treatment strategy of prolonged low-dose cytarabine and thioguanine in combination with peg-filgrastim administered in the outpatient setting. Preliminary findings demonstrate a surpising efficacy for this regimen. This is an updated report on our experience.

Method:
A retrospective single-centre study was performed at Royal North Shore Hospital, NSW, Australia. The study includes patients who were diagnosed with AML between April 2009 and April 2012 and treated using the low-dose chemotherapy protocol. The group includes de novo AML patients as well as patients refractory to other therapies. The analysis included an oncology pharmacy audit as well as review of medical records and pathology results. Treatment consists of daily subcutaneous cytarabine 20mg/m2 and oral thioguanine 80mg for 14 to 21 day periods on monthly cycles with continued treatment for a period of 2 years. Peg-filgrastim is given concomittently with chemotherapy when patients become neutropenic. Response is assessed by bone marrow aspiration after treatment cycles. Routine supportive care is provided.

Results:
Between March 2009 and May 2012, a total of 21 patients (13 with de novo AML and 9 with refractory/relapsed AML) received the low dose protocol. The median patient age was 75 (range 52 to 89 years). 12 (57%) patients had treatment-related or MDS-related AML. 7 (33%) patients had poor risk cytogenetics. A CR or CRi was achieved in 13 (62%) patients. The median follow-up time is 11.9 months. Of those that achieved CR or CRi, 9 patients (43%) have remained in remission with Kaplan-Meier estimated mean leukamia-free survival of 23.3 months (14–32.5, 95%CI). The Kaplan-Meier estimated mean overall survival for the group is 22.4 months (14.3–30.5, 95%CI). 6 patients have crossed over to other treatment modalities. 5 of 7 patients with poor cytogenetics achieved CR/CRi. 3 patients with abnormal cytogenetics achieved both morphologic and cytogenetic remission. The treatment was generally well tolerated. Outpatient administration of cytarabine is managed well with assistance from community nursing.

Conclusion:
The results reported here provide longer follow-up time and a larger number of patients as further evidence for the efficacy of the low-dose chemotherapy protocol and its feasibility in the outpatient setting. The remission rates acheived are comparable to those reported for intensive therapy with potential benefits of reduced toxicity, lower cost, fewer hospital admissions and improved quality of life. We suggest that this low-dose protocol may be a consideration for elderly patients deemed unsuitable or ineligible for intensive chemotherapy or azacitidine. A prospective study is underway to further evaluate this protocol.

Disclosures:
No relevant conflicts of interest to declare.