Abstract
Between May 2012 and May 2014, 15 elderly patients (median 64yrs, range 54-80yrs) who presented with acute myeloid leukemia (AML) with comorbidities preventing them from receiving standard induction, were treated with decitabine at a dose of 20 mg/m2 for 5 days at monthly intervals. All patients received a minimum of 3 cycles of decitabine with a range of 3-9 cycles. Bone marrow examination was conducted at the end of 3 cycles to assess response. As opposed to the 40% CR rate reported by Ritchie et al (2013) in an elderly western population, we observed a response rate of 60% in our cohort. 9 out of 15 patients achieved remission, with 7 of the 9 patients regaining normal blood counts. The median clinical follow-up was 375 days with a range of 74-800 days. All 9 patients who responded positively to decitabine are alive and well.
This 50% higher response rate to decitabine in Indian patients led us to examine the genetic basis for this observed difference. We conducted an observational prospective study of 14 Indian AML patients either at diagnosis or at relapse. Whole genome expression data from bone marrow aspirate samples was analyzed using PeCaSo™ (APT Life Sciences, Bangalore, India). PeCaSo is a genetic interaction network analysis platform that provides a ranked list of chemotherapeutic agents, as well as other approved pharmaceutical agents which can potentially be used as adjuvant therapy. For the 14 patients enrolled in the study, we looked at their response to decitabine as predicted by PeCaSo (see figure). As a comparison, PeCaSo was also used to retrospectively analyze whole genome expression data of Caucasian AML patients (n=16) available at The Cancer Genome Atlas (TCGA).
PeCaSo’s genomic network analysis indicates a higher response rate to decitabine for the Indian AML cohort when compared with a Caucasian cohort, strongly suggesting a potential genetic basis for the clinically observed difference.
This study provides supportive evidence for considering decitabine for induction therapy of AML in Indian patients. Our study’s genomic approach confirms that the heterogeneity and genetic basis of cancer has to be factored in prescribing personalized protocols for the treatment of cancer.
Damodar:APT Life Sciences, Bangalore, India: Research Funding. KS:APT Life Sciences, Bangalore, India: Research Funding. Purnaiya:APT Life Sciences, Bangalore, India: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Kumar:APT Life Sciences, Bangalore, India: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Nagaraj:APT Life Sciences, Bangalore, India: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Ram:APT Life Sciences, Bangalore, India: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.
