Use of a Disease-Specific Comorbidity Index To Describe Elderly Patients with Acute Myelogenous Leukemia (AML) and High Risk Myelodysplasia (MDS) Enrolled in a Phase II Study of CLORETAZINE™ (VNP40101M).

Background: Elderly patients (pts) with AML generally have an unfavorable clinical course and are under-represented in clinical studies. Comorbid conditions are common in the elderly and, for older pts with AML, may have a major influence on choice of treatment. The ability to objectively measure comorbidity in this population may help predict patients’ risk for unacceptable toxicity. Comorbidity indices developed from a general medical population may underestimate the risks of cytotoxic treatment. An index developed specifically for pts with hematologic malignancies may be useful in categorizing pts by risk before selection of leukemia induction therapy. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an index which captures comorbidities that predict non-relapse mortality (NRM) in pts with hematologic malignancies considered for allogeneic transplant (Sorror; Blood; 2005). The HCT-CI defines low risk with a score = 0, intermediate = 1–2 and high = ≥3. We used the HCT-CI to assess baseline comorbidity in an elderly pt population (median age 72) with untreated AML or high risk MDS enrolled in a single agent phase II study of CLORETAZINE.

Methods: Case report forms of 105 pts ≥ 60 years of age containing information about baseline medical history, concomitant medications, physical examination, and serum chemistries were reviewed. Using the HCT-CI definitions, pts were given scores representing the weighted sum of conditions that were active or required treatment at study entry.

Results: A total of 232 comorbid conditions were scored. In order of frequency, the most common were: cardiac (28%), including congestive heart failure, myocardial infarction, arrythmias, coronary artery stenosis requiring treatment, and valve disease; psychiatric disturbances (12%); hepatic dysfunction (11%); infection (11%); and ≥ grade 2 pulmonary disease (8%). Most pts (64%) had multiple comorbid conditions. Cardiac conditions were observed in 46% of all pts, psychiatric disturbances in 27%, hepatic disease in 25%, ongoing but controlled infections in 24%, and pulmonary disease in 18%. The response rate within each risk category is similar to the overall response rate, as summarized in the table below. The 19 early deaths (≤ 30 days) occurred in pts from the intermediate and high risk categories.

Conclusions: The HCT-CI is a helpful tool for defining comorbid conditions in elderly untreated AML pts. The majority of pts enrolled in the single agent Phase II CLORETAZINE study is at high risk for NRM as measured by HCT-CI score. Pts respond to CLORETAZINE across the HCT-CI scored risk groups.