P581: PHASE II STUDY OF LOWER-INTENSITY FRONTLINE THERAPY FOR NEWLY DIAGNOSED PATIENTS WITH AML WHO ARE UNFIT OR OTHERWISE NOT ELIGIBLE FOR FRONTLINE CLINICAL TRIALS

Abstract

Background: Pts with newly diagnosed (ND) AML frequently present with abnormal organ function, poor performance status (PS), concurrent active malignancies, and active infections. These factors often preclude these pts from enrollment on frontline clinical trials, since standard eligibility routinely exclude them. Aims: Therefore, we designed a lower-intensity regimen of cladribine plus low-dose cytarabine (LDAC) alternating with decitabine (DAC) with less stringent inclusion criteria in ND pts unfit or otherwise ineligible for existing clinical trials. Methods: Pts >18 years with untreated AML and ineligible for other frontline AML clinical trials were enrolled (NCT01515527). Eligibility criteria included either creatinine ≥2mg/dL; or total bilirubin ≥2 mg/dL; or ECOG PS of 3 or 4; or ineligible for participation in a higher priority protocol. Pts with active concurrent malignancies and ongoing infection related to their AML could be enrolled. Induction was cladribine 5 mg/m2 IV on D1-5, Cytarabine 20 mg SQ twice daily on D 1-10, followed by consolidation with cladribine 5 mg/m2 IV on D1-3, Cytarabine 20 mg SQ twice daily on D 1-10 alternating with decitabine 20 mg/m2 IV, daily on D 1-5. The primary objective was 60-d survival rate. Results: A total of 25 pts have been enrolled. The median age was 73 years (range, 52-82) with 76% of the cohort older than 70 years. Six pts (24%) had concurrent active malignancy, 4 (16%) had baseline creatinine >2mg/dL, and 9 (36%) had PS ≥3. 76% of them were adverse risk per ELN 2017. Baseline characteristics are shown in figure. Among 25 evaluable pts, 17 (68%) achieved a composite complete response (CRc) including 10 (40%) CR and 7 (28%) CR with incomplete count recovery (CRi). Among responders, 6 pts (35%) achieved MRD neg by flow. Of 7 pts with no response, all were ELN adverse risk. Median cycles to response was 1 (range: 1 - 4). 30- and 60 d mortality was 8% and 16%, respectively, including 2 pts (8%) who died due to pseudomonal sepsis on D8, and the other due to pneumonia on D11. At a median follow up of 9.4 months (range, 0.4- 19.9 m),median OS (6-mo OS% - 61 %), and EFS was 8.3 mo each (6-mo RFS% - 56 %) with a 60-d OS and EFS rate of 83% each, with a median RFS of 5.8 mo (2-mo RFS%-66%; 6-mo RFS% - 49 %). In this challenging patient population, this lower-intensity regimen was well tolerated, with an acceptable toxicity profile. Image:Summary/Conclusion: In an unfit patient population with a high comorbidity burden, that were ineligible for other clinical trials, induction therapy with Cladribine plus LDAC was feasible and effective in newly diagnosed pts with AML. The regimen produced high rates of response, encouraging EFS, OS, and low early mortality in a cohort predicted to have a high risk of early death. Treating this pt population on a clinical trial is feasible and can allow pts to achieve remission and move on to effective post-remission therapy.