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

e19028 Background: Pts with newly diagnosed(ND) AML often present with abnormal organ function, poor performance status (PS), concurrent active malignancies, and active infections precluding them from enrolling on frontline clinical trials, since standard eligibility routinely exclude them. We designed a lower-intensity regimen of cladribine plus low-dose cytarabine (LDAC) alternating with decitabine with less stringent inclusion criteria in ND pts unfit or 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; active concurrent cancer, infection, or ECOG PS of 3 or 4; or ineligible for participation in a higher priority protocol. 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. Primary objective was 60-d survival rate. Results: 25 pts have been enrolled. The median age was 73 yrs (range, 52-82) with 76% aged ≥70 yo. 6 pts (24%) had concurrent active malignancy, 4 (16%) had baseline creatinine >2mg/dL, and 9 (36%) had PS ≥3. 76% were adverse risk per ELN 2017 (Table). 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. Conclusions: In an unfit patient population of ND AML with high comorbidity burden, that were ineligible for other clinical trials, induction therapy with Cladribine plus LDAC was feasible and effective and can allow pts to achieve remission and move on to effective post-remission therapy. Clinical trial information: NCT01515527. [Table: see text]