Abstract
Abstract 186
Acute Myeloid Leukemia - Therapy, excluding Transplantation: Pediatric and Adult AML Therapy
F is a protein bound, cytotoxic, cyclin dependent kinase inhibitor. A prior Phase II trial of TST with FLAM, with F given by one hour bolus daily × 3 for adults with newly-diagnosed AML with poor-risk features demonstrated that the complete remission (CR) rate was 30/45 (67%) with median overall survival (OS) and disease-free survival (DFS) for CR patients being 12.6 and 13.3 months, respectively. We now compare FLAM using bolus F (50 mg/m2 daily × 3; Arm A) vs. FLAM using F given by pharmacologically-derived “hybrid” schedule (30 mg/m2 bolus over 30 min followed by 40 mg/m2 in a 4 hr infusion daily × 3; Arm B) in 70 newly-diagnosed AML patients (pts) with poor-risk features. Results: Pt demographics are presented below.
Age # < 50 Secondary AML Adverse Genetics MDS/MPD t-AML Single Complex Flt3 ARM A (n = 36) 59ü(24–78) 3 19 5 6 13 3 Total 24/36 = 67% Total 22/36 = 61% ARM B (n = 34) 58ü(20–73) 5 16 9 8 10 5 Total 25/34 = 74% Total 23/34 = 68%
Grade > 3 tumor lysis occurred in 4/70 (6%) with 1 death (A), 1 transient hemodialysis (A), 1 transient hyperkalemia (B), and 1 discontinuation of therapy (B). Four pts (6%) died from regimen toxicity before day 60 (1 A, 3 B). Median time for ANC >500/uL was Day 33 (range 22–71), and platelets > 50,000/uL Day 30 (21-80) for both arms. CR rate in Arm A is 23/36 (64%) including 16/24 (67%) with prior MDS and 13/19 (68%) with adverse cytogenetics and 3/3 (100%) with FLT3-ITD. CR rate in Arm B is 24/34 (71%) including 16/24 (67%) with prior MDS, 12/18 (67%) with adverse cytogenetics, and 4/5 (80%) with FLT3-ITD. As of 7/1/10, 20/23 Arm A CR pts have received chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HCT) in CR: 15/23 (65%) of these pts remain alive and in continuous CR for up to 14+ months, 2 relapsed 4 months post-HCT, and 2 died (1 FLAM consolidation, 1 HCT). Similarly, 20/24 Arm B CR pts have received chemotherapy and/or HCT in CR: 12/20 (60%) remain alive and in continuous CR for up to 18+ months. Of Arm B pts receiving FLAM consolidation, 1 relapsed at 2 months, 1 died at 8 months of cardiac failure, and 2 died during therapy. Three were unable to receive a second cycle and 1 refused. Overall, 51/70 (73%) of all pts and 40/47 (85%) of CR pts are alive 2+ - 19+ months after FLAM. Conclusions: TST with FLAM induces CR in >60% of newly diagnosed, poor-risk AML pts, including those with prior MDS and adverse genetics. There does not appear to be major difference in toxicity or responses between the two F schedules (bolus vs. “hybrid” bolus-infusion). Thus far, allogeneic HCT has been successfully undertaken in 21/47 (45%) of first CR patients, median age 57 (20-64), with 2 early relapses and 1 death from GVHD. Bolus F may be easier to administer than hybrid F and is therefore recommended for further study in newly diagnosed AML pts. These salutary results of FLAM in poor-risk pts will now be evaluated broadly in adults with AML and compared to traditional cytotoxic chemotherapy induction regimens.
Disclosures:
No relevant conflicts of interest to declare.
Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia