[296] Cytarabine, Daunorubicin and Etoposide (ADE) Chemotherapy in Acute Myeloid Leukemia (AML) Patients 60 Years (CALGB 9720). Session Type: Oral Session

Maria R. Baer, Stephen L. George, Ben L. Sanford, Sandra M. Bothun, Krzysztof Mrozek, Kieran L. O'Loughlin, Jonathan E. Kolitz, Joseph O. Moore, Richard M. Stone, Bayard L. Powell, Michael A. Caligiuri, Clara D. Bloomfield, Richard A. Larson Cancer and Leukemia Group B, Chicago, IL, USA

CALGB 9720 was a phase 3 trial evaluating the multidrug resistance modulator PSC-833 (Valspodar) in induction and consolidation, and subcutaneous interleukin-2 (IL-2) maintenance therapy (rx) in older AML patients (pts). The PSC-833-containing arm was closed after randomization of 120 pts due to excessive toxicity (Blood 2002;100:1224). All subsequent pts received ADE induction (A 100 mg/m²/d by 7-day continuous intravenous infusion, with D 60 mg/m² and E 100 mg/m² each daily for 3 days), a second induction if needed (same drugs and doses for 5, 2 and 2 days) based on day 14 marrow (BM) cellularity 20% and >5% blasts, and one consolidation course (same drugs and doses for 5, 2 and 2 days), and were then randomized to IL-2 or no further rx. We report outcome of ADE rx on this study in 610 pts 60 years (yrs; median=70.5 yrs) with de novo AML (n=396; 65%) or secondary AML (S-AML) defined by prior myelodysplastic syndromes or cytotoxic rx (n=168; 28%). Complete remissions (CR) were achieved in 283 (46%) of the 610 pts, 5 (<1%) met CR criteria for <4 weeks, 35 (6%) achieved CR with incomplete count recovery (CRi), and 287 (47%) were non-responders, including 121 with resistant disease and 119 who died during induction. Of 457 pts with day 14 BM data, 344 (75%) did not have BM hypoplasia, but only 99 (29%) received second induction courses. Among 583 pts with information available, 455 (78%) received one course and 128 (22%) two courses, with CR rates of 52% and 35%, respectively. CR rates were 27%, 44% and 51% for pts with complex karyotypes (3 abnormalities), rare aberrations (Blood 2006;108:63) and neither finding, respectively (p<0.0001); 53% and 36% for de novo and S-AML (p=0.0004); 53%, 42% and 27% for ages 60-69, 70-79 and 80 yrs (p=0.0007); and 38% and 54% for pts whose blasts did and did not overexpress P-glycoprotein (Pgp) (p=0.05). In a multivariable logistic regression model adjusted for log(WBC) and sex, predictors of CR success included non-complex/non-rare karyotypes vs. complex (3 abnormalities; p<0.0001); de novo vs. S-AML (p=0.0005); and decreasing age (p=0.0008). 253 pts (38%) received consolidation rx, and 157 were randomized to IL-2 (n=81) or no further rx (n=82), with no difference in outcome (Blood 2006;108:129a). Both disease-free survival (DFS) and overall survival (OS) were short, with medians of 6.8 and 7.3 months. In univariable analyses, DFS was worse for complex karyotypes (5 abnormalities; p<0.0001) and for S-AML (p=0.0023). In a multivariable analysis adjusted for sex and age, DFS was worse for complex (5 abnormalities) karyotypes (p<0.0001), increasing WBC (p=0.0005) and S-AML (p=0.008). In univariable analyses, OS was worst for complex karyotypes (5 abnormalities; p<0.0001); S-AML (p<0.0001); increasing age (p=0.0004); and Pgp (p=0.04). In a multivariable analysis adjusted for sex, OS was worse for complex karyotypes (5 abnormalities; p<0.0001); increasing WBC (p=0.0001); S-AML (p=0.0016); and increasing age (p=0.0003). Intensification of standard 7+3 AD rx by dose-escalation of D and addition of E did not improve outcomes compared with historical 7 + 3 trials, nor alter the influence of previously established adverse prognostic factors in older AML pts.
Abstract #296 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Acute Myeloid Leukemia|Induction Chemotherapy|Age
Disclosure: No relevant conflicts of interest to declare.

Monday, December 10, 2007 11:15 AM

Session Info:  Simultaneous Session: Acute Myeloid Leukemias: Therapy, excluding Transplantation-Results of Clinical Trials (11:00 a.m.-12:30 p.m.)