Browsing by Author "Appelbaum, Frederick R"

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    Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms.
    (Leukemia, 2018-11) Halpern, Anna B; Othus, Megan; Huebner, Emily M; Scott, Bart L; Becker, Pamela S; Percival, Mary-Elizabeth M; Hendrie, Paul C; Gardner, Kelda M; Chen, Tara L; Buckley, Sarah A; Orlowski, Kaysey F; Anwar, Asma; Appelbaum, Frederick R; Erba, Harry P; Estey, Elihu H; Walter, Roland B
    Outcomes with "7 + 3" are often unsatisfactory in acute myeloid leukemia (AML). Trials demonstrating improved outcomes with high-dose cytarabine, addition of cladribine, or escalated anthracycline doses prompted a phase 1/2 study (NCT02044796) of G-CSF, cladribine, high-dose cytarabine, and dose-escalated mitoxantrone (GCLAM) in adults with newly-diagnosed AML or other high-grade myeloid neoplasms. One hundred and twenty-one patients, median age 60 (range 21-81) years, were enrolled. In phase 1, cohorts of 6-12 patients were assigned to 12-18 mg/m2/day of mitoxantrone as part of GCLAM. Because all dose levels were well-tolerated, mitoxantrone at 18 mg/m2 was declared the recommended phase 2 dose (RP2D). 74/94 (79%) patients treated at the RP2D achieved a complete remission (CR; 67/74 without measureable residual disease [MRD]) for an overall MRDneg CR rate of 71% (primary phase 2 endpoint). Seven patients achieved a CR with incomplete blood count recovery (CRi; 7%, 5 MRDneg) for a CR/CRi rate of 81/94 (86%). Four-week mortality was 2%. After adjustment, the MRDneg CR and CR/CRi rates compared favorably to 100 matched controls treated with 7 + 3 at our center and 245 matched patients treated with 7 + 3 on a cooperative group trial. Our data indicate GCLAM with mitoxantrone at 18 mg/m2/day is safe and induces high-quality remissions in adults with newly-diagnosed AML.
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    Relative survival following response to 7 + 3 versus azacytidine is similar in acute myeloid leukemia and high-risk myelodysplastic syndromes: an analysis of four SWOG studies.
    (Leukemia, 2019-02) Othus, Megan; Sekeres, Mikkael A; Nand, Sucha; Garcia-Manero, Guillermo; Appelbaum, Frederick R; Erba, Harry P; Estey, Eli
    Here we quantify and compare the absolute and relative overall survival (OS) benefits conveyed by complete remission (CR) in AML and high-risk MDS, and by CR with incomplete count recovery (CRi) in AML and by hematologic improvement (HI) in MDS, following treatment with 7 + 3 versus azacytidine. We compared patients receiving 7 + 3 in SWOG studies S0106 (n = 301) and S1203 (n = 261) enrolling adults ≤ 60 years, with patients receiving azacytidine therapies in S0703 (n = 133 AML patients ≥ 60) and S1117 (n = 277 MDS patients ≥ 18). Absolute survival benefit was evaluated with 1-year, 3-year, and median OS; relative benefit was evaluated with univariate and covariate-adjusted hazard ratios. CR conveyed a relative survival advantage in multivariable analysis, with a similar relative effect of CR across studies. CR also conferred an absolute survival benefit, but with a smaller magnitude of absolute benefit in the azacytidine trials. In AML, OS was similar for CRi and failure to achieve CR/CRi. In MDS, CR conferred a survival advantage versus HI and HI versus failure. The relative survival benefit of CR was similar regardless of initial therapy for AML or high-risk MDS. With both therapies, CR has a beneficial effect on survival compared with CRi or HI.