Outpatient Bendamustine and Idarubicin for Upfront Therapy of Elderly Acute Myeloid Leukaemia/Myelodysplastic Syndrome: A Phase I/II Study Using an Innovative Statistical Design
Combinations of agents may improve outcomes among elderly acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS) patients. We performed an adaptive phase I/II trial for newly-diagnosed AML or high-risk MDS patients aged ≥50 years using a Bayesian approach to determine whether 1 of 3 doses of bendamustine (45, 60, 75 mg/m2 days 1-3), together with idarubicin (12 mg/m2 days 1-2), might provide a complete response (CR) rate ≥40% with <30% grade 3-4 non-haematological toxicity. We treated 39 patients (34 AML; five MDS with >10% marrow blasts; median age 73 years). None of the three bendamustine doses in combination with idarubicin met the required CR and toxicity rates; the 75 mg/m2 dose because of excess toxicity (two of three patients) and the 60 mg/m2 dose because of low efficacy (CR rate 10/33), although no grade 3-4 non-haematological toxicity was seen at this dose. Median survival was 7·2 months. All patients began treatment as outpatients but hospitalization was required in 90% (35/39). Although we did not find a dose of bendamustine combined with idarubicin that would provide a CR rate of >40% with acceptable toxicity, bendamustine may have activity in AML/MDS patients, suggesting its addition to other regimens may be warranted.
British Journal of Haematology
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Lionberger, Jack M.; Pagel, John M.; Sandhu, Vicky K.; Xie, Hu; Shadman, Mazyar; Mawad, Raya; Boehm, Alexandra; Dean, Carol; Dorcy, Kathleen Shannon; Scott, Bart L.; Deeg, Hans Joachim; Becker, Pamela S.; Hendrie, Paul C.; Walter, Roland B.; Ostronoff, Fabiana; Appelbaum, Frederick R.; and Estey, Elihu H., "Outpatient Bendamustine and Idarubicin for Upfront Therapy of Elderly Acute Myeloid Leukaemia/Myelodysplastic Syndrome: A Phase I/II Study Using an Innovative Statistical Design" (2014). Nursing & Healthcare Leadership Publications. 73.