Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia
Georg Hopfinger, Raymonde Busch, Natali Pflug, Nicole Weit, Anne Westermann, Anna-Maria Fink, Paula Cramer, Nina Reinart, Dirk Winkler, Günter Fingerle-Rowson, Stephan Stilgenbauer, Hartmut Döhner, Gabriele Kandler, Barbara Eichhorst, Michael Hallek, Marco Herling, Georg Hopfinger, Raymonde Busch, Natali Pflug, Nicole Weit, Anne Westermann, Anna-Maria Fink, Paula Cramer, Nina Reinart, Dirk Winkler, Günter Fingerle-Rowson, Stephan Stilgenbauer, Hartmut Döhner, Gabriele Kandler, Barbara Eichhorst, Michael Hallek, Marco Herling
Abstract
Background: Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab.
Methods: This prospective multicenter phase 2 trial assessed response, survival, and toxicity of a novel regimen in previously treated (n = 9) and treatment-naive (n = 16) patients with T-PLL. Induction by fludarabine, mitoxantrone, and cyclophosphamide (FMC), for up to 4 cycles, was followed by alemtuzumab (A) consolidation, up to 12 weeks.
Results: Of the 25 patients treated with FMC, 21 subsequently received alemtuzumab. Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). Median overall survival after FMC-A was 17.1 months and median progression-free survival was 11.9 months. Progression-free survival tended to be shorter for patients with high-level T-cell leukemia 1 oncoprotein expression. Hematologic toxicities were the most frequent grade 3/4 side effects under FMC-A. Exclusively in the 21 alemtuzumab-consolidated patients, 13 cytomegalovirus reactivations were observed; 9 of these 13 represented a clinically relevant infection.
Conclusions: FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data.
Copyright © 2013 American Cancer Society.
Source: PubMed