Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia
We gratefully acknowledge patient accrual by the contributing centers (see below). We thank reference pathologists A. Rosenwald, H.-K. Müller-Hermelink, A.C. Feller, H.-W. Bernd, M. Hummel, and H. Stein for review of the bone marrow biopsies.
Contributing centers (alphabetical order by city, with names of referring physicians at hospitals and outpatient offices): Celle, Allgemeines Krankenhaus (F. Marquard); Duisburg, St.-Johannes Hospital (A. Giagounidis); Erfurt, Helios-Klinikum (M. Herold); Essen, Universitätsklinikum (A. Hüttmann); Garmisch-Partenkirchen, Office (L. Schulz); Hof, Sana Klinikum (C. Lohse); Kiel, Universitätsklinikum Schleswig-Holstein Campus (M. Kneba); Linz, Krankenhaus der Elisabethinen (M. Girschikofski); Löbau-Zittau, Klinikum des Landkreises gGmBh (M. Schulze); Ludwigsburg, Office (T. Ulshöfer); Lübeck, Städt. Krankenhaus Süd (S. Fetscher); Mönchengladbach, Office (U. Grabenhorst); München-Harlaching, Städtisches Krankenhaus (H. Pohlmann); Osnabrück, Office (J. Wamhoff); Saarbrücken, Caritas-Klinik St. Theresia (A. Matzdorff); Saarbrücken, Office (G. Jacobs); Stuttgart, Diakonie-Klinikum (K.J. Kaesberger); Tübingen, Universitätsklinik (M. Sökler); Wien, Allgemeines Krankenhaus der Stadt Wien (U. Jäger); Wien, Hanusch-Krankenhaus (T. Nösslinger); Wiesbaden, Städt. Klinik, Dr. Horst-Schmid-Klinikum (N. Frickhofen); Würzburg, Office (R. Schlag); Villingen Schwenningen, Office (G. Köchling).
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.
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.
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.
FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data. Cancer 2013;119:2258–2267. © 2013 American Cancer Society.