Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia.

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.

• Authors: 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
• Journal: Cancer (Cancer) Vol. 119 Issue 12 Pg. 2258-67 (Jun 15 2013) ISSN: 1097-0142 [Electronic] United States
• PMID: 23512246 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2013 American Cancer Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• Proto-Oncogene Proteins
• TCL1A protein, human
• Alemtuzumab
• Cyclophosphamide
• Mitoxantrone
• Vidarabine
• fludarabine

Topics

• Adult
• Aged
• Alemtuzumab
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chromosome Aberrations
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Humans
• Leukemia, Prolymphocytic, T-Cell (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage)
• Proto-Oncogene Proteins (analysis, metabolism)
• Remission Induction
• Treatment Outcome
• Vidarabine (administration & dosage, adverse effects, analogs & derivatives)