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

Cancer. 2013 Jun 15;119(12):2258-67. doi: 10.1002/cncr.27972. Epub 2013 Mar 19.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

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

Substances

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