Fludarabine, mitoxantrone and dexamethasone as first line treatment of patients with indolent Non-Hodgkin's lymphoma (NHL): GATLA first interim report

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 21, 2007

Presenter: Milone, G.
Presenter's Affiliation: Instituto de Investigaciones Hematologicas, Buenos Aires, Argentina
Type of Session: Scientific

Advanced stage (Stage III/IV) indolent NHL is generally thought to be incurable, but can be treated successfully with single- and multi-agent chemotherapy regimens as well as anti-CD20 immunotherapy with or without linked radionuclides.

Fludarabine (F) monotherapy is as least as effective, as conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL in achieving objective response rates.

Better response rates can be achieved combining F with Mitoxantrone (N) and Dexamethasone (D) in indolent NHL patients.

The GATLA (Grupo Argentino de Tratamiento de la Leucemia Aguda) performed this study to evaluate the use of FND as a first line treatment for low grade NHL.

Materials and Methods

Design: Prospective, multi-center national study (Phase II)

Inclusion criteria:

  • low grade NHL not previously treated, age > 18 years old with symptomatic disease, ECOG performance status 0-2 and written informed consent.


  • 96 patients enrolled January 2002 to April 2006, 69 were evaluable at the time of analysis.
  • Median age 54 years (range: 21-79)
  • Gender: 51% male
  • Ann Arbor staging: I: 5.8%, II: 14.5%, III: 24.6% and IV: 55%


  • Chemotherapy (FND)
  • Fludarabine (F) 25 mg/m2 i.v. (days 1-3)
  • Mitoxantrone (N) 10 mg/m m2 i.v. (day 1)
  • Dexamethasone (D) 20 mg (days 1-5) each 28 days for 6 cycles.
  • All patients received oral antibiotics for intestinal decontamination, antifungal prophylaxis and trimethoprim-sulfamethoxazole for P. carinii prophylaxis for one year.


  • Overall response rate (ORR): 93%
    • 70% (48 pts) with complete response (CR)
    • 23% (16 pts) with partial response (PR)
    • Progressive disease and non-response: 7% (5 pts)
  • Event free survival (EFS) at 24 months: 60%
  • Overall survival (OS) at 24 months: 90%
  • Deaths: Two patients developed secondary malignancies after treatment and one died. Only one patient died in CR

Author's Conclusions

In this population FND treatment demonstrated a high CR rate with low toxicity and a high probability of EFS and OS.

Clinical/Scientific Implications

The response rate, EFS, and OS compare favorably with other single and multi-agent chemotherapy regimens for initial treatment of low grade lymphoma, however, it is difficult to compare these non-randomized study populations.

About 20% of the patients had Stage I or II disease, which could potentially be curable with the addition of external beam radiation therapy, however it is unclear radiation was part of their treatment.

The results of 131-iodine tositumomab radioimmunotherapy (RIT) for initial treatment of follicular lymphoma (Kaminski et al) appear to be as good or better than the results of this study using multi-agent chemotherapy (FND). Using RIT as initial treatment, the CR rate was 75%, the PFS at 2 years was over 65%, and the 5 yr PFS was 59%. Longer follow-up from this study will be needed to determine the durability of response.

The optimal initial treatment for indolent lymphoma is an open question. For early stage disease, cure may be possible using external beam radiation. In advanced stage disease, the goal is obtain the most reliable and durable responses with minimum toxicity.

See the patient-oriented summary of this study