Therapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) for Relapsed or Untreated Progressive Chronic Lymphocytic Leukemia (CLL): A Single Centre Experience

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 21 de marzo del 2007

Share article


Presenter: Pavlovsky, M A
Presenter's Affiliation: FUNDALEU, Argentina
Type of Session: Scientific

Background

Chronic lymphocytic leukemia (CLL) is an indolent neoplasm of B-cell origin, that is usually CD20+, CD5+, and CD23+. It is similar to small lymphocytic lymphoma (SLL) where the disease burden is predominantly in lymph nodes and the bone marrow is minimally involved.

Fludarabine is the most active single agent in CLL. Rituximab is an anti-CD20 antibody that has complementary activity with fludarabine with minimal toxicity.

The combination of fludarabine, cyclophophamide, and rituximab (FCR) has demonstrated superior rates of complete remission (CR), minimal residual disease (MRD) negativity, disease-free survival (DFS) and overall survival (OS) in previously treated and untreated patients with CLL, when compared with historical control groups using fludarabine alone or fludarabine and cyclophosphamide.

CD28 is a marker of worse prognosis in CLL

This study was undertaken to evaluate the efficacy of FCR in improving CR, DFS and OS rates in patients previously treated with chlorambucil-prednisone and untreated patients with CLL.

Materials and Methods
Phase II single institution, single-arm, prospective study in patients with either untreated or previously treated with chlorambucil-prednisone eligible for symptomatic treatment.

Patients:

  • 45 CLL patients started treatment with FCR.
  • Median patient age was 63 years (range 34–88 years)
  • Binet’s stage:
    • 8% stage A, 34% stage B, 58% stage C.
  • CD38 expression was positive (> 7% of cells) in 56% of patients and negative in 44%.
  • Untreated: 32 patients; Previously Treated: 8 patients
Treatment:
FCR chemotherapy: all agents were given intravenously every 4 weeks for 4–6 cycles
  • fludarabine (25 mg/m2/day x 3) and
  • cyclophosphamide (250 mg/m2/day x 3)
  • rituximab (375 mg/m2/day x 1)
Reponse Criteria:
  • CR was defined by CLL/NCI-WG criteria.
  • Minimal residual disease (MRD) negativity was < 1% of CD19 and CD5-positive cells in peripheral blood and bone marrow.

Results
41 patients completed treatment:

  •   16 following previous relapse
  •    25 previously untreated with progressive disease
  •    The median number of cycles was 4.5 cycles
Response:
  • CR: 80% (of these, 97% were MRD negative)
  • Nodular Rartial Remission: 16% (of these, 100% were MRD negative)
  • Partial Remission: 8% of patients
  • Stable Disease: 2%
Remissions were more common in previously untreated patients:
  • Untreated: 87% (of these, 96% were MRD negative)
  • Previously Treated: 53% (of these, 87% were MRD negative)
Disease Free Survival was worse in previously-treated and CD38 positive patients:
  •   Untreated: 91%; Previously Treated: 62% (p=0.02)
  •   CD38 negative: 89%; CD38 positive: 66% (p=0.04)
Toxicity:
  • Grade 3–4 neutropenia: 33% of patients

Author's Conclusions

FCR induces a high CR and DFS rate and increases MRD negativity. Significantly higher DFS rates were observed in patients who were CD38 negative.

Clinical/Scientific Implications

The combination regimen of fludarabine, cyclophosphamide, and rituximab in patients that were either treatment naïve or previously treated was associated with excellent remission rates. It was generally well-tolerated except for frequent neutropenic fever (33%).

This study confirms that previously treated patients have lower remission rates. Also, the cell surface marker, CD38 is a negative prognostic marker in CLL with this treatment regimen.

Rituximab has been a major addition to the armamentarium against B-cell diseases. It is particularly appealing for indolent B-cell NHL as it has minimal toxicity and can be combined fairly easily with other treatments. The ideal schedule of incorporation of rituximab is an active area of investigation in number B-cell histologies.


News
Progression-free survival up in chronic lymphocytic leukemia patients on combo treatment

Oct 4, 2010 - Adding the monoclonal antibody rituximab to the standard chemotherapy regimen of fludarabine plus cyclophosphamide significantly extends the lives of chronic lymphocytic leukemia patients compared to chemotherapy alone, according to the results of a phase III trial published in the Oct. 2, cancer-themed issue of The Lancet.



I Wish You Knew

How cancer patients have changed my life

View More



Blogs and Web Chats

OncoLink Blogs give our readers a chance to react to and comment on key cancer news topics and provides a forum for OncoLink Experts and readers to share opinions and learn from each other.




OncoLink OncoPilot

Frente a un nuevo diagnóstico de cáncer o de cambiar el curso de su tratamiento actual? Deje que nuestro personal de enfermería cáncer que ayudan a pasar!

Más información