Rituxan, Cytoxan, Dexamethasone 'Highly Effective' in AIHA, Low Grade Lymphoma

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[4726] Response to Rituximab, Cyclophosphamide and Dexamethasone as

Initial or Salvage Therapy in Low Grade Lymphoma and Immune Hemolytic

Anemia. Session Type: Publication Only

Neetu Radhakrishnan, Rajasree Roy, Reuven Yakubov, Kaufman,

Kanti Rai, Bhoomi Mehrotra, Dilip Patel Division of Hematology

Oncology, Long Island Jewish Medical Center, New Hyde Park, NY, USA;

Medicine

BACKGROUND: The combination of dexamethasone, cyclophosphamide, and

rituximab (RCD) have documented activity in lymphoproliferative

disorders without severe side effects and shows significant results

in the setting of AIHA (auto immune hemolytic anemia) in CLL (chronic

lymphocytic leukemia). We conducted a retrospective study of the

response to RCD in low grade lymphoproliferative disorders and in

AIHA at our institution.

METHODS: Between December 1998 and June 2006, 17 patients completed

therapy after a median of 6 cycles of RCD (rituximab 375 mg/m2 i.v.

on Day 1, dexamethasone 40 mg intravenously [i.v.] or [p.o.] on Days

1-4, cyclophosphamide at a dose of 750 mg/m2 i.v. on Day 2). Data

regarding patient characteristics, disease pathology, stage, IPI

scores, prior treatments, response using standard disease response

criteria and flow cytometric and/or molecular studies where

appropriate, and any recurrences were recorded. Stage IV responders

with undocumented post treatment bone marrows were classified as PR

(partial response).

RESULTS: The median age of the patients was 63 years (range : 28 80

years), 42% were male; (9/ 17) 52% had previously untreated disease;

and (9/17) 52% had follicular lymphoma, 35% had other indolent

lymphomas or CLL (2 marginal zone lymphoma (1 salvage), 1 mantle zone

lymphoma, 1 waldenstroms macroglobulinemia requiring frequent

plasmapheresis, 1 small cell lymphocytic lymphoma and 1 CLL) and 2

had steroid resistant AIHA. Median international prognostic index/

follicular lymphoma international prognostic index (IPI/ FLIPI) score

for the malignant lymphomas was 2 (range: 0-3).

Objective responses (OR) and complete responses (CR) were observed in

(16/17) 94% and (11/17) 64%, respectively. For patients with

follicular lymphoma, the respective OR and CR ratios were 5/5 (100%)

and 3/5 (60%) as first line therapy, and 4/4 (100%)and 2/4 (50%) as

salvage therapy. Both patients with heavily pretreated AIHA responded

completely and have not relapsed.

The median progression free survival (PFS) was 18 months (range: 1-

58 months) and median overall survival (OS ) was 28 months (range: 1 -

78 months). The PFS for follicular lymphomas was a median of

19months (range: 6 - 55months), with median OS of 45 months (range: 6-

78 months). Both patients with heavily pretreated AIHA achieved CR

without relapse. Recurrence of disease did not correlate with the

FLIPI/ IPI. Side effects were minimal and included grade II - III

neutropenia, hyperglycemia and steroid induced insomnia.

CONCLUSIONS: RCD is active as initial or salvage therapy in patients

with low grade lymphoproliferative disorders and is highly effective

in steroid refractory AIHA with minimal side effects. Addition of

rituximab prior to moderate doses of cytoxan and dexamethasone

significantly enhances the response rates.This chemotherapeutic

combination with a low side effect profile appears to produce

significant responses for low grade lymphomas and may translate into

better long term outcomes compared to previously utililized regimens.

Further studies are needed to evaluate whether this regimen may

improve the outcome of patients with low grade lymphomas.