2-CDA, Rituximab and GM-CSF

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ASH:

[4726] 2-Chlorodeoxyadenosine (2-CDA) with Weekly

Rituximab and Granulocyte-Macrophage Colony

Stimulating Factor (GM-CSF): A Highly Effective

Regimen for Advanced B-Cell Lymphoproliferative

Disorders (BLPD).

Purvi K. Shah, Jainulabdeen Ifthikharuddin,

Mintz, Felgar, Jane L. Liesveld, Camille N.

Abboud. Department of Hematology, University of

Rochester, Rochester, NY, USA; Department of

Pathology, University of Rochester, Rochester, NY, USA

Rituximab, the anti-CD20 monoclonal antibody, induces

apoptosis and acts as a chemosensitizer, synergizing

with chemotherapeutic agents, including nucleoside

analogues, such as fludarabine. GM-CSF increases

antibody-dependent cellular cytotoxicity (ADCC),

improves antigen presentation and upregulates CD-20

expression on B-lymphocytes in-vitro.

We report a highly active combination of Rituximab

with 2-CDA, in the presence of GM-CSF in 13 patients

with advanced B-cell lymphoproliferative disorders.

Clinical chracteristics of this cohort include: a

median age of 70 (46 to 90) years, ECOG performance

status of 0-3, histology: 3 small lymphocytic

lymphomas/chronic lymphocytic leukemias (1 with pure

red cell aplasia), 3 lymphoplasmacytic lymphomas, 2

follicular lymphomas, 1 mantle cell lymphoma in

leukemic phase, 1 prolymphocytic leukemia (PLL), 1

relapsed hairy cell leukemia, 1 bulky extranodal

marginal zone lymphoma and 1 transformed diffuse large

cell lymphoma. Seven patients had received a median of

3(1-6) prior therapies and 6 patients were

chemo-naive.

RESULTS: 6 patients or 46% achieved a complete

remission (CR), and 6 patients (46%) attained a

partial remission (PR) {related primarily to residual

lymphadenopathy on imaging studies}, resulting in an

overall response rate of 92%. One patient with

advanced refractory mantle cell lymphoma had nodal

extramedullary disease progession and died. Seven of 9

patients with extensive bone marrow involvement

(50-90%) achieved a complete hematologic response by

morphology and flow cytometry, rendering them

transfusion independent. The patient with advanced PLL

achieved a complete histologic and cytogenetic

response. Two of 3 patients, previously treated with

fludarabine also responded (1 CR and 1 PR).

As of last follow-up, all responders (12 of 13

patients) continued to remain in remission. Thus far,

response durations have ranged from 4+ to 12+ months.

This therapy was well tolerated except for infusion-

related events, associated with rituximab. Major

hematologic toxicities included severe lymphopenia in

the majority of patients, most likely secondary to

2-CDA and mild neutropenia and thrombocytopenia.

Serious infectious complications included 1 episode of

bacterial pneumonia and 1 of reactivated varicella-

zoster and CMV enteritis.

CONCLUSIONS: Chemoimmunotherapy combining rituximab,

2-CDA and GM-CSF appears to have significant activity

in a wide range of BLPDs. This regimen was well

tolerated in this elderly cohort of patients, had an

acceptable toxicity profile and could be administered

on an outpatient basis. A larger prospective clinical

trial with laboratory correlates is underway to

validate these promising results.

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