PCR Analysis for the t(14;18) Translocation in Patients With Recurrent Follicular Lymphoma Following Immunotherapy With Rituximab (IDEC-C2B8)

The chimeric monoclonal anti-CD20 antibody rituximab (Rituxan) has been shown to have clinical activity in patients with follicular lymphoma. It depletes normal and malignant B-cells, binds complement, and effects complement-dependent cytotoxicity and antibody-dependent cytotoxicity. In patients with recurrent disease, the overall response rate (complete response [CR] + partial response [PR]) is 40% to 50%.

The t(14;18) chromosomal translocation can be detected in the diagnostic material of up to 80% of patients with follicular lymphoma using polymerase chain reaction (PCR) assays. This has subsequently been used as a surrogate marker, particularly in the setting of minimal residual disease.

A multicenter trial to confirm the reported efficacy of rituximab in the therapy of follicular lymphoma has been undertaken in the United Kingdom. Seventy previously treated adults were enrolled; the clinical response rate for the 67 evaluable patients was 48% (1 CR and 31 PRs).

A parallel study was undertaken at St. Bartholomew’s Hospital to monitor minimal residual disease using a two-step nested PCR for t(14;18). Material, including lymph node biopsies, diagnostic bone marrow, and peripheral blood samples, was obtained from 58 patients. Of these 58 patients, 31 (53%) were PCR-positive either in lymph node (13), and/or bone marrow (12), and/or blood (20) prior to rituximab therapy.

Follow-up bone marrow and blood samples (obtained a month after the last infusion) were available in 28 of these patients. Overall, 17/28 (61%) became PCR-negative. Of the patients who had a PR, 10/15 (67%) were PCR-negative after therapy, while 7/13 (54%) nonresponders (stable or progressive disease) became PCR-negative. Conversely, 5/11 (45%) patients who remained PCR-positive had a PR.

CONCLUSION: This study suggests that rituximab is very effective in decreasing (or eliminating) the number of CD20-positive cells (including follicular lymphoma cells) in bone marrow and/or peripheral blood, irrespective of the clinical response. Therefore, although obtaining a PCR-negative state does not reflect the clinical outcome, such immunotherapy may be extremely useful as a means of in vivo purging prior to the harvesting of progenitor cells to support high-dose therapy in such patients with follicular lymphoma.

Click here for Dr. Bruce Cheson’s commentary on this abstract.