Our objective was to determine the efficacy of a fludarabine (Fludara)/mitoxantrone (Novantrone) regimen combined with the monoclonal anti-CD20 antibody rituximab (Rituxan) to induce clinical and molecular remissions in patients with relapsed follicular lymphoma.
A prospective trial was conducted in 18 consecutive relapsed patients with follicular lymphoma. Fludarabine at 30 mg/m2 days 1 to 3 and mitoxantrone at 10 mg/m2 day 1 were administered monthly for 4 months followed by rituximab at 375 mg/m2 weekly × 4. Eligible patients had relapsed nodal follicular non-Hodgkin’s lymphoma with bcl-2 and CD20-positive expression, Eastern Cooperative Oncology Group (ECOG) performance status < 3, normal liver and renal function, and no concomitant diseases. Both clinical and molecular responses were evaluated; polymerase chain reaction (PCR) assays for t(14;18) in peripheral blood and bone marrow prior to therapy, after fludarabine/mitoxantrone chemotherapy, and after rituximab treatment were completed.
Patients included (see table for details) 13 males and 5 females, with a mean age of 52.3 ± 13.4 years (range: 32 to 77 years), and ECOG status of 0 (11 patients), 1 (3), 2 (2), or 3 (2). Clinical stage was determined to be II (4 patients), III (5), or IV (9), with 1 (10 patients), 2 (3), or ³ 3 (5) previous therapies. Before therapy, bone marrow showed positive PCR t(14;18) in 10 cases (55.5%), and 4 (22.22%) were positive in peripheral blood.
A total of 16 patients were evaluable for response; after fludarabine/mitoxantrone therapy, 5 patients showed complete responses (CR) (31.25%), 10 partial responses (PR) (62.50%), and 1 failure (6.25%). After rituximab therapy (15 patients) the response rates were 9 CR (60.0%), 5 PR (33.33%), and 1 failure (6.66%). According to 10 cases with positive PCR t(14;18) in bone marrow, 8 (80.0%) achieved molecular remission (1 was after fludarabine/mitoxantrone therapy—the patient was excluded for rituximab therapy), 1 patient is continuously PCR t(14;18)-positive, and the remaining patient is under therapy.
CONCLUSION: Fludarabine/mitoxantrone therapy induces clinical response in 93.75% of patients with relapsed follicular lymphoma, with a CR rate of 31.25%. Rituximab therapy does not influence overall response but improves CR rate (60.0%). Furthermore, it is capable of obtaining in vivo purging in 77.77% of cases. For these reasons, combined fludarabine/mitoxantrone chemotherapy plus rituximab could be a good therapeutic scheme to produce in vivo purging before stem cell harvesting in patients undergoing autologous stem cell transplantation.