Results of Upfront Therapy for Marginal Zone Lymphoma.

BACKGROUND: Marginal zone lymphomas (MZLs) are indolent disorders composed of 3 subtypes: extranodal marginal zone lymphoma (MALT), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). Early-stage MALT is treated with radiotherapy or antibiotics, and advanced MALT and NMZL are managed with either watch and wait or chemotherapy. SMZLs are treated with splenectomy or rituximab. However, because these approaches have failed to cure patients with SMZL and NMZL, we have systematically used upfront chemotherapy for them, as well as for advanced MALT. We report the outcomes of this approach. PATIENTS AND METHODS: A total of 44 patients with MZL were identified from our database and divided into 2 groups. Group 1 (22 with early-stage MALT) patients received either radiotherapy (n = 17) or antibiotics with or without surgery (n = 5). Group 2 included 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Group 2 was treated with FND-R (fludarabine 25 mg/m2 on days 1 to 3, mitoxantrone 10 mg/m2 on day 1, dexamethasone 20 mg on days 1 to 5, and rituximab 375 mg/m2 on day 1; n = 14) or CHOP-R (cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50 mg/m2 on day 1, vincristine 2 mg intravenous push on day 1, prednisone 100 mg/m2 orally on days 1 to 5, rituximab 375 mg/m2 on day 1; n = 8), followed by maintenance rituximab for 70%. RESULTS: All patients achieved complete remission, and only 2 patients in group 1 had developed a relapse at 70 and 75 months. Both relapses were stage I MALT that had initially been treated with radiotherapy. Both were salvaged with FND-R and remained free of disease at 27 and 39 months after the relapse. At 10 years, the failure-free survival for the 44 patients was 80% and the overall survival was 100%. None of the patients in group 2 developed a relapse. The long-term toxicities have been acceptable. CONCLUSIONS: The excellent responses using upfront chemotherapy for MZL suggests that this disorder is curable. Our results should be confirmed in a prospective trial.

Front-line immunochemotherapy for aggressive non-Hodgkin lymphoma using dose-dense rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone plus granulocyte-macrophage colony stimulating factor and pegfilgrastim as support.

Granulocyte-macrophage colony stimulating factor (GM-CSF) has been associated with multiple immune effects, which could enhance the outcome of chemotherapy. For this reason we decided to explore the combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) given every 14 days with pegfilgrastim (Neulasta) and GM-CSF (Leukine). A total of 59 HIV-negative patients with aggressive-histology non-Hodgkin lymphoma were accrued. The median age was 56 years (range 25-87). Lactate dehydrogenase (LDH) was high in 36 patients (61%); performance status was 0-1 in 48 patients; International Prognostic Index (IPI) was 0-1 in 30 and 2-3 in 24 patients; and disease was stage I-II in 46% and III-IV in 56% of patients. Diffuse large B-cell lymphoma was the most common lymphoma type. Response rates were: complete remission (CR) in 51 (86%), partial remission (PR) in five (8%) and failure in three patients (5%). At a median follow-up of 26 months, the overall survival (OS) at 3 years was 76% and the 3-year failure-free survival (FFS) was 73%. No patient relapsed beyond 18 months. Patients with IPI ≥ 3 had a 3-year progression-free survival (PFS) of 54% versus 82% in those with IPI < 3 (p = 0.038). Patients aged < 60 years had a FFS of 77% while those aged ≥ 60 years had a FFS of 69% (p = 0.29). Both the CR rate and the quality of CRs were satisfactory, with only 5/51 (10%) of complete responders having lost their remissions to date. Of interest is that age ≥ 60, an important adverse prognostic factor, appeared to have lost some of its importance, since the difference between those aged < 60 and ≥ 60 years was minimal in our study. The results with R-CHOP-GM-CSF every 14 days are encouraging, and merit a prospective comparative clinical trial against R-CHOP-14 in order to elucidate the contribution of GM-CSF.