Patients with Limited Stage Extranodal Marginal Zone Lymphoma Have Excellent Overall Survival Regardless of Choice of Therapy Type or Observation

Patients with limited stage marginal zone lymphoma (MZL) are typically treated with radiotherapy, surgery, and/or antibiotics with curative intent. Some patients, however, are not candidates for these treatments or decline treatment. A retrospective series (Advani et al. J Clin Oncol 2004;22: 1454) suggested that patients with limited stage follicular lymphoma who did not receive radiotherapy still had an excellent prognosis. We hypothesized that patients with stage I-II MZL who deferred or declined potentially curative therapy had an overall survival similar to patients who received such therapies.

We identified 113 patients with MZL who were seen at Weill Cornell Medical Center between 1999 and 2010. We reviewed the medical records of these patients and obtained demographic, prognostic, diagnostic, and treatment information. We used the medical records and a Social Security death index to establish dates of death/survival. Treatment with curative intent was defined as any first-line therapy consisting of surgery, external beam radiation therapy, or H. pylori eradication therapy. Overall survival (OS), time to treatment (TTT) from diagnosis, and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate Cox proportional hazards regression analysis was used to assess for correlation between OS and international prognostic index (IPI), curative treatment, and TTT.

Forty patients with stage I-II MZL were identified. All had extranodal disease. Median age was 61 years (range 34–78). Sixteen were male and 24 were female. The 5-year OS from diagnosis was 89%. IPI, curative treatment, and TTT were not found to predict OS (HR 3.86, p=0.18; HR 0.40, p=0.46; and HR 1.00, p=0.99, respectively), although there were only three deaths.

Seventeen patients received potentially curative treatment first line. All patients had extranodal limited stage MZL. The following sites were involved: GI tract (9), orbit (3), skin (2), lung (1), parotid (1), and submandibular (1). All patients with available data had low or low-intermediate risk IPI scores. Three patients were treated with radiotherapy alone, 2 underwent surgery alone, and 8 received antibiotic treatment alone. Two were treated with surgery and radiotherapy, one with antibiotics and radiotherapy, and one with antibiotics and rituximab. Eight of 10 patients who received antibiotics had GI involvement; five were H. pylori positive. Two patients with extranodal MZL outside of GI tract (orbit and skin) were H. pylori positive and therefore treated with antibiotics. Median TTT for first therapy was 0.5 months (range 0.5–14). Median PFS was 54 months (95% CI 37-NR). Six of the 17 patients were known to have relapsed. Two were subsequently treated with radiotherapy, two with surgery, one with a second course of antibiotics, and one with rituximab. The 5-year OS from diagnosis in this group was 100%. Due to the lack of events, we were not able to look for an association between OS and IPI, curative treatment, and TTT in this group.

Twenty-three patients did not receive curative treatment. All of these patients had extranodal disease – all diagnosed by biopsy without complete resection. Extranodal MZL was located in lung (7), GI tract (5), parotid (3), skin (3), breast (2), orbit (2), and infratemporal area (1). Seven patients with sufficient data had an IPI score of 0 and 3 each had scores of 1, 2, and 3. Median follow up time was 26 months (range 0.5–135). To date, 12 patients have received no treatment (3 GI, 3 lung, 2 breast, 2 parotid, and 2 skin). Four received rituximab as a single agent and 2 received both rituximab and prednisone. Five received systemic chemotherapies with R-CVP, chlorambucil, fludarabine, or methotrexate. Sixteen patients were observed for at least 3 months before receiving any therapy. Median TTT from diagnosis for the 21 patients with data was 26 months (range 0.5–82). The 5-year OS was 78%. TTT did not correlate with OS (HR 0.99, p=0.78).

Patients with early stage MZL have an excellent prognosis regardless of whether they are treated for curative intent, observed, or offered systemic therapy. Our data suggest that overall survival is not impacted by choice of therapy type or observation.

Coleman:Immunomedics: Membership on an entity's Board of Directors or advisory committees. Leonard:glaxosmithkline: Consultancy; EMD Serono: Consultancy; Sanofi Aventis: Consultancy; Pfizer: Consultancy; Immunomedics: Honoraria; Cell Therapeutics: Consultancy; Celgene: Consultancy; Johnson and Johnson: Consultancy; Calistoga: Consultancy; Cephalon: Consultancy; Biogen IDEC: Consultancy; Hospira: Consultancy; Millenium: Consultancy; Novartis: Consultancy; Abbott: Consultancy; Seattle Genetics: Consultancy. Martin:Millennium Pharmaceuticals Inc.: Research Funding, Speakers Bureau.