Outcomes in Patients with Splenic Marginal Zone Lymphoma or Marginal Zone Leukemia/Lymphoma Treated with Immunotherapy, Chemoimmunotherapy, or Chemotherapy.
Authors: Tsimberidou Apostolia-Maria , Catovsky Daniel , Schlette Ellen , O’Brien Susan , Kantarjian Hagop , Wierda William G. , Wen Sijin , Lerner Susan , Keating Michael J. 
Published: April 2020

Abstract
Purpose: The optimal management of splenic marginal zone lymphoma (SMZL) or marginal-zone leukemia/lymphoma (MZL) is controversial. We retrospectively assessed the clinical outcome of patients with SMZL/MZL treated with systemic therapy.
Patients and Methods: Patients were assessed by the time of their first treatment at U. T. M. D. Anderson Cancer Center, Dept. of Leukemia (5/95 to 10/04). Diagnosis was confirmed in 70 patients by slide review. The indications for treatment were the same as those used for patients with CLL.
Results: The median age was 64 years (range, 33–88); and 61% of patients had monoclonal gammopathy. The median number of CD20 molecules/cell was 65.2 x 103 (16–260 x 103). Of the patients who required systemic therapy, 26 were treated with immunotherapy (rituximab, 25; alemtuzumab, 1); 6 with chemoimmunotherapy (CI/T; rituximab combined with a fludarabine-based regimen); and 11 with chemotherapy (C/T). Ten patients had splenectomy, and 17 were in the observation group. The overall response rates were 88% (CR, 31%) in the immunotherapy group, 83% (CR, 17%) in the CI/T group, and 55% (CR, 18%) in the C/T group. The median follow-up was 2.7 years. Patients treated with immunotherapy +/− C/T had higher rates of overall and failure-free survival compared with those treated with C/T.
Figure Figure
In univariate analysis, the only factors predicting longer survival were age &gt;60 years (p=0.01) and immunotherapy +/− chemotherapy (p=0.04). Seventeen (24%) of 70 patients had other malignancies prior to (n=8) or after (n=8) treatment of SMZL/MZL or both (n=1). Changes in bone marrow and blood counts in patients treated with rituximab (n=25) were compared with those of patients who had splenectomy as initial therapy (n=17, including 7 who had subsequent therapies). Rituximab resulted in the disappearance of a palpable spleen (median size, 6 cm; range 0–20cm) in 23 (92%) patients. Rituximab was superior to splenectomy in normalizing the white blood cell (WBC) counts (p&lt;0.001) and absolute lymphocyte counts (ALC)(p&lt;0.001). Splenectomy resulted in higher platelet counts compared with rituximab, but platelet counts remained within the normal range in all patients treated with rituximab. Hemoglobin levels and bone marrow cellularity did not reach statistical significance, but there was a trend towards a significantly lower proportion of lymphocytes in patients treated with rituximab (p=0.1).
Conclusions: Rituximab with or without C/T induces durable remissions and prolongs survival in patients with SMZL/MZL, probably because CD20 molecules/cell are higher in SMZL/MZL than in CLL. Our data demonstrate that rituximab effectively controls SMZL, as evidenced by improvement in WBC and ALC and splenomegaly, and may be the treatment of choice, at least in older SMZL patients with comorbid diseases. Clinical trials of immunotherapy or CI/T are warranted.