Treatment of Splenic Marginal Zone Lymphoma with Rituximab Monotherapy in 59 Patients
Authors: Kalpadakis Christina H. , Pangalis Gerassimos , Vassilakopoulos Theodoros P. , Sachanas Sotirios P. , Kontopidou Flora , Yiakoumis Xanthi , Kokoris Styliani , Dimitriadou Evangelia , Dimopoulou Maria , Moschogiannis Maria , Korkolopoulou Penelope , Kyrtsonis Marie-Christine , Siakantaris Marina , Papadaki Helen A. , Angelopoulou Maria K. 
Published: October 2019

Abstract
Abstract 2712
Treatment of splenic marginal zone lymphomas (SMZL) is traditionally based on splenectomy. However, preliminary data suggest that rituximab monotherapy is highly effective in SMZL patients. The aim was to assess the efficacy of rituximab administration in a large series of patients with SMZL, as upfront therapy.
Fifty-eight patients with the diagnosis of SMZL were prospectively treated, between September 2003 and July 2011, with rituximab monotherapy. Patients' clinical characteristics are shown on table 1. Rituximab was given in two phases: Induction phase at a dose of 375mg/m2 per week for 6 weeks and maintenance phase at the same dose every 2 months for 1–2 years. Evaluation of response was performed 2 months after induction and 2 months after the end of maintenance phase.Table 1.Clinical and Laboratory Findings of SMZL patients at Diagnosis According to Treatment ApproachFeatures# % of patientsN58Age –median (range)64 (41–91)Sex:Male26 45Â symptoms1 2Palpable splenomegaly(cm, below left costal margin, range)10 (2–16)Lymphadenopathy*14 24Bone marrow involvement58 100Anemia (Hb<10g/dl)21 36Neutropenia (<1.5x109/l)10 17Lymphocytosis (>4.0x109/l)27 47Thrombocytopenia (<100x109/l)9 16LDH>normal values20/57 35M component19/50 38Hepatitis C0International Prognostic IndexLow risk17/57 30Low-intermediate27/57 47High-intermediate12/57 21High risk4/57 7*by computerized tomography
Fifty-five patients were evaluable for response. The overall response rate (ORR) after the end of induction phase was 94% (52/55) with 45% (25/55) presenting complete response (CR), 27% (15/55) unconfirmed CR (CRu) (in those who did not undergo bone marrow reevaluation), 22% (12/55) partial response (PR). The median time to hematologic and clinical response was 2 and 3 weeks respectively. 29/52 rituximab responders have already completed maintenance therapy and were evaluable for response (10 did not receive maintenance therapy due to refusal, 13 have not completed this phase yet). Evaluation of response after the end of maintenance phase disclosed that 21 patients sustained their initial response while in 7 patients a further improvement of response was documented: PR after induction phase was converted to CR after the end of maintenance phase. However one patient lost her initial response (CR) during maintenance therapy. The 5-year OS and PFS for rituximab treated patients was 94% and 68% respectively. Of the 10 patients, who did not receive maintenance, three (33%) relapsed at 24, 29 and 38 months respectively. On the other hand, among the 29 patients who have already completed maintenance therapy, 4 relapsed (14%) at a median time of 43 months (range, 35–48). None of the 13 patients who are currently receiving maintenance has relapsed so far. Maintenance phase was clearly associated with better PFS: Median PFS was 38 months for pts not receiving maintenance, but it has not been reached yet in pts receiving maintenance. At 4 years PFS was 79% vs 27% (p=0.001), for patients who received maintenance or did not, respectively. A total of 7/52 rituximab responders (13%) relapsed at a median time of 37 months (range, 24–48). 6/7 patients were retreated with rituximab and 4 of them responded for a response rate of 67%. One out of the 4 responders to rituximab reinduction experienced a second relapse 30 months later. This patient was retreated with rituximab and remains in CRu for 26 months. Three deaths were recorded in the rituximab group: 1 patient died of unrelated cause and 2 of lymphoma.
Rituximab is a very effective and well tolerated therapy and may substitute splenectomy as first-line treatment for SMZL. Maintenance with rituximab might prolong the duration of response, although this warrants further evaluation.

Disclosures:
No relevant conflicts of interest to declare.