Ocular adnexal lymphomas (OALs) represents 8% of primary extranodal lymphomas, 80% of OALs constitutes extranodal marginal zone lymphomas (EMZL). In the last years the incidence of OLAs has increased more rapidly than Non Hodgkin Lymphoma at other extranodal site. Radiotherapy is associated to high rates of local disease control, but also to the risk of relapse and immediate and delayed complications, such as xerophtalmy, corneal ulcerations, cataract and retinal damage. Surgery is a feasible option, but not always satisfactory in terms of disease control. Single-agent chemotherapy with alkylating agents is used for the treatment of low-grade lymphomas, including OALs. Rituximab, a chimeric anti-CD20 monoclonal antibody, is effective in EMZL and in OALs.
We investigated the efficacy and the safety of a combination of chlorambucil and rituximab as first line treatment in patients with OALs.
Patients with histologically proven low-grade OALs were enrolled in this study. Staging included CT-scan of the orbit, neck, chest and abdomen, MR of the orbit, Chlamydia psittaci (Cp) detected by PCR and bone marrow biopsy. Treatment consisted of chlorambucil (0,1 mg/Kg/die for 45 days, then on days 1 to 15 monthly for 4 months) and rituximab (375 mg/sqm weekly for 4 doses, then monthly for 4 infusions). Toxicities were reported according to WHO criteria. At the end of treatment patients were restaged clinically and with a MR of the orbit.
Since November 2003 to November 2010 twenty consecutive, histologically proven, low-grade OALs (19 EMZL, a grade I follicular lymphoma) have been treated according to protocol. The median interval between onset of the first symptoms and diagnosis was 13 months (range, 4 months – 3 years). Twelve pts were female (60%) and eight pts were male (40%). Median age at diagnosis was 68 years (range, 35–86 years). Disease was localized in the conjunctiva in 15 patients (75%), in the lacrimal glands in 2 patients (10%) and in other orbital sites in the last three patients (15%). Nineteen patients presented a stage I disease, one stage IV, and no patient showed B-symptoms. LDH was within normal range in 17 of 20 patients (85%), ECOG-PS was 0 and International prognostic Index (IPI) was low or low-intermediate in all patients. We evaluated PCR for Chlamydia psittaci in the first ten consecutive pts and it was negative. All patients completed the treatment without delay; there was no grade III-IV toxicities neither hospitalizations. Five patients had grade 1–2 rituximab infusion-related reactions usually during the first infusion and haematological toxicity was mild. At the end of treatment 19 patients (95%) resulted in CR, and one obtained a partial remission (5%). After a median follow-up of 56 months (range, 21–106 months) all patients are alive, 17 maintained CR and two relapsed (after 3 and 5 years), one was retreated with the same protocol and attained a new CR and the other relapsed systemically as follicular lymphoma. The patient in PR after first line obtained CR with second line therapy (rituximab fludarabine and cyclophosphamide). The median PFS was 43 months (range, 3–98 months). All patients performed ophthalmologic follow-up visits: we did not report ocular toxicities, and all patients conserved a normal visual function, including acuity. No secondary myelodisplatic syndrome or secondary neoplasms are reported.
After a long follow-up the combination of rituximab and chlorambucil proved to be low toxic, feasible and effective therapy for primary OALs. No delayed ocular or haematological complications are reported. For this reason the combination of immunotherapy and mild chemotherapy should be considered for the treatment of this indolent lymphoma.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.