Multicenter Retrospective Cohort Study of 694 Patients with Ocular Adnexal Marginal Zone B-Cell Lymphoma on Behalf of the Chinese Ocular Lymphoma Collaborative Group (COLCG)

Background:

Ocular adnexal marginal zone B-cell lymphoma (OAML) is a rare entity of indolent lymphoma with lesions confined to the ocular adnexal, although few patients also have extraocular involvement. Recently, the Chinese Ocular Lymphoma Collaborative Group (COLCG) published “Chinese expert consensus on the diagnosis and management of ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma”. To better provide guidance for improved treatment of OAML, we conducted a multicenter study including 694 patients to demonstrate the real-world data concerning clinical characteristics, treatments, and long-term outcomes.

Methods

A total of 694 patients with OAML from 11 centers of China were included. Baseline characteristics, treatments, long-term outcomes and treatment-related adverse events were collected. This study was approved by the Ethics Committee of Beijing Tongren Hospital.

Results

The median age was 57 years old (13-91). 33 patient had an ECOG-PS score of ≥2, and 25 patients had systemic B symptoms. 12 patients reported baseline auto-immune diseases, mainly sicca syndrome and systemic lupus erythematosus. 42 patients had previous diagnosis of eye diseases, mainly cataract and xerophthalmia. 17 patients had a past medical history of non-hematologic malignancies and had stable diseases at the time of OAML diagnosis. 29 patients carried infectious diseases, mainly hepatitis B or C. Because chlamydia psittaci was not routinely tested in China, only one patient was found to be positive for chlamydia psittaci.

The diagnosis of OAML was confirmed by surgical resection or biopsy of ocular lesions. PET-CT and/or MRI scan were performed to stage the disease. 144 patients had bilateral ocular disease (20.7%), and the frequency of affected ocular lesions from most to least were bulbar conjunctiva, eyelid, lacrimal gland, optic nerve, and paranasal sinus, etc. Only one patient had intracranial involvement by direct lymphoma infiltration. Bone marrow biopsy was performed in 217 patients, among whom 16 patients were defined positive for bone marrow infiltration of lymphoma (7.4%), and the baseline PET-CT scan could not predict the bone marrow status for these patients. Using Ann-Arbor staging system (data was available for 524 patients), 421 patients had stage I disease (80.3%), 30 patients had stage II disease (7.1%), and 73 patients had advanced diseases. Due to the heterogeneity of ocular lesions, TNM staging system was also used for OAML patients. 156 patients were staged as T1, 295 patients were staged as T2, and the remaining patients were staged as T3 or T4.

After diagnosis of OAML, 229 patients underwent a regular watch and wait (W&W) strategy due to no residual lymphoma or no symptoms. 160 patients (34.4%) received radiotherapy (RT). 187 patients (40.2%) were treated with immunochemotherapy regimens, such as R-CHOP, R-CVP, BR, etc. Local ocular injection of rituximab was done in eight patients. Best response evaluation was available for 455 patients who received post-surgery consolidation therapy. The overall response rate (ORR) was 94.5% (including 237 patients with complete response and 193 patients with partial response), and five patients had progressive disease. At a median follow-up time of 731 days (12-7443), a total of 142 patients got disease progression or relapse (20.5%), among whom 130 patients had intraocular relapse and 12 patients had extraocular relapse (8.5%). Only one patient was defined as histological transformation to DLBCL. 47 patients were treated with salvage RT, among whom 45 patients responded (95.7%, including 23 patients with complete response). 18 patients died, among whom only three patients died from lymphoma-related events. The 10-year overall survival rate was 95.5%, and 10-year lymphoma-specific overall survival rate was 99.3%. Concerning adverse events for patients who received RT, 33 developed dry eye syndrome (20.6%), 16 patients had diminution of vision (10%), and only two patients got cataract (1.3%).

Conclusions:

Chinese patients with OAML had favorable long-term outcomes, and the risk of histological transformation was very low. The application of RT as front-line consolidation strategy is insufficient, and the side effects of RT were tolerable. Future studies should focus on use of low-dose RT as upfront therapy for OAML to further reduce the relapse rate and improve the quality-of-life.