Uncovering the Natural History of Primary Ocular Adnexal MALT Lymphoma

Primary ocular adnexal MALT lymphoma (POAML) is the most common orbital tumor affecting patients in the United States, but little is known about the natural history of the disease. In a report published in Blood, Amrita Desai, MD, from the Division of Hematology and Oncology at the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, and authors conducted a retrospective analysis of patients with POAML to characterize the long-term outcome, response to treatment, and the incidence of relapse or transformation to lymphoma in patients with the disease.

“While studies have implicated a role for auto-antigen–induced activation of the B-cell receptor in the pathogenesis of POAML … a large gap in knowledge of POAML exists, primarily due to the rarity of this disease,” Dr. Desai and authors wrote. “The majority of POAML clinical studies are small and retrospective with limited follow-up, resulting in non-reproducible findings and an incomplete understanding of the disease. The absence of prospective, randomized, phase III studies has resulted in no official level I recommendations on optimal treatment.”

The analysis includes data from the largest single-center study of patients with POAML, consisting of 182 patients enrolled at one of three centers at the University of Miami (including Bascom Palmer Eye Institute, Jackson Memorial Hospital, and Sylvester Comprehensive Cancer Center) between January 1984 and December 2015. Patients were included if their diagnosis met morphologic and immunophenotypic criteria for MALT lymphoma, with primary ocular adnexa involvement at the eye socket, the conjunctiva, lacrimal gland, or eye.

Median age at diagnosis was 63 years (range = 7-92 years) and, consistent with previous reports, the disease was more common in women (female-to-male ratio of 1.5:1). The most frequent involvement site was the eye socket (n=102; 56%), followed by the conjunctiva (n=51; 28%) and lacrimal gland (n=29; 16%).

The majority of patients (80%; n=145) presented with Ann Arbor stage I disease and, the authors noted, “relevant, previous history was remarkable for prior diagnosis of autoimmune diseases, cancer, and eye disorders in 18 (12%), 26 (19%), and 26 (19%) patients, respectively.”

Patients were treated according to disease stage at the discretion of their physicians. A total of 174 patients had available data on first-line treatment and response.

Radiation therapy was the most commonly used first-line treatment modality (67%; n=117), at doses ranging from 22.0 to 45.0 Gy (median = 30.6 Gy). Other methods included chemotherapy alone or a combination of radiation therapy and chemotherapy.

Over a median follow-up of 63.5 months (range = 1-387 months), 84 percent of patients achieved a complete response after firstline therapy, while 8 percent achieved a partial response, 3 percent had stable disease, and 5 percent had progressive disease.

Median overall survival (OS) and progression-free survival (PFS) for all patients were 250 months (range = 222-not reached) and 134 months (range = 87-198), respectively. “Median lymphoma-specific OS was not reached and eight-year lymphoma-specific OS was 98.7 percent,” Dr. Desai and authors said.

Estimates for PFS for all patients were:

  • 1 year: 91.5% (95% CI 86.1-94.9)
  • 5 years: 68.5% (95% CI 60.4-75.6)
  • 10 years: 50.9% (95% CI 40.5-61.6)

In multivariate analyses, the risk of shorter PFS was significantly greater for patients >60 years old (hazard ratio [HR] = 2.44; p=0.01) and for those who were treated with radiation therapy <30.6 Gy (HR=4.17; p=0.0003). In patients with stage I disease who were receiving radiation therapy, higher doses (≥30.6 Gy) were associated with significantly longer PFS. Ten percent of patients had bone marrow involvement, but the authors found that it did not affect outcomes for these patients, suggesting that it is not a necessary component of initial disease staging.

According to Dr. Desai and authors, these results confirm the indolent nature and “excellent clinical outcome” of POAML, characterized by long survival and a low rate of lymphoma-attributed mortality; however, they noted, POAML is associated with a persistent risk for relapses and a low, but significant, risk for transformation to diffuse large B-cell lymphoma (n=7; 4%).

Local and systemic relapses occurred continuously over time in patients with stage I disease, the researchers observed, regardless of the radiation therapy dose or initial clinical response. The estimated incidence of cumulative relapse or progression was 5.1 percent at one year, 17.5 percent at five years, and 31 percent at 10 years. Five patients with stage I disease (4.5%) developed recurrent disease in the central nervous system.

The study is limited by its retrospective design, the variability in treatment, and the lack of standardized staging evaluation methods for this rare disease.

“These limitations preclude derivation of recommendations on the dose of radiation therapy, but [they] indicate the need for prospective, randomized trials that should address this question,” Dr. Desai and authors concluded.


Desai A, Joag MG, Lekakis L, et al. Long term course of patients with primary ocular adnexal malt lymphoma: a large single institution cohort study. Blood. 2016 October 27. [Epub ahead of print]