CLINICAL NEWS
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 nonreproducible 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 lymphomaspecific 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 . ●
REFERENCE
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 ]
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